bluuebunny/crossref_metadata_2025_split huggingface dataset:
History of Apoptosis Research
Authors: Jiang Lijing 
Published: April 2013

AbstractApoptosis‐like cell death was first observed in developing tissues using histological methods in the mid‐nineteenth century. Having been frequently rejected as experimental artefacts, such biologically active, well‐regulated cell death phenomena were reconfirmed in various research contexts during the first half of the twentieth century. In 1972, three pathologists observed cell death in pathological tissues and coined the term ‘apoptosis’ to distinguish the concept of physiological cell death from the concept of passive cell death, necrosis. In the 1980s and 1990s, modern molecular biotechnology transformed apoptosis research from a subject for mostly morphological investigation to a multivalent, interdisciplinary field important to developmental biology, biogerontology and cancer research.Key Concepts:Apoptosis is biologically active, well‐regulated physiological cell death mechanism that is involved in development, tumour suppression, tissue homoeostasis and degenerative diseases.Apoptosis was discovered and defined initially through its unique morphology.The discovery of apoptosis in development challenged assumptions in embryology in the early twentieth century.Molecular methods transformed apoptosis research into an important biological and biomedical field.
Neurobiology of Overeating
Authors: Stice Eric , Burger Kyle S 
Published: April 2013

Abstract

The fact that some people are able to maintain a healthy weight, despite the omnipresence of high‐fat and high‐sugar foods, whereas others experience unhealthy weight gain, has prompted theories regarding individual difference factors that may increase risk for overeating. Some have proposed that individuals who experience less reward from food intake overeat to compensate for this reward deficit. Others have suggested that it is individuals who experience greater reward from food intake who are at risk for overeating. There is data from neuroimaging studies that investigate individual differences in response to food intake and food cues, as well as animal studies that support the reward deficit model, yet there is similar data to support the reward surfeit model. However, neither of these models fit with all of the data. We have therefore proposed a dynamic vulnerability model that appears to better account for the findings in the literature. This working model points to initial vulnerability factors as well as neural adaptations to overeating which may perpetuate overeating in a feed forward manner.

Key Concepts:

Advances in neuroimaging techniques allows for the direct assessment of how food reward can impact eating behaviour.

Multiple, conflicting theories of food reward and obesity have been presented.

Emerging animal and prospective human data suggest that reduced reward when consuming foods and hyper‐responsivity to food cues may evolve from overeating and perpetuate further overeating.

Initial hyper‐responsivity of brain regions that encode the reward value of food cues, coupled with greater responsivity of gustatory/oral somatosensory regions may be initial vulnerability factors of overeating.

Reduced inhibitory activation in response to food stimuli, and genotypes associated with compromised dopamine function may increase risk for overeating/weight gain.

Collectively, data point toward a dynamic vulnerability of overeating and obesity.
Pupillary Disorders
Authors: Walsh Ryan D , Liu Grant T 
Published: April 2013

AbstractPupillary abnormalities range from benign isolated findings to harbingers of significant, even life‐threatening, conditions. A complete understanding of the neuroanatomy underlying the innervations to the antagonistic pupillary sphincter and dilator muscles is essential to detecting, and discerning the importance of, a particular pupillary abnormality. The sphincter muscle receives neuronal input from the parasympathetic division of the autonomic nervous system, whereas the dilator muscle receives input from the sympathetic division. Afferent input carrying light information to the brain is transmitted by retinal ganglion cell axons via the optic nerves, chiasm, and tracts. The parasympathetic innervation to the pupil originates in the Edinger‐Westphal nucleus in the midbrain. The sympathetic innervation to the pupil consists of a three‐neuron pathway originating in the hypothalamus. Important pupillary disorders include physiologic anisocoria, relative afferent pupillary defect, amaurotic pupil, Argyll Robertson pupils, cranial nerve III palsy, pharmacologic mydriasis, tonic pupil, and Horner syndrome.Key Concepts:Examination of the pupil is an important part of the physician's neurological and ophthalmological evaluation of a patient.The size of the pupil is controlled by the actions of antagonistic muscles located within the iris: the pupillary sphincter and dilator.Constriction of the pupils is mediated by the parasympathetic nervous system, whereas dilation of the pupils is mediated by the sympathetic nervous system.Pupillary constriction to light occurs via an involuntary reflex arc.Retinal ganglion cell axons involved in carrying light information for the pupillary light reflex exit the optic tract (proximal to the lateral geniculate nucleus) to synapse in the midbrain pretectal nucleus.The parasympathetic output controlling pupillary constriction originates in the Edinger‐Westphal nucleus in the midbrain and terminates at the pupil sphincter muscle.Pupillary dilation involves a ‘three‐neuron’ sympathetic pathway, which originates in the posterolateral hypothalamus and terminates at the pupil dilator muscle.A relative afferent pupillary defect is caused by a decreased amount of light information from the affected eye reaching the pretectal nuclei in the midbrain and is most commonly a sign of ipsilateral optic nerve pathology.Damage to cranial nerve III can result in injury to the parasympathetic fibres travelling to the pupillary sphincter muscle, thus disrupting the efferent arc of the pupillary light reflex, resulting in deficient pupillary constriction on the involved side.Horner syndrome, characterised by miosis, ptosis, and facial anhidrosis, results from disruption of the oculosympathetic pathway.
Genomic Novelty at the Vertebrate Ancestor
Authors: Kuraku Shigehiro 
Published: April 2013

AbstractThe group of vertebrates includes diverse evolutionary lineages, and typical laboratory‐model vertebrates are confined to only limited groups (tetrapods and teleost fishes) of its entire diversity. Accumulating information of the molecular sequence for the still‐missing lineages including jawless fishes can now provide deeper insights into the definition of the taxon Vertebrata at the genomic level. Above all, the so‐called two‐round whole genome duplications are described to have occurred in the early vertebrate evolution. Recent molecular phylogenetic analyses for some gene families resulted in a scenario in which the genome expansion might have been completed before the split of the lineage of cyclostomes (extant jawless fishes including hagfishes and lampreys) from the future jawed vertebrate lineage. In addition to this genome expansion, key features of genomic contents of the vertebrate ancestor are inferable, provided secondary changes introduced later in individual lineages are taken into deep consideration in ancestral phylogenetic reconstruction.Key Concepts:Large‐scale sequencing of genomes and transcriptomes of non‐model vertebrates in crucial phylogenetic positions provided valuable information about the vertebrates' entire diversity.The two‐round genome duplications likely define the vertebrates genomically.De novogenes should also have contributed to the vertebrate gene repertoire.Lineage‐specific molecular changes should be taken into deep consideration in reconstructing the ancestral state as in morphological comparison.Large‐scale sequence resources for early branching vertebrates are expected to provide clearer insights into the genomics' novelty which established the vertebrates.
Global Population and Global Justice: Equitable Distribution of Resources Among Countries
Authors: West‐Oram Peter GN , Widdows Heather 
Published: April 2013

AbstractAnalysing the demands of global justice for the distribution of resources is a complex task and requires consideration of a broad range of issues. Of particular relevance is the effect that different distributions will have on global population growth and individual welfare. Since changes in the consumption and distribution of resources can have major effects on the welfare of the global population, and the rate at which it increases, it is important to establish meaningful principles to ensure a just distribution of resources. In order to establish such principles we must consider the scope of any reproductive rights, and rights to other goods, such as food and health care, as well as examine the extent of duties correlating to those rights. In addition to the impact that distributions of global goods have on the welfare of current generations, it is also important to consider what duties we have, if any, to future generations.Key Concepts:Questions relating to global justice are concerned with the justice of international institutions and events; they are also concerned with establishing fundamental moral principles, which form the basis of international law.Human rights are those rights which are held by all people in virtue of their status as human beings, rather than because of any specific law or in virtue of belonging to a specific group or country.The distribution and consumption of resources is important in discussion of global justice since the way in which resources are allocated will have a major effect on human welfare and ability of individuals to enjoy their rights.Distributive Justice can be analysed on a range of scales, from the local to the global and deals with questions relating to the distribution of resources and other important goods; these can be things like money, health care, or food, as well as more intangible concepts like freedom and liberty.Environmental sustainability is important in the global justice context because environmental degradation can have severe impacts on human welfare; as such, the sustainability of different types, and rates, of resource consumption will be more or less just, depending on the harm that is caused by it.Egalitarianism is the view, common in discussions of justice that all human beings are morally equal and that as a result, should be given equal moral consideration.Prioritarianism is the view in theories of justice that a specific group, for example the citizens of a particular country, or those living in poverty should have their needs prioritised over the needs of other groups.Sufficientarianism is the view that justice requires only that everyone has enough and that all people have sufficient resources or are above a specific welfare threshold, contrary to egalitarianism, sufficientarianism is compatible with the existence of unequal distribution of goods.
Philosophy of Neuroscience
Authors: Bickle John , Hardcastle Valerie Gray 
Published: April 2013

AbstractSince its inception more than a quarter‐century ago, the philosophy of neuroscience has grown into a recognised field in the philosophy of the special sciences. It focusses on foundational issues in the discipline, but also anticipates developments in the neurosciences that bear on epistemological, ethical and cultural concerns. In this paper, life scientists are introduced to three current issues in the philosophy of neuroscience: a new version of the old reductionism‐versus‐integrationism debate, spurred recently by ‘new mechanist’ philosophers of neuroscience; a challenge to ‘dynamicist’ explanations in neuroscience, as either covertly mechanistic or nonexplanatory; and a brief introduction to the burgeoning field of neuroethics and neurolaw, which is finding new discoveries in neuroscience that bear on both familiar ethical debates and generate novel ethical and legal concerns.Key Concepts:Philosophy of neuroscience is now a recognised field in the philosophy of the special sciences (biology, psychology and economics).The reductionism‐versus‐integrationism debate has reemerged in an interesting new form due to the recent work by ‘new mechanist’ philosophers of neuroscience.The debate among mechanist‐integrationists, mechanistic reductionist and ruthless reductionists turns on the viability and extent of nested hierarchies of mechanisms in neuroscience.Some ‘new mechanists’ have challenged dynamicist explanations in neuroscience, suggesting that such explanations are not distinct from causal‐mechanistic explanations, and even questioning whether such ‘explanations’ are genuine at all.Neuroethics includes both the study of ethical issues raised or influenced by neuroscientific discoveries, and the neuroscience of ethical judgment and decision‐making.Brain interventionist technologies and neuropharmacology raise difficult questions about the ethical dimensions of potential cognitive enhancement.Existing and foreseeable brain interventions encroach upon deep philosophical questions about personal identity and basic fairness.The increasing use of neuronal evidence in law courts raise troubling issues about brain‐realism and the potential impact such evidence may have on juries and judges.
Obesity Hormones in Health and Disease
Authors: Caylak Emrah 
Published: April 2013

Abstract

Obesity is a medical condition as excess body weight in the form of fat, resulting from a chronic imbalance of energy homoeostasis. The prevalence of obesity in adults and children is rapidly rising and it is now the major contributors to metabolic disorders. Energy balance is controlled with short‐ and long‐term signals generated by the central nervous system, gastrointestinal tract and adipose tissue. The knowledge of obesity hormones (adipokines) released by adipose tissue will allow us to develop new anti‐obesity pharmacotherapies amplifying anorexigenic and lipolytic signalling or blocking orexigenic and lipogenic signalling.

Key Concepts:

Obesity is a medical condition resulting from the failure of energy homoeostasis. Obesity is most prevalent in westernised countries, associated with some chronic diseases (i.e. type 2 diabetes, cardiovascular diseases and cancers), shortens life duration and the increases mortality rates.

There has been important endocrine alterations in many physiological systems are attracting interest to understand the pathological mechanisms of obesity.

Although adipose tissue can be considered as storage organ of excess energy, adipocytes released adipokines to control the growth of adipose tissue or the energy homoeostasis and body weight regulation.

Obesity hormones (adipokines) released by adipose tissue to play a major role in the regulation of energy homoeostasis such as adiponectin, apelin, angiotensin II, ASP, leptin, PAI‐1, MCP‐1, omentin, resistin, visfatin, proinflammmatory cytokines and glucocorticoids.

Understanding the physiological and pathological roles of adipokines in health and disease in humans will allow us to find potential therapeutic targets for the treatment of obesity‐related disorders.
The Transcription/
DNA
Repair Factor
TFIIH
Authors: Radu Laura , Maglott‐Roth Anne , Poterszman Arnaud 
Published: April 2013

Abstract

Transcription factor IIH (TFIIH) is a eukaryotic multicomponent macromolecular assembly composed of 10 subunits including two
deoxyribonucleic acid
(DNA)‐dependent helicase activities of opposite polarities and a
kinase
. Mutations in the helicases xeroderma pigmentosum group D protein (XPD) and xeroderma pigmentosum group B protein (XPB) as well as in the p8/TTD‐A subunit of human TFIIH are associated with three dramatic genetic disorders: xeroderma pigmentosum (XP), Cockayne syndrome (CS) and trichothiodystrophy (TTD). Initially recognised as a basal factor responsible for transcription initiation of protein coding genes and transition from initiation to elongation, TFIIH also plays a critical role in nucleotide excision repair via its DNA‐opening helicase activity at the site of a lesion. A subcomplex, harbouring its kinase activity, phosphorylates the carboxy‐terminal domain (CTD) of
ribonucleic acid
(RNA) polymerase II as well as a number of transcription regulators including nuclear hormone receptors.

Key Concepts:

TFIIH is a prime example of multienzyme multitasking macromolecular assembly. Recent data suggest that several components are found in nonTFIIH complexes and that the function of TFIIH is regulated by its subunit composition.

The human transcription/DNA repair factor TFIIH is a multi‐subunit complex composed two functional and structural entities: core‐TFIIH consists of XPB, p62, p52, p44, p34 and p8, whereas the CDK‐activating kinase (CAK) subcomplex contains cyclin‐dependent kinase 7 (CDK7), cyclin H and MAT1. XPD bridges the core‐TFIIH to the CDK activating kinase (CAK) complex, which also exists as a free complex with a distinct function.

Although identified as a basal factor responsible for transcription initiation, TFIIH also plays a critical role in nucleotide excision repair and is implicated in the control of cell cycle progression.

Key insights into TFIIH result from investigations centred on the analysis of mutations identified in XP, CS and TTD patients.

Most mutations identified in patients reside within the noncatalytic regions of the helicases and do not affect the enzymatic activity of TFIIH
per se
but rather disturb the interactions of the catalytic subunits with their regulatory partners, impairing transcription and DNA repair.
Ethics of Complementary Medicine
Authors: Ernst Edzard 
Published: April 2013

AbstractThe ethical principles which apply to medicine in general also apply to complementary medicine (CM). However, the fact that CM is largely unregulated means that certain issues are of particular relevance to this area. These issues include the following: the use of ineffective procedures, the publication of misleading health claims, the misuse of titles, the lack of informed consent, the failure to monitor and report adverse effects, the nondisclosure of conflicts of interest and the fabrication of research. This article provides a brief outline of these themes.Key Concepts:Complementary medicine has to adhere to the same principles of ethics as any other type of medicine.The unregulated nature of much of complementary medicine means that certain ethical issues are more relevant to complementary medicine than to other fields.Despite the widespread use of complementary medicine, there has so far been relatively little attention to ethical issues in this area.
Molecular Genetics of
CHARGE
Syndrome
Authors: van Ravenswaaij‐Arts Conny M A , Hoefsloot Lies H 
Published: April 2013

Abstract

Coloboma of the eye, heart defects, atresia of the nasal choanae, retardation of growth and/or development, genital abnormalities and ear abnormalities and deafness (CHARGE) syndrome is a highly variable, multiple congenital anomaly syndrome with an estimated prevalence of 1 in 17 000. The main features are hypoplasia of the semicircular canals, coloboma, choanal atresia, heart defects, hypogonadotropic hypogonadism, ear malformations, deafness, cranial nerve dysfunction and cleft/lip palate. The phenotype shows a remarkable variability that cannot be explained by different genotypes. In most patients a

de novo

autosomal dominant loss‐of‐function mutation of chromodomain helicase
deoxyribonucleic acid
(DNA)‐binding gene 7 (
CHD7
) is found. The CHD protein family plays a role in transcription regulation by chromatin remodelling. Expression studies as well as studies in stem cells, neural crest cells and animal models have revealed that CHD7 has a tissue‐ and embryonic stage‐specific function in enhancer‐mediated transcription. The broad phenotypic spectrum involving many organ systems that is seen in CHD7 haploinsufficiency can be explained by cell type‐specific binding sites, protein complexes and target genes of CHD7.

Key Concepts:

CHARGE syndrome is a multiple congenital anomaly syndrome with a highly variable and broad clinical spectrum.

CHARGE syndrome shows remarkable clinical overlap with other multiple congenital anomaly syndromes. In contrast,
CHD7
mutations do not cause nonsyndromic congenital defects.

CHD7
is the main causal gene in CHARGE syndrome and codes for a chromodomain protein.

Chromodomain proteins are important during embryonic development.

CHD7 has a function in enhancer‐mediated transcription.

Both the expression of CHD7 and its binding sites to genomic enhancer regions are cell type‐ and embryonic stage‐dependent.

CHD7 haploinsufficiency alters transcription of tissue‐specific target genes that are normally regulated by CHD7 or complexes in which CHD7 is involved.

CHD7 plays an important role in neural crest cells and the interaction of the neural crest with other tissues.

Investigation of overlapping phenotypes and converging molecular pathways gives insight into the pathogenesis.
Molecular Genetics of Alkaptonuria
Authors: Zatkova Andrea 
Published: April 2013

AbstractAlkaptonuria (AKU), the first defined human genetic disease with a recessive trait, is caused by mutations within the homogentisate1,2‐dioxygenase(HGD) gene (3q13.33). This prototypic inborn error of metabolism is characterised by typical bluish‐black pigmentation in connective tissue ochronosis and severe form of osteoarthritis caused by the deposition of ochronotic pigment in the joints. AKU belongs to a group of rare diseases (1:250 000–1:1 000 000), however, several ethnities were reported, where an increased incidence of AKU was observed (Slovakia, Dominican Republic, Jordan and India). Mutation analysis was so far performed in approximately 350 out of more than 650 worldwide reported AKU patients. Rather high heterogeneity was observed with 122 AKU‐causing mutations that are listed together with HGD polymorphisms in the global HGD mutation database (http://hgddatabase.cvtisr.sk/). Because HGD enzyme functions as hexamer, dimer of trimers, genotype/phenotype correlations are difficult to perform in this rare disease.Key Concepts:Alkaptonuria (AKU) is a prototypic inborn error in the metabolism of phenylalanine and tyrosine, characterised by the inability to metabolise homogentisic acid (HGA).The raised HGA levels in plasma and extracellular fluid lead to ochronosis, the deposition of polymers of HGA as pigment (ochronotic pigment) in connective tissues including cartilage, heart valves and sclera.Ochronosis leads to painful destruction of large weight‐bearing joints as well as fusion of the vertebrae, scoliosis and tendon and ligament ruptures.AKU is caused by homozygous or compound heterozygous mutations in the homogentisate‐1,2‐dioxygenase gene (HGD) mapping to the chromosome 3q13.33.AKU belongs to a group of rare diseases (1:250 000–1:1 000 000), however, several ethnities were reported, where an increased incidence of AKU was observed (Slovakia, Dominican Republic, Jordan and India).In approximately 350 patients reported worldwide so far 122 differentHGDmutations have been reported.It was also shown that AKU is caused also by the apparently partial loss‐of‐function mutations, however, the heterozygous carriers of AKU are healthy.HGDhaplotype analysis helps to identify the origin of individual AKU‐causing mutations in different countries.The triketone herbicide nitisinone or Orfadin inhibits the 4‐hydroxyphenylpyruvate dioxygenase enzyme, which produces HGA, thus, it can decrease HGA and should therefore potentially be able to modify AKU.It has been shown that AKU is a novel type II AA amyloidosis, which opens new important perspectives for its therapy, since the control of the underlying inflammatory disorder can result in regression of the disease.Research on ochronosis in this monogenic disease can help to elucidate the molecular pathogenesis of the more common varieties of osteoarthritis, particularly the biochemical and structural changes at its initial stages.