bluuebunny/crossref_metadata_2025 huggingface dataset:
Sickle Cell Disease as a Multifactorial Condition
Authors: Verhovsek Madeleine M , Steinberg Martin H
Published: September 2010

The phenotype of sickle cell anaemia is heterogeneous. Although all patients have the identical sickle cell mutation, the type, severity and frequency of complications is variable. The products of epistatic modifying genes and the sickle haemoglobin gene, along with environmental influences, interact to determine the disease phenotype. Haemoglobin F concentration and distribution among erythrocytes is likely the most important genetic modulator of sickle cell disease severity. Several genetic loci are associated with haemoglobin F expression, including

BCL11A

in chromosome 2p, the

HBS1L

‐

MYB

locus on 6q23, the C‐T polymorphism 5′ to

HBG2

on chromosome 11p, and the olfactory receptor genes,

OR51B6

and

OR51B5

, also on 11p. α‐Thalassaemia is another modulator of sickle cell disease. There is evidence that genes associated with endothelial activation, inflammation, red blood cell hydration and hemostasis might all play a role in phenotypic diversity.

Key Concepts:

Sickle cell anaemia is a single‐gene disorder with heterogeneous clinical features.

The phenotype of sickle cell anaemia is affected by epistatic modifier genes.

Haemoglobin F is the best‐known genetic modifier of sickle cell anaemia.

Polymorphisms in three established quantitative trait loci modulate haemoglobin F.

Co‐inheritance of α‐thalassaemia is associated with reduced rates of haemolysis and vasculopathic complications, but increased incidence of viscosity‐vaso‐occlusive manifestations.

Candidate gene and genome‐wide association studies have identified genes that potentially affect sickle cell disease phenotype by modifying disease pathogenesis.
22q11 Deletion Syndrome: A Role for Tbx1 in Pharynx and Cardiovascular Development
Authors: Calmont Amelie , Scambler Peter
Published: September 2010

DiGeorge and velocardiofacial syndromes result from a chromosomal deletion involving proximal chromosome 22 and affected individuals commonly present with congenital heart defects, feeding problems, speech delay and learning problems. Psychiatric illness may present later in life. Mutation analysis and creation of mouse models which mimic the human disorder have identified that the

Tbx1

(T‐box 1) transcription factor is the major dosage‐sensitive gene in the deletion region and have allowed exploration of the underlying developmental pathways and signalling networks disrupted in these syndromes. Of particular importance in this regard are
Fgf
(fibroblast growth factor) and retinoic acid signalling.

Tbx1

is in genetic epistasis with loci encoding several transcription factors and signalling molecules, providing some rationale for the very variable clinical presentation. Gain‐of‐function, or duplications containing

Tbx1

, is also associated with heart defect.

Key Concepts:

The presence of a dominant phenotype secondary to gene hemizygosity is called haploinsufficiency.

Genetic epistasis is the phenomenon where the effects of one gene are modified by one or several other genes, which are called modifier genes.

Each pharyngeal arch surrounds an arch artery that connects the heart, by means of the aortic sac, to the dorsal aortae.

The neural crest is a pluripotent embryonic neuroectodermal cell population that migrates extensively and differentiates into diverse structures such as the face, neck, heart, adrenal gland, peripheral nervous system and skin.

Low copy number repeat are 1–400 kb blocks of genomic sequence that are duplicated in one or more locations on a chromosome and can act as substrates for aberrant recombination events.
Tuberous Sclerosis Complex and the Mammalian Target of Rapamycin Pathways
Authors: Yu Jane
Published: September 2010

Tuberous sclerosis complex (TSC) is an autosomal dominant disease in which the
mammalian target of rapamycin complex 1
(
mTORC1
) is hyperactivated. Lymphangioleiomyomatosis (LAM) is the pulmonary manifestation of TSC which occurs primarily in women. The TSC proteins
tuberin
and
hamartin
regulate the small
guanosine triphophatase
(
GTPase
)
Rheb
(
Ras
homologue enriched in brain), a direct activator of
mTORC1
. Activation of
mTORC1
has been observed in TSC tumours and other human tumours, and
mTORC1
inhibitors have been tested for the treatment of TSC and for malignancies including renal cancer. In this article, we discuss diagnostic features, updated molecular basis, evidences of
mTORC1
activation, preclinical models and completed clinical trials of
mTORC1
inhibitors in TSC. We also review the evidence of
mTORC1
‐independent functions of the TSC proteins, and discuss future therapeutic perspectives combining
mTORC1
inhibitors with agents targeting other cellular pathways.

Key Concepts:

Tuberous sclerosis complex (TSC) is a hereditary disease characterised by the development of seizures, mental retardation, autism and hamartomas in multiple organs including the brain, retina, kidney, heart and skin.

Lymphangioleiomyomatosis (LAM) is the metastatic pulmonary manifestation of TSC occurring almost exclusively in women, in whom the lungs are infiltrated with abnormal smooth muscle‐like cells and there is degeneration of lung parenchyma.

Metastasis is the multistep process in which tumour cells at the primary site spread to distant tissues/organs to proliferate.

Loss of heterozygosity refers to the loss of a normal allele on a chromosome while the other allele has a genetic alteration or mutation.

Mammalian target of rapamycin (mTOR) refers to the
FRAP1
gene product, a serine/threonine protein kinase that controls ribosome biogenesis, protein translation, cell growth and metabolism.
LDL
Receptor and Its Role in Inherited Disease
Authors: Soutar Anne K
Published: September 2010

The low‐density lipoprotein (LDL) receptor mediates the specific uptake of LDL from the circulation and its intracellular degradation by a process known as the LDL receptor pathway. LDL receptor gene expression is regulated by intracellular sterol content, and is limited mainly to the liver

in vivo

. Mutations in

LDLR

, the gene encoding the LDL receptor, cause familial hypercholesterolaemia (FH), a dominantly inherited disease where accumulation of LDL in the circulation increases the risk of coronary heart disease. Defects in other genes, including

APOB

, encoding the ligand for the LDL receptor,

ARH

, encoding a protein required for its internalisation and
proprotein convertase subtilisin/kexin type 9
(

PCSK9

), encoding a protein that reduces LDL receptor protein levels, cause a similar disorder because the encoded proteins are involved in the LDL receptor pathway. FH can readily be treated with cholesterol‐lowering drugs to reduce cardiovascular risk effectively, and identification of the causal genetic defect allows unequivocal and early diagnosis.

Key Concepts:

The LDL receptor mediates specific uptake and intracellular degradation of serum LDL.

Inherited defects in the LDL receptor pathway cause familial hypercholesterolaemia (FH), characterised by increased serum LDL and increased risk of coronary heart disease.

Most FH patients have mutations in
LDLR
, but defects in other genes cause a similar disorder.

A recessive form of FH is caused by null mutations in ARH, a clathrin adaptor protein required for LDL receptor internalisation.

A dominant form of FH is caused by gain‐of‐function mutations in
PCSK9
, which encodes a protein that promotes degradation of LDL receptor protein.

Dominant loss‐of‐function mutations in
PCSK9
reduce serum cholesterol and risk of coronary heart disease.

One relatively common dominant mutation in
APOB
, encoding the ligand for the LDL receptor, causes familial defective apoB (FDB).

LDLR
transcription is regulated by sterol response element‐binding proteins (SREBP) in a complex mechanism involving several other proteins.

FH can readily be treated with cholesterol‐lowering drug therapy to abolish the increased risk of coronary disease, but is currently under‐diagnosed.

Identifying causal mutations in known patients and screening their relatives should identify more affected individuals.
Molecular Genetics of Hereditary Spastic Paraplegias
Authors: Stevanin Giovanni
Published: September 2010

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

Combinations 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

Nonsense 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

With 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

Biological 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

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

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

The 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

Introduction

Synthesis from Ketones, Aldehydes and Esters

Synthesis from Ketenes, Isocyanates and Acyl Halides

Synthesis from Carbon Monoxide and Carbonyl Complexes

Synthesis via Cleavage of Ethers and Related Compounds

Synthesis from Oxo, Hydroxo or Alkoxo Complexes

Oxygenation Reactions

Miscellaneous Reactions

Acknowledgments
Catalysis Using β‐Diketonato Metal Complexes
Authors: Westcott Stephen A.
Published: September 2010

Introduction

Hydroformylation

Oxidation

Hydrogenation

Addition of Main Group Compounds

C

C
Bond Formation

Isomerization

Acknowledgment
Biological Aspects of Metal Enolates
Authors: Ming Li‐June
Published: September 2010

Introduction

Metal Enolates in Biological Systems

Metalloenolates and Associated Enzymes
The Chemistry of Metal Ynolates
Authors: Shindo Mitsuru
Published: September 2010

Introduction

Preparation of Alkali Metal Ynolates

Properties of Metal Ynolates

Reactions of Metal Ynolates

Preparation of Silyl Ynolates

Reactive Heteroatom Analogues of Metal Ynolates
Lanthanide Enolates as Nuclear Magnetic Resonance Shift Reagents
Authors: Wenzel Thomas J. , Provencher Katelyn A.
Published: September 2010

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
Deposition of Metals and Metal Oxides by Means of Metal Enolates
Authors: Lang Heinrich , Buschbeck Roy
Published: September 2010

Introduction

Deposition Techniques

Metal Deposition

Metal Oxide Deposition
The Brønsted Acid/Base Character of Hydroxylamines, Oximes and Hydroxamic Acids
Authors: E. Bartmess John
Published: September 2010

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

Organometallic 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.

Introduction

Synthesis, Structure and Reactions of Organometallic Derivatives of Oximes

Conclusions
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

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

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

The 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

This 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

The 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.
Biodegradable Thermogelling Poly(D,L‐lactide‐co‐p‐dioxanone)‐Poly(ethylene glycol)‐Poly(D,L‐lactide‐co‐p‐dioxanone) Triblock Copolymer
Authors: Chen Rui , Hao Jianyuan , Xiong Chengdong , Deng Xianmo
Published: September 2010

Thermogelling poly(D,L‐lactide‐co‐p‐dioxanone)–poly(ethylene glycol)–poly (D,L‐ lactide‐co‐p‐dioxanone) [P(LA‐PDO)–PEG–P(LA‐PDO)] triblock copolymers were successfully prepared by ring‐opening copolymerization of D,L‐lactide and p‐dioxanone in the presence of PEG as a macromolecular initiator and stannous octoate as a catalyst. The aqueous solutions of the copolymers underwent clear double sol–gel and then gel–sol transitions with increasing temperature from 0 to 50 °C. It was found that the lower critical solution transition (LCST) temperature could be effectively controlled by adjusting the molar ratio of LA/PDO or PEG length in the copolymers. The introduction of PDO units into the hydrophobic block has greatly accelerated the water dissolution rate of the copolymers and facilitated the drug formulation. The developed thermosensitive hydrogel has suitable sol–gel transition temperature and is a promising injectable material for drug delivery depot and tissue engineering scaffold.
Biomimetic Composites: Protein Localization in Silica Nanospheres Derived via Biomimetic Mineralization (Adv. Funct. Mater. 18/2010)
Authors: Cardoso Mateus B. , Luckarift Heather R. , Urban Volker S. , O'Neill Hugh , Johnson Glenn R.
Published: September 2010

Lysozyme‐templated precipitation of silica synthesized by sol‐gel chemistry produces a composite material with antimicrobial properties. This study investigates the structural properties of the composite material that allow for retention of the antimicrobial activity of lysozyme. Scanning (SEM) and transmission (TEM) electron microscopy reveal that the composite has a hierarchical structure composed of quasi‐spherical structures (∼450 nm diameter), which are in turn composed of closely packed spherical structures of ∼8–10 nm in diameter. Using small‐angle neutron scattering (SANS) with contrast variation, the scattering signatures of the lysozyme and silica within the composite were separated. It was determined that the lysozyme molecules are spatially correlated in the material and form clusters with colloidal silica particles. The size of the clusters determined by SANS agrees well with the structural architecture observed by TEM. BET analysis revealed that the surface area of the composite is relatively low (4.73 m2/g). However, after removal of the protein by heating to 200 °C, the surface area is increased by ∼20%. In addition to demonstrating a well organized sol‐gel synthesis which generates a functional material with antimicrobial applications, the analysis and modeling approaches described herein can be used for characterizing a wide range of mesoporous and ultrastructural materials.
Hydrothermal Growth: Polymer‐Templated Hydrothermal Growth of Vertically Aligned Single‐Crystal ZnO Nanorods and Morphological Transformations Using Structural Polarity (Adv. Funct. Mater. 18/2010)
Authors: Kim Ki Seok , Jeong Hyun , Jeong Mun Seok , Jung Gun Young
Published: September 2010

Position‐configurable, vertical, single‐crystalline ZnO nanorod arrays are fabricated via a polymer‐templated hydrothermal growth method at a low temperature of 93 °C. A sol‐gel processed dense c‐oriented ZnO seed layer film is employed to grow nanorods along the c‐axis direction [0001] regardless of any substrate crystal mismatches. Here, one‐beam laser‐interference lithography is utilized to fabricate nanoscale holes over an entire 2‐in. wafer during the preparation of the polymer template. As such, vertically aligned ZnO nanorods can be grown from the seed layer exposed at the bottom of each hole. Furthermore, morphological transformations of the ZnO nanorods into pencil‐like, needle‐like, tubular, tree‐like, and spherical shapes are obtained by controlling the growth conditions and utilizing the structural polarity of the ZnO nanorods.
Immobilization of a Modified Tethered Rhodium(III)‐p‐Toluenesulfonyl‐1,2‐diphenylethylenediamine Catalyst on Soluble and Solid Polymeric Supports and Successful Application to Asymmetric Transfer Hydrogenation of Ketones
Authors: Dimroth Jonas , Keilitz Juliane , Schedler Uwe , Schomäcker Reinhard , Haag Rainer
Published: September 2010

Catalyst immobilization through covalent attachment onto a support is one strategy to provide recyclable systems. Here, soluble and surface‐functionalized solid polymers were used as supports for a modified tethered rhodium(III)‐p‐toluenesulfonyl‐1,2‐diphenylethylenediamine [Rh(III)‐TsDPEN] complex. The supported catalysts were applied to the asymmetric transfer hydrogenation of phenyl ketones in aqueous solution of sodium formate. High ee values (up to 99%) and good activities were achieved. It was discovered that the solid polymer‐supported catalyst could be recycled at least four times without a significant decrease of the activity when a mixture of sodium formate and formic acid was used as the hydrogen source. This catalytic system provides a promising approach towards an ecologically and economically rational production of enantioenriched building blocks.
Multi‐objective state feedback control for linear delay systems
Authors: Xie Wei , Eisaka Toshio
Published: September 2010

This paper provides new linear matrix inequalities (LMI)‐based formulae for mixed H2/H∞state‐feedback synthesis of linear continuous‐time systems with state delays of any size. The proposed delay‐independent LMI‐based conditions enable us to parameterize a memoryless state‐feedback controller without involving the Lyapunov variables in the formula. Compared with previous results based on a common Lyapunov variable, the proposed formula provides less conservative results.

Copyright © 2010 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society
Communicating bioenergy: a growing challenge
Authors: McCormick Kes
Published: September 2010

Bioenergy is rapidly growing in many parts of the world. But continued investments in bioenergy do not depend entirely on technological advances, feedstock availability, and economic conditions. The social acceptance of bioenergy by the general public appears to be essential to the political legitimacy of the bioenergy industry, and the willingness of policy‐makers to introduce or maintain supportive policy schemes for bioenergy. In the context of Europe, this perspective argues that communication strategies will become increasingly important for the bioenergy industry as it continues to expand. In short, this perspective discusses four main questions, including: What is the current social acceptance of bioenergy among citizens in Europe? What are the key lessons from experiences with communication on bioenergy? What are the emerging ‘hot’ topics for the bioenergy industry? What international efforts are underway to inform the general public about bioenergy? Overall, this perspective aims to provide insights into the linkages between the social acceptance and the political legitimacy of bioenergy, and the role of communication strategies. © 2010 Society of Chemical Industry and John Wiley & Sons, Ltd
Bioenergy and water: risks and opportunities
Authors: Berndes Göran
Published: September 2010

Increasing biomass demand can be challenging from a water balance perspective. © 2010 Society of Chemical Industry and John Wiley & Sons, Ltd
Bringing the excitement and motivation of research to students; Using inquiry and research‐based learning in a year‐long biochemistry laboratory
Authors: Knutson Kristopher , Smith Jennifer , Wallert Mark A. , Provost Joseph J.
Published: September 2010

A successful laboratory experience provides the foundation for student success, creating active participation in the learning process. Here, we describe a new approach that emphasizes research, inquiry and problem solving in a year‐long biochemistry experience. The first semester centers on the purification, characterization, and analysis of a novel fusion protein within a guided research experience. Throughout the semester, students gradually acquire skills as they are allowed to work independently. A fusion protein, malate dehydrogenase‐green fluorescent protein with a histidine affinity tag (MGH), is used throughout the semester. The fusion protein allows for a high throughput analysis and is stable for duration of the semester. Students start with the purification and analysis of the plasmid DNA and end with an enzymatic analysis of MGH. As students take ownership of their experiments and choose two different chromatographic resins, they make many choices throughout the semester. Skills, motivation, confidence levels, and attitudes were assessed before and after the semester. Students achieved high levels of critical biochemical laboratory skills and critical thinking while increasing their confidence and motivation for working in a biochemical research setting.
Bringing the excitement and motivation of research to students; Using inquiry and research‐based learning in a year‐long biochemistry laboratory
Authors: Knutson Kristopher , Smith Jennifer , Nichols Paul , Wallert Mark A. , Provost Joseph J.
Published: September 2010

Research‐based learning in a teaching environment is an effective way to help bring the excitement and experience of independent bench research to a large number of students. The program described here is the second of a two‐semester biochemistry laboratory series. Here, students are empowered to design, execute and analyze their own experiments for the entire semester. This style of laboratory replaces a variety of shorter labs in favor of an in depth research‐based learning experience. The concept is to allow students to function in independent research groups. The research projects are focused on a series of wild‐type and mutant clones of malate dehydrogenase. A common research theme for the laboratory helps instructors administer the course and is key to delivering a research opportunity to a large number of students. The outcome of this research‐based learning laboratory results in students who are much more confident and skilled in critical areas in biochemistry and molecular biology. Students with research experience have significantly higher confidence and motivation than those students without a previous research experience. We have also found that all students performed better in advanced courses and in the workplace.
Evaluation of software for introducing protein structure
Authors: White Brian , Kahriman Azmin , Luberice Lois , Idleh Farhia
Published: September 2010

Communicating an understanding of the forces and factors that determine a protein's structure is an important goal of many biology and biochemistry courses at a variety of levels. Many educators use computer software that allows visualization of these complex molecules for this purpose. Although visualization is in wide use and has been associated with student learning, it is quite challenging to develop visualizations that allow students to interactively observe the effects of altered amino acid sequence on protein structure. A software simulation, the protein investigator (PI), has been developed to specifically facilitate this type of exploration. When using the PI, students enter or edit an amino acid sequence; the software then simulates its folding in two dimensions using the major forces involved in protein structure. This study explores freshman undergraduate students' use of visualization and simulation when learning about protein structure. It also evaluates some of the learning outcomes from these two approaches. Our results show that simulation leads to similar learning outcomes as visualization. Because simulation allows a more interactive exploration, a combination of the two approaches may be an effective approach to introducing the basic principles of protein structure.
Calibrated peer review for computer‐assisted learning of biological research competencies
Authors: Clase Kari L. , Gundlach Ellen , Pelaez Nancy J.
Published: September 2010

Recently, both science and technology faculty have been recognizing biological research competencies that are valued but rarely assessed. Some of these valued learning outcomes include scientific methods and thinking, critical assessment of primary papers, quantitative reasoning, communication, and putting biological research into a historical and broader social context. This article presents examples of Calibrated Peer Review (CPR) assignments that illustrate a computer‐assisted method to help students achieve biological research competencies. A new release of CPR is appropriate for engaging students online in reading and writing about investigations. A participant perception inventory was designed for use as a repeated measure to discriminate among beginning, middle, and ending student perceptions. Examples are provided to demonstrate how to assess student perceptions of what they gain from instruction related to science research competencies. Results suggest that students in a large enrollment class consider CPR to be useful for helping them learn about quantitative and categorical research variables; the use of the experimental method to test ideas; the use of controls; analysis, interpretation, and presentation of data; and how to critically read primary papers.
Quantification of nicotine in commercial brand cigarettes
Authors: Vieira Carlos A. , de Paiva Sabina A. A. , Funai Milena N. S. , Bergamaschi Mateus M. , Queiroz Regina H. C. , Giglio José R.
Published: September 2010

The main objective of this experiment is to determine the amount of nicotine in commercial brand cigarettes by means of a nonaqueous acid‐base titration. A simple glass device simulating a smoker is proposed, which allows the determination of the volatilized, filter retained, and inhaled portions. Students will readily see that the amount of nicotine/cigarette stated on the label (∼0.5–1.0 mg) refers indeed to the inhaled portion only, rather than to the total amount/cigarette (usually more than 10 mg). Even so, values for inhaled nicotine may be significantly higher than those reported for several brands. Students will also be able to make a critical evaluation of the true content of nicotine in the inhaled portion and confront it with the reported value for a given brand. In addition, the theoretical approach, supported by HPLC data, provides an excellent experience on nonaqueous acid‐base volumetric analysis.
Bridging the educational research‐teaching practice gap
Authors: Schönborn Konrad J. , Anderson Trevor R.
Published: September 2010

External representations (ERs), such as diagrams, animations, and dynamic models are vital tools for communicating and constructing knowledge in biochemistry. To build a meaningful understanding of structure, function, and process, it is essential that students become visually literate by mastering key cognitive skills that are essential for interpreting and visualizing ERs. In this article, first we describe a model of seven factors influencing students' ability to learn from ERs. Second, we use this model and relevant literature to identify eight cognitive skills central to visual literacy in biochemistry. Third, we present simple examples of tasks as a foundation for designing more sophisticated and complex items for assessing and developing students' visual literacy. We conclude that visual literacy is fundamental to the development of sound conceptual understanding and it is crucial to develop visual skills in parallel with meaningful learning outcomes in all biochemistry curricula.