bluuebunny/crossref_metadata_2025_split huggingface dataset:
Viral Transneuronal Tracing Technology: Defining the Synaptic Organisation of Neural Circuits
Authors: Strick Peter L , Card J Patrick 
Published: April 2013

Abstract

Viral transneuronal tracing is a powerful approach that has been widely used to define the cellular organisation of functionally defined systems that underlie brain function. The method exploits the ability of neurotropic viruses to infect neurons and produce infectious progeny that pass through the intimate synaptic connections among neurons to infect polysynaptic pathways. A number of important technological advances in recent years have dramatically improved the ability of this experimental approach to define the synaptology of complex neural circuits. In this chapter we provide an overview of the method as well as mechanisms that contribute to its effectiveness for circuit analysis. We focus on alpha herpesviruses and rabies virus as these pathogens have been most widely applied in transneuronal tracing studies.

Key Concepts:

Viral transneuronal tracing exploits the invasive properties of neurotropic viruses.

Knowledge of the functional organisation of the viral genome is fundamental to an informed application of the viral transneuronal tracing method.

Circuit architecture is influential in determining the progression of viral infection through a neural circuit.

Isogenic recombinant viruses expressing unique reporters permit analysis of collateralisation of projections within complex neural circuits.

Colocalisation of reporters of infection with neurotransmitters and peptides permits neurochemical phenotyping of neurons within labelled circuits.
Molecular Genetics of Pulmonary Hypertension
Authors: Southgate Laura , Machado Rajiv D 
Published: April 2013

Abstract

Pulmonary arterial hypertension (PAH) is a progressive vascular disorder with high levels of mortality and morbidity. Approximately 10% of PAH patients have a family history of disease in which the disease segregates as an autosomal dominant trait. Employing a classical positional cloning approach comprising microsatellite linkage analysis and candidate gene screening, the causal gene for PAH in families was identified as
BMPR2
, encoding a type II receptor of the transforming growth factor beta (TGF‐β) signalling network. Subsequent functional investigation has revealed the molecular mechanisms of disease and together with protein–protein interaction studies underpinned key factors in disease progression. Taken together with the recent discovery of rare mutations in additional members of the TGF‐β family these data have served to underline the central importance of this pathway in the development and maintenance of the pulmonary vasculature.

Key Concepts:

Pulmonary arterial hypertension specifically constricts and obstructs the small arteries of the lung.

Vasoconstriction and arteriole occlusion is caused by the uncontrolled proliferation of pulmonary vascular endothelial and smooth muscle cells.

In the absence of treatment death occurs as a result of right heart failure.

Twice as many females as males are affected.

The major genetic factor underlying disease is heterozygous mutations of
BMPR2.

The predominant molecular mechanism of disease is haploinsufficiency.

BMPR2
mutations have been identified in nonfamilial PAH and, on rare occasions, PAH associated with other disorders and risk factors.

The identification of rare mutations in additional members of the TGF‐β pathway point to the importance of this signalling system in the maintenance of the pulmonary vascular bed.

The genetic architecture of pulmonary hypertension remains to be fully elucidated.
Mitotic Spindle Assembly: The Role of Motor Proteins
Authors: Titus Janel , Wadsworth Patricia 
Published: April 2013

Abstract

The mitotic spindle, a microtubule‐based structure, is required for chromosome segregation during cell division. Motor proteins are molecular machines that utilise the energy of
adenosine triphosphate (ATP)
hydrolysis to move along microtubules. During cell division, motor proteins are required for spindle formation, chromosome alignment and segregation. Thus, mitotic motor proteins are required for the cell to avoid aneuploidy, a hallmark of cancer.

Key Concepts:

Molecular motors, including dynein/dynactin and several families of kinesin, are required for mitosis.

Kinesins contribute to establishing spindle bipolarity, positioning chromosomes between spindle poles and focusing spindle poles.

Dynein contributes to the metaphase checkpoint, spindle positioning, regulating spindle length and pole focusing.

To establish and maintain a mitotic spindle, motor proteins achieve a balance of forces on microtubules.
The Role of the RanGTPase in Mitotic Spindle Assembly
Authors: Renshaw Matthew J , Wilde Andrew 
Published: April 2013

Abstract

Mitosis is the process whereby a cell separates its paired chromosomes into two new identical daughter cells. To achieve this and maintain the correct amount of
deoxyribo nuclic acid
(DNA) in the cells, the cell forms a framework called the mitotic spindle onto which the chromosomes attach and then get pulled into the new daughter cells. The mitotic spindle is made up of microtubules and associated proteins. The GTPase Ran, which is important for nuclear import and export, plays important roles in regulating the formation of the mitotic spindle. Ran can bind and hydrolyse guanosine triphosphate (GTP), which enables it to regulate several cellular processes. Generation of Ran‐GTP at the chromosomes creates an intracellular gradient that provides directionality to nuclear cytoplasmic transport during interphase and creates an environment around the chromosomes to facilitate spindle assembly.

Key Concepts:

Ran is a small GTPase.

During interphase, spindle assembly factors bind to Importin‐β and are transported into the nucleus.

Ran‐GTP is generated at chromosomes and releases spindle assembly factors from inhibitory binding to Importin‐β.

Gradients of Ran‐GTP and released cargo proteins are generated in mitotic cells that are important for regulating many activities.
Muscle Satellite Cell Structure, Proliferation and Fusion
Authors: Partridge Terence A 
Published: April 2013

Abstract

Skeletal muscle comprises some 30–40% of body mass, consisting mainly of contractile muscle fibres. For most vertebrates, survival is compromised by any serious loss of mobility arising from failure of efficient muscle function. This places a high priority on rapid and efficient repair and on a finely tuned adjustment in size and strength both during postnatal growth and on change in imposed workload. The muscle fibres themselves are syncytia containing large numbers of myonuclei, which are postmitotic and do not proliferate during growth or repair. Thus the functions of cellular replacement in this tissue fall largely, if not entirely on a small population of ‘satellite cells’, so‐called because of their position between the plasmalemma of the muscle fibre and the overlying basement membrane. The precise role of these cells and their relationships to other cell types are topics of current research and debate.

Key Concepts:

The differentiated skeletal muscle cell is an ‘end cell’ that cannot proliferate to replace itself.

The muscle satellite cell is the predominant identified source of myogenic cells for growth repair and regeneration of postnatal skeletal muscle.

The anatomically defined muscle satellite cell appears to be heterogeneous.

Non‐satellite cell sources of myogenic cells have been identified in skeletal muscle.

There is evidence of conversion of non‐satellite cells to a myogenic fate and of satellite cells to non‐myogenic fates but the importance of these processes
in vivo
has not been ascertained.
History and Ethics of Stem Cell Research
Authors: Blasimme Alessandro , Dröscher Ariane 
Published: April 2013

Abstract

The history of stem cell research is considered a recent one, yet, it began as early as the middle of the nineteenth century and is rich in questions, approaches, concepts, tools, methodologies and lines of thought. There are at least nine disciplines or research fields which have made major contributions: botany and horticulture; cell theory; evolutionary biology; embryology and developmental biology; haematology; cell and tissue culture; regeneration biology; teratology and teratogeny and cancer research. Moreover, as soon as efforts aimed at extracting and culturing pluripotent cells from human embryos proved successful in 1998, stem cells became objects of bioethical controversy. The moral status of the embryo will be discussed, together with proposed technical means to avoid its destruction, such as altered nuclear transfer, single blastomere biopsy, cytoplasmic hybrids and induced pluripotent stem cells, and the possible ethical problems associated with future medical uses of stem cells.

Key Concepts:

Far from being a simple technology or a commodity, the study of stem cells concerns a broad spectrum of issues lying at the heart of the phenomenon of life itself, and thus touches on questions that have been on the agenda of biological inquiry for a long time.

Like most biological research fields, the history of stem cell research shows a constant weaving and unweaving of many concepts and tools, coming from different experimental settings, lines of thought and at least nine different biomedical areas.

At some moments of its history, the ‘stem cell’ has become a more concrete and even manageable object, at other moments it was found difficult to localise the phenomenon of self‐renewal in one or in a few cells.

Recently, stem cell research is characterised by harsh bioethical controversy, mainly revolving around the issue of the moral status of human embryos.

Scientists have proposed some technical ways for circumventing ethical problems, but other morally relevant issues still lie before stem cell research.

In the future, medical innovation through stem cell‐based regenerative medicine is likely to give rise to issues regarding safety, ethical oversight and distributive justice.
Role of Natural Selection in Chromosomal Speciation
Authors: Faria Rui , Neto Sandra , Noor Mohamed AF , Navarro Arcadi 
Published: April 2013

AbstractSpeciation can occur in the face of gene flow if there are mechanisms that are able to neutralise it. Two such mechanisms or forces are divergent selection and the suppression of recombination. New data and theory suggest that chromosomal rearrangements (CRs) facilitate speciation with gene flow mainly by suppressing recombination. However, the role of natural selection in chromosomal speciation is less clear. According to recent models, natural selection can play a role in speciation by facilitating the fixation of CRs; and later, acting synergistically with CRs, by allowing the accumulation of incompatibilities along large regions of the genome. Interestingly, instead of resulting exclusively from disruptive selection among populations, a potential signal of selection within CRs may also result from the inability of favourable mutations to migrate between populations. However, empirical evidence for natural selection in suppressed‐recombination chromosomal speciation is scarce, reinforcing the need for further multidisciplinary studies.Key Concepts:For evolutionary biologists, speciation has always been a controversial topic, both in terms of mechanisms and geographical context.Although allopatry has been the most consensual geographic context of speciation, the divergence of taxa in the face of gene flow is not a rare observation.In purely genetic terms, speciation can be viewed as the evolution of restrictions on the freedom of genetic recombination.Recombination originates new genetic combinations upon which natural selection can act, transforming the genomes of lineages connected by gene flow into a mosaic of genetic information.The molecular characterisation of genes involved in reproductive isolation between someDrosophilaspecies suggests that natural selection has shaped their evolution.The functional characterisation of genes involved in reproductive isolation suggests that genetic conflicts may have a more important role in speciation than what it was initially thought.The formalisation of suppressed‐recombination models of speciation was highly influenced by research performed in fruit flies and sunflowers (DrosophilaandHelianthus).CRs may play an important role in the origin and accumulation of incompatibilities between parapatric populations but also by avoiding species fusion after a secondary contact.Signatures of selection within CRs may result from divergent environmental conditions but also from universally advantageous alleles.Although, in theory, natural selection facilitates the role of CRs in speciation, signatures of natural selection within CRs have not been universally found in the species so far investigated.
Experimental Evolution in Viruses
Authors: Sanjuán Rafael , Domingo‐Calap Pilar 
Published: April 2013

AbstractExperiments in which evolution takes place in real time can help us establish cause–effect relationships that are difficult to infer from the analysis of natural populations. The simplicity, rapid evolution and biomedical relevance of viruses make them a particularly interesting model system for experimental evolution. Bacterial, animal and plant viruses can be passaged under a variety of conditions, either in simple cell culture systems orin vivoto test population biology hypotheses, study the genetic basis of evolution, or predict evolutionary change in nature. Experimental evolution is a conceptually simple and flexible tool which allows us to address issues ranging from the molecular to the ecosystem level. In addition to studying basic processes such as mutation, adaptation, or random genetic drift, viruses can be experimentally evolved to better understand the emergence of drug resistance, explore new antiviral strategies such as lethal mutagenesis, create better attenuated vaccines, or target cancerous cells.Key Concepts:Experimental evolution can be done with many different model organisms, but microorganisms and viruses offer a series of advantages including their easy manipulation, storability and biomedical relevance.The setup of an evolutionary experiment is conceptually simple and essentially consists of serially transferring viruses from flask to flask or,in vivo, from host to host. However, a careful experimental design is needed to be able to demonstrate which factors are responsible for the evolutionary changes observed in the laboratory.Molecular biology is a powerful tool in virus experimental evolution because it allows us to manipulate viral genomes and to study the molecular basis of evolution.Viruses can adapt to many different laboratory environments, but these adaptations often come at the cost of decreased performance in alternative environments, demonstrating the existence of certain limits to adaptation, or fitness tradeoffs.Viral experimental evolution has both stochastic and deterministic components. Therefore, although viral evolution is not easy to predict, it shows some regular patterns.The role played by population–genetic factors such as the population size or the mutation rate have been extensively studied in viruses, and several important generalisations have been established.Experimental evolution has inspired new strategies to combat viral disease, including the use of selective mutagens to damage viral genomes or the use of less evolvable strains to create more effective and safer vaccines.
Geographical Origin of the Domestic Dog
Authors: Klütsch Cornelya FC , Savolainen Peter 
Published: April 2013

Abstract

The domestic dog (

Canis familiaris

) is considered to be the oldest domestic animal in the world. World‐wide mitochondrial
deoxyribonucleic acid
(mtDNA) studies clearly indicate a single origin in time and place in Southeast Asia less than 16 000 years ago including a high number of female foundation wolves resulting in 10 subhaplogroups within three haplogroups. Later hybridisation events in East Asia, the Middle East, Scandinavia and possibly North America formed 3–4 small haplogroups. In contrast, the archaeological record, favours other, sometimes multiple, regions for dog domestication (mainly Europe and Middle East), but suffers from a lack of samples from Southeast Asia and is problematic, because of the difficulty of distinguishing between wolf and dog in fossil remains. Future studies including, for example, paternal markers such as the Y‐chromosome, autosomal markers like SNPs, and ancient DNA samples of both wolves and dogs may give new insights into early domestication history and the dog's migration routes.

Key Concepts:

The dog is considered to be the oldest domestic animal species and it is widely accepted that its only ancestor is the wolf (
Canis lupus
).

Archaeological records of early potential dog remains are fragmentary and controversial as well as biased in their geographical coverage, focusing mainly on fossils found in Europe and the Middle East.

Recent genetic studies based on mtDNA suggest a single origin in Southeast Asia from numerous wolves less than 16 000 years ago as well as later hybridisation events in East Asia, the Middle East, Scandinavia and possibly North America.

New World dogs are likely to be descendants of Eurasian domesticated dogs, thereby ruling out North America as a centre of domestication.

The dingo is an ancient, originally domesticated, but now feral, dog which arrived to Australia about 5000 years before present (YBP).

Future studies may include ancient DNA approaches and additional markers such as Y‐chromosome and genome‐wide markers like SNPs to give additional insight into domestication history and migrations of early domestic dogs.
Adaptive Evolution of Centromeric Proteins
Authors: Roach Kevin C , Ross Benjamin D , Malik Harmit S 
Published: April 2013

AbstractKinetochore proteins assemble at centromeres and mediate chromosome segregation during eukaryotic cell division. This conserved function conceals a paradox; essential inner kinetochore proteins, CenH3 and CENP‐C, evolve rapidly under positive selection in primates, plants and insects. This paradox may be explained by a genetic conflict between selfish DNA sequences at the centromere and the kinetochore proteins that bind them. The centromere drive hypothesis provides a framework for understanding this conflict and makes predictions for patterns of evolution in the composition of the kinetochore. In contrast with the rapidly evolving inner kinetochore, the components of the outer kinetochore do not make contacts with centromeric DNA and evolve more slowly. Furthermore, genetic conflict at the centromere may underlie observed taxonomic differences in the rate of evolution of kinetochore proteins among species with different meiotic programs.Key Concepts:Despite an essential and conserved function, some centromere‐binding proteins evolve rapidly.In contrast to canonical histone H3, the centromeric variant of histone H3 displays striking patterns of positive selection in functionally critical domains.CENP‐C displays rapid evolution across a diverse taxa; the functional consequences of this rapid evolution have not yet been studied.Asymmetric female meiosis provides an opportunity for competition among centromeres for evolutionary success but has deleterious consequences in male meiosis leading to genetic conflict.Genetic conflict between centromeres and centromere‐binding proteins can explain the divergent patterns of evolution between inner and outer kinetochore proteins, as well as taxonomic differences in rapid evolution of centromeric proteins.
Magnetic Tweezers
Authors: Carrasco Pulido Carolina , Moreno‐Herrero Fernando 
Published: April 2013

Abstract

Magnetic tweezers is a technique that allows applying a constant pulling force and torque on a nucleic acid molecule while measuring its elongation in real time. By means of two magnets, the polymer is stretched and twisted between a magnetic bead and the surface of a glass cover slide. In the course of an experiment, the position of the magnetic bead is followed in real time while a buffer containing proteins, adenosine triphosphate (ATP), etc. is introduced in the experiment chamber. This approach has been used to study
deoxyribonucleic acid
(DNA) condensation, mechanical properties of nucleic acids and dynamics of protein–DNA interactions. In this article an introduction to the Magnetic Tweezers technique is given and some examples of application presented.

Key Concepts:

Magnetic Tweezers allow stretching and twisting nucleic acids (NA) using magnetic microspheres and a magnetic field.

An NA is attached at one end to a magnetic bead and at the other end to a transparent glass surface.

The position of the bead is determined from the optical image given by a video camera.

The force acting on the NA is calculated from the movements of the tethered magnetic bead.

Magnetic Tweezers are used to study mechanical properties of NA and real‐time dynamics of protein–DNA interactions.
Computational Methods for Interpretation of
EM
Maps at Subnanometer Resolution
Authors: Baker Matthew L , Baker Mariah R , Cong Yao 
Published: April 2013

Abstract

Driven by a remarkable number of technological advances in recent years, electron cryo‐microscopy (cryo‐EM) has played an increasingly important role in deciphering macromolecular structure and function. Today, cryo‐EM routinely achieves subnanometer resolutions, with current state‐of‐the‐art reconstructions approaching atomic resolutions. Though achieving high‐resolution density maps is still a challenging aspect of cryo‐EM, it is possible to isolate individual subunits, identify secondary structures elements and accurately fit atomic models in reconstructions of large macromolecular assemblies. Additionally, computational modelling and feature recognition tools are routinely employed to construct backbone and atomic models of entire assemblies directly from a density map. Together, these tools provide researchers with unprecedented insight into structure and function, revealing everything from subunit arrangements to complex sets of interactions in macromolecular assemblies.

Key Concepts:

Cryo‐EM is capable of imaging large macromolecular assemblies in order to understand their structure and function.

Analysing macromolecular assemblies requires a variety of complex computational tools.

In subnanometer resolution cryo‐EM density maps, it is possible to see individual protein subunits, as well as higher‐resolution structural features.

It is now possible to construct backbone and atomic models directly from cryo‐EM density maps at near‐atomic resolutions.