bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid Evolution of Genes on the Human X Chromosome
Authors: Kvikstad Erika M , Makova Kateryna D 
Published: September 2013

Abstract

There is considerable interest in determining the sequences that are evolving rapidly in our genome, as these may well confer an advantage that has helped to propel the evolution of our species. Owing to sex chromosome‐specific modes of natural selection, genes on the human X chromosome are evolving rapidly in comparison to genes located on autosomes. However, it is not clear to what extent these loci are evolving adaptively or due to other molecular (mutation and recombination) and evolutionary (selection and drift) processes. Biological factors in addition to selection could contribute to elevated rates, such as the evolutionary history and genomic features of the X chromosome. Additionally, genes on the X are distributed in a nonrandom fashion, potentially influencing their evolution. Furthermore, the function and expression profile of each X‐linked gene may play a role in determining its evolutionary rate. Recent technological advances have provided rich datasets for the investigation and unravelling of these confounding factors.

Key Concepts:

The human X chromosome is a compilation of biological contradictions: it is remarkably conserved in gene content between species, while being highly diverged from its Y counterpart; it is present in twice as many copies in females than males, and yet enriched for genes with male‐biased expression.

The theory of fast‐X evolution is based on the observation that genes on the X in XY males will be more easily targeted by natural selection, thus accelerating the rate of adaptive evolutionary change for beneficial mutations.

Many genes on the X tend to evolve more slowly than their Y counterparts, due to the higher mutation rate in the male germline.

Genes on the X are likely to be involved in reproduction, sex biased in their expression profile and tissue‐specific in nature – each of these factors has been linked to accelerated rates of sequence and/or expression divergence independently of the fitness advantage of the associated allele.

Although fast‐X has been observed in different taxa, the relative contribution of the underlying evolutionary forces (selection for advantageous mutations versus drift of slightly deleterious mutations) can be very different between species.
Developmental Models for Wound Healing
Authors: Matsubayashi Yutaka , Millard Tom H 
Published: September 2013

AbstractThe bodies of animals and humans frequently sustain damage as a result of injury or disease, and the ability to repair this damage is essential for life. Tissue repair, or wound healing, is a complex process which is difficult to study experimentally and is, therefore, not fully understood. Over recent years, various studies have identified striking similarities between tissue repair and the process of morphogenesis in which tissues are originally formed during embryonic development. This has raised the possibility of using developmental processes as model systems to help in better understanding of tissue repair. This article describes how comparative studies of embryonic morphogenesis and tissue repair have improved understanding of the mechanisms of repair. The article further discusses the key processes and regulatory mechanisms that are shared between development and repair, including important recent developments in the field.Key Concepts:The behaviour of cells during the repair of damaged tissues often parallels that observed when tissues are initially formed during embryogenesis.Developmental processes such asDrosophiladorsal closure and mouse eyelid closure can be used as models to help in understanding of wound healing.Common cytoskeletal and signalling machineries regulate cell behaviour during the reepithelialisation episode of wound healing and also during developmental epithelial closure events.Key regulators of epithelial closure include the Rho GTPases, the JNK cascade and the planar cell polarity pathway.Coordinated collective migration of many cells is necessary for both wound healing and developmental epithelial remodelling.Mechanical signalling seems to be important for tissue remodelling, but its molecular mechanisms still largely remain elusive.Inflammatory cells play instructive roles during tissue remodelling.Novel techniques such as advanced bioimaging and mathematical modelling will help to uncover the general mechanisms underpinning wound healing and developmental tissue remodelling.
Patch Fluorometry
Authors: Zheng Jie , Yang Fan 
Published: September 2013

Abstract

Patch fluorometry is a biophysical technique that combines the power of patch clamping and optical recording, with the aim of correlating local conformational rearrangements in ion channel protein with the channel gating process. This is achieved through simultaneous recordings of fluorescence and current signals from the same population of ion channels in a membrane patch. The method can be applied to studies of ion channel structure–function relationship as well as membrane protein dynamics. Unlike nuclear magnetic resonance or other biophysical methods for structural study, patch fluorometry provides real‐time dynamic structural information from ion channels in their native membrane environment whereas they carry out their functions. Recent advances greatly expand the scope of this powerful method, allowing researchers to follow structural changes in channel protein with unprecedented spatial and temporal resolutions and accuracy.

Key Concepts:

Ion channels achieve their cell‐sensor functions through changes in conformation in response to physical or chemical stimuli.

Conformational changes in an ion channel protein do not always alter the current, and are thus invisible to patch clamp recording.

Fluorescence emission is highly sensitive to the local environment of fluorophores.

Site‐directed fluorophores serve as sensors for local structural changes.

Patch fluorometry allows direct correlation between channel protein conformational changes and the functional states of the channel.
Forkhead Transcription Factors in Genetic Disease
Authors: Baetens Dorien , Verdin Hannah , Cools Martine , De Baere Elfride 
Published: September 2013

AbstractForkhead transcription factors represent an important family of proteins, for which more than 2000 family members have been identified so far, 26 of which can be found in humans.FOXgenes exhibit many important functions in both development and adult life. Therefore, it is not surprising that alterations in these genes can cause of a broad range of developmental diseases and cancer. Today, 13FOXgenes are associated with developmental disorders. Mutations in five of them (FOXC1,FOXC2,FOXD3,FOXE3andFOXL2) lead to an ocular phenotype, while mutations in three genes (FOXG1,FOXP1andFOXP2) are a known cause for neurodevelopmental disorders, mutations in two (FOXL2andFOXO3A) are associated with premature ovarian failure and mutation in other two genes (FOXN1andFOXP3) are involved in immunodeficiency syndromes. Finally,FOXF1mutations cause a lung development disorder. In this article, the different developmental disorders caused by mutations inFOXgenes are reviewed. In addition, the article briefly touches cancers caused by genetic defects inFOXgenes.Key Concepts:Forkhead transcription factor genes represent an important gene family, consisting out of more than 2000 members. In human, 26 family members have been identified and there are 8FOXgene clusters.The forkhead domain is built up by three α‐helices, two β‐sheets and two loops. These loops resemble wings of a butterfly, giving the family its nickname: winged helix transcription factors.Forkhead transcription factors play important roles in a wide range of signalling pathways.Mutations inFOXgenes are known to cause hereditary developmental disorders. Five mutatedFOXgenes are associated with an ocular phenotype.Forkhead transcription factors are also involved in cancer and ageing.
Genetics of Phosphate Regulation Disorders
Authors: Gattineni Jyothsna 
Published: September 2013

AbstractPhosphate is an abundant anion in humans and plays an important role in many metabolic processes. Maintenance of phosphate homoeostasis is critical, and kidney plays an important role in the regulation of phosphate homoeostasis. Phosphate reabsorption by the kidney is the final determinant of serum phosphate levels. Fibroblast growth factor 23 (FGF23), parathyroid hormone and Klotho are important hormones that regulate phosphate homoeostasis. Dysregulation of FGF23 is the most common inherited cause of hypophosphatemic and hyperphosphatemic disorders. Mutations of sodium phosphate cotransporters, responsible for phosphate reabsorption, also result in inherited disorders of phosphate homoeostasis. Recent discoveries in the field of FGF23 have led to better understanding of the pathophysiology of many of the inherited hypophosphatemic and hyperphosphatemic disorders.Key Concepts:Maintenance of normal phosphate homoeostasis is integral for many bodily functions.Both hyperphosphatemia and hypophosphatemia have detrimental effects.Fibroblast growth factor 23 (FGF23), parathyroid hormone and Klotho are well‐known phosphaturic hormones.Sodium phosphate cotransporters (NaPi‐2a and NaPi‐2c) that are present in the proximal tubule of the kidney are the final regulators of phosphate reabsorption. Mutations of sodium phosphate cotransporters result in hypophosphatemia.Disturbances in hormones such as FGF23, parathyroid hormone and Klotho result in many inherited hypophosphatemic and hyperphosphatemic disorders.X‐linked hypophosphatemic rickets is the most common form of inherited rickets in children and is due to excess FGF23.Autosomal dominant hypophosphatemic rickets, autosomal recessive hypophosphatemic rickets, fibrous dysplasia and osteoglophonic dysplasia are also inherited hypophosphatemic disorders resulting from excessive FGF23.Tumoural calcinosis is an inherited hyperphosphatemic disorder resulting from decreased FGF23 activity.
Genomic Studies of Adaptation in Natural Populations
Authors: Martin Simon H , Jiggins Chris D 
Published: September 2013

Abstract
Understanding the genetic basis of adaptive evolution is a problem almost as old as evolutionary biology itself. Recent advances in genome sequencing and the ability to generate genomic samples from natural populations promises to provide answers to many long‐standing questions. The recent surge in genomic studies of adaptation has been accompanied by the development of numerous powerful techniques to analyse these enormous data sets. The state of the field is reviewed in this article, with an emphasis on the various approaches used. This article covers both ‘top‐down’, used to identify the genetic basis of a known trait, and ‘bottom‐up’ approaches, used to identify the footprints of selection on the genome. It shows how recent studies highlight the benefits of combining multiple methods and also discusses important goals for the future of the field.

Key Concepts:

Association mapping is used to identify genomic loci that control a trait of interest, by identifying molecular markers that display genotype‐by‐phenotype associations.

Either offspring from controlled crosses or population samples can be used as the recombinant ‘mapping population’.

Numerous loci underlying important adaptive traits have been identified using association mapping; however, this approach is biased towards loci of large effect and may not accurately capture the true genetic architecture of a trait.

Genome‐wide scans for the footprints of selection are less sensitive to effect‐size biases but are naive with regard to the trait(s) under selection.

Selective sweeps can be identified by the presence of reduced variation, enhanced linkage disequilibrium and a shift in the ‘site frequency spectrum’.

Loci under divergent selection between populations can be identified as outliers displaying greater differentiation between populations than expected under neutral evolution.

By comparing between‐species divergence with within‐species polymorphism at synonymous and nonsynonymous sites, it has been estimated that a large proportion of the genome is involved in adaptive evolution.
Molecular Evolution of Genes Involved in Vertebrate Sex Determination
Authors: Ito Michihiko , Mawaribuchi Shuuji 
Published: September 2013

Abstract

Four sex‐determining genes (SDGs) had been reported in vertebrates until 2011: Y‐linked
Sry
in eutherian mammals, Z‐linked
Dmrt1
in the chicken, W‐linked
Dm‐W
in the African clawed frog

Xenopus laevis

and Y‐linked
Dmy
(also called as
dmrt1bY
) in the teleost fish medaka. These genes encode
deoxyribonucleic acid (DNA)
‐binding proteins. Both
Dm‐W
and
Dmy
emerged through duplication of
Dmrt1
, whereas
Sry
evolved from allelic
Sox3
. Interestingly, in 2012, four different types of SDGs, which might not encode DNA‐binding proteins, were reported in teleost fish: Patagonian pejerrey
amhy
,

Oryzias luzonensis

GsdfY
,

Takifugu rubripes

Amhr2
, and rainbow trout
sdY
. Although these SDGs are all sex chromosome‐linked, a variety of them may be involved in the evolution of sex chromosomes. A coevolution model of SDGs and sex chromosomes has been proposed: undifferentiated or specialised sex chromosomes could allow diversity of SDGs or tend to fix a certain SDG, respectively, during species diversity in vertebrates.

Key Concepts:

There are a variety of SDGs including transcription factor genes and TGF‐β signal‐related genes.

SDGs could be classified into two types: insertion and mutations after duplication, and mutations of an allelic gene.

SDGs
Dmy
/
Dm‐W
and
Sry
, which evolved through duplication of
Dmrt1
and an allelic mutation of
Sox3
, respectively, have a higher substitution rate than their prototype genes.

Cis
‐regulatory elements in most of the SDGs should have evolved for their mRNA expressions at a sex‐determining stage, but only an amino acid change by SNP between
Amhr2
alleles could determine the sex in fugu fish.

SDGs and sex chromosomes would have coevolved during vertebrate evolution: undifferentiated or specialised sex chromosomes could allow diversity of SDGs or tend to fix a certain sex‐determining gene, respectively.
Causes and Consequences of Structural Genomic Alterations in the Human Genome
Authors: Hart Lesley , O'Driscoll Mark 
Published: September 2013

Abstract

The revolutionary development and application of microarray‐based comparative genomic hybridisation (aCGH) technology within the past decade or so represents a profound and continuing fundamental contribution to the molecular dissection and characterisation of complex human disorders: disorders ranging from developmental pathologies including intellectual disability, schizophrenia and autism spectrum disorders to more common conditions such as cancer. A unifying underlying feature here is that these disorders are associated with complex structural rearrangements in chromosomes. aCGH technology application has also enabled the refinement of ‘old’ and identification of ‘new’ mechanisms to explain the origin of these complex chromosomal alterations. Interestingly, these structural variations can also incorporate genes whose products play fundamental roles in aspects of
deoxyribonucleic acid
repair, replication and recombination, thereby having an impact on genome‐wide stability and integrity. In this article, the mechanisms underlying complex structural chromosomal rearrangements are reviewed and their implications with respect to genome‐wide stability are discussed.

Key Concepts:

The locus‐specific frequency of CNVs are orders of magnitude higher than SNPs.

CNVs are a significant contributor to human disease.

CNVs can be recurrent or nonrecurrent.

Nonallelic homologous recombination between low copy number repeats is a common mechanism of recurrent CNV.

Nonhomologous end joining can underlie nonrecurrent CNVs.

Complex Chromosomal Rearrangements (CCRs) are complex CNVs involving multiple contiguous changes in copy number.

DNA replication based‐mechanisms have been invoked to explain CCRs.

CNVs are fundamental contributors to cancer development and progression.

CNVs incorporating genome instability pathway components can adversely impact on genome‐wide stability.

Certain genomic disorders are characterised by impaired genome stability.
Concepts in Fetal Gene Therapy
Authors: Mattar Citra N , Biswas Arijit , Choolani Mahesh , Chan Jerry KY 
Published: September 2013

AbstractMany congenital anomalies have a genetic basis. With the evolution of fetal therapy over the past half‐century since the first intrauterine transfusion was performed, novel treatments including genetic correction of such diseases may be possible. Using a variety of therapeutic vector constructs, proof of concept for fetal gene therapy (FGT) has been achieved in several single‐gene disorders including thalassaemia and haemophilia B. The current challenge is to determine the long‐term safety and efficacy of FGT, as well as important maternal bystander effects, in clinically relevant large‐animal models, and to individualise FGT strategies according to the disease of interest, with respect to target organ and vector construct.Key Concepts:Fetal gene therapy research has been directed towards monogenic diseases, but there is scope for this target to be expanded to include chromosomal and structural anomalies in the near future.The fetus, weighing several log‐fold less than an infant or child, allows gene therapy to be economised, facilitating a widespread effect with a smaller amount of vector, and an easier task in adjusting vector dose to achieve the desired outcome.The goal of fetal gene therapy is to achieve phenotypic rescue of a lethal or severely morbid monogenic disease. If cure is not achievable, correction of the disorder to the point of downgrading its severity is the other worthy goal.In addition to genetic correction, treatment initiated in early gestation may encourage tolerance to the gene therapy vector and transgenic protein, events critical to facilitating sustained transgene expression.Gene therapy may be achievedin vivo, through the direct introduction of the transgene enveloped in a vector, orex vivowith the use of genetically manipulated stem cells to achieve the desired effect.Proof of this concept has been demonstrated using viral vectors in small genetic knockout models of diseases, including haemophilia B and inborn errors of metabolism disease.Evidence of safety and efficacy has been demonstrated in sheep and nonhuman primates which, being physiologically more representative of human pregnancies, are considered robust preclinical models.The success of this intervention depends on the efficacy of cellular transduction, accessibility of the target organ, the type of vector used, immune maturity and route of vector administration.Fetal gene therapy must be optimised to each condition of interest, in terms of appropriate gestation at intervention, efficacy of vector and principal objectives of therapy (gestation at which peak transgene expression is desired, importance of immune maturity and desired duration of transgene expression).Several ethical issues raised by fetal gene therapy have to be considered in anticipation of eventual clinical translation. These include reliance on data from preclinical large animal models that are not genetic knockouts, the consequences of partial correction, the possibility of germ‐line transmission and the long‐term risk of oncogenesis.
Inorganic Spintronic Materials
Authors: Bao Ningzhong , Gupta Arunava 
Published: September 2013

Abstract
Utilization of the spin degree of freedom in metallic, semiconducting, and insulating materials is an active pursuit for spin‐based devices. Besides some existing devices, many new ones have been proposed on the basis of spin‐dependent transport. For these devices to become reality, new materials and methods for efficient injection, manipulation, and detection of electron spins are required. In this article, we present an overview of the research progress in inorganic spintronic materials, with emphasis on their structural and magnetic properties. The materials discussed include perovskite‐type oxides, spinel ferrites, transition metal monoxides, iron oxides, nickel oxides, chromium oxides, layered ruthenates, and chromium‐based chalcogenides. Recent advancements related to single‐phase multiferroic materials are also presented.
B. Electron Motion in Highly Excited States and Radiationless Transitions. General Dynamical Theory and Experiment. Intramolecular Dynamics and Charge Separation in Large Systems
Authors: Jortner Joshua , Bixon M. 
Published: September 2013

AbstractWe adopt the theory of intramolecular dynamics to explore charge separation and recombination in two classes of ‘isolated’ solvent‐free molecular systems: (A) Supermolecules containing bridged electron donor and electron acceptor, where electron transfer occurs on a spatial scale of ≈︁ 10 Å. (B) Ultrahigh molecular Rydberg excitations with a principle quantum number n ≃ 50−300 and spatial dimensions of ≈︁ 104 Å, where relaxation processes, e.g., electron‐core recombination via internal conversion or predissociation, and charge separation by autoionization, are manifested. The molecular limit for photoinduced long‐range ET in isolated supermolecules [class (A)] is treated on the basis of the statistical limit for interstate radiationless transitions, which involve either a direct or a mode‐selective mediated coupling. The level structure, optical excitation modes and dynamics of high molecular Rydbergs [class (B)] interrogated by time‐resolved ZEKE (zero‐electron kinetic energy) spectroscopy, are treated by the effective Hamiltonian formalism. We pursue the formal analogy between the coupling, accessibility and decay of ultrahigh Rydbergs in an external weak (F = 0.01−1.0 V/cm) electric field and intramolecular (interstate and intrastate) relaxation in a bound level structure. Model calculations for the field‐induced (l) mixing reveal that the Rydberg dynamics is characterized by two distinct (≈︁ ns and ≈︁μs) time scales. Up to date, long time‐resolved (10 μs − 100 ns time scales) nonexponential decay of ZEKE Rydbergs was experimentally documented, in accord with our analysis. The predicted existence of the short decay times (1 − 10 ns) was not yet subjected to an experimental test.
F. Laser Control and Femtosecond Dynamics. Femtosecond Dynamics of Reactions: Elementary Processes of Controlled Solvation
Authors: Zewail Ahmed H. 
Published: September 2013

AbstractThe summary presented here attempts to describe recent studies in our laboratory of the effect of microscopic solvation, controlled in a cluster cage or fluid environment, on the elementary dynamics of reactions. We selected reactions of two atoms (dissociation) and many atoms, proton transfer in acid‐base reactions and double‐bond twisting in isomerization reactions.
Quantum Calculations of Femtosecond Pump‐Probe Spectroscopy in K2 for Low Laser Field Intensities
Authors: De Vivie‐Riedle Regina , Reischl Birgit 
Published: September 2013

AbstractQuantum dynamical simulations of pump‐probe femtosecond experiments of the potassium dimer are presented for low laser field excitation. The results show that a (1 + 2)‐photon pump‐probe process takes place. The 21 Π g state determines as an optimal resonant state the transition process. Its properties open the pathway for the 2‐photon ionization in the outer turning point region. The oscillations in the total ion yield of K2+ correspond to the motion of the vibrational wavepacket prepared by the pump laser in the A1Σu+ state of the neutral K2 molecule. Contributions of wavepackets in other electronic states are not detected in the ionization signal.