bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethics of Human Enhancement and its Relevance to Disability Rights
Authors: David Wasserman 
Published: April 2013

Abstract

The prospect of biotechnological enhancement has provoked opposing and sometimes ambivalent responses from scholars concerned with the interests and rights of people with disabilities. The divergence is particularly sharp with respect to radical enhancement, which would raise human functions above current species norms. Disability scholars and activists fall on both sides of this debate. Critics regard radical enhancement as a threat to people with disabilities, increasing their comparative disadvantage and exacerbating their stigmatisation. Proponents regard radical enhancement as potentially liberating for people with disabilities, enabling them to dramatically improve their practical functioning and freeing them from the oppressive sway of species norms. Both sides of the debate have legitimate concerns; both may oversimplify the complex and varied effects of biotechnological enhancement on disability interests and rights.

Key Concepts:

There is a sharp disagreement about the impact of enhancement, especially radical enhancement, on the rights and interests of people with disabilities.

Proponents of radical enhancement argue that it would dramatically increase the opportunities and reduce the stigmatisation of most people with disabilities.

Critics of radical enhancement argue that it would worsen the comparative disadvantage of people with disabilities and increase the proportion of people stigmatised as disabled.

The claims of proponents may be more plausible with respect to physical disabilities; the claims of critics with respect to intellectual disabilities.

Disability scholars and advocates are on both sides of this complex debate.
Alien Hand Syndrome: Ethical Issues
Authors: Cheshire William P 
Published: April 2013

AbstractAt the nexus of theories of mind and the science of the brain is alien hand syndrome, a rare neurologic disorder in which one hand displays complex nonvolitional behaviours. The causative lesion disconnects brain regions that initiate hand movement from those needed for conscious recognition of volition. The aberrant behaviours may be unwilled and automatic, or in other cases they may be unconsciously willed yet unrecognised as the patient's own. Although sometimes touted as proof that free will does not exist, scientific descriptions of alien hand phenomenon are neutral in regard to competing philosophical theories attributing human decision to free agency or to determined physical processes. How one thinks about the nature of free will is important for ethics, which respects the validity of personal autonomy in moral decision making. Demonstration that some purposeful actions may be unwilled does not mean that all thoughts are predetermined. Therefore, neuroscientific explanations of alien hand syndrome can help to inform but do not dismantle traditional approaches to biomedical ethics.Key Concepts:Alien hand syndrome is a neurologic condition in which the affected hand exhibits complex nonvolitional behaviours.It results from disconnection of brain regions that control the hand from those that signal conscious recognition of volition.Other clinical examples of complex involuntary behaviours are recognised.Purposeful yet nonvolitional behaviour calls into question common understandings of free will.If no human decisions were freely made, then the ethical principle of respect for autonomy would be meaningless.Personal culpability for unwilled harmful actions is ethically and legally diminished.Just because some actions may be unwilled does not mean that all are.Scientific accounts of alien hand syndrome are philosophically neutral with respect to theories of agency versus determinism.Some instances of alien hand syndrome may be a form of agnosia of agency.
Catalysis of Disulfide Bond Formation by the Quiescin Sulfhydryl Oxidases
Authors: Alon Assaf , Fass Deborah 
Published: April 2013

AbstractQuiescin sulfhydryl oxidase (QSOX), an enzyme that catalyses disulfide bond formation in the late secretory pathway and extracellular environment, is emerging as an important player in extracellular matrix assembly, with apparent physiological and pathological functions in development and cancer, respectively. High‐resolution views into the QSOX catalytic machinery are providing information not only on the QSOX enzymes themselves but also on the larger protein disulfide isomerase family of oxidoreductases and on thioredoxin‐fold superfamily proteins more generally. The two redox‐active sites of QSOX are present within domains flexibly tethered to one another, but the sites cooperate tightly and productively to generate disulfide bondsde novoand transfer them to substrate proteins. Backbone and side‐chain dynamics in the vicinity of the redox‐active disulfides of QSOX enzymes appear to modulate the local electrostatics during catalysis, facilitating electron transfer in dithiol/disulfide exchange reactions.Key Concepts:QSOX enzymes accomplish both the generation of disulfidesde novoand the delivery of disulfides to substrate proteins using a redox relay.The amino (N)‐terminal portion of QSOX is structurally and functionally similar to domains of protein disulfide isomerase family proteins.The carboxy (C)‐terminal portion of QSOX appears to have arisen by domain duplication and fusion from an Erv‐family sulfhydryl oxidase precursor.QSOX enzymes have structural features and appropriately positioned functional groups to enhance electron transfer between the two modules.
Accounting for Genetic Testing: Familial and Professional Perspectives
Authors: Arribas‐Ayllon Michael , Sarangi Srikant , Clarke Angus 
Published: April 2013

AbstractGenetic testing is more than a laboratory procedure; it is a complex social activity involving clients, their families and genetic‐counselling professionals. This complexity is occasioned by the fact that genetic testing is distinct from other kinds of medical testing because the hereditary nature of risk and disease accentuates issues of responsibility and blame. The rise of genetic counselling with its ethos of nondirectiveness seeks to help clients make difficult decisions in the face of risk/uncertainty and unintended consequences following the test results. Genetic counselling thus requires challenging and encouraging clients to engage in socio‐moral reflection. The notion of ‘accounts’ is central to understanding how professionals and families routinely explain, defend and negotiate the consequences of genetic risk. A comprehensive review of the literature to date examines the extent to which decisions to (not) test and (not) disclose test results are experienced as tensions across autonomy, responsibility and blame.Key Concepts:Genetic testing is an inherently complex socio‐moral activity in which clients, families and professionals navigate dilemmas that often centre on themes of autonomy, responsibility and blame.Genetic counselling maintains an ethos of nondirectiveness to promote an ethic of self‐governance and client‐centred practice.In contemporary liberal society, the high premium placed on rational autonomy shifts the burden of responsibility and blame to the bearer of choices and to their ability to make decisions wisely.Genetic counselling often requires eliciting ‘accounts’ to challenge or encourage clients to engage in socio‐moral reflection.Accounts are linguistic/rhetorical devices that involve subtle negotiation of individual actionsvis‐à‐viscultural values, moral norms and social expectations.
Mitochondrial Carriers
Authors: del Arco Araceli , Satrústegui Jorgina 
Published: April 2013

Abstract

In eukaryotic cells, the exchange of metabolites across the inner mitochondrial membrane is performed by members of the mitochondrial carrier family (MCF), the largest family of solute transporters. Mutations in MCF genes are associated with rare genetic diseases underscoring the relevance of individual MCF members. Mitochondrial carriers have a common tripartite structure made up by tandem repeats of 100 amino acids each containing two transmembrane α‐helices and one conserved MCF signature. MCF members are present in two states, c and m, with binding sites for substrates facing either the intermembrane (c) or matrix (m) space. X‐ray crystallography of the mitochondrial ADP/ATP carrier in the c‐state has shown that the six α‐helices form a compact bundle shaping a cavity sealed on the matrix side by a salt‐bridge network. Substrate binding perturbs the salt‐bridge network triggering conformational changes that cause the opening of the carrier towards the matrix coupled to substrate transport.

Key Concepts:

Mitochondrial carriers perform the exchange of metabolites, nucleotides and cofactors through the inner mitochondrial membrane.

Mitochondrial carriers form an evolutionary conserved family present in all eukaryotic cells.

Mitochondrial carriers share a tripartite structure made up by repeats of 100 amino acids containing two α‐helices connected by a hydrophilic loop.

Phylogenetic analyses have shown the existence of a limited number of mitochondrial carrier subfamilies involved in the transport of structurally related substrates.

Mutations in nine mitochondrial carriers cause autosomal recessive disorders in humans.

Mitochondrial carriers are present in either one of two different states, c and m, in which binding sites for substrates face the intermembrane (c) or matrix (m) spaces.

During the transport cycle, substrate binding in each of these states induces a transition to the other state which is coupled to substrate transport.

The three‐dimensional structure solved for the ADP/ATP carrier in the c state is consistent with a bundle of six transmembrane α‐helices forming an aqueous cavity closed towards the matrix by electrostatic interactions. Specific interactions of substrates with the substrate‐binding site within the aqueous cavity will disturb the electrostatic interactions that maintain the carrier closed to the matrix side.

Substrate translocation by mitochondrial carriers occurs coupled to conformational movements of the α‐helices that open the carrier.
Organ Donation: Opt In and Opt Out Strategies
Authors: Saunders Ben 
Published: April 2013

Abstract

Opt‐in strategies only take organs from those who have specifically consented to donation, whereas opt‐out strategies treat everyone as a willing donor unless they exempt themselves. Both strategies allow individuals (or their next of kin) power to determine what happens to their cadaveric organs; the difference between them is the ‘default’ treatment of someone who has expressed no wish either way. Opt‐out strategies are likely to increase donation rates, because those who do not register a preference either way will be treated as donors. Opt‐out strategies are often called ‘presumed consent’ and critics contend that this is unjustifiable. In fact, numerous other justifications for such a policy are available, for instance it may be that those who do not opt out thereby tacitly consent to the use of their organs.

Key Concepts:

Opt‐in donation strategies means no one's organs are used without their consent.

Opt‐out donation strategies mean that everyone is treated as a donor unless they specifically refuse.

Few countries operate ‘pure’ opt‐in or opt‐out strategies, because consent is usually sought from next of kin.

It is difficult to measure or predict the effects of a change in policy, but likely that an opt‐out strategy will procure more organs than an opt‐in strategy.

An opt‐out strategy should not be identified with ‘presumed consent’.

There are a variety of possible justifications for an opt‐out strategy, including tacit consent and normative consent.

‘Tacit consent’ means that one's consent is implied by one's silence.

Tacit consent does not necessarily meet the conditions of informed consent.
Genetics of Dyskeratosis Congenita
Authors: Mason Philip J , Reeves Dara , Perdigones Nieves 
Published: April 2013

Abstract

Dyskeratosis congenita (DC) is a rare, inherited, skin and bone marrow failure disease. It is a multisystem disorder which is heterogeneous at the genetic and clinical levels. Genetically, nine genes have so far been identified whose mutation causes DC, and inheritance of the disease can be X linked, autosomal dominant or recessive. Clinically, the disease can present in childhood as classical DC with a characteristic triad of nail dystrophy, leukoplakia and abnormal skin pigmentation along with progressive bone marrow failure. More severe forms presenting in infancy and milder forms in adults, as aplastic anaemia or pulmonary fibrosis, exist. All forms of the disease with known pathogenesis are due to failure of telomere maintenance, often leading to stem cell exhaustion. Recent progress in the identification of mutations in human syndromes has revealed that DC overlaps clinically and genetically with a number of other rare syndromes.

Key Concepts:

The major cause of death in DC is bone marrow failure.

The most common form of DC is X linked.

In the X‐linked form, females are not, or very mildly, affected, but they show extremely skewed X‐inactivation, with cells expressing the mutated gene being outgrown by cells expressing the wild type gene.

Dyskeratosis congenita is a disease caused by defective telomere maintenance.

Nine genes have been discovered to cause dyskeratosis congenita when mutated, and their products are involved in telomerase and its assembly or as part of the telomere.

When the disease is caused by mutations in the core components of telomerase, TERT and
TERC
families show an increase in severity of the disease in later generations, a phenomenon known as genetic anticipation.

Genetic anticipation is due to shortening of telomeres from one generation to the next.

Some DC mutations are also known causes of pulmonary fibrosis, liver fibrosis and Coats retinopathy.

Now that genes responsible for rare syndromes are being discovered, it is becoming evident that there is overlap between DC and several other rare syndromes that have been described.
Molecular Genetics of
MUTYH
‐Associated Polyposis
Authors: Nielsen Maartje , Aretz Stefan , Sampson Julian R 
Published: April 2013

Abstract

MUTYH‐associated polyposis (MAP) is an autosomal recessive condition characterised by the development of multiple colon polyps and colorectal cancer (CRC). It is caused by biallelic germline mutations in the human mutY homologue
(MUTYH)
gene on 1p34.3. The MUTYH protein is a base excision repair glycosylase involved in the repair of oxidation of a guanine leading to 8‐oxo‐7,8‐dihydro‐2′‐deoxyguanosine. MUTYH recognises an oxoG:A mismatch and excises the undamaged adenine base using a base‐flipping mechanism.

Most carriers of biallelic
MUTYH
mutations develop between 10 and 500, predominantly adenomatous polyps and CRC, but a number of MAP patients have CRC without polyps. The lifetime CRC risk in MAP patients is between 40% and 100% in the absence of timely surveillance. The lifetime risk for duodenal cancer is approximately 4% and a modest, but significant increase in incidence has been shown for ovarian, bladder and skin cancer.

Key Concepts:

MUTYH‐associated polyposis (MAP) is an autosomal recessive inherited polyposis and CRC syndrome.

MAP is caused by mutations in both alleles of the
MUTYH
gene.

One of the key functions of the MUTYH protein is prevention of mutagenesis caused by oxidative DNA damage of guanine.

Loss of MUTYH activity leads to somatic G>T transversions.

In the North West (NW) European population, two founder missense mutations, the p.G396D and p.Y179C, compromise more than 90% of mutations reported.

A somatic hotspot
KRAS2
mutation in codon 12 (c.34 G>T) is present in about half of MAP‐associated colon tumours.
Molecular Biology of Small Heat Shock Proteins associated with Peripheral Neuropathies
Authors: Holmgren Anne , Bouhy Delphine , Timmerman Vincent 
Published: April 2013

AbstractHeat‐shock proteins (HSPs) are molecular chaperones that protect the cell from various types of stress. Although regulated by stress, some of these proteins are constitutively expressed and responsible for quality control and protein folding. Based on their molecular weight, the HSP family mainly consists of two groups: large and small HSPs. The large HSPs requireadenosine triphosphate(ATP) for their functioning, whereas the small HSPs (HSPBs) are ATP independent. The latter bind improperly folded proteins and assist in the targeting process for refolding or degradation. These HSPBs are not only molecular chaperones but they are also involved in many essential cellular processes such as apoptosis, autophagy, splicing, cytoskeleton dynamics and neuronal survival. This review focusses on the small HSPs HSPB1, HSPB3 and HSPB8, as mutations in these proteins are causative for Charcot–Marie–Tooth (CMT) disease and distal hereditary motor neuropathies (dHMN). Moreover, this review discusses the functional consequences of these mutations and their role in the length‐dependent neurodegeneration typical of CMT diseases.Key Concepts:The molecular signature of the small HSPs is the conserved α‐crystallin domain.Mutations in HSPB1, HSPB3 and HSPB8 are associated with dHMN and CMT subtypes.Mutant HSPB1 causes instability of the cytoskeletal elements and therefore disorganisation of the neuronal cytoskeleton could underlie the peripheral neuropathies.Mutant HSPB8 may induce pathomechanisms leading to CMT diseases through a loss of autophagy function, rather than a toxic gain of function.The HSPB3 protein differs considerably from the other members regarding sequence similarity such as the poor conservation in theN‐terminal region and the very shortC‐terminal domain.It remains fragmentary how mutations in these small HSPs initiate a molecular cascade leading to progressive axonal degeneration.
Molecular Genetics of Ehlers–Danlos Syndrome
Authors: Mayer Karin 
Published: April 2013

AbstractEhlers–Danlos syndrome (EDS) subsumes a clinically and genetically heterogeneous group of rare connective tissue diseases, characterised by tissue fragility and a highly variable clinical spectrum involving skin, ligaments, joints, blood vessels and internal organs. Based on clinical criteria as well as genetic and biochemical data, the current Villefranche classification subdivides EDS into six major subtypes, which are caused by mutations in genes encoding fibrillar collagens or enzymes involved in collagen biosynthesis. Mutations in type V and type III collagen cause classic and vascular EDS, respectively, whereas mutations affecting the processing of type I collagen lead to the kyphoscoliotic, arthrochalasic and dermatosparactic EDS types. During the last years, specific biochemical and molecular investigations identified several new EDS variants and have brought new insights into the molecular pathogenesis of EDS. Establishing the correct EDS subtype has important implications for genetic counselling and management and offers the opportunity for clinical trials, which are still at the beginning.Key Concepts:EDS is a clinically and genetically heterogeneous group of connective tissue diseases.The Villefranche classification distinguishes six major EDS subtypes.The most frequent molecular causes in EDS are mutations in fibrillar collagens or enzymes involved in collagen metabolism.Recent and ongoing research is leading to the discovery of new EDS variants and to an improvement of understanding the molecular pathology of EDS.Defining the EDS subtype has an important value for the patient and is the basis for clinical management and possible future clinical trials.
Molecular Genetics of Nail–Patella Syndrome
Authors: McIntosh Iain 
Published: April 2013

Abstract

Nail–patella Syndrome (NPS) is a pleiotropic disorder affecting development of the limbs, kidneys, eyes and central nervous system, which is the result of heterozygous, loss‐of‐function mutations in the transcription factor, LIM‐homeobox 1β (LMX1B). There is no correlation between the type or nature of individual mutations and the severity of the phenotype. The availability of animal models, together with analysis of gene expression patterns during development, has substantiated that the range of clinically relevant signs and symptoms is greater than appreciated previously. Evidence is building that attention deficit±hyperactivity disorder and depression may be constituent parts of the syndrome. The variation in the range and severity of symptoms, and the diverse range of affected tissues, make NPS an appropriate model in which to study the effects of gene interactions on the observed phenotype.

Key Concepts:

NPS is a pleiotropic, clinically variable autosomal dominant disorder.

LMX1B is a member of a gene family primarily involved in regulating neuronal patterning.

Loss of function mutations in LMX1B cause NPS but do not predict disease severity.

Analysis of Lmx1b expression has helped explain previously unknown neural aspects of NPS.

Physicians should be aware of the extra‐skeletal aspects of NPS and institute appropriate monitoring and treatment.
Fluid Drag Reduction with Shark‐Skin Riblet Inspired Microstructured Surfaces
Authors: Bixler Gregory D. , Bhushan Bharat 
Published: April 2013

AbstractEngineering marvels found throughout living nature continually provide inspiration to researchers solving technical challenges. For example, skin from fast‐swimming sharks intrigue researchers since its low‐drag riblet microstructure is applicable to many low drag and self‐cleaning (antifouling) applications. An overview of shark skin related studies that have been conducted in both open channel (external) and closed channel (internal) flow experiments is presented. Significant work has been conducted with the open channel flow, and less with closed channel flow. The results provide design guidance when developing novel low drag and self‐cleaning surfaces for applications in the medical, marine, and industrial fields. Experimental parameters include riblet geometry, continuous and segmented configurations, fluid velocity (laminar and turbulent flow), fluid viscosity (water, oil, and air), closed channel height dimensions, wettability, and scalability. The results are discussed and conceptual models are shown suggesting the effect of viscosity, coatings, and the interaction between vortices and riblet surfaces.
Materials and Fabrication Processes for Transient and Bioresorbable High‐Performance Electronics
Authors: Hwang Suk‐Won , Kim Dae‐Hyeong , Tao Hu , Kim Tae‐il , Kim Stanley , Yu Ki Jun , Panilaitis Bruce , Jeong Jae‐Woong , Song Jun‐Kyul , Omenetto Fiorenzo G. , Rogers John. A. 
Published: April 2013

AbstractMaterials and fabrication procedures are described for bioresorbable transistors and simple integrated circuits, in which the key processing steps occur on silicon wafer substrates, in schemes compatible with methods used in conventional microelectronics. The approach relies on an unusual type of silicon on insulator wafer to yield devices that exploit ultrathin sheets of monocrystalline silicon for the semiconductor, thin films of magnesium for the electrodes and interconnects, silicon dioxide and magnesium oxide for the dielectrics, and silk for the substrates. A range of component examples with detailed measurements of their electrical characteristics and dissolution properties illustrate the capabilities. In vivo toxicity tests demonstrate biocompatibility in sub‐dermal implants. The results have significance for broad classes of water‐soluble, “transient” electronic devices.