bluuebunny/crossref_metadata_2025 huggingface dataset:
Disulfide Bonds
Authors: Morgan Bruce , Herrmann Johannes
Published: January 2017

A disulfide bond is a covalent bond between two sulfur atoms. Disulfide bonds are prevalent in biology and found in a range of biological molecules, for example between the sulfur atoms of protein cysteine residues. Protein disulfide bonds can fulfil a wide range of functions including promoting protein stability and regulating protein activity or function. Dedicated disulfide generating and transferring machineries that promote the introduction of disulfide bonds during oxidative protein folding can be found in the endoplasmic reticulum, mitochondrial intermembrane space and bacterial periplasm. Regulatory disulfide bonds are formed by different pathways to the structural disulfides. For example, hydrogen peroxide (H
2
O
2
) may regulate protein activity by inducing the formation of disulfide bonds. In a few cases, H
2
O
2
may directly oxidise cysteine residues, but evidence is accumulating that thiol peroxidases may first react with H
2
O
2
and subsequently transfer their disulfide to specific target proteins.

Key Concepts

Disulfide bonds have multiple functions in proteins including instability and regulation of protein activity.

Dedicated machineries to generate and transfer disulfide bonds to newly folding proteins are found in the endoplasmic reticulum, the mitochondrial intermembrane space and the bacterial periplasm.

Cysteine residues in some proteins can react with H
2
O
2
leading to the formation of a disulfide bond that can regulate protein activity.

Proteins that react efficiently with H
2
O
2
harbour specific mechanisms to increase the reaction efficiency.

Thiol peroxidases can react extremely sensitively with H
2
O
2
leading to the formation of a disulfide bond.

Thiol peroxidases can transfer their disulfide bond to specific target proteins. These peroxidase‐based redox relays may represent an important mechanism of H
2
O
2
‐mediated protein oxidation.
Eusociality and Cooperation
Authors: Keller Laurent , Chapuisat Michel
Published: January 2017

Ants, termites and many species of bees and wasps form tightly integrated social groups in which permanently nonreproducing workers help rear the offspring of a few fertile individuals, the queens and males. Such societies with marked reproductive division of labour are called eusocial. The evolution of eusociality puzzled Darwin: How could workers pass on their characteristics to the next generation if they did not reproduce? Kin selection, the indirect transmission of genes through relatives, is the key process explaining the evolution and maintenance of permanently nonreproducing workers. Overall, eusociality evolved in life‐long associations of monogamous parents and offspring, which jointly exploit and defend common resources. Robust and efficient division of labour contributes to the great ecological success of eusocial species. Yet, despite high levels of integration, conflicts among individuals are still common in eusocial groups, and several sophisticated mechanisms have evolved to maintain social cohesion.

Key Concepts

Eusociality is characterised by reproductive division of labour, cooperative brood care and overlap of generations.

The hallmark of eusociality is the presence of a caste that is permanently committed to a nonreproductive helper role.

Eusociality confers great ecological success, but has a scattered taxonomic distribution.

Kin selection is the key process explaining the evolution of permanently nonreproducing helpers.

Eusociality evolved in groups of highly related individuals, typically comprising the offspring of a monogamous pair.

Eusociality is linked with division of labour, which is sometimes associated with morphological castes.

The allocation of workers to tasks is a self‐organising process that occurs without central control and emerges from local interactions.

In social insects, division of labour is remarkably robust and flexible to cope with unpredictable changes in the environment.

Individuals in animal societies are not clones; they have partially divergent genetic interests, which can lead to various forms of conflicts.

Some types of conflicts are controlled by social means such as bribing, coercion or punishment.
Receptors and Human Nervous System Disorders
Authors: Knoflach Frédéric , Bertrand Daniel
Published: January 2017

Neurons, building blocks of the mammalian nervous system, mainly communicate with each other through synapses in which signal transmission is mediated by neurotransmitters released from the presynaptic neuron and sensed by the postsynaptic neuron. These endogenous chemicals released from the nerve terminal diffuse through the very narrow extracellular space between the neurons and bind to specific membrane proteins called receptors, thereby mediating signal propagation. Receptors are divided into two large families comprising those causing the activation of second messengers and those including an ionic pore which opens upon neurotransmitter binding and which controls flow of ions across the cell membrane. Also called ligand‐gated ion channels (LGIC), they mediate fast neurotransmission essential for the complex signal processing in the central nervous system. Reliable transmission of signals between neurons is highly dependent on accurate functioning of LGICs. Genetically transmissible nervous system disorders can be caused by mutations in genes coding for LGICs, resulting in dramatically altered neurotransmission.

Key Concepts

In this work we review the determinant role of ligand gated ion channels in brain function and the alterations related to genetic variants.
Psychiatric Disorders: The Search for Genes
Authors: McMahon Francis J
Published: January 2017

Psychiatric disorders are common illnesses whose core features include disturbances of mood, perception, cognition and behaviour that cause distress or interfere with daily functioning. Genes contribute substantially to risk, but multiple genes and environmental factors are involved, leading to complex patterns of inheritance. Many genes and genetic markers have already been identified that contribute to schizophrenia, bipolar disorder and autism, but each individual gene plays a small role and much of the inherited risk for these disorders remains unexplained. Most of the identified genetic risk factors are common and each one has a small impact. Some rare genetic variants have also been discovered that have a larger impact on risk, especially for schizophrenia or autism. Ongoing studies are beginning to uncover how multiple genetic risk factors act together in the development of psychiatric disorders, but much more remains to be learned before we can use genetic discoveries to develop better methods of diagnosis and treatment.

Key Concepts

Most psychiatric disorders are strongly influenced by genes.

Genome‐wide association studies have identified numerous common genetic markers associated with major psychiatric disorders.

Each common allele confers little risk, but many add together to confer susceptibility to psychiatric illness.

Rare copy number variants, which influence the dosage of many genes, confer substantial risk for schizophrenia, autism spectrum disorders and intellectual disability.

Rare, gene‐damaging point mutations, most of which arise
de novo
, can also confer substantial risk for schizophrenia, autism spectrum disorders and intellectual disability.

The ultimate goal of gene identification for mental illness is to develop better methods of diagnosis and treatment.
Inherited Neuromuscular Disease
Authors: Kichula Elizabeth A , Ferguson Toby A , Lynch David R
Published: January 2017

Inherited neuromuscular disease encompasses a broad array of diseases afflicting people at all stages of life. The main categories of inherited neuromuscular disease are diseases of peripheral nerve (neuropathy), neuromuscular junction (myasthenia), diseases of muscle (myopathy and dystrophy) and diseases of spinal cord motor neurons (motor neuron disease). The number of genes underlying such disorders has expanded greatly in the past 10 years. The discovery of such genes has allowed development of specific therapeutic approaches based on genetic diagnosis, as well as the ability to tackle pathways involved in multiple disorders. It has also complicated diagnosis, with mutations in single genes causing multiple clinical phenotypes. Research is starting to have concrete benefits, with treatments beginning to emerge from basic science research with the hope that many more will show efficacy over the next decade.

Key Concepts

Expanded genetic testing has led to the identification of dozens of new genes implicated in neuromuscular disorders.

Single genes can cause a wide spectrum of neuromuscular disease, and multiple genes can cause very similar clinical phenotypes.

Identification of pathways involved in neuromuscular disease may allow for therapies that are not specific to a single gene or mutation.

Pathways involved in inherited neuromuscular disorder are also involved in sporadic and acquired disease.

Gene‐specific therapy is being developed for multiple inherited neuromuscular disorders, including antisense oligonucleotides and gene therapy.
Nitric Oxide Signalling in Plants
Authors: Hancock John T , Wilson Helen R , Neill Steven J
Published: January 2017

Nitric oxide (NO) is a small simple molecule, but one which is instrumental in cell signalling in a range of organisms including plants. It is a gas, often found in the form of a radical. It is produced in cells in an orchestrated manner, usually by dedicated enzymes and often following stress. It leads to numerous responses. In plants it is involved in seed germination, seedling development, stomatal responses, senescence and protection against pathogens, so is an instrumental signalling molecule used throughout the life of the plant. Responses to NO may involve the generation of other signalling molecules such as cGMP or the covalent modification of proteins in a process known as S‐nitrosation. However, it should be noted that NO signalling will not be isolated in the cell and NO will impinge on other signalling pathways, such as those involving reactive oxygen species. Therefore, NO should be considered as part of a suite of signalling components which enable plants to thrive and survive.

Key Concepts

NO, along with reactive oxygen species (ROS), is produced by plants during normal growth and development and its production is often increased as part of stress responses.

NO is involved in a range of plant processes including pollen recognition and germination, seed germination, senescence, pathogen attack, gravitropism and stomatal responses.

NO can be generated enzymatically or nonenzymatically in cells.

Nitrate reductase is a key enzyme which generates NO.

NO may lead to increases in cGMP levels in cells.

NO, or downstream products, may lead to modification of proteins and hence their activities.

Removal of NO is important for signalling.

The signalling involving NO will affect, and be affected by, other signalling pathways including those involving reactive oxygen species and hydrogen sulfide.
Environmental Stochasticity
Authors: Fujiwara Masami , Takada Takenori
Published: January 2017

Environmental stochasticity refers to unpredictable spatiotemporal fluctuation in environmental conditions. The term is often used in the literature on ecology and evolution. Unpredictability is defined as an inability to predict the future state precisely such that only its distribution can be known. The environment is typically defined as any set of abiotic (e.g. temperature and nutrient availability) and biotic (e.g. predator, competitor and food) conditions that organisms experience. Environmental stochasticity influences how population abundance fluctuates and affects the fate (e.g. persistence or extinction) of populations. In an evolutionary timescale, environmental stochasticity also affects the life history strategy of organisms. Environmental stochasticity is included in population models using univariate difference equations, stochastic matrix population models, stochastic differential equations and partial differential equations. Ecological data are analysed to determine the effect of environmental stochasticity using methods such as spectral analysis, capture–recapture analysis, state‐space analysis, generalised linear models and multivariate statistical analyses.

Key Concepts

Environmental stochasticity is unpredictable spatiotemporal fluctuations in environmental conditions.

Observed population dynamics consist of fluctuation due to environmental stochasticity, but it is often confounded with other factors such as observational errors, deterministic fluctuation and demographic stochasticity.

Environmental stochasticity is reflected in the fluctuations in ecological processes and affects their fate (e.g. extinction or persistence of populations).

Environmental stochasticity plays an important role in the evolution of life history strategies of organisms by affecting their fitness.

Stochastic discrete‐time models, stochastic matrix population models, stochastic differential equation models and partial differential equation models are the four basic population models that include environmental stochasticity.

Spectral analysis, state‐space model analysis, capture–recapture analysis, generalised linear models and multivariate statistical analysis are commonly used for separating the effects of environmental stochasticity in data.
Evolution and Ecology of Plant Mating Systems
Authors: Pannell John R , Voillemot Marie
Published: January 2017

The mating system provides a description of the distribution of mating unions in a population; in hermaphrodites, such as most flowering plants, this amounts to the rate of self‐fertilisation versus outcrossing. Selfing has evolved numerous times in flowering plants, probably because selfers transmit an extra copy of their genes to their seed progenies and/or because they can reproduce in the absence of mates. Nevertheless, selfed progenies tend to be less fit, and selfing detracts from an individual's outcrossing potential. As a result, most plants avoid selfing via a number of physiological, morphological or phenological adaptations. The mating system also has important implications for the genetic structure of individuals and populations: selfing individuals show reduced heterozygosity, reduced effective recombination and reduced effects of genetic conflict and populations of selfers tend to be more genetically differentiated from one another than do those of outcrossers.

Key Concepts

The mating system describes and quantifies the distribution of mating unions in a population; in hermaphroditic plants, the mating system typically refers to the selfing or outcrossing rates.

Self‐fertilisation confers an automatic selective benefit because selfed progenies carry two copies of a parent's genome rather than just one. An important possible cost of self‐fertilisation is inbreeding depression, where selfed progenies have lower fitness than their outcrossed counterparts.

Self‐fertilisation can be costly because pollen used up in selfing is unavailable for competition to sire outcrossed progenies; this is known as pollen discounting. Similarly, self‐fertilised ovules are unavailable for outcrossing (seed discounting), also constituting a cost.

Self‐fertilisation may be advantageous when mates or pollinators are scarce because it provides reproductive assurance by allowing uniparental reproduction.

Inbreeding depression can be caused by either overdominance, where heterozygotes have an advantage over both corresponding homozygotes, or partial dominance, where fitness is reduced on one homozygote by the expression of deleterious recessive alleles.

Plants avoid self‐fertilisation through physiological self‐incompatibility reactions, the spatial separation of the sexual functions within and/or among flowers (herkogamy or dicliny) or the temporal separation of the sexual functions (dichogamy).
Immunity, Granzymes and Cell Killing
Authors: Trapani Joseph A
Published: January 2017

Cytotoxic lymphocytes protect us from viral infection and cancer by directly killing tumour cells or cells harbouring a virus. One crucial mechanism they use to kill their targets is known as the ‘granule exocytosis’ pathway. This involves secretion of a potent mix of toxins, resulting in transfer of granule proteases (granzymes) from the killer cell into the target cell, where they cleave various intracellular substrates to activate diverse signalling pathways to cell death. Access to the target cell cytosol depends on a pore‐forming protein toxin, perforin. Because granule exocytosis is a crucial part of the body's natural defence against such dangerous cells, understanding how granzymes kill their targets may yield novel strategies and identify new molecular targets for anticancer or antiviral therapies. Indeed, recent advances in cancer immunotherapy such as checkpoint blockade and adoptive transfer of chimeric antigen receptor (CAR) T cells all ultimately rely on activating the granule exocytosis pathway to kill cancer cells.

Key Concepts

The critical role of cytotoxic T lymphocytes and natural killer cells is to eliminate abnormal cells, thereby defending higher organisms against intracellular infection.

An important additional function of cytotoxic lymphocytes also encompasses their role in surveillance against transformed cells.

Perforin and granzymes synergise to kill target cells. Perforin is critical to this process and its role is to enable granzyme proteases to access key substrates in the target cell.

Perforin functions by punching large pore‐like defects in the target cell membrane, permitting direct granzyme diffusion into its cytosol.

Granzyme B is the most potent proapoptotic granzyme, as it shares with caspases the capacity to cleave its substrates after key aspartate residues.

Cytotoxic lymphocytes have developed a plethora of different signalling pathways to bring about target cell death. This is critically important as viruses are adept at blocking cell death to maximise their opportunity for viral replication and spread to uninfected cells.

These granzyme‐dependent cell death pathways are mechanistically distinct and arranged in a hierarchy in terms of their potency and kinetics.

Apart from inflicting cell death, granzymes have additional functions such as directly interfering with viral replication and in cytokine processing, leading to amplification of the inflammatory response to pathogens.

Dysregulation of cytotoxic T‐cell function can sometimes lead to adverse effect such as autoimmune tissue damage.
Posttranslational Modifications in Plant Disease Resistance
Authors: Casey Milena , Srivastava Moumita , Sadanandom Ari
Published: January 2017

Under constant attack from an ever‐evolving array of pathogens, the multilayered plant immune system provides a broad‐spectrum resistance that is the result of millions of years of coevolution of plants and microorganisms. Driving the arms race for survival is the continual diversification of defence and attack mechanisms. This process can be rapidly and efficiently achieved by posttranslational modifications (PTMs). Phosphorylation and ubiquitination are important PTMs involved in plant immune signalling that are exploited by pathogens and plants alike. Identified connections between the two PTMs have been shown to either positively or negatively regulate each other, affecting the activity of a growing number of immune proteins. In various instances, this crosstalk has been shown to link the two alleged levels of innate plant immunity: PAMP‐triggered immunity (PTI) and effector‐triggered immunity (ETI). Understanding how this occurs will lead us to unravel the web that is the plant immune signalling interactome.

Key Concepts

Natural selection drives the diversification of pathogen virulence and plant resistance mechanisms.

Posttranslational modifications are essential for providing rapid and efficient diversification of defence and attack proteins.

Phosphorylation and ubiquitination are important posttranslational modifications involved in plant immune signalling.

Crosstalk between ubiquitination and phosphorylation regulates plant immune signalling.

Crosstalk between ubiquitination and phosphorylation can link different levels of the plant immune system.
Genetics of Adverse Drug Reactions
Authors: Wang Chuang‐Wei , Chung Wen‐Hung , Hung Shuen‐Iu
Published: January 2017

Adverse drug reactions (ADRs) remain a common and a major problem in healthcare. Many kinds of ADRs are predictable, dose‐dependent and associated with the pharmacodynamic and pharmacokinetic of drugs. However, some are unpredictable, dose‐independent and termed as idiosyncratic reactions. A number of recent studies have demonstrated that ADRs possess strong genetic predisposition, and the associated risk variants include HLA alleles [e.g.
HLA‐B*15:02
for carbamazepine‐induced Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN),
HLA‐B*58:01
for allopurinol‐induced SJS/TEN and
HLA‐B*57:01
for abacavir hypersensitivity], drug‐metabolising enzymes (e.g.
CYP2C9*3
for phenytoin‐induced severe cutaneous adverse reactions and
NUDP15
missense variants for thiopurine‐induced leukopenia) and drug transporters (e.g.
SLCO1B1
variants for statin‐induced myopathy). These findings not only give insights into the pathogenesis of ADRs but also lead to the development of useful tests to reduce the incidences of ADRs.

Key Concepts

ADRs possess strong genetic predisposition, and the identified important risk factors include genes encoding human leukocyte antigens (HLA), drug‐metabolising enzymes and drug transporters.

The human HLA alleles are highly polymorphic and associated with different types of ADRs, including cutaneous adverse reactions and drug‐induced liver injury. The association has characteristics of drug‐, ethnic‐ and phenotype‐specificity.

The human HLA alleles exhibit strong association with severe cutaneous adverse reactions, for example,
HLA‐B*15:02
and carbamazepine‐induced SJS/TEN,
HLA‐B*58:01
and allopurinol‐induced SJS/TEN/DRESS and
HLA‐B*57:01
and abacavir hypersensitivity.

Polymorphisms of cytochromes P450 (e.g.
CYP2D6
,
CYP2C9
and
CYP2C19
) and other drug‐metabolising enzymes (e.g. g
lucose‐6‐phosphate dehydrogenase
and
nucleoside diphosphate linked moiety X‐type motif 15
) can cause defective or altered enzyme activity, and are associated with different kinds of ADRs.

The genetic alterations of drug transporters (e.g.
ATP‐binding cassette (ABC)
and
solute carrier (SLC) transporters
) are also linked to ADRs.

The epigenetic effects on drug‐metabolising enzymes and drug transporters may also contribute to the individual susceptibility to ADRs.

Implementation of the genetic screen before drug prescription has been applied in clinical practice, and these pharmacogenetic tests show efficacy for preventing ADRs.
Genetics of Suicidality
Authors: Blackman Olivia , Jessica Lasky‐Su
Published: January 2017

Suicide is the 15th leading cause of death, making it a serious public health problem. While external life influences tend to be the focus of why suicide attempts occur, there is consistent evidence that underlying genetic determinants contribute substantially to suicidal ideation. In this article, we first review the general epidemiology of suicide and then discuss the various ways genetic determinants result in suicidal ideation, suicide attempts and suicide itself. Specifically, we discuss how other psychiatric illnesses, including depression, bipolar disorder, alcoholism and schizophrenia are comorbid with suicidality, thereby making the genetic determinants for these other psychiatric conditions also genetic risk factors for suicidality. We do this by reviewing the current genetic research findings from these psychiatric conditions and link the findings to suicidality.

Key Concepts

Suicidality is a complex disease that is a result of both genetic and environmental influences.

Suicidality often cooccurs with other psychiatric conditions.

There is often an environmental trigger, which, in conjunction with a genetic predisposition, can result in suicide attempts.

Several of the genetic underpinnings for other psychiatric disorders are likely also associated with suicidality.

More research is necessary to identify and confirm genetic variants for suicidality.
CpG
Island Methylator Phenotype in Cancer
Authors: Kim Jung H , Bae Jeong M , Kang Gyeong H
Published: January 2017

Aberrant deoxyribonucleic acid (DNA) methylation is an important epigenetic change in various cancers. During carcinogenesis, DNA methylation preferentially occurs in promoter CpG islands, which do not usually undergo DNA methylation in normal cells. Promoter CpG island methylation causes transcriptional silencing of the corresponding gene and is thus regarded as one of the mechanisms of tumour suppressor gene inactivation. In human cancers, the unique molecular phenotype characterised by extensive promoter CpG islands hypermethylation has been referred to as the CpG island methylator phenotype (CIMP). Although characteristic clinicopathological and molecular associations of CIMP have been identified in some types of malignancies, there has been a lack of consensus regarding the diagnostic criteria for CIMP, and prognostic/predictive values of CIMP in cancers have been controversial.

Key Concepts

Aberrant DNA methylation is one of the molecular hallmarks of cancers.

The CpG island methylator phenotype (CIMP) indicates a subtype of cancer characterised by widespread promoter CpG islands methylation.

CIMP has been identified representatively in colorectal cancers, gastric cancers and brain gliomas.

CIMP+ colorectal cancers are associated with the serrated neoplasia pathway and poor prognosis, but the predictive value of CIMP remains controversial.

CIMP+ gastric cancers are associated with Epstein–Barr virus (EBV) positivity and/or microsatellite instability‐high (MSI‐H) status.

CIMP+ gliomas are associated with isocitrate dehydrogenase (IDH) mutations.
Cell Signalling Mechanisms in Plants
Authors: McAinsh Martin R , Taylor Jane E
Published: January 2017

Plants are exposed to a wide range of environmental and developmental signals to which they must respond if they are to grow and reproduce. To allow this, plants have evolved complex mechanisms by which these different signals are perceived and transduced to bring about an appropriate physiological response. While these signalling pathways are highly diverse, they all possess two key properties: signal amplification and signal specificity. In addition, many of the components of plant cell signalling pathways are common to all eukaryotes. These include membrane receptors that recognise individual stimuli and numerous proteins, including kinase and phosphatase enzymes, and small molecules that transfer the signals from where they are perceived to their site of action within cells. However, the manner in which these components function in plants can often be different from how they function in other organisms.

Key Concepts

Plants monitor and respond to a diverse and continually changing stream of environmental and developmental signals.

Chains of proteins and other signalling intermediates connect the perception of signals to the appropriate physiological response in cells.

Signal transduction pathways share common properties.

The plasma membrane is the main site of signal perception.

Interaction between signalling pathways to form signalling networks within cells allows the integration of information from different signals.

Second messengers and protein phosphorylation cascades allow amplification of signals.

Cell signalling pathways can result in changes to cellular metabolism, function and movement, and altered gene expression and development.
Developmental Compartments
Authors: Blair Seth S
Published: January 2017

Developing tissues are in some cases subdividing into developmental compartments. These are spatially restricted regions between which proliferating and migrating cells cannot mix, even though cells in adjacent compartments can be immediate neighbours in a single epithelium or mesenchyme. Compartments not only serve to subdivide tissues but also, through signalling between compartments, often establish boundary zones that themselves become organising centres for the tissue. First described in the fruit fly
Drosophila melanogaster
, examples have also been described in vertebrate tissues including the neuroepithelium and limb bud. To establish compartments, cells must retain stable compartmental properties that restrict intermixing of cell lineages at compartmental boundaries. A great deal is now known both about the specification of compartmental cells and their impact on patterning, but much remains to be learned especially about the molecular basis of cell segregation.

Key Concepts

Developmental compartments require that cells acquire stable regional identities and have mechanisms that prevent intermixing with unlike cells.

Sharply defined regions in developing tissues are not necessarily compartments: cells can also maintain regions using regionalised signalling to change their identities.

Techniques for tracing cell lineages, each with its own advantages and pitfalls, are required to establish the existence of a compartment.

Compartmental cell identities can be specified by the expression of one or two selector transcription factors or by more complex combinations.

Cell segregation can require the establishment of compartment boundary cells.

Several alternative mechanisms have been proposed to segregate cells between specific developmental compartments.

The most well‐defined molecular mechanism for compartmental cell segregation is the Eph–Ephrin signalling of the rhombomeres of the vertebrate hindbrain.
Genetic Nondiscrimination Legislation in the
U
nited
S
tates and Elsewhere – A Growing Body of Law and Its Impact on Employment
Authors: Krajewska Atina
Published: January 2017

This analysis compares three regulatory models addressing genetic discrimination in employment. As such it has three main aims. First, it aims to determine whether the fear of litigation expressed by employers is warranted in light of the current legal regulation of genetic testing in the field of employment in the US, UK and EU law. As such, it analyses the three main regulatory approaches to the use of genetic data in the workplace. Second, drawing on international law and domestic legal systems, it aims to analyse the existing provisions and remaining points of uncertainty. Finally, it proposes the directions for future research necessary for the comprehensive understanding of the use of genetic data by employers.
Nucleoplasmin: A Versatile Histone Chaperone
Authors: Franco Aitor , Fernández‐Rivero Noelia , Prado Adelina , Muga Arturo
Published: January 2017

Cells have evolved an ingenious way to tightly pack the genetic information in a nucleoprotein complex called chromatin. The functional unit of chromatin is the nucleosome, which is made of DNA wrapped around histones. Dynamic modulation of nucleosome structure by regulating the association/dissociation of histones to/from DNA is essential for DNA replication, repair and transcription.
In vivo
, a group of histone chaperones facilitate and regulate nucleosome assembly. Recent structural, biophysical and biochemical studies have begun to shed light on the molecular mechanisms whereby histone chaperones promote chromatin assembly, disassembly and histone exchange. This review focuses on the structure and function of Nucleoplasmin (NP), a key component of the amphibian chromatin remodelling machinery during fertilisation and early embryonic development.

Key Concepts

Histone chaperones are key components of the machinery that regulates chromatin dynamics.

The function of histone chaperones is based on their interaction with histone surfaces involved in binding to DNA and other histones.

Histone chaperones can be classified into two main groups, specific and generic chaperones, according to their ability to bind only a particular histone or all kind of linker and core histones with similar affinity, respectively.

Nucleoplasmin is a generic histone chaperone able to interact with both linker and core histones.

Nucleoplasmin uses the same protein region, the intrinsically disordered, acidic distal face to interact with all histones, favouring competition for NP binding and thus histone exchange.

The oligomeric structure of NP builds a large histone‐binding region that allows the chaperone to bind different association states of histones, including the octamer.
A Biophysical Toolkit for Molecular Interactions
Authors: Santiveri Clara M , López‐Méndez Blanca , Huecas Sonia , Alfonso Carlos , Luque‐Ortega Juan R , Campos‐Olivas Ramón
Published: January 2017

Intermolecular interactions inside and around the cell are key to maintain basic cell homeostasis and to sense and react to external stimuli. Moreover, the action of therapeutics and other xenobiotics occurs through physical interactions of these agents with biomolecules present in the cell or tissue, thereby interfering with the ‘native’ interactions of the biomolecules. Biophysical characterisation of molecular interactions is a bottom‐up reductionist approach that implies measuring the physicochemical properties of the interacting species (two biomacromolecules or a biomacromolecule and a small‐molecule ligand) in order to quantify the binding strength (thermodynamics) and association and dissociation speed (kinetics) between them. A large variety of macroscopic experimental techniques are available and constitute a biophysical toolkit to study molecular interactionsin vitro. Among others, isothermal titration calorimetry, surface plasmon resonance, analytical ultracentrifugation, nuclear magnetic resonance, microscale thermophoresis, thermal shift and fluorescence‐based methods are most commonly used.

Key Concepts

The strength (affinity) and speed (kinetics) of interactions between biomolecules can be quantified using biophysical experimental methods.

Isothermal titration calorimetry (ITC), fluorescence and nuclear magnetic resonance (NMR) spectroscopies, thermal shift assay (TSA), analytical ultracentrifugation (AUC), microscale thermophoresis (MST) and surface plasmon resonance (SPR) are arguably the most used and versatile techniques to study bindingin vitroand constitute a biophysical toolkit.

Equilibrium affinity constants can be robustly obtained by titration using ITC, fluorescence, NMR, MST, AUC and SPR.

Kinetic information can be obtained from time‐resolved fluorescence spectroscopy and SPR methods. The recently developed kinITC method allows obtaining kinetic information from ITC data.

Biophysical techniques can tackle the study of a wide range of systems and great progress has been made in the characterisation of interactions taking place at the cell membrane.

Basically, all biophysical methods can be automatised to screen for small‐molecule ligands of proteins and other macromolecules, providing starting points for chemical biology and drug discovery.
Human Dignity in Bioethics
Authors: Muders Sebastian
Published: January 2017

In recent years, the concept of human dignity has become an important resource for debates in bioethics. The most important form is personal dignity, a norm or value, which typically is attributed to individual human beings. This kind of dignity protects its bearer in important ways; it cannot be alienated but only violated, and its basic form is possessed by all of its bearers to the same degree. Any adequate theory of human dignity must define the rights and other norms this notion comprises, elaborating the quality or qualities that ground its attribution to beings and the specific goods or interests it protects. While some conceptions of human dignity seek to empower their bearers by equipping them with various rights, thereby increasing their autonomy, others require of the bearers duties to themselves in addition, thereby restricting their possible choices. Both conceptions of dignity as empowerment and dignity as constraint are at play in contemporary bioethical debates on abortion, assisted suicide, organ sale and human enhancement.

Key Concepts

A better understanding of the concept of human dignity.

An overview of the different elements a theory of human dignity typically contains.

An overview of how human dignity is employed in certain bioethical debates.

An overview of the problems and challenges for certain conceptions of human dignity in these applied debates.

An overview of three key characteristics that are typically attributed to human dignity.
Deciduous Dentition of Fossil Hominins
Authors: Bailey Shara E
Published: January 2017

The deciduous dentition is the first of two successive sets of teeth in humans. It consists of 20 teeth that are shed and replaced by the permanent teeth, of which there are 32. The most significant differences in the teeth of fossil hominins and great apes are the reduction of canine size, the change in canine shape and the increased complexity of the deciduous lower first molar. At about 2.5 million years ago, one hominin lineage –
Paranthropus
– continued to increase size and complexity of molars, and reduce canine and incisor size, while the lineage leading to our species
Homo sapiens
underwent dental reduction and simplification. Compared to earlier hominins, the deciduous teeth of recent humans are greatly reduced in size and complexity. However, the range of size and morphological variation among geographic populations is very wide, especially for deciduous first molars.

Key Concepts

Hominin deciduous teeth differ from those of great apes primarily in the size and shape of the upper and lower canines and shape of lower first molar.

Hominin deciduous incisors are smaller than those of great apes and early hominin upper incisors are more heteromorphic (greater differences in size between lateral and central incisors).

Hominin deciduous canines are shorter, smaller and less pointed than those of great apes.

Hominin deciduous canines are more diamond shaped and less conical than those of great apes.

Hominin deciduous lower first molars are nonsectorial and have more cusps than those of great apes.

Hominin deciduous molars are larger and may be morphologically more complex than those of great apes.

The genus
Homo
is characterised by incisor expansion, further canine diminution and molar reduction.

Neanderthals can be statistically distinguished from
Homo sapiens
in the shape and cusp size of deciduous molars.

Recent humans are highly variable compared to their fossil relatives, but tend to have even smaller and more simplified canines and postcanine teeth.
Cranial Vault Thickness in the Genus

H
omo
Authors: Copes Lynn E
Published: January 2017

Cranial vault thickness (CVT) has been noted to vary across members of the genus
Homo
, peaking in
Homo erectus
and declining more recently.
Homo sapiens
, for example, have been noted to have particularly thin vaulted crania. However, the variation within and between species has less frequently been investigated. Cranial vaults are also made up of component layers: two cortical and one trabecular (diploë), and the thickness of these layers may vary independently or in predictable ways. The data on variation in CVT in modern
H. sapiens
and extinct members of the genus
Homo
are reviewed along with the hypotheses for the purported hypertrophic vaults in
H. erectus
. The hypotheses include interpersonal violence providing selective pressure for increased CVT, biomechanical pressures from elongated vault shape, allometric scaling, mechanical forces from increased mastication and systemic increases in growth hormones from exercise.

Key Concepts

Cranial vaults are made up of three layers: inner and outer layers are cortical or compact bone, which sandwich a middle trabecular layer called diploë.

Total cranial vault thickness in modern
Homo sapiens
may vary with age, sex, bone type or genetic ancestry.

Some fossil human ancestors had thicker or thinner cranial vaults than modern humans.

There are no clear reasons for why one species or one individual has a thicker vault than another.
Mechanism of Dynamic Formation of Ultrafine Ferrite Grains during High Temperature Processing in Steel
Authors: Zhao Lijia , Park Nokeun , Tian Yanzhong , Shibata Akinobu , Tsuji Nobuhiro
Published: January 2017

The grain refinement mechanism of ferrite dynamically transformed (DT) from austenite is investigated in a 10Ni–0.1C steel. For decades, it has been debated whether dynamic recrystallization (DRX) contributes to the grain refinement of DT ferrite. Here, the authors show that the role of DRX has been previously underestimated in grain refinement of ferrite and intrinsically it is the DRX that leads to ultra grain refinement of DT ferrite. The DT ferrite shows an unconventional grain growth behavior, that is, grain coarsening at an early stage of transformation with subsequent grain refinement by DRX, which strongly depends on the strain rate. The high strain concentration on fine ferrite grains within the austenite + ferrite structure produced by DT mainly contributes to the occurrence of DRX to form ultrafine‐grained ferrite structures.
“Naked” Magnetically Recyclable Mesoporous Au–γ‐Fe2O3 Nanocrystal Clusters: A Highly Integrated Catalyst System
Authors: Shang Lu , Liang Yunhui , Li Mengzhu , Waterhouse Geoffrey I. N. , Tang Pei , Ma Ding , Wu Li‐Zhu , Tung Chen‐Ho , Zhang Tierui
Published: January 2017

Naked magnetically recyclable mesoporous Au–γ‐Fe2O3 clusters, combining the inherent magnetic properties of γ‐Fe2O3 and the high catalytic activity of Au nanoparticles (NPs), are successfully synthesized. Hydrophobic Au–Fe3O4 dimers are first self‐assembled to form sub‐micrometer‐sized Au–Fe3O4 clusters. The Au–Fe3O4 clusters are then coated with silica, calcined at 550 °C, and finally alkali treated to dissolve the silica shell, yielding naked‐Au–γ‐Fe2O3 clusters containing Au NPs of size 5–8 nm. The silica protection strategy serves to preserve the mesoporous structure of the clusters, inhibit the phase transformation from γ‐Fe2O3 to α‐Fe2O3, and prevent cluster aggregation during the synthesis. For the reduction of p‐nitrophenol by NaBH4, the activity of the naked‐Au–γ‐Fe2O3 clusters is ≈22 times higher than that of self‐assembled Au–Fe3O4 clusters. Moreover, the naked‐Au–γ‐Fe2O3 clusters display vastly superior activity for CO oxidation compared with carbon‐supported Au–γ‐Fe2O3 dimers, due to the intimate interfacial contact between Au and γ‐Fe2O3 in the clusters. Following reaction, the naked‐Au–γ‐Fe2O3 clusters can easily be recovered magnetically and reused in different applications, adding to their versatility. Results suggest that naked‐Au–γ‐Fe2O3 clusters are a very promising catalytic platform affording high activity. The strategy developed here can easily be adapted to other metal NP–iron oxide systems.
A Continuous Carbon Nitride Polyhedron Assembly for High‐Performance Flexible Supercapacitors
Authors: Lu Chao , Wang Dongxing , Zhao Jingjing , Han Song , Chen Wei
Published: January 2017

Flexible supercapacitors with high power density, flexibility, and durability have shown enormous potential for smart electronics. Here, a continuous graphitic carbon nitride polyhedron assembly for flexible supercapacitor that is prepared by pyrolysis of carbon nanotubes wired zeolitic imidazolate framework‐8 (ZIF‐8) composites under nitrogen is reported. It exhibits a high specific capacitance of 426 F g−1 at current density of 1 A g−1 in 1 m H2SO4 and excellent stability over 10 000 cycles. The remarkable performance results from the continuous hierarchical structure with average pore size of 2.5 nm, high nitrogen‐doping level (17.82%), and large specific surface area (920 m2 g−1). Furthermore, a flexible supercapacitor is developed by constructing the assembly with interpenetrating polymer network electrolyte. Stemming from the synergistic effect of high‐performance electrode and highly ion‐conductive electrolyte, superior energy density of 59.40 Wh kg−1 at 1 A g−1 is achieved. The device maintains a stable energy supply under cyclic deformations, showing wide application in flexible and even wearable conditions. The work paves a new way for designing pliable electrode with excellent electronic and mechanic property for long‐lived flexible energy storage devices.
Biofunctionalization of Nerve Interface via Biocompatible Polymer‐Roughened Pt Black on Cuff Electrode for Chronic Recording
Authors: Lee Yi Jae , Kim Han‐Jun , Kang Ji Yoon , Do Sun Hee , Lee Soo Hyun
Published: January 2017

Peripheral nerve cuff electrodes with roughened Pt black (BPt) are coated with polyethylene glycol (PEG) and Nafion (NF). Although the influence of coated PEG and Nafion on roughened BPt on the electrical properties is weak, the cuff electrode with BPt/PEG and BPt/Nafion exhibits some very important properties. For example, it markedly decreases interfacial impedance, increases charge storage capacity (CSC) due to retaining the BPt surface structure, good stability without exfoliation in repetitive cyclic voltammetry scanning because it is protected by PEG or Nafion coating. In cell viability test, Nafion‐coated BPt does not show cytotoxicity to rat Schwann cell line (S16) at 24 and 72 h with the Nafion coating ranging from 0.1 to 10 mg cm−2. In addition, real‐time polymerase chain reaction (PCR) analysis indicates that Schwann cell differentiation (S100 calcium‐binding protein B, myelin basic protein, peripheral myelin protein 22), proliferation (proliferating cell nuclear antigen, cyclin‐dependent kinase 1 (CDK1)), and adhesion molecules (neural cell adhesion molecule, laminin, fibronectin) are upregulated up to 5 mg cm−2 of Nafion. In animal study, the BPt/Nafion reduces infiltration of fibrotic tissue with high axonal maintenance with upregulation of proliferation (CDK1), adhesion (laminin, neuronal cell adhesion molecule), and neurotrophic factor receptor‐related (gdnf family receptor alpha 1) mRNA expressions.
Hydroquinone‐Based Biarylic Polyphenols as Redox Organocatalysts for Dioxygen Reduction: Dramatic Effect of Orcinol Substituent on the Catalytic Activity
Authors: Lebeuf Raphaël , Nardello‐Rataj Véronique , Aubry Jean‐Marie
Published: January 2017

A series of 18 new biaryls has been synthesized and investigated with regard to their organocatalytic efficiency. They consist of a hydroquinone core linked to a phenol or a resorcinol moiety. It is shown that the resorcinol moiety substituted on its meta position has a strong impact on the catalytic activities of these compounds towards the reduction of dioxygen by diethylhydroxylamine (DEHA) in aqueous medium. While the derivative consisting of the two cores spaced by three methylene units is completely inactive, substitution on the hydroquinone part leads to tremendously active catalysts, especially the biaryl consisting of methoxyhydroquinone‐orcinol. Two mechanisms are proposed to explain the dramatic efficiency of the novel hydroquinone‐based biarylic polyphenols for the catalytic reduction of dioxygen, both considering the influence of the orcinol moiety on the semiquinone anion intermediate. As a first hypothesis, this substituent could promote its direct reduction by DEHA to regenerate the hydroquinone, which will react again to regenerate the semiquinone. On the other hand, an intramolecular hydrogen bond could enhance the reactivity of the semiquinone anion toward dioxygen by an addition–elimination mechanism. In this case, the elimination would provide the corresponding quinone but, since the reduction of the quinones by DEHA is much slower than the observed kinetics, a reduction by DEHA prior to the elimination has to be considered to generate the semiquinone anion instead of the quinone.

magnified image