bluuebunny/crossref_metadata_2025 huggingface dataset:
Gel Sonovaginography
Authors: Sibal Mala
Published: November 2016

Gel sonovaginography is a new way of assessing local cervical and vaginal disorders, in which regular transvaginal sonography is known to have limitations. In gel sonovaginography, 20 mL of ultrasound gel is instilled into the vagina, followed by examination with a transvaginal transducer. In a study involving 28 women with known or suspected disorders such as cervical and vaginal cancer, cervical polyps, vaginal septa, and deep infiltrating endometriosis, a substantial improvement in visualization and assessment of local lesions and structures was noted with gel sonovaginography. This simple technique appears to be valuable for accurate diagnosis of local cervical and vaginal disorders.
Mercator—Independent rover localization using stereophotoclinometry and panoramic images
Authors: Palmer Eric E. , Head James N. , Gaskell Robert W. , Sykes Mark V. , McComas Brian
Published: November 2016

We present a navigation technique for a lunar vehicle based upon matching horizon imagery with a database of synthetic panoramas generated from ultrahigh‐resolution topographic models created by stereophotoclinometry. We conducted two tests, one with lunar topography and fully synthetic panoramas, and another using Earth‐based data and actual panoramic images. We have shown that the horizon‐matching technique can search a wide area for a vehicle's location and determine that location to within 6 m using readily available imagery.
Large Saharan dust storms: Implications for chlorophyll dynamics in the Mediterranean Sea
Authors: Gallisai Rachele , Volpe Gianluca , Peters Francesc
Published: November 2016

We investigate the large (LDE) and very large (VLDE) Saharan dust deposition events that occurred between 2000 and 2007 and their short‐term impact on the dynamics of marine phytoplankton in the Mediterranean Sea. A total of 153 LDE were identified unevenly distributed over the years. Events were more frequent during winter, in the eastern Mediterranean, and autumn, when they affected both the western and the central Mediterranean. Most of the 31 VLDE occurred during winter and autumn in the central Mediterranean. The dynamics of chlorophyll after VLDE were studied as a proxy for phytoplankton response to atmospheric dust. A significant response of chlorophyll to dust addition was evident; this appeared to be especially true for the western Mediterranean where a chlorophyll increase of up to 345% was recorded, whereas in the central Mediterranean it was up to 146% and in the eastern Mediterranean up to 121%. Chlorophyll response behavior was quite heterogeneous probably as a result of the uniqueness of each VLDE, the differences between Mediterranean areas, the community structure of phytoplankton, and the interaction between bacteria and phytoplankton for new resources. An eastward decreasing trend in chlorophyll response was observed, which is in accordance with the relative importance of bacterial activity with respect to phytoplankton. The increase in mineral aerosols with increased aridity in the region together with the decrease in the depth of the mixed layer of the oceans should boost the importance of aerosols fueling marine production.
Identification of OSSO as a near‐UV absorber in the Venusian atmosphere
Authors: Frandsen Benjamin N. , Wennberg Paul O. , Kjaergaard Henrik G.
Published: November 2016

The planet Venus exhibits atmospheric absorption in the 320–400 nm wavelength range produced by unknown chemistry. We investigate electronic transitions in molecules that may exist in the atmosphere of Venus. We identify two different S2O2 isomers, cis‐OSSO and trans‐OSSO, which are formed in significant amounts and are removed predominantly by near‐UV photolysis. We estimate the rate of photolysis of cis‐ and trans‐OSSO in the Venusian atmosphere and find that they are good candidates to explain the enigmatic 320–400 nm near‐UV absorption. Between 58 and 70 km, the calculated OSSO concentrations are similar to those of sulfur monoxide (SO), generally thought to be the second most abundant sulfur oxide on Venus.
Present‐day zonal wind influences projected Indian Ocean Dipole skewness
Authors: Ng Benjamin , Cai Wenju
Published: November 2016

A prominent feature of the Indian Ocean Dipole (IOD) is its positive skewness, where positive phases tend to be stronger in amplitude than the negative phase. Positive IOD events are associated with devastating floods over parts of East Africa and India, while Australia and Indonesia experience dry conditions. Under greenhouse warming, climate models project a weakening of the positive IOD skewness, but their simulation of present‐day skewness is too weak. Here we show that this bias and the projected skewness change are related to the simulation of the climatological zonal wind in the central equatorial Indian Ocean. In particular, models with overly weak present‐day westerlies, which is a common model bias, generate overly weak present‐day skewness and a smaller projected reduction in skewness. Improving the ability of models in simulating stronger westerly winds may lead to stronger present‐day simulated skewness and a larger skewness reduction in a warmer climate.
Void structure of O+ ions in the inner magnetosphere observed by the Van Allen Probes
Authors: Nakayama Y. , Ebihara Y. , Ohtani S. , Gkioulidou M. , Takahashi K. , Kistler L. M. , Tanaka T.
Published: November 2016

The Van Allen Probes Helium Oxygen Proton Electron instrument observed a new type of enhancement of O+ ions in the inner magnetosphere during substorms. As the satellite moved outward in the premidnight sector, the flux of the O+ ions with energy ~10 keV appeared first in the energy‐time spectrograms. Then, the enhancement of the flux spread toward high and low energies. The enhanced flux of the O+ ions with the highest energy remained, whereas the flux of the ions with lower energy vanished near apogee, forming what we call the void structure. The structure cannot be found in the H+ spectrogram. We studied the generation mechanism of this structure by using numerical simulation. We traced the trajectories of O+ ions in the electric and magnetic fields from the global magnetohydrodynamics simulation and calculated the flux of O+ ions in the inner magnetosphere in accordance with the Liouville theorem. The simulated spectrograms are well consistent with the ones observed by Van Allen Probes. We suggest the following processes. (1) When magnetic reconnection starts, an intensive equatorward and tailward plasma flow appears in the plasma lobe. (2) The flow transports plasma from the lobe to the plasma sheet where the radius of curvature of the magnetic field line is small. (3) The intensive dawn‐dusk electric field transports the O+ ions earthward and accelerates them nonadiabatically to an energy threshold; (4) the void structure appears at energies below the threshold.
Porphyromonas gingivalis‐derived outer membrane vesicles promote calcification of vascular smooth muscle cells through ERK1/2‐RUNX2
Authors: Yang Wen Wei , Guo Bin , Jia Wen Yuan , Jia Yue
Published: November 2016

The outer membrane vesicle (OMV) derived from Porphyromonas gingivalis plays an essential role in causing inflammation which, in turn, plays an important part in the pathogenesis of cardiovascular diseases such as atherosclerosis and thromboembolism. However, the contribution of oral bacteria to vascular calcification is yet to be determined. Here, we evaluated the effect of OMV on vascular smooth muscle cell (VSMC) calcification both in vitro and ex vivo. We established a reproducible P. gingivalisOMV‐induced differentiation and calcification model of VSMCs in vitro. The results indicate that OMV promotes VSMC calcification in a concentration‐dependent manner, modulating the expression of bone markers and SMC markers both on genes and proteins that are important for osteoblastic differentiation and mineralization of VSMCs. We also showed that the key osteogenic transcription factor, runt‐related transcription factor 2 (Runx2), which is affected by upstream extracellular‐regulated kinase (ERK) signaling, is a key regulator of OMV‐induced VSMC differentiation and calcification. Taken together, our research demonstrates that Runx2 is a crucial component of OMV‐induced calcification of VSMCs, and ERK signaling plays a vital role in mediating Runx2 up‐regulation and VSMC calcification.
Glycoproteins
Authors: Brooks Susan A
Published: November 2016

Glycoproteins are proteins that contain covalently bound oligosaccharides (glycans) which may be N‐ or O‐linked to the protein. The interacting factors controlling glycosylation are complex and include the protein sequence and structure, specificity of relevant glycosyltransferases, availability of donor sugars and other environmental factors. There is therefore, unsurprisingly, great variety in glycosylation, and a single protein may be synthesised in a variety of glycoforms with glycosylation influencing activity and properties of the protein. Glycosylation provides a means of modifying the function of proteins that is not directly dependent on their deoxyribonucleic acid (DNA) template. Some aspects of glycosylation are common to all eukaryotes, but evolution has led to species‐specific features. Glycans function in development, cell–cell recognition, identity, interaction with pathogens and are altered in some diseases such as cancer. Interest in the field is growing, and advances in analytical technology now make the field accessible to a wider community.

Key Concepts

Proteins are frequently modified post‐translationally, the most frequent modification being glycosylation.

Glycosylation may play an important role in protein folding through interaction with the chaperones calnexin and calreticulin.

As many as 70% of all proteins may be glycosylated.

The glycosylation of a protein may vary extensively depending on the cell in which it is produced which may enable the same protein to function in different ways depending where it is expressed.

On the cell surface, glycoprotein glycans are frequently involved in cell–cell interactions.

Glycosylation of the same protein may change during development or in maturation, for example, in cells of the immune system.

Glycosylation differs between species even if they are closely related, for example, between great apes and man.

There are many common features in glycosylation in bacteria, parasites, insects, plants and mammals, but also differences. This has implications for the biotechnology industry when recombinant proteins destined for human use are expressed in non‐human cells.

In spite of recent advances, glycan analysis remains a complex and specialist field.

Particular features of glycosylation may only have functional significance in a particular time and place but can be widely distributed which can make assignment of function to glycan structure difficult.
Small Regulatory
RNAs
in Bacteria
Authors: Delihas Nicholas
Published: November 2016

Intergenic regions of bacteria contain small regulatory ribonucleic acid (sRNA) genes whose transcripts control expression of distal genes. These transcripts, referred to as sRNAs, primarily act at the level of translation where they bind messenger ribonucleic acids (mRNAs) and inhibit or activate a target mRNA. Base pairing with mRNAs is generally imperfect and can include noncanonical base pairs. The RNA chaperone protein Hfq is involved in many RNA/RNA interactions and ribonucleases RNase E and RNase III have been implicated in destabilisation of target mRNAs. Many sRNAs can inhibit multiple mRNAs; however, some sRNAs bind proteins and can regulate transcription or translation indirectly. Some act like ‘sponges’ that bind and sequester proteins involved in global gene regulation. Many sRNA genes are activated by environmental stress factors, and the sRNA genes have complex upstream regulatory sites. Further insight into broad functions of sRNAs comes from human host cells infected by pathogenic bacteria, which reveals a role of sRNA in both virulence and response in human host cell molecular functions, for example changes in long noncoding RNAs and microRNAs. Bacterial regulatory RNAs are proving to be remarkable factors in both cell physiology and bacterial pathogenesis and these RNAs have opened a new world in molecular biology.

Key Concepts

Small regulatory RNA genes have been found in most bacterial species. sRNA transcripts are generally less than 200 nt.

sRNAs can control gene expression at the level of translation or transcription.

sRNAs respond to environmental or internal stress conditions.

sRNAs generally form small and imperfect RNA/RNA base pairing with target mRNA; noncanonical base pairs can also be present.

sRNAs can inhibit translational and/or induce degradation of target mRNA.

Many sRNAs regulate multiple target mRNAs.

sRNAs can indirectly regulate the expression of global genes, some by binding proteins that control gene expression.

sRNAs can play a major role in bacterial pathogenicity and influence eukaryotic host molecular functions such as levels of host cell microRNA and long noncoding RNA.
Chromatin Diminution
Authors: Streit Adrian , Davis Richard E
Published: November 2016

Chromatin diminution is defined as chromosomal fragmentation, followed by the elimination of part of the chromosome during mitosis. The process was first observed in early cleavage divisions of the parasitic nematodeParascaris equorumembryo by Boveri in 1887. It was later found to also occur in some other parasitic nematodes, as well as a number of unicellular and metazoan species in diverse taxonomic groups. While chromatin diminution occurs in diverse higher order taxa, within individual taxa, it occurs only in a rather small number of species. The process appears to play different biological roles in different organisms, may use different mechanisms and is likely to have arisen multiple times during evolution.

Key Concepts

The term ‘chromatin diminution’ describes the programmed elimination of parts of chromosomes during mitotic divisions and is distinguished from chromosome elimination, during which entire chromosomes are eliminated.

Chromatin diminution, like chromosome elimination, can affect both copies of a chromosome leading to the complete removal of the corresponding genetic information.

Alternatively, chromatin diminution or chromosome elimination can affect only one of the two homologous chromosomes leading to a reduction in gene dose. In other systems such a state where in one cell different regions of the genome are present at different copy numbers can be achieved by differential amplification of various regions of the genome.

If chromatin diminution occurs only in some of the cells of an individual, it leads to a deviation from the dogma that all cells in an organism contain equal genetic information.

In most known cases, chromatin diminution creates a difference between somatic and germ line cells or between the sexes.

Chromatin diminution is a mechanism to silence genes (throwing them away approach to gene regulation) or reduce gene dosage.

Chromatin diminution may also serve to reduce the burden of ‘selfish DNA’ in somatic cells while maintaining it in the gem line.

Chromatin diminution has arisen independently multiple times during evolution (convergent evolution) and its mechanisms likely differ.
Blood Groups and Transfusion Science
Authors: Reid Marion E , Lomas‐Francis Christine
Published: November 2016

Determination of blood group antigens is an integral part of safe blood transfusion and the management of pregnancy. The antigens are carried on proteins, glycoproteins and glycolipids on the surface of erythrocytes and, thus, can elicit an immune response in a recipient who has a different profile of antigens (only identical twins will have erythrocytes with the same profile). Traditionally, haemagglutination has been used to determine blood group antigen profiles on erythrocytes and to detect and identify blood group antibodies. In current transfusion medicine practice, haemagglutination and deoxyribonucleic acid testing are adjuncts. There are 36 blood group systems that harbour 308 antigens. Blood group antigens and antibodies are clinically important in blood transfusion, maternofoetal blood group incompatibility, autoimmune haemolytic anaemia and organ transplants.

Key Concepts

Blood group antigens are carried on proteins, glycoproteins and glycolipids on the surface of erythrocytes.

Blood group antigens can elicit an immune response in a recipient who has a different profile of antigens.

Blood group antibodies are important in blood transfusion, maternofoetal blood group incompatibility, autoimmune haemolytic anaemia and organ transplants.

The determination of blood group antigen profiles and the detection and identification of blood group antibodies is achieved by a combination of haemagglutination and DNA testing.

A group of antigens encoded by alleles at a single gene locus or at gene loci so closely linked that crossing over does not occur or is very rare, constitute a blood group system.

ABO grouping is the single most important test performed in the transfusion service because it is the fundamental basis for determining blood compatibility.

Immune antibodies most often are IgG but may be IgM; they mostly react at body temperature (37°C) and most are considered clinically significant.
TransferRNAin Decoding and the Wobble Hypothesis
Authors: Tuite Mick F , von der Haar Tobias
Published: November 2016

Translation of the genetic code stored in messenger ribonucleic acid (RNA) requires significantly fewer transfer RNAs (35–45) than there are codons (61, amino acid specifying). This is achieved through an increased flexibility in the allowable base‐pair interactions between the messenger RNA and the transfer RNA involving the third position of the codon and the first position of the corresponding anticodon. The rules governing this RNA:RNA interaction were originally summarised in Crick's ‘wobble hypothesis’. Covalent modification of the first base of an anticodon of a transfer RNA can profoundly affect the degree of flexibility in its base‐pairing potential by either extending or restricting such interactions. Recent studies suggest that the rate at which a codon is processed by the ribosome is influenced by whether or not decoding of that codon is via wobble base interactions. Yet, in spite of this flexibility and different rates of processing, decoding by transfer RNAs is achieved with considerable accuracy.

Key Concepts

The genetic code is decoded via transient interactions between messenger RNA (mRNA) and a series of ‘adaptor’ RNA molecules called transfer RNAs (tRNAs).

The mRNA–tRNA interaction occurs on the ribosome via the complementary base pairing between the three‐base anticodon of the tRNA and the three‐base codon in the mRNA.

A greater degree of flexibility of allowable base‐pair interactions between mRNA and tRNA allows most organisms to have far fewer tRNA species than there are codons.

Specific non‐Watson–Crick base‐pair interactions occur between the third base of a codon and the first base of the anticodon of a tRNA during decoding, the so‐called wobble.

Wobble base pairing enables the decoding of two or more codons by the same tRNA.

Certain modified bases, for example inosine (I) can extend or restrict the degree of flexibility in the range of mRNA:tRNA interactions.

Codons that are decoded by wobble base interactions are processed at a slower rate in the ribosome.

Certain antibiotics, for example streptomycin can promote misreading at the wobble third position of a codon.

The genetic code assignments are not universally conserved particularly in organellar genes, for example mitochondrial genes.
GAS5

Gene
Authors: Aly Mahmoud Khamis , Hirose Tetsuro
Published: November 2016

Growth arrest‐specific 5 (
GAS5
) is a nonprotein‐coding small nucleolar ribonucleic acid (snoRNA) host gene. Ten box C/D snoRNAs are encoded within the 11 introns of the human
GAS5
gene, whereas the spliced exons have little protein‐coding potential.
GAS5
has been classified as a member of the 5′ oligopyrimidine tract (5′ TOP) gene family. Growth‐dependent translation mediated by the 5′ TOP sequence determines the level of the
GAS5
spliced transcript (
GAS5
long noncoding RNA (lncRNA)) by a mechanism of translation‐linked RNA degradation.
GAS5
lncRNA plays a critical role in arresting cell growth and inducing apoptosis. The decreased expression of
GAS5
in multiple cancers suggests that
GAS5
acts as a tumour suppressor.
GAS5
lncRNA controls the gene expression of critical cell cycle and apoptosis regulators.
GAS5
lncRNA suppresses steroid‐responsive transcription by direct association with several steroid receptors and acts as a molecular decoy.
GAS5
lncRNA also sequestrates a specific functional microRNA.

Key Concepts

GAS5
is a nonprotein‐coding small nucleolar RNA host gene.

A translation‐linked mRNA decay pathway controls growth arrest‐specific accumulation of
GAS5
by way of its 5′‐terminal oligopyrimidine tract (5′ TOP).

GAS5
functions to arrest cell growth and induce apoptosis.

GAS5
controls expression of genes for critical regulators of the cell cycle and apoptosis.

GAS5
binds to steroid hormone receptors through its 3′‐terminal stem‐loop structure to suppress steroid‐responsive transcription.

GAS5
sequestrates a specific functional microRNA.
Criminal Responsibility and Genetics
Authors: Bostock Jennifer , Adshead Gwen
Published: November 2016

What potential influence would a genetic predisposition to crime have on traditional, moral and legal accounts of responsibility? What do we mean by crime? Is there any truth in the claims that genetics may predispose some individuals to criminal activity? And what about the most serious of criminal activity, homicide? Could a genetic defence affect conviction or sentencing? Does this evidence, and should it affect jurors' perceptions of guilt and innocence? What, if anything, does genetic evidence say about how we determine risk, punishment and moral responsibility? This article addresses these questions by exploring some of the legal cases that have attempted to use genetic evidence as mitigation in homicide trials. The authors conclude that despite advances in genetic science and attempts to forward genetic defences, our key understanding of legal and moral responsibility remains unchanged.

Key Concepts

Criminal, antisocial and violent activity are not synonymous terms.

There is no evidence for a ‘criminal gene’.

There is a question regarding the usefulness of evidence of genetic predispositions to violent criminal activity.

The role of genetic evidence in mitigation against homicide is limited and unsuccessful.

Genetic defence evidence may impact upon jurors' perceptions of guilt or length of sentence.

The quest to find a scientific answer to the question of what causes violent criminal activity may result from the desire to find ways of preventing this activity.

Science cannot determine whether an individual is morally responsible for his/her actions.
Genome Databases
Authors: Castrignanò Tiziana , Chillemi Giovanni
Published: November 2016

All the instructions needed by a cell to direct its activities are contained in its genome. The crucial advances in biology we are witnessing have an impact on genome databases, as the genome is the natural reference frame for mapping information about genes and proteins. Both primary databases, containing the exponentially growing raw information produced by the genomic initiatives, and secondary databases, containing functional annotations of genes and proteins, are the primary entry points for an increasing number of research communities, from biologists to geneticists, from clinical researchers to pharmacologists and more. The elaboration and extraction of new information from this huge amount of genome data is a key challenge that is met by interdisciplinary teams, including high‐throughput data analysts and high‐performance computing technologists.

Key Concepts

Genome databases are the official repositories of the ever‐growing amount of genomic sequences.

The genome represents a natural framework for mapping the biological data of an organism.

Genome browsers provide integrated and customisable views of the information.

Genome databases and their associated tools are the primary entry points for accessing biological information for an increasing number of species.

As more data on individual genomes become available, genome databases allow the reconstruction of whole ‘genetic landscapes’ of a pathology, population or species.

Future challenges are not only related to the sheer size of the data, but also to the need of protecting sensitive information without hampering the exploitation of data for new discoveries.
Lod Score
Authors: Thompson Elizabeth A
Published: November 2016

Lod scores are test statistics used to detect genetic linkage, which is the dependence in descent of deoxyribonucleic acid (DNA) at locations that are nearby in the genome. Lod scores are based on likelihood ratios and hence require parametric models for both trait and genetic marker phenotypes. The classical two‐locus lod score is introduced, and its use in linkage detection is described. Given a genetic marker map, a multilocus map‐specific lod score may be used to map causal trait loci against that framework map. Issues of ascertainment and trait‐model uncertainty are briefly described. A basic assumption of lod score analysis is that dependence between trait and marker data is only through the dependence in DNA descent. Modern genetic marker data allow accurate estimates of shared genome descending to currently observed individuals. This descent may then be used in trait data analyses, providing new approaches to lod score analyses.

Key Concepts

DNA that is at locations on the same chromosome is genetically linked.

DNA at linked locations tends to cosegregate from parents to offspring.

Linkage analysis is the determination of locations of DNA‐affecting traits of interest from evidence of this cosegregation in defined pedigrees.

Genetic markers at known positions in the genome provide a framework against which DNA‐affecting traits of interest may be mapped.

The lod score is a statistic that measures the strength of dependence in segregation between DNA affecting a trait and DNA at locations of specified markers.

The lod score is based on likelihood, and so requires a parametric model for trait data and genetic marker data.

The classical lod score is robust to ascertainment through trait phenotypes.

Modern genetic marker data permit inference of shared descent of genome, even in the absence of a specified pedigree structure.

The lod score may be based on this inferred shared genome among individuals with observed trait phenotypes.
Bayes' Factors
Authors: Johnson Valen E
Published: November 2016

Bayes' factors play a pivotal role in Bayesian hypothesis testing, representing the factor through which the prior odds between competing hypotheses are transformed to the posterior odds between the hypotheses. Mathematically, Bayes' factors are defined as the ratio of the marginal probability assigned to the data by one hypothesis to the marginal probability assigned to data by the other hypothesis. In many parametric statistical tests, hypotheses are defined by the specification of prior densities on unknown parameters. When the prior density on a parameter concentrates on a single value under both the null and alternative hypotheses (resulting in two ‘simple’ or ‘point’ hypotheses), the Bayes factor equals the likelihood ratio. More generally, Bayes' factors represent the ratio of an averaged likelihood function, averaged with respect to the different prior densities assigned to the unknown parameter under each hypothesis. Inconsistencies in the limiting behaviour of Bayes' factors may arise when hypotheses are defined with respect to prior densities that have overlapping support.

Key Concepts

Bayes' factors are used in Bayesian hypothesis tests and are the key factors through which experimental data determine the posterior probability assigned to scientific hypotheses.

Bayes' factors represent the ratio of the probability assigned by competing hypotheses to a common set of data.

When testing whether one of the two simple hypotheses is true, the Bayes factor equals the likelihood ratio between the hypotheses.

Bayes' factors equal the posterior odds divided by the prior odds between hypotheses.

The natural logarithm of a Bayes' factor is called the weight of evidence.
Brain Tumours
Authors: López Giselle Y , Cummings Thomas J , Bigner Darell D , McLendon Roger E
Published: November 2016

Brain tumour genetics allow for improved classification and development of therapeutic options for primary brain tumours. Tumours with specific genetic alterations and molecular profiles are also associated with certain inherited familial cancer syndromes, including Li–Fraumeni syndrome, neurofibromatosis, tuberous sclerosis and Turcot syndrome. Advances in genetic profiling, including karyotypic analyses, genome‐wide sequencing, epigenetic studies and gene expression studies, have greatly improved the understanding of the genetic basis for these tumours. Genome‐wide sequencing identified three key pathways as mutated in the majority of primary glioblastomas, namely, the p53, retinoblastoma and receptor tyrosine kinase pathways. These studies have also identified characteristic genetic alterations in many tumours, such as
IDH1/2
mutations in oligodendrogliomas and progressive astrocytomas,
TERT
promoter mutations in primary glioblastomas and oligodendrogliomas and
BAF47
loss in atypical teratoid/rhabdoid tumours. Further analysis may prove key to identifying likely the therapeutic targets.

Key Concepts

The most common primary malignant brain tumour of adults is glioblastoma, a grade IV astrocytoma with an average survival of approximately 1 year following diagnosis.

The specific genetic alterations present in brain tumours are critical to prognosis and treatment decisions; new diagnostic criteria for brain tumours now integrate molecular classification with the previous histologic classification.

Genome‐wide expression analyses have identified distinct expression patterns in primary glioblastoma patients which predict survival and may eventually be used to target therapies.

Three key pathways altered in the majority of primary glioblastomas include the receptor tyrosine kinase, p53 and retinoblastoma signalling pathways.

Mutations in IDH1 or IDH2 are the most common abnormality in both oligodendrogliomas and progressive astrocytomas, making these tumours genetically distinct from primary glioblastoma.

The most characteristic chromosomal abnormality in oligodendrogliomas is complete allelic losses of chromosomes 1p and 19q.

Gene expression microarray data has made possible the classification of medulloblastomas into four subgroups: Sonic hedgehog pathway subgroup, Wnt pathway subgroup, group 3 and group 4.

Many paediatric brain tumours are characterised by alterations in genes involved in histone/chromatin modifications.
Theory of Cooperation
Authors: Gardner Andy , Griffin Ashleigh S , West Stuart A
Published: November 2016

Cooperation is defined as any adaptation that has evolved, at least in part, to increase the reproductive success of the actor's social partners. Inclusive fitness theory reveals that cooperation can be favoured by natural selection owing to either direct fitness benefits (mutually beneficial cooperation) or indirect fitness benefits (altruistic cooperation). Direct fitness benefits can arise as a simple by‐product of cooperation, or else owing to the existence of enforcement mechanisms, which may be fixed or conditioned according to the individual's cooperative behaviour. Indirect fitness benefits can arise when cooperation occurs between genetically similar individuals, as a consequence of limited dispersal, kin discrimination or greenbeard mechanisms. These theoretical mechanisms are illustrated with empirical examples, from laboratory experiments to field studies.

Key Concepts

The function of Darwinian adaptation is to maximise the organism's inclusive fitness.

Inclusive fitness describes how well an organism transmits copies of its genes to future generations.

Direct fitness is the part of inclusive fitness that comes from the organism's own reproductive success.

Indirect fitness is the part of inclusive fitness that comes from the reproductive success of the organism's genetic relatives.

Cooperation is any adaptation whose function is, at least in part, to increase the reproductive success of a social partner.

Cooperation is mutually beneficial if the actor also benefits and altruistic if the actor suffers a net loss of reproductive success.

Mutually beneficial cooperation is favoured by direct fitness benefits.

Direct fitness benefits can arise as a by‐product or owing to enforcement mechanisms.

Altruistic cooperation is favoured by indirect fitness benefits.

Indirect fitness benefits can arise as a consequence of limited dispersal, kin discrimination or greenbeard mechanisms.
Microbial Inhibitors of Apoptosis
Authors: Häcker Georg
Published: November 2016

Infection with microbial agents (bacteria, fungi, viruses and parasites) is a challenge to a host cell. The host cell's response to infection is complex and entails changes in the activity of a number of intracellular signalling pathways, commonly including the apoptotic machinery. Microbes, if they have evolved the capacity to infect mammals or other complex hosts, have to be able to deal with such defence systems. The lifestyle of microbes varies substantially – viruses, for instance, depend on an intact cell, whereas many bacteria grow on surfaces and are not sensitive to host cell apoptosis. What we know about microbial interference with host cell apoptosis is in accordance with these lifestyles. Viruses often directly target and inhibit the apoptosis machinery with specific proteins, whereas other microbes frequently also interfere with host apoptosis, but this interaction is more frequently indirect.

Key Concepts

Microbes (bacteria, fungi, viruses and parasites) can vary widely in terms of growth requirements and intimacy of association with host cells.

Apoptosis may be induced in cells infected with microbes as a defence mechanism.

A number of viruses carry genes whose products can directly interfere with the host cell's apoptosis apparatus.

Activation of host cells by microbes may enhance survival of the host cell or a responding immune cell.

Activation of antiapoptotic pathways in immune cells by microbial components is a regulatory mechanism of the immune response.
Identifying Genes Underlying Human Inherited Disease
Authors: Natanzon Yanina , Stein Catherine M , Cooke Bailey Jessica N
Published: November 2016

The field of genetic epidemiology seeks to identify the genetic risk factors underlying human disease. First, one must assess whether the trait has an underlying genetic influence, by estimating familial relative risk and/or conducting segregation analysis. In order to discover genes influencing human disease, both family‐ and population‐based studies are designed, and linkage and association methods are used to analyse the relationship between the trait(s) of interest and genetic markers. In general, linkage analysis is more powerful for detecting rare genes with large effects, whereas association analysis is more powerful for detecting common alleles with smaller effects. For the genetics of complex traits, additional factors must be considered, including rare variants, interactions with other genes and the environment, parent‐of‐origin effects and structural variants. Finally, casualty needs to be established beyond statistical implication of association with disease.

Key Concepts

Genetic epidemiologists design both family‐ and population‐based studies to find genes influencing disease risk.

Before conducting a gene‐mapping study, one must first ascertain whether the trait is influenced by genetic effects.

Linkage and association analysis are two complementary methods used to analyse the relationship between trait(s) and genetic markers.

The approach used (linkage vs association) depends on the study design, and these approaches depend on the genetic parameters (rare vs common alleles and large vs small effects).

Other factors – rare variants, gene–gene and gene–environment interaction, existence of structural variants and parent‐of‐origin effects – further complicate the search for disease genes.
Studying Genomic and Epigenetic Aberrations by Microarray Profiling
Authors: Walker Logan C , Nones Katia , Patch Ann‐Marie , Waddell Nicola
Published: November 2016

Genomic (genetic and epigenetic) changes are important for interindividual variation and can cause or influence a person's predisposition for a wide range of human diseases, including cancer. An important tool for the study of these genetic and epigenetic changes is the microarray. For example, high‐density single nucleotide polymorphism (SNP) arrays have been used extensively to study inherited traits using genome‐wide association studies (GWASs). SNP arrays have also been commonly used to profile copy number changes which occur in and are specific to cancer cells. The same microarray technology can be used to assay deoxyribonucleic acid (DNA) methylation status across the genome. Despite the emergence of next‐generation sequencing, microarrays are a relatively low cost and high‐throughput platform that will continue to play a role in unravelling the complexity of human diseases.

Key Concepts

Genomic variation exists between individuals.

Microarrays can assay SNPs, copy number and methylation changes.

Microarrays have been used to study human diseases, inherited genetic traits and cancer.

Compared to single nucleotide polymorphisms, the contribution of inherited copy number variants to human development and disease remains relatively understudied.

Microarray analysis remains simpler and cheaper than next-generation sequencing, but lack the resolution of next‐generation sequencing.
Molecular Genetics of Craniosynostosis
Authors: Lattanzi Wanda
Published: November 2016

Craniosynostosis (CS) is a relatively prevalent congenital malformation, due to the premature ossification of calvarial sutures that articulate skull bones, leading to a variable alteration of craniofacial landmarks and shape. CS is extremely heterogeneous in both clinical and a etiological aspects. It occurs as an isolated defect (i.e. nonsyndromic) in most cases, while it is syndromic in less than one fourth of cases. A genetic aetiology (i.e. mutations inFGFR,TWIST1,EFNB1,MSX, andERFgenes, among others) is known for most syndromes. Recent studies helped clarifying the genetic basis of new CS syndromes and nonsyndromic forms. The discovery of new genes (includingRUNX2,ALX4,TCF12andZIC1) enabled deciphering the complex signalling network that orchestrates craniofacial development. In this light, the entire CS disease spectrum can be regarded as a nosological continuum, with variable degree of severity, in which a strong genetic component provides the background for environmental factors that contribute to the aetiopathogenesis of the birth defect.

Key Concepts

Craniosynostosis is a frequent congenital defect with a high degree of clinical and genetic heterogeneity.

Nonsyndromic forms are more frequent, although their aetiology is still poorly understood.

Many developmental syndromes include craniosynostosis in their phenotype.

Different closely interacting genes (FGFR,TWIST1,MSX2,ERF,TCF12, among others) are involved in the molecular genetics of the best characterised and more frequent syndromic craniosynostoses.

Most genes involved in the etiopathogenesis of craniosynostosis interact within a common gene network.
Role of
ATRX
Chromatin Remodelling Factor in α‐Thalassaemia
X
‐Linked Mental Retardation
Authors: Young Kevin G , Picketts David J
Published: November 2016

α‐Thalassaemia X‐linked mental retardation (ATR‐X syndrome) is a congenital disorder typified by intellectual disability, abnormalities in growth and genital formation, and mild anaemia. Mutations resulting in the reduced function of the ATRX chromatin remodelling protein underlie these symptoms. Variability in the severity of disease characteristics may be associated either with mutations that affect different regions of ATRX or with individual variability in the chromosome landscape targeted by it. ATRX associates with proteins involved in regulating chromatin structure and repression of gene expression in repetitive, transcriptionally silent regions of the genome. Loss of ATRX function can be associated with altered gene expression, including reduced α‐globin expression; impairment in DNA repair; and the maintenance of chromosome stability, which may most critically affect normal development within tissues such as the brain and testes. The current standard of care for ATR‐X syndrome focuses on the management of symptoms, with targeted therapeutics lacking.

Key Concepts

ATR‐X syndrome is caused by loss‐of‐function mutations that result in the diminished expression, or reduced functionality, of the ATRX protein.

Though clinical features of ATR‐X syndrome show variability, common characteristics include facial dysmorphism, stunted growth, hypotonia, microcephaly, intellectual disability, mild anaemia with detectable haemoglobin H (HbH) and genital abnormalities.

ATR‐X syndrome is a nonprogressive disorder, involving abnormal development.

ATRX is a widely expressed chromatin remodelling protein, whose function affects both genomic stability and gene expression.

The histone chaperone complex formed by DAXX and ATRX is critical for loading the histone variant H3.3 onto chromatin.

The function of ATRX may be most critical during the rapid expansion of cells that occurs during development within particular organs, such as the expansion of cortical neurons in the brain or Sertoli cells in the testes.
Congenital Disorders of Glycosylation (
CDG
): Review
Authors: Witters Peter , Morava Eva
Published: November 2016

Glycosylation is the most important posttranslational change for proteins. There are more than 100 different types of congenital disorders of glycosylation (CDG). The most frequent is PMM2‐CDG with over 700 patients described.

N‐Linked glycosylation starts from the cytoplasm through the endoplasmic reticulum to the Golgi apparatus, leading to CDG‐I and CDG‐II defects, respectively. Secretory N‐glycosylation abnormalities can be demonstrated by transferrin isoelectric focusing (the screening test for most CDG types). There are also congenital O‐linked, combined and lipid‐linked glycosylation defects.

Clinically, there is often multisystem involvement or a neurologic phenotype. Multiple abnormalities are usually present by routine laboratory analysis (e.g. increased serum transaminases, decreased coagulation factors and endocrine anomalies).

Aetiologic treatment is limited to a handful of CDG (mannose supplementation for MPI‐CDG and galactose for PGM1‐CDG). The mainstay is supportive care. Twenty percent of patients with PMM2‐CDG die within 2 years; once the age of 4 year is reached, chances for survival rise dramatically.

Key Concepts

Glycosylation is essential for the normal function of glycosylated proteins (and lipids), and plays a role in many biologic processes such as endocrine regulation, coagulation, immunity, cell–cell interaction and organogenesis.

From the different types of glycosylation defects, N‐linked glycosylation defects are the most common and lead to an easily detectable, mostly multisystem disease.

Serum transferrin isoelectric focusing detects the missing negative charges of sialic acid in almost all secretory N‐linked glycosylation defects.

Tissue‐specific O‐linked glycosylation defects and GPI‐anchor‐linked glycosylation defects are mostly recognisable syndromes diagnosed by genetic diagnostic methods.

The most common CDG type, PMM2‐CDG, shows a phenotype of inverted nipples, abnormal fat pads, strabismus, hypotonia and feeding difficulties from a few months of age.

Congenital anomalies are relatively common in CDG, including cerebellar vermis hypoplasia, eye malformations, cardiac defects, abnormal fat distribution, skeletal dysplasia, arachnodactyly or cleft palate.

Specific treatment is only available for PMI‐CDG, namely oral mannose supplementation.

Galactose treatment is beneficial for the endocrine, liver and coagulation problems in PGM1‐CDG.
The Local Microscale Reverse Deformation of Metallic Material under Laser Shock
Authors: Lu Guoxin , Liu Jide , Qiao Hongchao , Cui Chuanyong , Zhou Yizhou , Jin Tao , Zhao Jibin , Sun Xiaofeng , Hu Zhuangqi
Published: November 2016

A striking phenomenon is found that local plastic deformations, with an opposite direction to the external force, applied on metallic target surface under a given laser shock condition. Laser shock treatment is carried out on a number of metallic materials, and the surface topographies after laser shock treatment are observed via White Light Interferometer (WLI) measurement. The results show that many surface relief structures with irregular shapes and random distributions appear on target surfaces under the action of invisible shock waves. It personifies the real plastic flow behavior of metallic materials suffer to pressure waves, and the local reverse deformation.
A Novel Ultrafine Needle (UN) for Innocuous and Efficient Subcutaneous Insulin Delivery
Authors: Li Cheng Guo , Ma Yonghao , Huh Inyoung , Lahiji Shayan Fakhraei , Lee Sang‐Guk , Jung Hyungil
Published: November 2016

Subcutaneous (SC) insulin injection has been demonstrated to be the most effective method for treatment of diabetes mellitus but is conventionally performed by hypodermic needles, leading to poor management of diabetes because of the pain, needle phobia, and tissue trauma. Identification of a viable, safe, and pain‐free alternative method has been a longstanding challenge in modern health care. Here, the thermoplastic droplet stretching technique is developed to create an ultrahigh‐aspect‐ratio needle mold with simple microstructure control. The optimized ultrafine needle (UN) with 4 mm length, minimized 120 µm outer diameter, and 15° sharp bevel angle is formed via electroplating of a metallic layer on the surface of a needle mold with forcing sharp tip. This novel UN enables minimally invasive 4 mm skin insertion to deliver insulin in the targeted SC layer. The similar relative areas under the curves of insulin concentration within UN and 31G needle in vivo insulin administration indicate that UN can ensure stable insulin absorption for secure blood glucose management. Additionally, the proposed fabrication method may facilitate industrialization and commercialization of the UN, holding great promise for replacement of hypodermic needles and for improvement of quality of life among patients with diabetes.
Real‐Time Probing Nanopore‐in‐Nanogap Plasmonic Coupling Effect on Silver Supercrystals with Surface‐Enhanced Raman Spectroscopy
Authors: Ma Cong , Gao Qiangqiang , Hong Wei , Fan Jie , Fang Jixiang
Published: November 2016

Nanopore structures have displayed attractive prospects in diverse important applications such as nanopore‐based biosensors and enhanced spectroscopy. However, on the one hand, the fabrication techniques to obtain sub‐10 nm sized nanopores so far is very limited. On the other hand, the electromagnetic enhancement of nanopores is still relatively low. In this work, using a facile chemical etching strategy on 2D plasmonic Ag nanoparticle supercrystals, fine nanopore arrays with sub‐10 nm pore size have been successfully fabricated and a “nanopore‐in‐nanogap” hybrid plasmon mode has been investigated. An in situ etching and surface‐enhanced Raman spectroscopy (SERS) detection indicate that novel hybrid plasmon structure may create an enhanced electromagnetic coupling and increase SERS signal at ≈10× magnification. The breaking of plasmon bonding dipolar mode and generation of antibonding‐like plasmon mode contribute to this enhanced electromagnetic coupling. The facile etching strategy, as a common approach, may open the doors for the fabrication of nanopores in various compositions for numerous applications.