bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Imaging of Nervous Systems Using Voltage‐Sensitive Dyes
Authors: Salzberg Brian M 
Published: December 2009

Abstract

Voltage‐sensitive dyes are small molecules that bind to cell membranes and change their optical properties, absorption or fluorescence, in response to changes in membrane potential, the voltage across the membrane. These optical changes are extremely rapid and tend to be linear reporters of local electrical events. Thus, these ‘potentiometric probes’ behave as molecular voltmeters and can be used, with a high‐speed camera or other image dissector, for functional imaging of electrical activity including action potentials, synaptic potentials, and passive (electrotonic) signals. No physical contact with the object is required and spatial and temporal resolution is limited primarily by signal‐to‐noise considerations. Such millisecond time‐resolved functional imaging can be of single cells, of regions of cells or of nervous systems, of cardiac muscle or of any other electrically active tissue. In the nervous system, functional imaging of electrical activity can lead to an understanding of the spatio‐temporal relationships between neurons and of their functional connectivity.

Key Concepts:

In electrically excitable cells, the membrane potential can change extremely rapidly.

Some coloured molecules (dyes) change their optical properties in response to changes in the local electric field.

Changes in the optical properties of the molecules that stain‐cell membranes can be used to follow rapid changes in membrane potential.

A high‐speed camera, usually with a microscope, can be used together with these dyes to monitor the electrical activity at hundreds or even thousands of sites, virtually simultaneously.

Functional imaging of electrical activity can lead to an understanding of the spatio‐temporal relationships in nervous systems, and to the functional connectivity among neurons.
Coltiviruses and Seadornaviruses
Authors: Mohd Jaafar Fauziah , Mertens Peter , Attoui Houssam 
Published: December 2009

Abstract

Coltiviruses and seadornaviruses are members of family
Reoviridae
, which encompasses alongside genera

Coltivirus

and

Seadornavirus

13 other genera of viruses that can infect mammals, birds, aquatic animals, reptiles, insects, plants, fungi and protists. Coltiviruses are transmitted by hard ticks of the family
Ixodidae
, whereas seadornaviruses are mosquito‐borne. These viruses can infect humans, following the bite of adult‐infected female ticks or mosquitoes, causing febrile illnesses and are occasionally responsible for encephalitis. Coltiviruses are principally endemic in the northwestern parts of the USA and Canada and were also reported in European countries, including France and Germany. Antibodies to coltiviruses have also been identified from patients in the former Czechoslovakia and in South Korea. Seadornaviruses are principally endemic in the south east of Asia, although recent data showed that there has been an expansion of their distribution northwards, reaching the north‐western Chinese borders.

Key concepts:

Coltiviruses are transmitted by adult female tick (family
Ixodidae
) bite and have animal reservoirs.

Coltiviruses can infect humans causing febrile illnesses and can cause encephalitis in rare cases.

Seadornaviruses are transmitted by mosquitoes and no animal reservoir is known to date.

Seadornaviruses can infect animals and humans causing febrile illnesses and were reported to be responsible for cases of encephalitis.

Coltiviruses show an evolutionary relationship to the turreted mycoreoviruses, aquareoviruses and orthoreoviruses.

Seadornaviruses show an evolutionary relationship to the nonturreted rotaviruses.

Coltiviruses seem to represent a missing link between turreted and nonturreted members of family
Reoviridae.

Differential diagnostic serological and molecular assays for coltiviruses and seadornaviruses are available.

Structure of the viral particles of Banna virus shows striking similarities to that of the rotaviruses.
Death Receptor‐induced Necroptosis
Authors: Declercq Wim , Van Herreweghe Franky , Berghe Tom Vanden , Vandenabeele Peter 
Published: December 2009

Abstract

Recent studies on cellular

in vitro

models have made it clear that death receptor (DR)‐induced necrosis, also called necroptosis, is a programmed form of necrotic cell death. In contrast, accidental necrosis is mainly induced by physicochemical stress, such as heath or chemicals. Many DRs signal to apoptosis or necroptosis depending on whether caspases are active or not. The
kinase
activities of
receptor‐interacting protein 1
(
RIP1
) and
RIP3
have emerged as crucial regulators of DR‐induced necroptosis. The precise execution mechanisms during necroptosis are still poorly understood but involve different cellular compartments such as the mitochondria, the lysosomes and the cell membrane.

In vivo

, necroptosis occurs mainly in pathophysiological processes such as ischaemia‐reperfusion injury in heart, brain and kidneys, viral infection and pancreatitis, and is capable of killing tumour cells that have developed strategies to evade apoptosis. Thus, detailed knowledge of necroptotic signalling may be exploited in therapeutic strategies.

Key concepts:

Necrosis is characterized by swelling of the endoplasmic reticulum, mitochondria and cytoplasm, with subsequent rupture of the plasma membrane and lysis of the cells.

Death receptor‐induced necrosis, also called necroptosis, is a programmed form of necrotic cell death. This is in contrast to necrosis induced by physicochemical stress, such as heath or hydrogen peroxide.

The necrosis‐signalling complex, or necrosome, consists of a complex containing FADD, caspase‐8, RIP1 and RIP3.

Expression of RIP3 renders cells permissive to death receptor‐induced necroptosis.

RIP1 and RIP3 kinase activity is crucial for necroptotic signalling.

Apoptosis counteracts necrotic signalling by cleavage of RIP1 and RIP3.

Necroptosis forms a back‐up cell death mode in case caspases activity is prevented or inhibited.

In vivo
, necroptosis occurs mainly in pathophysiological processes such as ischaemia‐reperfusion injury in heart, brain and kidneys, viral infection and pancreatitis, and is capable of killing tumour cells that have developed strategies to evade apoptosis.
Caspases, Substrates and Sequential Activation
Authors: Walsh John G , Martin Seamus J 
Published: December 2009

AbstractSuperfluous, aged or damaged cells are eliminated from tissues via a controlled cell death process, called apoptosis. Apoptosis is coordinated by a group ofcysteine aspartic acid‐specific proteases(caspases) that become specifically activated within cells destined to die. Some of these proteases act as initiators, their role being to interface with signalling events and initiate the proteolytic cascade, whereas others act as executioner enzymes and carry out the internal dismantling of the cell that results in death. During the terminal phase of apoptosis the executioner caspases (caspases‐3 and ‐7) simultaneously cleave hundreds of protein substrates to terminate cell viability and produce the characteristic apoptotic phenotype. This large‐scale proteolysis also dismembers the cell into discrete fragments that are recognized and removed by scavenging phagocytes. Recent evidence also suggests that the actions of executioner caspases may disable molecules that are capable of initiating or exacerbating immune responses if released into the extracellular space.Key Concepts:Pro‐apoptotic stimuli lead to the activation of caspases.Caspase activation takes the form of a cascade of sequential activation events.Caspases mediate the structural changes characteristic of apoptotic cell death by processing key protein substrates.Caspase‐dependent demolition of the apoptotic cell facilitates its safe removal by surveying phagocytes.
Structural Variation in Great Ape Genomes
Authors: Aerts Jan A , Tyler‐Smith Chris 
Published: December 2009

AbstractStructural variation within and between Great Ape genomes affects more nucleotides than single‐base variation, yet its extent and phenotypic consequences are much less well understood. The most‐studied structural variants are copy number variations (CNVs) which can be generated by several different mechanisms including non‐allelic homologous recombination, non‐homologous end‐joining anddeoxyribonucleic acid(DNA) replication‐related fork stalling and template switching. CNVs are closely related to segmental duplications (SDs): SDs can stimulate the formation of CNVs and themselves started out as CNVs, but became fixed in a species. Structural variation can be neutral but has also influenced our phenotypic evolution, for example our susceptibility to disease and our ability to digest certain types of food. Our understanding of the extent of structural variation is increasing rapidly, but it will be much more difficult to understand its phenotypic consequences.Key conceptsStructural variation includes balanced variants such as inversions and translocations, and unbalanced ones such as duplications and deletions (copy number variations or CNVs).Structural variants can arise by several mechanisms, including nonallelic homologous recombination (NAHR), nonhomologous end‐joining (NHEJ) and DNA replication‐based fork stalling and template switching (FoSTeS).CNV is closely linked to segmental duplication, but is not exactly the same. Segmental duplications can stimulate CNV formation by NAHR, and themselves arise from CNVs that have become fixed.Segmental duplications did not appear uniformly during the evolution of the Great Ape species, but rather during a burst of activity around the time of the divergence of gorilla from the human/chimpanzee ancestor.Duplicated genes play a critical role in the evolution of a genome as they act as ‘spare parts’ than can evolve to perform new or more specialized functions.Effects of structural variation on gene expression can be identified but only a few examples of the consequences for species biology have been documented.CCL3L1copy number varies within humans and has been reported to influence HIV susceptibility. It has been reported to differ in copy number between humans and chimpanzees as well, although other research shows no species difference, illustrating the technical complications associated with such analyses.Humans have more copies of the amylase geneAMY1than chimpanzees and so are better able to digest starch, which forms a larger part of their diet.Chimpanzees have deleted several inflammatory‐response genes (APOL1,APOL4,CARD18,IL1F7andIL1F8) and are thus likely to differ in this pathway, but the specific evolutionary force that has driven this change, if any, is unknown.
Antibiotics and the Evolution of Antibiotic Resistance
Authors: Martinez Jose L , Baquero Fernando 
Published: December 2009

Abstract

Antibiotics were introduced for human therapy few decades ago and their utilization has produced the rapid evolution of bacterial pathogens towards resistance. Before this recent and fast evolution, antibiotics and their resistance genes have evolved for millions of years in environmental microorganisms. Recent results suggest that, besides serving for inhibiting the growth of competitors, antibiotics might be signalling molecules in natural ecosystems and that some metabolic enzymes and signal‐trafficking efflux pumps might render a phenotype of resistance in the presence of high concentrations of antibiotics. Antibiotic resistance can be developed by mutation or by the acquisition of resistance determinants by means of horizontal gene transfer. Spread of resistance is achieved through the combination of different elements, from resistance genes to plasmids and bacterial clones. The release of high amounts of antibiotics and resistance genes in natural habitats is challenging the microbial populations present in these ecosystems.

Key concepts

Some antibiotics can be involved in intermicrobial communication at the low concentrations likely found in most natural ecosystems.

The origin, spread and diversification of mechanisms of antibiotic resistance is an excellent model for studying real‐time evolution.

The fact that a given gene confers resistance when transferred to a bacterial human pathogen does not necessarily mean that it plays the same functional role in its original host.

Exaptation is an evolutionary process by which a given determinant changes its function, without changing its structure, as the consequence of an environmental change.

Anthropogenic antibiotic pollution in the environment might modify the genetic structure of bacterial populations and communities.

Antibiotic resistance evolves frequently in a modular fashion, combining sequences, genes, genetic platforms and genetic vehicles.

The association of several antibiotic resistance genes in the same genetic vehicle favours their dissemination and persistence.

The spread of antibiotic resistance frequently occurs by the global dissemination of particularly transmissible bacterial resistant clones.

Antibiotic resistance is fixed in human or animal populations when the resistance genes enter into endemic clones.

Prediction of evolutionary trajectories should constitute the ultimate way to demonstrate the truth of hypothesis in evolutionary sciences.
Inhibitors of Initiation Phase of Bacterial Protein Synthesis
Authors: Marquez Viter , Sohmen Daniel , Wilson Daniel N 
Published: December 2009

Abstract

The initiation phase is the rate‐limiting step in protein synthesis where messenger
ribonucleic acid
(mRNA), initiator‐transfer RNA (tRNA) and ribosomal subunits are assembled together in the presence of specific initiation factors. This process is the target for a diverse subset of antibiotics that inhibit the initiation step in a variety of different ways. Dissecting the mechanism of action of these antibiotics has provided insight not only into their inhibitory action but also into the process of translation initiation itself. With the dramatic increase in resistance of bacterial strains to many clinically relevant antibiotics, the discovery of improved inhibitors is becoming more important. Because the known initiation inhibitors bind to distinct regions of the ribosome compared with clinically used antibiotics, revisiting the initiation inhibitors may open new avenues to the development of novel antimicrobial agents.

Key Concepts:

Initiation of protein synthesis in bacteria operates through a 30S pre‐initiation complex.

Aurintricarboxylic acid is a nonspecific compound that
in vitro
at least can prevent translation initiation by perturbing binding of mRNA to the small ribosomal subunit.

Kasugamycin binds within the path of the mRNA on the small subunit to prevent correct interaction between initiator tRNA and start codon to prevent translation initiation.

Binding of edeine to the small subunit induces base pair formation between G795 and C693 and prevents binding of initiator tRNA to the small subunit.

Pactamycin binds in the E‐site in the path of the mRNA and prevents the first translocation reaction in a tRNA‐dependent fashion.

Evernimicin binds to the large subunit and prevents IF2‐dependent formation of the 70S initiation complex.

The tetrapeptide GE81112 binds to the 30S subunit to inhibit 30S initiation complex formation.

Antibiotics that inhibit translation also induce ribosomal assembly defects.
SUMO
ylation
Authors: Schimmel Joost , Vertegaal Alfred CO 
Published: December 2009

Abstract

SUMOs
are Small
Ubiquitin
‐like MOdifier proteins that are covalently attached to hundreds of known target proteins to regulate their function. SUMOylation is the process of conjugating
SUMOs
to target proteins via
E1
,
E2
and
E3
enzymes and occurs mostly at specific SUMOylation consensus sites in targets. SUMOylation is a reversible process;
SUMO‐specific proteases
remove
SUMOs
from target proteins. It has been established that reversible protein SUMOylation is critical for eukaryotic life. A wide variety of cellular processes are regulated by SUMOylation including
deoxyribonucleic acid
(DNA) metabolism, transport, ribosome biogenesis and translation. Proteins can also associate with
SUMO
noncovalently via
SUMO
interaction motifs (SIMs). This affects target protein function and can also affect the subcellular localization of target proteins. Similar to
ubiquitin
,
SUMOs
can form polymers via internal SUMOylation sites. Crosstalk between SUMOylation and other posttranslational modifications such as phosphorylation, acetylation and ubiquitination is required for appropriate control of target protein activity.

Key concepts:

SUMOs are Small Ubiquitin‐like MOdifiers that are covalently attached to lysines in target proteins.

SUMOylation, the process of SUMO conjugation to a target protein, frequently occurs on a lysine situated in a SUMOylation consensus site.

Conjugated SUMOs can be removed from target proteins by SUMO‐specific proteases.

Vertebrates express three different SUMO isoforms, SUMO‐1, SUMO‐2 and SUMO‐3, encoded by three different genes.

SUMOs can form polymers via internal SUMOylation sites in SUMO‐2 and SUMO‐3.

Several proteins can bind noncovalently to SUMOs via SUMO interaction motifs (SIMs).

A finely balanced SUMOylation/deSUMOylation system is required for eukaryotic life.

Crosstalk between SUMOylation and other posttranslational modifications like acetylation, phosphorylation and ubiquitination, is important for full control of target protein activity.
Purifying and Analysing Cytosolic Protein Complexes
Authors: Phillips Theresa M 
Published: December 2009

Abstract

The study of cytosolic protein complexes, called systems or functional proteomics, is complicated by the challenges associated with purifying unadulterated, functional complexes, and with developing analytical methods for studying protein structure that can accommodate high molecular masses, or weak and transient protein–protein interactions. Development of new analytical techniques has progressed considerably in recent years, with the adaptation of mass spectrometry (MS) and nuclear magnetic resonance (NMR) for large complexes, in particular, adaptations using the popular electrospray ionization (ESI) coupled with a ToF (time‐of‐flight) analyser. Purification methods that have been adapted for the study of protein–protein interactions include electromobility shift assays, formaldehyde crosslinking, tandem affinity purification (TAP) and coexpression purification techniques, whereas flow field‐flow fractionation (F4) has been cited as having many significant advantages over all of these. New approaches to study posttranslational modifications, and adaptation of detection methods for quantitative analyses, are also being used to advance the study of protein complexes.

Key Concepts:

Functional proteomics aims to identify how proteins interact with each other and other macromolecules.

Purification of protein complexes is more difficult than that of individual proteins.

Techniques for protein complex purification include methods such as formaldehyde crosslinking and tandem affinity purification.

The introduction of electrospray ionization made it possible to create aerosols of proteins that could be analysed by mass spectrometry.

Methods for isolation of a complex for study include
in vitro
reconstitution, coexpression and endogenous complex purification.

Protein complexes with transient interactions can be studied using nuclear magnetic resonance.

Formaldehyde crosslinking stabilizes protein interactions during purification.

The yeast two‐hybrid technique is usually used to isolate transcriptional proteins from the nucleus.

A modification of the Western blot, called a gel overlay assay, is used to detect proteins with binding affinity for one another.
EM
Analysis of Protein Structure
Authors: Ohi Melanie D 
Published: December 2009

Abstract

Proteins carry out most cellular processes in the context of dynamic multiprotein assemblies. Although mapping the large number of protein interactions found within cells is progressing rapidly, we still lack knowledge about how proteins assemble into macromolecular machines to perform their functions. Electron microscopy can be used to determine the shape and structures of biological molecules that are difficult to study by more traditional structural approaches, such as X‐ray crystallography and NMR analysis. However, since biological molecules are composed mainly of low electron scattering atoms and contain large amounts of water, it is necessary to use special preparation techniques to protect the structural integrity of biological specimens in the vacuum of the electron microscope and improve the amount of contrast created by the sample. Negative staining, rotary shadowing and cryo‐EM are all powerful techniques that are useful for examining the structures and molecular organization of biological complexes by EM.

Key concepts:

Negative staining is a valuable approach to characterizing the structural homogeneity of a sample.

Negative staining can be used to quantify major conformational shifts of proteins and complexes in response to the addition of inhibitors, activators or ligands.

Rotary shadowing provides information about the surface topology of a specimen.

Cryo‐EM preserves specimens in a near‐native environment and is used to generate high‐resolution 3D structures of large macromolecular complexes.
Positive Interspecific Interactions
Authors: Hacker Sally D 
Published: December 2009

Abstract

Cooperative relationships between species have been recognized for centuries but, until recently, their acceptance as important forces in community ecology has lagged behind that of antagonistic interactions. Interspecific positive interactions are defined as relationships between different species that result in better growth, reproduction and/or survival for at least one species involved in the interaction without negatively affecting the other species. They may be trophic or nontrophic and act directly or indirectly (through a third species). Positive interactions are not static but vary in their strength and symmetry depending on the context under which they occur. They can act to promote species coexistence especially under harsh physical or biological stress and thus are important to species diversity, species invasions and the conservation and management of highly impacted systems.

Key concepts:

Recent attention to the cooperative relationships among species shows that they are important forces in shaping community structure.

Positive interspecific interactions are defined as cooperative relationships between different species that result in better growth, reproduction and/or survival for at least one species involved in the interaction without negatively affecting the other species.

Positive interactions can be trophic and nontrophic, can act directly or indirectly (mediated by a third species) and can be symmetric (species have equal effects) or asymmetric (species have unequal effects).

Positive species interactions are not static but vary in their outcome depending on the context under which they occur.

Theory and experiments show that positive interactions are more likely to occur under stressful physical or biological contexts.

Studies demonstrate that succession in any community is driven by a complex array of species interactions but that positive interactions are important forces especially early when physical and biological conditions may be harsh.

Positive interactions should promote species coexistence and thus increase species diversity.

Species invasions are facilitated by other species although positive feedbacks between multiple non‐native species have rarely been shown.

Restoration of degraded communities can involve reintroducing dominant species that promote the colonization and maintenance of rare species by providing basic habitat and/or favourable physical modifications to the environment.