bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution and Ecology of Plant Mating Systems
Authors: Pannell John R , Voillemot Marie 
Published: January 2017

AbstractThe 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 ConceptsThe 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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract
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

Abstract

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

AbstractIntermolecular 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 ConceptsThe 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

Abstract

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.