bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumour Immunology
Authors: Copier John , Dalgleish Angus 
Published: September 2013

Abstract

Tumour immunology is central to our understanding of the mechanisms of both tumour rejection and tumour progression. Virtually every known cell type of the immune system is represented in the tumour microenvironment, but as yet the functional significance of intratumoral effector cells is not fully understood. Moreover, the complex interactions between these immune cells within the tumour have yet to be fully elucidated. Although many individual effector cells have the capacity to kill tumour cells
in vitro
, they are frequently suppressed within the tumour microenvironment through a range of mechanisms. In this article, the known functions of immune effector cells within the tumour and the suppressive processes limiting the function of those cells are described. The purpose of tumour immunology should be to give us a better understanding of how to manipulate the immune system to fight cancer. Some relevant applications of tumour immunotherapy are therefore described.

Key Concepts:

Tumours are infiltrated by a broad range of immune cell types, all of which have demonstrable functions within the tumour microenvironment.

The immune system can play a role in tumorigenesis and metastasis.

The concept of immunesurveillance means that the innate and adaptive immune response is able to seek out and kill tumours, particularly at early stages in development.

Cells of the innate immune system play a crucial role in both antitumorigenic and protumorigenic processes. NK, NKT and γδ T cells all have tumoricidal functions.

The discovery of TAAs that make tumours immunologically different from other healthy tissues explains the ability of the adaptive immune system to recognise tumours as ‘nonself’.

The current paradigm suggests that a TH1 effector response is required for effective antitumour T‐cell responses. CD8+ T cells recognise tumour cells bearing peptides derived from TAAs in the context of self‐MHC.

Antibodies may play a role in the adaptive response to tumours. A number of mechanisms have been defined (such as ADCC and CDC), which are dependent on antibody responses. Monoclonal antibody therapy for cancer has shown the potential power of humoral responses.

The tumour microenvironment is infiltrated by immune suppressive cells, including T‐regs, MDSCs and TAMs. These cells play a key role in both suppression of adaptive and innate responses against tumours, and also contribute towards tumour progression.

Tumour cells are known to have the capacity to escape the immune response by modulating the expression of key target molecules.

Over the last 30 years advances in our understanding of tumour immunology have led to an array of new cancer therapies based on manipulation of the immune system.
Dinosaur Physiology: Were Dinosaurs Warm‐Blooded?
Authors: Quick Devon E , Hillenius Willem J 
Published: September 2013

Abstract

To evaluate the possible physiology of dinosaurs, comparisons must be made with their closest living relatives: birds and crocodilians. Although crocodilians maintain ectothermic metabolic rates and have anatomy reflective of this, modern birds achieve high, endothermic metabolic rates through specialised soft tissues supported by unique skeletal attributes. Finding similar shared characters in dinosaurs that are functionally linked to metabolic rates in birds or crocodilians allows plausible reconstruction of dinosaur physiology. Examinations of dinosaur remains reveal no structures with clear functional association with bird‐like respiratory or metabolic physiology, and in some cases indicate crocodilian‐like anatomy. Consequently, dinosaurs were most likely ectothermic, with resting and maximal metabolic rates that were lower than those of modern mammals or birds. However, given the favourable Mesozoic climatic conditions, most dinosaurs were probably able to maintain high, constant body temperatures through behavioural or inertial thermoregulation.

Key Concepts:

Reconstructing the biology of extinct forms relies on comparison with living taxa that share the same specialised features linked to specific function.

Stable body temperature can be achieved through behavioural mechanisms or through virtue of large mass, and need not rely on a particular metabolic strategy.

The closest living relatives of dinosaurs are birds and crocodilians, which have widely different metabolic rates supported by different respiratory and skeletal anatomy.

Some dinosaur remains preserve evidence, such as postcranial pneumaticity, that may be superficially suggestive of modern bird‐like respiratory anatomy, but they lack other features critical for the ability to ventilate bird‐like lungs or achieve bird‐like aerobic capacity.

No dinosaur remains show evidence of respiratory turbinates, a skeletal character functionally associated with modern endothermy.

Endothermy was not likely achieved in dinosaurs, but was first present in mid‐Cretaceous birds.

Some dinosaurs may have increased aerobic capacity using a crocodilian‐like ventilatory mechanism.
Gymnosperms
Authors: MacKinnon Andy 
Published: September 2013

Abstract

Gymnosperms are a diverse group of plants with the common characteristic of having a ‘naked’, or unprotected, seed. (This contrasts with the other major seed‐bearing plant group, the angiosperms, whose seeds are enclosed in layers of tissue during development.) Historically common, today only approximately 1000 species exist worldwide. Four broad divisions (cycads, ginkgos, conifers and gnetophytes) are generally recognised. Gymnosperms are found in a wide variety of habitats, throughout most of the world. Many are trees: conifers are mostly evergreen trees with needle‐ or scale‐like leaves; cycads are palm‐like trees; ginkgos are deciduous, broad‐leaved trees and gnetophytes are mostly woody climbers (vines) or shrubs. The conifers are the most significant group of timber‐producing trees, and provide the majority of solid wood products worldwide. The economies of many countries depend on ‘softwood’ lumber derived from conifers.

Key Concepts:

Gymnosperms are plants with a ‘naked’, or unprotected, seed.

Gymnosperms live in a variety of habitats worldwide.

There are approximately 1000 species of gymnosperms alive today, in four broad divisions: cycads, ginkgos, conifers and gnetophytes.

Many gymnosperms are trees, and some are economically important as a source of timber and pulp.

Most gymnosperms are evergreen, woody perennials.
Single‐Step Method of Total
RNA
Isolation by Guanidine–Phenol Extraction
Authors: Chomczynski Piotr , Wilfinger William , Mackey Karol 
Published: September 2013

Abstract

The original single‐step method is the first procedure to isolate purified total
ribonucleic acid (RNA)
from a variety of sources including tissues and cells from human, animal, plant, yeast, bacterial and viral origins, without the requirement of high‐speed ultracentrifugation. The method is based on liquid‐phase separation resulting in sequestration of pure RNA into the aqueous phase. RNA is precipitated from the aqueous phase, dissolved, reprecipitated and washed with alcohol before the final solubilisation step. The entire procedure can be completed in less than 4 h and it provides RNA that is suitable for many sensitive downstream applications such as RNase protection assays, northern blotting, sequencing studies and reverse transcription‐polymerase chain reaction. This pioneering methodology has served as the impetus for the development of newer and improved RNA extraction methodology that now enable investigators to extract and purify RNA in less than 60 min.

Key Concepts:

Enzymes within living cells rapidly degrade RNA after a tissue sample is removed from the donor. To prevent RNA degradation, tissue samples that cannot be immediately processed must be rapidly frozen with dry ice or liquid nitrogen and stored frozen at −80 °C until the RNA can be extracted.

At the time of RNA extraction, frozen cells or tissues must be immersed in the denaturing solution and rapidly homogenised before the tissue thaws in order to inactivate RNAse and avoid RNA degradation.

The quality of the recovered RNA is dependent on a delicate balance of salt concentration and optimal pH. Overloading the extraction solution with too much tissue or diluting the denaturing solution beyond what is specified in the protocol will impact the quality of the resulting RNA.

The extraction of RNA from samples that have a high buffering capacity, such as blood, plasma or tissue culture medium, requires greater care in order to maintain optimal salt balance and pH control.

Overdrying of the RNA pellets will impede RNA solubilisation.

RNA should be solubilised at a concentration that will be appropriate for meaningful spectrophotometric quantitation as well as subsequent downstream molecular biology applications.

Enzymes that are involved in RNA degradation are ubiquitous and special care must be taken to avoid RNAse contamination during RNA solubilisation and storage.
Mammalian Sex Chromosome Evolution
Authors: Wyckoff Gerald J , Malcom Christine M 
Published: September 2013

Abstract
Although they are highly dissimilar in sequence content in extant organisms, the mammalian sex chromosomes (i.e. the X and Y) evolved from a pair of autosomes. Differentiation of the sex chromosomes during evolution was initiated by the suppression of X–Y recombination, likely through changes in genomic structure. This was followed by the degeneration of genes on the Y chromosome, with specific instances of gene specialisation on the nonrecombining portion of the Y. Findings of evolutionary ‘strata’ on the sex chromosomes of mammals suggest that multiple events have given rise to the current arrangement of genes on the X and Y chromosomes of mammals. However, new studies utilising more divergent genomic data are challenging conclusions regarding the number and frequency of events that led to the current arrangement of mammalian sex chromosomes, and future studies with complete genomic sequences of marsupials will continue to further our understanding of the evolution of these critical chromosomes.

Key Concepts:

Mammalian sex chromosomes arose from a pair of autosomes.

Genomic rearrangements repressed recombination in a stepwise fashion on these chromosomes.

Genes on these chromosomes diverged due to a combination of forces, including sexual antagonism and removal of deleterious mutations.

Chromosomal studies outside placental mammals continue to contribute to our understanding of mammalian sex chromosome evolution.

Groups of genes on sex chromosomes with similar evolutionary origins are called gene ‘strata’ and exist on both the X and Y chromosomes in the nonrecombining regions.
Evolutionarily Conserved Noncoding
DNA
Authors: Jegga Anil G , Aronow Bruce J 
Published: September 2013

Abstract

Noncoding
deoxyribonucleic acid (DNA)
, which includes all sequences within the genome except exon sequences that encode the protein‐reading frames, harbours a wide variety of regulatory genomic features and elements. The availability of increasingly complete and accurate genomic sequence data from evolutionarily separated species – as well as diverse strain and ethnic variants within species – is providing an unprecedented opportunity to identify potentially functional regions within the genomic noncoding DNA. A variety of computational approaches enable genome‐wide detection, characterisation and visualisation of highly conserved sequences and the occurrence of potentially functional elements within both the conserved and evolved elements. As a result of the continued discovery of these functional elements, the nongenic genetic neighbourhoods are now considered as keys to identifying regulatory elements that are essential for gene and chromosomal function. In this article is given an overview of the various known components of the noncoding DNA landscape and present some of the bioinformatic‐based approaches and resources to identify and analyse the potential regulatory regions in genomic sequences.

Key Concepts:

An indeterminate fraction of the noncoding proportion of the human genome has a decisive role in regulating gene expression.

Comparisons among genome sequences are keys to identifying the functional regions of noncoding DNA.

Identifying and analysing ‘phylogenetic footprints’ is a standard approach to examine for potential regulatory regions.

Two common features of long‐range regulatory elements are that they are frequently conserved in other mammals and are unique within the human genome.

It is not only the conservation of the noncoding DNA but also the loss of the same that holds some of the clues to understand our phenotypic complexity and diversity.

Post‐ENCODE, the genome is viewed as a network of collaborating RNA transcripts with many of the regulatory regions of proteins transcribed into RNA and serve as regulators (e.g., microRNAs and siRNAs).
Human Lineage‐Specific Gene Inactivation
Authors: Grus Wendy E , Zhang Jianzhi 
Published: September 2013

Abstract

Pseudogenes are nonfunctional vestiges of genes. Investigating genes that were inactivated specifically on the human lineage or within humans can reveal the genetic basis of interspecies differences between humans and chimpanzees and interindividual differences within humans. It can also help understand the selective pressures that altered during human evolution or vary among human populations. Recent genome‐wide surveys showed that human‐specific pseudogenisation events occurred much more frequently to chemosensory and immune response genes than to other genes. Although nondeleterious pseudogenisation events were traditionally considered to be neutral, emerging evidence suggests that some of them are beneficial. One well‐characterised case is the human
CASP12
locus, where the null allele decreases the incidence of sepsis and has apparently been selected for in human evolution. Exploration of roles of pseudogenisation in genome evolution and phenotype evolution has started.

Key Concepts:

Pseudogenes in our genome can be (1) shared with other species, (2) functional only in non‐human species or (3) functional in some but not all humans.

According to the ‘less‐is‐more’ hypothesis, human‐specific pseudogenes that are functional in related primates reveal insight into how gene loss helped shape human evolution.

Large‐scale human genetic variation databases reveal hundreds of segregating pseudogenes, suggesting individual and population differences in functional gene content.

Although most gene‐disrupting variants are under negative selective pressure, some population genetic studies of segregating pseudogene loci reveal signatures of positive selection for the disrupted allele, suggesting that gene loss can be beneficial.

Among fixed and segregating human‐specific pseudogenes, chemoreception and immune response are over‐represented functional categories.
Tricks and Tracks in the Identification and Quantification of Endocannabinoids
Authors: Lerner Raissa , Lutz Beat , Bindila Laura 
Published: September 2013

Abstract

The endocannabinoid system serves pivotal roles in a diverse range of physiological and pathophysiological states, including behavior, pain, schizophrenia, obesity, Alzheimer disease, multiple sclerosis and cardiovascular disease. A number of endocannabinoids (eCBs) and their receptors have been characterised and identified in a plethora of biological matrices. The eCBs include
N
‐arachidonoyl ethanolamine (anandamide), 2‐arachidonoyl glycerol, 2‐arachidonoyl glyceryl ether (noladin ether),
O
‐arachidonoyl ethanolamine (virodhamine) and
N
‐arachidonoyl dopamine. Advanced targeted mass spectrometry methods, particularly the selected reaction monitoring, has facilitated sensitive quantification of eCBs owing particularly to minimisation of the complex and abundant lipid matrix, invariably accompanying the eCBs in biological extracts. In this article, state‐of‐the‐art analytical workflows for eCBs extraction and mass‐spectrometry identification and quantification are concisely reviewed. Challenges and considerations on the isolation and analytical conditions to prevent artificial interferences in the measurement of eCBs concentration will be highlighted.

Key Concepts:

Endocannabinoids are lipid signalling molecules with pivotal role in a plethora of physiological and pathophysiological states, including anxiety, fear, learning and memory, pain
etc
.

Imbalances in the ECS activity underlie various psychiatric, neurological, metabolic and immunological diseases, and thus ECS is emerging as an appealing therapeutic target.

Quantitative profiling of endocannabinoids in various biological tissues is imperative to discover their site of action and determine the reference and altered concentration values.

Chemical isomerisation of eCBs, as well as
ex‐vivo
degradation and synthesis can occur during biological matrix sampling and processing, leading to artificial changes in the endogenous levels of eCBs.

Conditions for biological matrix sampling, storage, transportation and eCBs extraction methods have to be tailored and standardised with respect to biological matrix to achieve a reliable determination of reference and disease or pathological state‐related altered concentrations of eCBs in tissues and bodily fluids.

LC–ESI/SRM is the method of choice for eCBs quantification owing to the increased selectivity, specificity, robustness, precision and accuracy of quantification.

Validation and standardisation of LC/MS assays, biological matrix sampling and processing from tissues and bodily fluids are pivotal to allow comparison of eCB levels across studies and for prospective clinical research.
Application of Exome Sequencing to Mendelian Disorders and the Emergence of Personalised Medicine
Authors: Raszek Mikolaj M 
Published: September 2013

Abstract

Since the introduction of next‐generation sequencing, the field of genomic medicine has expanded rapidly. Whole‐exome sequencing (WES) can sequence thousands of functional genes at a time and has become the tool of choice for the discovery of causative genetic variants, especially for Mendelian diseases. This approach also expands the knowledge of novel mutations of established genes linked to a particular disease, and helps to uncover the complex interplay between modifier variants that contribute to a disease phenotype. For these reasons, WES can perform diagnoses that would be difficult to accomplish with traditional methods, particularly for diseases that exhibit a broad genetic or phenotypic heterogeneity. Together, these trends already have begun to influence the quality of patient care and appear to fulfil the promise of personal medicine. The article summarises recent literature that highlights these trends, and discusses the limitations and ethical considerations surrounding this new technology.

Key Concepts:

Next‐generation sequencing is driving the emergence of personalised medicine.

Superiority of WES as a diagnostic tool over traditional genetic methods is apparent, especially for diseases that are genetically and phenotypically heterogenous.

WES utility is a rapidly expanding field of genetic aetiology.

The underlying genetic complexity of monogenic diseases might have been underappreciated.

The clinical manifestation of monogenic diseases is driven by a complex interplay of a multitude of genetic modifiers.

The incidentalome remains an important ethical issue, but important steps forward have been taken with the work of Dr. Berg and collaborators commencing in 2011.

The rapidly expanding field of genomics faces important technical limitations: storage space and analysis capability.

Important ethical questions need to be addressed with regard to the use of NGS technology; this includes rights to data access and issues regarding follow‐up data reanalysis.
Stazione Zoologica Anton Dohrn
Authors: Groeben Christiane 
Published: September 2013

AbstractTheStazione Zoologica di Napoli(SZN) was founded in 1872 by the German zoologist Anton Dohrn as an independent and international research institute for marine biology. Owing to Dohrn's vision and managerial skill the Naples Station was soon considered the Mecca of zoologists. Darwin defined it ‘a great service’ to Science. The administrative and scientific internationality was based on the table system, that is, the renting out of lab space. With World War I the station ceased to be the private property of Dohrn's son and successor Reinhard. In 1923, the SZN was changed into an Italian semiprivate institution (Ente Morale); in 1982 it became a National Research Institute under the supervision of the Italian Ministry of Instruction, University and Research (MIUR). Its scientific policy changed during the 1990s from guest research to in‐house research programmes, still focussed on interdisciplinary and international research.Key Concepts:Research institutions are organisms of their own right.The balance between vision and management allows for a sustainable mission.Research institutes are political structures.The Naples Station has maintained its scientific autonomy due to the sustainable vision of its founder.Hospitality at the scientific, theoretical and social level is a key factor to keep an institute alive and competitive.Networking and sharing resources is essential for marine stations.
Congruence of Cranial and Genetic Estimates of Old World Primate Phylogeny
Authors: von Cramon‐Taubadel Noreen 
Published: September 2013

Abstract
Inferring the phylogenetic relationships amongst fossil hominins is necessarily based on morphological data. Attempts to reconstruct fossil hominin phylogeny have yielded inconsistent and inconclusive results. Old world primates – apes and old world monkeys – provide key referents for understanding the phylogenetic signal in cranial data. Application of phylogenetic methods to cranial data from primate taxa has failed to uncover the known molecular genetic relationships of these major primate groups, suggesting that hominin phylogeny based on morphological data cannot be estimated with complete accuracy. Propositions regarding the potential efficacy of individual cranial regions have been empirically tested in both apes and old world monkeys. No clear criteria have been uncovered to predict the potential efficacy of cranial regions. However, recent studies have suggested that the taxonomic scale of the analysis and the allometric scaling relationships amongst taxa may both play key roles in determining the phylogenetic efficacy of cranial data.

Key Concepts:

Palaeoanthropologists rely on fossilised cranial remains to infer evolutionary history of hominins.

Extant primates form necessary inference models for understanding human evolution.

Attempts to reconstruct hominin phylogenies have generated inconsistent results.

Some cranial traits are likely to be more reliable for reconstructing phylogeny than others.

Masticatory traits have higher within‐taxon variance than nonmasticatory traits, but do not have lower phylogenetic efficacy.

Basicranial traits may have higher phylogenetic efficacy in some primate groups.

No clear rules exist for deciding which cranial traits have the greatest potential to uncover hominin relationships.

Allometric scaling relationships among taxa affect the inference of phylogenetic relatedness.

Taxonomic scale at which cranial–genetic congruence analyses are conducted may also be important.