bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retinoblastoma
Authors: Lohmann Dietmar R , Gallie Brenda L 
Published: March 2011

Abstract

Retinoblastoma is a malignant tumour that originates in the developing retina and is usually diagnosed in children under age of 5 years. Mutations in both alleles of the tumour suppressor gene

RB1

are a prerequisite for this tumour. In nonheritable retinoblastoma the two mutations have occurred in somatic cells and are not passed to offspring. Germline mutations in one allele of the

RB1

gene cause heritable predisposition to retinoblastoma and a spectrum of other tumours (second cancers). In families this trait is autosomal dominant with variable phenotypic expression. Analysis of genotype–phenotype associations has shown that the mean number of tumour foci that develop in carriers of mutant

RB1

alleles becomes smaller depending on which, and to what extent, functions of the normal allele are retained. The function of the

RB1

gene product, pRb, that is understood best is as a gatekeeper that negatively regulates progression through G
1
phase of the cell cycle. However, a more important role in cancer progression may be prevention of
deoxyribonucleic acid
(DNA) instability. Recently, the

RB1

gene was found to be imprinted, which may explain some of the observed parent‐of‐origin effects.

Key Concepts:

Two‐step mutational inactivation of the retinoblastoma gene (
RB1
) is a prerequisite for development of retinoblastoma.

Germline mutations in the
RB1
gene cause heritable retinoblastoma which is transmitted as an autosomal dominant trait with incomplete penetrance and variable expressivity.

Variable phenotypic expression of heritable retinoblastoma is in part explained by allelic heterogeneity of RB1 gene mutations.

In patients with nonheritable retinoblastoma, the two alleles of the retinoblastoma gene are inactivated by somatic mutations.

The human
RB1
gene is imprinted with skewed expression in favour of the maternal allele.
Alternative Splicing and Human Disease
Authors: Stamm Stefan 
Published: March 2011

Abstract

Almost all human protein coding genes undergo alternative splicing, and an increasing number of diseases is associated with the selection of ‘wrong’ splice sites. Alternative missplicing can be caused by
deoxyribonucleic acid
point mutations, changes in repetitive sequences or alterations in proteins that regulate splicing. The effect of these mutations can be evaluated by bioinformatic means, but these predictions need to be verified experimentally. With the exception of premature stop codons that are introduced by aberrantly spliced exons, the mechanism of pathological exon usage that leads to a disease is generally poorly understood. A pathological change in the activity of splicing factors typically results in numerous small changes in exon usage. Numerous screening efforts identified oligonucleotides and small molecular weight substances that can be tested as therapeutic approaches for diseases caused by missplicing.

Key Concepts:

Alternative splice site selection is regulated by combinatorial control through a network of protein–protein, protein–RNA and RNA–RNA interactions.

Mutations in the splice sites, exonic and intronic sequences lead to aberrant exon usage.

Mutations can cause exon skipping, a change in the degree of exon usage or activate sequences on the pre‐mRNA to become a new exon.

Synonymous mutations in exons can cause their aberrant usage, which can be a disease mechanism.

A pathological change in the activity of splicing regulatory proteins results in numerous, individually small changes of alternative exon usage.

Aberrant exon usage can be targeted by rationale therapies, several oligonucleotide‐based treatments are tested in clinical trials and small molecules were identified that change splice site selection by high‐throughput screens.
Balancing Selection in the Human Genome
Authors: Andrés Aida M 
Published: March 2011

Abstract

Balancing selection maintains advantageous diversity in populations by a variety of mechanisms. As a source for functional polymorphism, it contributes to the genetic and phenotypic diversity of present‐day human populations. Classically, most of our understanding of the influence of balancing selection in humans was based on few well‐known examples, but recent advances at the genome scale (made possible by newly available genomic databases and analytical methods) provide further insights on the influence and targets of balancing selection in humans. Such studies have pointed out the uniqueness of the MHC locus, but suggest that more typical cases of balancing selection exist. Our growing understanding of the targets of balancing selection in humans suggests that although this is not a pervasive force in the human genome, it has played a role in the maintenance of functionally relevant polymorphism in humans.

Key Concepts:

Balancing selection maintains genetic and phenotypic diversity in populations.

Different mechanisms constitute balancing selection, all of which maintain advantageous polymorphism in populations.

Balancing selection is not pervasive in humans, but it has shaped the evolution of critical genes for individual survival.

The MHC complex in chromosome 6 shows striking, and unique, genetic signatures of balancing selection.

Advantageous diversity for MHC‐dependent antigen presentation has shaped the patterns of diversity of diverse genomic loci.

The genetic signatures of balancing selection can be identified both by studying individual genes and by analysing genome‐wide patterns of diversity.

Genome‐wide analyses are key to identify previously unknown (and unsuspected) targets of natural selection.

Targets of balancing selection remain undiscovered in the human genome.
Sequence Finishing on New Platforms
Authors: van Tonder Andries J , Grafham Darren 
Published: March 2011

Abstract

In the past five years, next generation sequencing (NGS) technology platforms have been released and have become the tool of choice for sequencing genomes. Methods for sequence finishing have had to be updated to deal with the issues created by NGS platforms. Finishing begins with the assembling of the reads produced by the sequencing machines before computational gap closure is attempted. Remaining gaps are identified and suitable experimental techniques such as polymerase chain reactions are used to close these. Until recently, the aim for many genome sequencing projects has been to fully finish genomes. However, due to the time and cost associated with finishing, the majority of future genomes will only reach a high‐quality draft. New genome standards have had to be defined to better reflect the types of sequencing now being undertaken. Improvements to the current generation of sequencing machines along with the advent of the third‐generation technologies means that new ways of dealing with the data volume will need to be sought.

Key Concepts:

Next generation sequencing platforms have generated new issues for sequence finishing, which have required novel solutions.

Genome standards have had to be updated to better reflect NGS data.
Molecular Biology of Breast Cancer
Authors: Caffarel Maria M , Pensa Sara , Wickenden Julie A , Watson Christine J 
Published: March 2011

Abstract

Breast cancer is a common disease affecting approximately 1 in 10 women at some time in their lives. Moreover, it is not a single disease but is characterised by distinct pathological types with different clinical outcomes. In the past decade, considerable progress has been made in understanding these different cancer subtypes at the molecular level. In particular, global gene expression studies have identified five predominant subtypes that have unique expression signatures. Unlike many other cancers, where a hierarchy of genetic mutations that leads to tumorigenesis has been identified, breast tumours have diverse genetic mutations that affect a variety of signalling pathways. The recent discovery of
micro ribonucleic acids
(microRNAs) and their role in tumour metastasis has opened up a whole new area of research. Although some highly successful treatments have been developed, the challenge for the future is the development of individualised therapies that are specific to each patient's tumour type.

Key Concepts:

Breast cancer is a heterogeneous disease characterised by distinct pathological types with different outcomes.

Breast tumours have diverse genetic mutations that affect a variety of signalling pathways.

Breast tumours can be classified into different subgroups according to their molecular expression profiles.

It is not clear whether specific molecular pathways establish the subtype of breast cancer or whether different cell types become transformed and give rise to each tumour subtype.

Breast cancer patients would benefit from individual therapeutic regimens designed to treat their particular type of cancer.
Hsp70 Chaperones
Authors: Craig Elizabeth A , Marszalek Jaroslaw 
Published: March 2011

Abstract

Via their interaction with client proteins, Hsp70 molecular chaperone machines function in a variety of cellular processes, including protein folding, translocation of proteins across membranes and assembly/disassembly of protein complexes. Such machines are composed of a core Hsp70, as well as a J‐protein and a nucleotide exchange factor as co‐chaperones. These co‐factors regulate the cycle of adenosine triphosphate (ATP) hydrolysis and nucleotide exchange, which is critical for Hsp70's interaction with client proteins. Cellular compartments often contain multiple Hsp70s, J‐proteins and nucleotide exchange factors. The capabilities of Hsp70s to carry out diverse cellular functions can result from either specialisation of an Hsp70 or by interaction of a multifunctional Hsp70 with a suite of J‐protein co‐chaperones. The well‐studied Hsp70 systems of mitochondria provide an example of such modes of diversification and specialisation of Hsp70 machinery, which are applicable to other cellular compartments.

Key Concepts:

Fundamental biochemical properties of different Hsp70 systems are very similar, yet very adaptable.

Diversification of Hsp70 function is often due to multiple J‐protein partners.

Although most Hsp70s bind a broad array of peptide sequences, some have become specialised and have a very restricted binding specificity.
Aptamers
Authors: Gopinath Subash C. B. 
Published: March 2011

AbstractAptamers are artificial nucleic acid ligands that can be generated against a wide range of targets including amino acids, drugs, proteins, and other molecules. They are isolated from complex libraries of synthetic nucleic acid by an iterative process of adsorption, recovery, and reamplification. They have potential applications in analytical sensing devices, target validation, and as therapeutic agents. Aptamers are now widely accepted as substitutes for antibodies, especially in the diagnostic front. Aptamers are approved as drugs for therapeutics, and several aptamers are under clinical trials with the ultimate aim for commercialization.
Melendez‐Diaz v.Massachusetts—The Admissibility of Laboratory Reports
Authors: Layne DesPortes Betty 
Published: March 2011

AbstractThe Sixth Amendment of the US Constitution provides seven basic rights to the accused in criminal prosecutions, including the right “to be confronted with the witnesses against him.” This right is referred to as the right to confrontation and the provision is known as “the Confrontation Clause.” InMelendez‐Diaz v. Massachusetts, 129 S.Ct. 2527 (2009), the US Supreme Court continued the reformation of the Confrontation Clause that began 4 years before inCrawford v. Washington, 541 U.S. 36 (2004), which severed the right to confrontation from the rules of evidence concerning hearsay. InCrawford, the Court had held that the constitutional protections of the Confrontation Clause extended to all “testimonial statements” and that the right to confrontation was not satisfied by a mere consideration of the “reliability” of the statements to be presented; the right to confrontation required the reliability of the statements to be assessed by a particular procedure—by the in‐court presentation of witness testimony subjected to the rigors of cross‐examination. InMelendez‐Diaz, the Court continued to define “testimonial statements,” holding that laboratory reports of forensic analysis were “testimonial” in nature. This holding meant that for the forensic reports to be admissible over defense objection, the Confrontation Clause required the presentation of the forensic analyst for in‐court testimony with the opportunity for cross‐examination.
Ear Photographs: Examination and Forensic Potential
Authors: Monge Janet M. 
Published: March 2011

AbstractAlthough the potential exists for the identification of humans based on measurement and observational features of the human ear, this potential has yet to be fully explored scientifically. As such, although it is tempting to apply both visual inspection and measurement criteria to exposed ears viewed in video surveillance, its efficacy in meeting evidential standards has yet to be established. Certainly a large amount of variation exists in the various features that compose the human ear but how those variations are patterned remains unknown on the individual, familial, and the population levels. Compounding these essential issues are difficulties in controlling for the quality and detail resolution of the visual representations (video and/or still photographic) used for comparisons within a forensic context.
Microbial Forensics
Authors: Budowle Bruce , Williamson Phillip C. 
Published: March 2011

AbstractOur safety and security are constantly being challenged. One of the vulnerabilities is that due to a bioterrorism attack. There are many targets and many bioweapons that are easily accessed. The continued advancements in technology that benefit mankind can also be exploited for nefarious acts. Forensic science can contribute to criminal interdiction or the investigative response after an attack. The field of microbial forensics has been developed to provide another avenue in the goal toward forensic attribution. Microbial forensics is the scientific discipline dedicated to analyzing evidence from a bioterrorism act, biocrime, hoax, or inadvertent microorganism/toxin release for attribution purposes. Microbial forensics combines the practices of epidemiology with the characterization of microbial and microbial‐related evidence to assist in determining the specific source of the sample, in ways that are as individualizing as possible, and/or the methods, means, processes and locations involved to determine the identity of the perpetrator(s) of an attack. Because of the impact of microbial forensic evidence high quality assurance and quality control practices must be in place and the limitations of any analysis properly understood.
New Approaches to the Characterization of Drug Candidates by Solid‐StateNMR
Authors: Vogt Frederick G. , Clawson Jacalyn S. , Strohmeier Mark , Pham Tran N. , Watson Simon A. , Edwards Andrew J. 
Published: March 2011

AbstractSolid‐state NMR (SSNMR) spectroscopy has been found to be very useful technique for pharmaceutical development. This technique is currently applied for the study of pharmaceutical solids, ranging from detailed structural studies of active pharmaceutical ingredients (APIs) forms to analysis of complex drug products and formulations. The study suggests that solid‐state structure of a pharmaceutical product can influence its properties, manufacturability, and stability. It is essential to regulate and control over solid‐state structure and subsequent properties. The studies show that SSNMR is closely related to the widely used technique of solution‐state NMR and possesses many of the same features. Further the study concludes that field of pharmaceutical SSNMR continues to advance at a rapid rate and will develop new molecular classes and new formulations and delivery modes in near future.
Stereoselective Reactions of Organoselenium Reagents Including Catalysis
Authors: Singh Fateh V. , Wirth Thomas 
Published: March 2011

AbstractIn the last decades, organoselenium chemistry has been developed as an important tool for synthetic and medicinal chemistry. The variety of organoselenium reagents has led to many versatile and new approaches in synthetic organic chemistry. Various synthetic moieties can be selectively introduced into complex molecules under very mild reaction conditions. The unique properties of selenium allow the development of novel and highly selective transformations, which can be employed for the synthesis of synthetic and naturally occurring chiral building blocks. This chapter highlights some recent developments of stereoselective reactions using organoselenium reagents including asymmetric catalysis.
Characterization and Validation of Cre‐Driver Mouse Lines
Authors: Gofflot Françoise , Wendling Olivia , Chartoire Nathalie , Birling Marie‐Christine , Warot Xavier , Auwerx Johan 
Published: March 2011

AbstractConditional gene manipulations in mice are increasingly popular strategies in biomedical research. These approaches rely on the production of conditional genetically engineered mutant mouse (GEMM) lines with mutations in protein‐encoding genes. These conditional GEMMs are then bred with one or several transgenic mouse lines expressing a site‐specific recombinase, most often the Cre recombinase, in a tissue‐specific manner. Conditional GEMMs can only be exploited if Cre transgenic mouse lines are available to generate somatic mutations, and thus the number of Cre transgenic lines has significantly increased over the last 15 years. Once produced, these transgenic lines must be validated for reliable, efficient, and specific Cre expression and Cre‐mediated recombination. In this overview, the minimum level of information that is ideally required to validate a Cre‐driver transgenic line is first discussed. The vagaries associated with validation procedures are considered next, and some solutions are proposed to assess the expression and activity of constitutive or inducible Cre recombinase before undertaking extensive breeding experiments and exhaustive phenotyping. Curr. Protoc. Mouse Biol. 1:1‐15. © 2011 by John Wiley & Sons, Inc.
Standardized Post‐Mortem Examination and Fixation Procedures for Mutant and Treated Mice
Authors: Antal Cristina , Muller Stéphanie , Wendling Olivia , Hérault Yann , Mark Manuel 
Published: March 2011

AbstractA procedure for post‐mortem examination (or necropsy) of mice is provided. The aim is to obtain a “holistic” picture of organs and systems at the anatomical and histological levels. The major issue is tissue preservation, which is achieved by rapid transfer into a fixative solution, usually neutral buffered formalin. Fixation is the first of the four basic steps in histopathological analyses of tissues, which also include embedding, sectioning, and staining. The protocols provided here describe routine methods for tissue fixation, as these methods are integral parts of any necropsy procedure. There is also a Strategic Planning section that addresses the overall approach to histopathological evaluation, as well as specifics such as age and gender of the mice, cohort size, and controls. Curr. Protoc. Mouse Biol. 1:17‐53. © 2011 by John Wiley & Sons, Inc.
Assessment of Spontaneous Locomotor and Running Activity in Mice
Authors: Thomas Charles , Marcaletti Stefan , Feige Jérôme N. 
Published: March 2011

AbstractThe locomotor activity of laboratory mice is a global behavioral trait which can be valuable for the primary phenotyping of genetically engineered mouse models as well as mouse models of pathologies affecting the central and peripheral nervous systems, the musculoskeletal system, and the control of energy homeostasis. Basal levels of mouse locomotion can be recorded using infrared monitoring of movements, and further information can be gathered by giving the animal access to a running wheel, which will greatly enhance its spontaneous physical activity. Described here are two detailed protocols to evaluate basal locomotor activity and spontaneous wheel running. Curr. Protoc. Mouse Biol. 1:185‐198. © 2011 by John Wiley & Sons, Inc.
Design and Generation of Gene‐Targeting Vectors
Authors: Wefers Benedikt , Wurst Wolfgang , Kühn Ralf 
Published: March 2011

AbstractThis unit provides an overview of the major types of mutant alleles that can be generated by gene targeting in ES cells. It presents the growing public resources of premade gene targeting vectors, modified ES cells, and mutant mice. General guidelines for the design of targeting vectors are followed by protocols for the construction of vectors to generate knockout (KO), conditional KO, and subtle mutant alleles. Curr. Protoc. Mouse Biol. 1:199‐211. © 2011 by John Wiley & Sons, Inc.
Mouse Breeding and Colony Management
Authors: Ayadi Abdelkader , Ferrand Gisèle , Cruz Isabelle Goncalves da , Warot Xavier 
Published: March 2011

AbstractThe possibility to genetically modify the mouse genome has enabled the creation of numerous lines of genetically engineered mouse models (GEMMs). As a result, the demand for housing space in research facilities is increasing. Knowledge of the basis of mouse reproduction and of the methods to handle colonies of GEMMs is therefore mandatory to efficiently populate facilities. The mouse has a short generation period, produces large progenies, and can breed all year round. However, environmental parameters (bedding, diet, cage type, temperature, hygrometry, light, noise, and sanitary status) strongly influence the breeding efficiency and experimental data, and must be tightly controlled. Efficient GEMM colony management requires adequate recording of breeding and proper identification and genotyping of animals. Various mating types and breeding schemes can be used, depending on the type of studies conducted. The recent development of assisted reproduction methods helps circumvent some of the issues faced with those lines especially difficult to breed. Curr. Protoc. Mouse Biol. 1:239‐264. © 2011 by John Wiley & Sons, Inc.
Self‐Assembly and Shape Morphology of Liquid Crystalline Gold Metamaterials
Authors: Draper Michael , Saez Isabel M. , Cowling Stephen J. , Gai Pratibha , Heinrich Benoït , Donnio Bertrand , Guillon Daniel , Goodby John W. 
Published: March 2011

AbstractGold nanoparticles offer the possibility of creating metamaterials; however, such nanoparticles are not particularly stable. Conversely, liquid crystals offer the possibility of creating self‐organizing and self‐assembling materials, which can be designed to be relatively stable. Potentially, combining these two concepts could provide materials that can be induced to assemble in a controlled way and that would have unique optical properties. This article describes some of the groundwork made in the preparation of stable liquid‐crystalline metamaterials and the investigation of their structures and physical properties. In particular, spherically substituted materials are found to be deformed into tactoids with anisotropic properties, most notably their dielectric anisotropies.
Asymmetric Friedel–Crafts Reaction of Indoles with Ethyl Trifluoropyruvate Using a Copper(I)‐Bisoxazolidine Catalyst
Authors: Wolf Christian , Zhang Peng 
Published: March 2011

AbstractBisoxazolidine 1 is an effective ligand in the copper(I)‐catalyzed Friedel–Crafts reaction of alkyl trifluoropyruvates and indoles. A range of ethyl 2‐(3′‐indolyl)‐3,3,3‐trifluoro‐2‐hydroxypropanoates was produced in up to 99% yield and 94% ee within 30 min to 4 h. The effect of temperature on conversion and enantioselectivity proved to be substrate specific and was optimized individually. Of particular interest is that this method tolerates the presence of substituents in various positions in the indole ring. Yields ranging from 90–97% and ee values between 90 and 94% were obtained at optimized temperatures with substrates carrying substituents in position 1 or 7.