bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Genetics of Hereditary Spastic Paraplegias
Authors: Stevanin Giovanni 
Published: September 2010

Abstract

Hereditary spastic paraplegias (HSPs), also known as Strümpell–Lorrain disease, are rare neurological conditions characterised by gradual spasticity and weakness of the lower limbs usually caused by developmental failure or degeneration of motor axons in the corticospinal tract. The course is generally slowly progressive, with considerable variation in age at onset and severity of spasticity. There are also complex forms of HSP, with additional neurological features or extra‐neurological signs. HSPs are transmitted according to all modes of inheritance, and 21 of the 43 genes localised have been identified. In recent years, genetic studies have shown abnormal membrane trafficking, axonal transport, cholesterol homeostasis and mitochondrial dysfunction to be the major physiopathological mechanisms in HSP. A new classification is now emerging taking into account clinical, genetic and pathological mechanisms.

Key Concepts:

Hereditary spastic paraplegias are among the most highly heterogeneous neurodegenerative disorders.

The clinical presentation in patients can be pure or complex, variably associating additional, neurological and non‐neurological signs.

Mutations or genomic rearrangements in at least 43 genes can lead to spastic paraplegia.

Intracellular trafficking and maintenance of axon/myelin are the main systems altered in these diseases.
Molecular Genetics of Type 1 Diabetes
Authors: Ye Yi , Mehers Kay L , Gillespie Kathleen M 
Published: September 2010

AbstractCombinations of susceptibility genes interact with environmental modifiers to precipitate autoimmune destruction of islet beta cells and type 1 diabetes (T1D). This interaction has become increasingly penetrant in recent decades with annual increases in incidence of T1D of 3% per year and the greatest increase occurring in young children. Although the major genetic determinant thehuman leucocyte antigen(HLA) on chromosome 6 has been known for decades, recent advances in genetic technology coupled withdeoxyribonucleic acid(DNA) collections from large cohorts of individuals with T1D and controls have resulted in an explosion of information on the genetic determinants of autoimmune diabetes. To date, more than 40 predisposing loci have been identified and hundreds are in the pipeline but the molecular effects of most remain to be determined.Key Concepts:The incidence of T1D is increasing at a rate of 3% per year.Multiple susceptibility genes and environmental determinants interact to precipitate disease.The HLA is currently the best genetic determinant of risk of future T1D. Improving methodologies have resulted in identification of multiple susceptibility genes.
Nonsense Mutations Causing Inherited Diseases: Therapeutic Approaches
Authors: Bidou Laure , Allamand Valérie 
Published: September 2010

AbstractNonsense mutations are single nucleotide variations within the coding sequence of a gene that result in a premature termination codon (PTC). The occurrence of such PTCs most often leads to a complete loss of protein function and a reduction in messengerribonucleic acid(mRNA) levels due to the nonsense‐mediated mRNA decay (NMD), a cellular surveillance mechanism that triggers selective degradation of mutant transcripts. Therapeutic approaches to circumvent the consequences of nonsense mutations may act at different levels: (i) the genomicdeoxyribonucleic acid(DNA) by replacing the defective gene; (ii) the mRNA by inducing the excision of the mutation‐bearing exon during splicing, or by inhibiting the NMD‐associated degradation and (iii) the protein by suppressing the premature termination of translation using transfer RNA (tRNA) suppressors or drugs inducing readthrough. Indeed, a combination of these approaches may be necessary, and it is most likely that they will lead to a mutation‐specific, personalised medicine.Key Concepts:Nonsense mutations may lead to loss or gain of function pathological mechanisms.Premature termination codons (PTC) resulting from nonsense mutations trigger transcript degradation through the nonsense‐mediated mRNA decay (NMD) mechanism.Mutant mRNA escaping NMD lead to the synthesis of truncated proteins potentially deleterious.Skipping of nonsense mutation‐bearing exons can be induced by antisense oligonucleotides and leads to internally deleted proteins that retain some functionality.tRNA suppressors enable the reintroduction of a ‘sense’ amino acid and the translation of the full‐length protein by competing with the termination factor eRF1.Drug‐induced readthrough of PTC may allow synthesis of full‐length functional proteins.Synergetic action between NMD inhibitors and readthrough inducers may potentialise reexpression of full‐length proteins with restored functionality.Therapeutic approaches will most likely be mutation and disease specific.
Molecular Genetics of the α‐Thalassaemias
Authors: Aguilar‐Martinez Patricia , Gulbis Béatrice 
Published: September 2010

AbstractWith the exception of rare non‐α‐globin gene‐related forms and of acquired forms in patients with myelodysplasia, α‐thalassaemias are very widespread worldwide. However, the most severe forms are found among populations of Asian and Mediterranean ancestry. Clinical manifestations of α‐thalassaemia are highly variable, ranging from asymptomatic subjects to a more or less severe haemolytic anaemia. The most severe form, haemoglobin (Hb) Bart's hydrops fetalis (absence of functional α‐globin genes), leads to deathin uteroor at birth. Antenatal screening is available for couples at risk for this severe form, that is, carriers of an α zero thalassaemia allele (absence of any functional α gene on one chromosome 16). Carrier detection is first based on red blood cell indices and confirmed by molecular analysis. Selective advantage against severePlasmodium falciparuminfection has been demonstrated for individuals with α‐thalassaemia. α‐Thalassaemia is also a genetic modifier in sickle cell syndromes.Key Concepts:α‐Thalassaemia has become a widespread genetic disorder worldwide due to the relative protection it confers against life‐threatening malarial anaemia.There are four main forms of α‐thalassaemia depending on the number of remaining functional α‐globin gene(s) in the individual.α‐Thalassaemia can be a severe condition: absence of three α genes results in chronic haemolytic anaemia of variable severity (Hb H disease), whereas the total absence of functional α‐globin gene leads to haemoglobin Bart's hydrops fetalis, a usually lethal condition.In uterotransfusion therapy and stem cell transplantation may improve the outcome of fetuses and infants with Hb Bart's hydrops fetalis in very rare cases.α‐Thalassaemia carriers are usually clinically asymptomatic; however, detection of carriers of α zero thalassaemia is of utmost importance to prevent hydrops fetalis.α‐Thalassaemia carriers may benefit from the diagnosis of their condition, as this may avoid unnecessary iron therapy due to the presence of microcytosis.α‐Thalassaemia is a genetic modifier of sickle cell disease severity through the reduction in the haemolytic rate and a higher haemoglobin level.
Evolutionary Responses to Climate Change
Authors: Skelly David K , Freidenburg L Kealoha 
Published: September 2010

AbstractBiological responses to contemporary climate change are abundantly documented. We know that many species are shifting their geographic range and altering traits, including the timing of critical life history events such as birth, flowering and diapause. We also know from comparative studies of species found across the earth that a strong relationship exists between a species trait and the climatic conditions in which it is found. Together, these observations suggest that ongoing climate change may lead to evolutionary responses. Where examined, evolutionary responses have been uncovered in most cases. The effort needed to disentangle these genetic contributions to responses is substantial and so examples are few. In general, the documented evolutionary responses feature traits that are likely to alter responses to seasonal change or to change tolerance to environmental conditions. Currently available research provides hints that climate‐mediated evolutionary responses are likely to be enormously diverse. It is clear, that the current presumption of many climate change scientists, that evolution can be safely ignored, does not have a basis in evidence.Key Concepts:Biological responses to changing climate are well documented but the role of evolutionary mechanisms is typically unknown.Parsing the genetic from the nongenetic contributions to climate change responses is challenging.Evolution is rapid enough that natural selection is a plausible response to contemporary climate change.In the small number of cases where it has been evaluated, there is evidence supporting evolutionary responses to changing climate.Documented evolutionary responses to changing climate are diverse, but feature traits presumed to alter phenological responses or tolerance of changing climatic conditions.
Ant–Plant Mutualisms
Authors: Heil Martin 
Published: September 2010

Abstract

Ants and plants are engaged in thousands of mutualisms, which can be categorised in two major groups: dispersal and defence mutualisms. Myrmecochory, the dispersal of plant seeds by ants, is usually facilitated by the elaiosome, an appendix of the seed that is used as a reward. Because elaiosomes represent a nutritional supplement rather than a full diet, dispersal mutualisms are facultative ones. Only in ant‐gardens, the ants use the dispersed epiphytes as support to construct their carton nests, and these mutualisms tend to be obligate ones. In facultative defensive mutualisms, plants provide ant rewards, such as cellular food bodies (FBs) or extrafloral nectar (EFN), to foraging ants that serve as an indirect defence against herbivores. Obligate defensive mutualisms, by contrast, are based on the provisioning of nesting space. Ants dominate most terrestrial ecosystems. Owing to their mobility and social structure, they appear perfect partners for plant dispersal and defence.

Key Concepts:

Plants can benefit from indirect defence that is mediated through the third trophic level.

Ants are the dominant animal group in terrestrial ecosystem and – being common predators – have a high potential to defend plants against herbivores.

Plants can provide food resources or nesting space to ants in order to increase their presence and capacity to function as defenders.

Ants can also transport seeds and thereby function in dispersal.

Obligate ant–plant mutualisms reach high levels of reciprocal specialisations.

The evolutionary origins of most interactions remain to be investigated.
Origin and Spread of Goat Pastoralism
Authors: Pereira Filipe , Amorim António 
Published: September 2010

Abstract

Goats were the first wild herbivores to be domesticated in the Near East around 11 000 years ago at the beginning of the revolutionary transition from hunter‐gatherer to agriculture‐based societies. Ever since that time, goats have fulfilled a vital economic, cultural and religious role in many human civilisations. A collaborative research effort that integrates genetics and archaeology has vastly expanded our ability not only to detect the context, locations and timing of initial goat domestication but also to trace the migratory trajectories used by humans to spread this farm animal worldwide. The successful geographical diffusion and exponential growth of goat populations around the world clearly demonstrate the remarkable adaptability of this ruminant species to extreme climates and difficult terrains and offer an excellent opportunity to assess the rise and fall of human migratory and commercial networks during historical times.

Key Concepts:

Animal domestication was one of the most important events in human history.

Goats (
Capra hircus
) were probably first domesticated in the Fertile Crescent region of the Near East around 11 000 years ago from the bezoar goat (
Capra aegagrus
).

Studies of archaeological assemblages suggest that the transition from the hunting to the herding of goats was a long‐term process.

Mitochondrial DNA (mtDNA) is the most widely used genetic tool in the study of goat populations.

The domestication of goats involved multiple maternal lineages carrying considerable pre‐existing mtDNA diversity.

Goats were taken to nearly every corner of the world alongside humans in migratory movements.

Goats are the most adaptable and geographically widespread livestock species.
Cambrian Explosion
Authors: Fernàndez‐Busquets Xavier 
Published: September 2010

AbstractThe Cambrian explosion of life was a relatively short periodc.540 Mya when a sudden acceleration in evolution led to the rise of multicellular animals, but the cause of this key biological event remains elusive. Diverse environmental, developmental and ecological causes have been put forward as potential triggering events, but none of them has so far succeeded in obtaining widespread acceptance. Probably the correct answer has to be sought in a unifying theory capable of taking into account several of the most likely candidate factors and using adequate physiological experimental models such as marine sponges, the oldest extant Precambrian metazoan phylum. The Cambrian explosion might have been unleashed by the coincidence in time of primitive metazoans endowed with self‐/non‐self‐recognition and of a surge in sea water calcium that increased the binding forces between their calcium‐dependent cell adhesion molecules.Key Concepts:The Cambrian explosion is widely regarded as one of the most relevant episodes in the history of life on Earth, when about half of living animal phyla first appear in the fossil record.The proposals to explain the occurrence of the Cambrian explosion in terms of why and when it happened have been various and usually fall within environmental, developmental and ecological reasons.The triggering event of the Cambrian explosion likely has not only environmental, developmental or ecological causes, but a mixture of them all.The development of self‐/nonself‐recognition in primitive metazoans was a necessary innovation for the consolidation of multicellularity.The molecular basis of the Cambrian explosion should be understood based on mechanisms which could generate organismal diversity by utilising pre‐existing genes but not by creating new genes with novel function.Marine sponges are an ideal candidate model to provide answers dealing with molecular, cellular, organismal and populational aspects of the Cambrian explosion.Calcium‐based cell adhesion is essential for the integrity of marine sponges.There was a well‐referenced substantial increase in sea water calcium levels around the beginning of the Cambrian period.The calcium increase in Cambrian oceans coincided with the existence of primitive sessile metazoans, endowed with allogeneic recognition and carrying cell adhesion molecules which had significantly longer dissociation times at the new calcium concentrations.The Cambrian explosion might have been triggered by the coincidence in time of primitive animals endowed with self‐/nonself‐recognition and of a surge in sea water calcium that increased the binding forces between their calcium‐dependent cell adhesion molecules.
Synthesis of Metal Enolato Complexes
Authors: Vicente José 
Published: September 2010

AbstractIntroductionSynthesis from Ketones, Aldehydes and EstersSynthesis from Ketenes, Isocyanates and Acyl HalidesSynthesis from Carbon Monoxide and Carbonyl ComplexesSynthesis via Cleavage of Ethers and Related CompoundsSynthesis from Oxo, Hydroxo or Alkoxo ComplexesOxygenation ReactionsMiscellaneous ReactionsAcknowledgments
Lanthanide Enolates as Nuclear Magnetic Resonance Shift Reagents
Authors: Wenzel Thomas J. , Provencher Katelyn A. 
Published: September 2010

Abstract

Introduction

General Considerations

Applications of Achiral Shift Reagents

Coupling of Achiral Shift Reagents to Chiral Derivatizing and Solvating Agents

Chiral Shift Reagents

Binuclear Lanthanide–Silver Shift Reagents
The Brønsted Acid/Base Character of Hydroxylamines, Oximes and Hydroxamic Acids
Authors: E. Bartmess John 
Published: September 2010

Abstract
A summary is presented for hydroxylamines, oximes, and hydroxamic acids, of their gas phase Bronsted acidities and basicities, acidities in DMSO solvent, and aqueous solution acidities and basicities. The gas phase experiemtnal values are supplemented with computational values. An analysis of structural effects on the acid/base values is presented.

Introduction

Hydroxylamines

Oximes

Hydroxamic Acids

Final Comparisons

Acknowledgment
Synthesis, Structure and Reactions of Organometallic Derivatives of Oximes
Authors: Abele Edgars , Lukevics Edmunds 
Published: September 2010

AbstractOrganometallic derivatives of oximes were reviewed. These derivatives were selected and presented according to the place of the metal in the periodic table. Formation and reactions of disalts of oximes of type RC(CHMR′)=NOM (R, R′ = H, alkyl, aryl) and monosalts of oximes of type RC(CHMR′)=NOR″ (R″ = alkyl, aryl, M = alkali metal) were presented. Synthesis and reactions of silicon, germanium, tin, phosphorus containing oximes were included too. Beside this, oxime metal derivatives (for example, oxime palladacycles) as valuable catalysts in organic synthesis were described. In addition, oxime metal complexes exhibit wide spectrum of biological activity. Using of technetium‐99m hexamethylpropyleneamineoxime (CeretecTM) and related oxime complexes in diagnosis was described. Silicon and tin oxime complexes as excellent agrochemical agents were presented. Some cobalt, platinium and silicon containing oxime ethers exhibit high antitumor and cytotoxic activity and will be perspective targets for the further investigations.IntroductionSynthesis, Structure and Reactions of Organometallic Derivatives of OximesConclusions
Peroxynitrogen: A Study of Nitrogen/Oxygen Heterocycles with
N

O
and
O

O
or
N

O

O
Bonding
Authors: SLAYDEN SUZANNE W. , GREER ALEXANDER , LIEBMAN JOEL F. 
Published: September 2010

Abstract
Hydroxylamines, oximes and hydroxamic acids that are also associated with a peroxy group are considered. To be both brief and selective, only those species that are heterocycles with NO and OO or NOO bonding are included. Plausible, but inadequately characterized, classes of compounds are also discussed.
The Chemistry of Manganese Enolates
Authors: Concellón José M. , Rodríguez‐Solla Humberto , Del Amo Vicente 
Published: September 2010

Abstract
While organometallic compounds derived from other metals have found broad applications in organic synthesis, the use of organomanganese compounds has only recently been developed. In this chapter, we discuss methods of preparation of manganese enolates and their applications in organic synthesis. It is organized taking into account the synthetic method used to generate the manganese enolates. Accordingly, we summarize the formation of manganese enolates from: i) active manganese metal; ii) by deprotonation processes employing manganese amides; iii) by transmetalation reactions; and iv) using trialkylmanganates. Each section shows some synthetic applications of these enolates. In summary, this collection of reports shows the enormous potential of manganese enolates in synthetic organic chemistry. Their easy and mild preparation surely anticipates a bright future for these not‐so‐much yet used species.
Structures and Reaction Mechanisms of Manganese Oxidants
Authors: Lee Donald G. 
Published: September 2010

AbstractThe chemistry of manganese based oxidants (permanganate, manganese dioxide, manganese(III) acetate and manganese(V) complexes) is reviewed. Possible mechanisms for the reactions between manganese based oxidants and organic compounds are described and the evidence, both experimental and theoretical, on which the proposed mechanisms are based is presented. Special emphasis is placed on identification of the structures of the transition states and reactive intermediates that are formed as these reactions proceed.
s‐Block‐Metal‐Mediated Manganation Reactions
Authors: Layfield Richard A. 
Published: September 2010

AbstractThis chapter summarizes the recent advances that have been made in the synthetic applications of mixed‐metal organometallic reagents in which manganese(II) is combined with an s‐block metal. The chapter concentrates primarily on metallation reactions in which organic acids are readily deprotonated in a selective manner by s‐block metal manganates, and takes a combined organic‐inorganic approach to the area by examining a range of important reactions. Specific attention is devoted to the electrophilic quenching reactions of manganese(II)‐containing enolates and arenes that cannot otherwise be generated using existing reagents, or whose quenching reactions lead to the formation of products with poor selectivity. Also considered are the crystal structures of a family of well‐defined s‐block metal manganates in which the metal centres reside in low‐coordinate environments, and how these structures can be used to rationalize their highly potent yet selective reactivity. The key insight that can be gleaned into this reactivity and selectivity through the use of X‐ray crystallography is described in detail.
Cationic (η6‐arene)‐ and Neutral (η5‐cyclohexadienyl)‐tricarbonylmanganese Complexes: Synthesis and Reactivity
Authors: Rose‐Munch Françoise , Rose Eric , Eloi Antoine 
Published: September 2010

AbstractThe tricarbonyl‐chromium and ‐manganese groups are known to easily coordinate arene rings to form η6‐arene complexes. The electrophilic nature of the tricarbonyl metal fragments makes the arene electron‐deficient and renders it susceptible to nucleophilic attack. It is for these reasons that a new trend has emerged, the study of the chemistry of (η5‐cyclohexadienyl)Mn(CO)3complexes which are easily obtained by addition of a nucleophile to the arene ring. In the last ten years, the discovery of new methods of functionalization involving Pd cross‐coupling and lithiation reactions has greatly expanded the scope of the (η5‐cyclohexadienyl)Mn(CO)3complexes and consequently represents a key step in the development of the arene manganese chemistry since [(η6‐arene)Mn(CO)3]+complexes can be easily obtained by rearomatization of the corresponding (η5‐cyclohexadienyl)Mn derivatives. The present review aims to describe the situation for the synthesis and the reactivity of η6‐arene‐Mn complexes as well as that of η5‐cyclohexadienyl‐Mn complexes to highlight the recent breakthrough in their chemistry. The main reactivities described for η5Mn complexes correspond to nucleophilic addition, lithiation/electrophilic quench, lithium/halogen exchange and Pd catalyzed reactions. These types of reactions can be efficiently compared with those well studied in η6arenetricarbonylchromium complexes. All these recent developments in the functionalization of η5‐ and η6‐Mn complexes described in this chapter clearly open a revival period for this type of complexes which are starting to emerge as a valuable and versatile class of compounds more environmentally friendly than their Cr analogs.