bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune Vasculitis
Authors: Flint Julia D , Savage Caroline OS 
Published: March 2010

Abstract

Vasculitis comprises a broad group of diseases characterized by inflammation and necrosis in the walls of blood vessels, resulting in narrowing or occlusion of the lumen. The conditions are usually classified according to the predominant size of the vessels involved. A wide range of immunopathological mechanisms have been implicated in the aetiology of the vasculitides and a subset of small‐vessel vasculitides are strongly associated with antineutrophil cytoplasmic antibodies (ANCA). The distribution of blood vessel involvement varies considerably, resulting in a heterogeneous clinical presentation, often involving multiple organ systems. This makes both classification and diagnosis of these diseases challenging. Clinical management is hindered by our limited understanding of the immunopathogenesis of these conditions. However, research in this area is active, many treatment trials are in progress and the morbidity and mortality has fallen in recent years.

Key concepts:

Vasculitis may be ‘idiopathic’ or ‘primary’ but it is important to rule out common mimics of vasculitis and the many underlying conditions that can induce a ‘secondary’ vasculitis.

Vasculitides are usually classified according to the predominant size of the vessels involved, but there is ongoing debate as to the most accurate and clinically useful way to classify the conditions.

Immunopathological mechanisms are diverse, with roles for both humoral and cellular immune mechanisms.

A subset of small‐vessel vasculitides are strongly associated with antineutrophil cytoplasmic antibody (ANCA) and this is often used as a biomarker to aid diagnosis.

There is strong evidence for a pathogenic role of ANCA in the ‘ANCA associated vasculitides’, but the extent of this continues to be debated.

Vasculitis is usually considered a ‘systemic’ disease with the propensity to affect blood vessels throughout the body, but individual clinical presentations may be limited to specific organ systems.

Many patients initially experience a prodrome of nonspecific symptoms such as malaise, fatigue, fever, night sweats or weight loss.

The prevalence of vasculitis is increasing. This may be due to the increased rates of diagnosis, due to clinical suspicion and use of biomarkers such as ANCA; increased survival post‐diagnosis or a true increased incidence.

Further research into the underlying pathological processes is vital to identifying potential treatment targets.

Many trials are currently in progress and will contribute to the improving rates of morbidity and mortality in systemic vasculitis.
Mastocytosis and Mast Cells
Authors: Horny Hans‐Peter 
Published: March 2010

Abstract

Mastocytosis is defined by abnormal accumulation of mast cells in various sites in the body. The clinical features of this chronic, multifaceted disorder originate from mast cell infiltration leading to systemic and local effects induced by numerous pharmacological mediators. Since mastocytosis is an unusual disorder and presents a multiplicity of symptoms, it is an often overlooked consideration in a differential diagnosis that includes not only asthma, chronic diarrhoea, urticaria, syncope, peptic ulceration but also various haematological neoplasms. Diagnosis of mastocytosis can be confirmed only by the pathologist using a combined immunohistochemical and molecular approach. Recognition and subtyping of its rare, life‐threatening high‐grade disease variant (i.e. mast cell leukaemia) includes not only the investigation of tissue samples (usually bone marrow) but also the blood and bone marrow smears.

Key concepts:

Mastocytosis is an unusual haematopoietic disorder derived from transformed bone marrow progenitor cells.

Clinically and histologically, mastocytosis presents an extremely broad spectrum of subvariants ranging from a benign, sometimes even regressive, cutaneous disease to the progressively fatal mast cell leukaemia.

Mastocytosis is a histological diagnosis established by the pathologist and cannot be confirmed by clinical findings alone.

Most patients with systemic mastocytosis carry the activating point mutation KITD816V in the c‐kit proto‐oncogene.

The presence of KITD816V not only explains pathophysiological disease characteristics but also enables targeting therapy using the recently developed tyrosine kinase inhibitors.

Although stated in the recent WHO classification book on haematopoietic neoplasms, mastocytosis should not be grouped among myeloproliferative neoplasms.

Mastocytosis should be considered as a separate group of disorders among haematological neoplasms.

Mastocytosis must be separated from a variety of reactive (i.e. mast cell hyperplasia) and neoplastic (i.e. basophilic leukaemia) states.
Neutrophil Functional Disorders
Authors: Rosenzweig Sergio D , Malech Harry L 
Published: March 2010

Abstract

The phagocytic system is one of the first lines of defence against invading microorganisms. Diseases and disorders that impair phagocyte function can lead to a profound immunodeficiency. Egression from the bone marrow, adhesion, migration, activation, phagocytosis and microorganism killing describe basic mechanisms associated to phagocytic cells. When any of these activities is affected, severe, recurrent and relapsing bacterial as well as fungal infections usually occur. Chronic granulomatous disease is a paradigmatic example of a functional disorder in phagocytic cells. This clinically and genetically heterogenous disease has served during the past 50 years as a model for understanding genotypic–phenotypic correlations of infections susceptibility in primary immunodeficiencies, the utility of anti‐infectious and cytokine prophylactic therapy, hematopoietic stem cell transplantation and gene therapy.

Key Concepts

Patients with neutrophil functional disorders usually present early in life with recurrent bacterial or fungal infections.

Certain infections, such as
Burkholderia cepacia
,
Nocardia
,
Aspergillus nidulans
or nontuberculous mycobacteria should always prompt an inquiry to the possibility of an underlying immune defect.

Specific infection locations, such as omphalitis, gingivitis or osteomyelitis, should raise the suspicion of phagocytic cell abnormalities.

Abnormal aspects of host response, such as lack of fever, local inflammation or pus, should immediately alert the clinician to the possibility of a neutrophil defect.

It is better to perform the right test once than the entire battery of immune defect tests several times. Careful consideration of the clinical and microbiologic presentation usually indicates the right path to pursue.

There is no substitute for the right drug, and that requires knowing the pathogen. Because the spectrum of infection in these diseases may range over several microbiologic kingdoms, empiric therapy is to be discouraged in favour of firm diagnoses.

Prophylactic antibiotics, antifungal agents and cytokines are highly successful in treating chronic granulomatous disease, and appear to be useful in some other immunodeficiencies as well.

A molecular diagnosis should be sought whenever possible. The expanding knowledge of genotype–phenotype relationships suggests that not all defects, even those within the same gene, are created equal.

BCG vaccination should be avoided in individuals with CGD, as well as in their newborn close relatives until the defect is ruled out. In general, attenuated viral vaccines are not contraindicated in individuals with primary neutrophil disorders, as antiviral cell‐mediated immunity is intact.
HMG
Domain Superfamily of
DNA
‐bending Proteins:
HMG
,
UBF
,
TCF
,
LEF
,
SOX
,
SRY
and Related Proteins
Authors: Koopman Peter 
Published: March 2010

Abstract

SRY
, the Y‐chromosome‐encoded male sex‐determining factor, is the signature member of a larger family of related transcription factors, the
SOX
proteins.
SOX
proteins are related by a DNA (
deoxyribonucleic acid
)‐binding domain known as the
HMG
(
high mobility group
) domain, which in turn unites a larger superfamily of proteins.
SRY
and
SOX
proteins are thought to regulate gene transcription through binding to specific DNA sequence motifs and causing the DNA to bend – a property of so‐called architectural transcription factors. Similarly, a related family of proteins, including
TCF‐1
(
T‐cell factor 1
),
LEF‐1
(
lymphoid enhancer factor 1
) and their relatives, regulates transcription by virtue of sequence‐specific DNA binding. A third family, the true or canonical
HMG
proteins, differs by containing multiple
HMG
domains, not binding to specific target DNA sequences, and having poorly defined roles. Here, we examine the diversity, origins, molecular functions and biological roles of the
HMG
domain superfamily.

Key Concepts:

The 80 amino acid HMG domain characterizes a superfamily of proteins found in plants and animals.

HMG domain proteins associate with DNA and usually bend it, thereby influencing transcription of genes.

The most ancient family of these proteins, represented by the canonical HMG proteins HMG‐1 and HMG‐2, have multiple HMG domains, and do not bind to any specific DNA sequences.

Genes encoding canonical HMG proteins may have evolved into two further families of genes encoding proteins that have single HMG domains and bind to specific DNA sequence motifs.

These families include SRY (the mammalian Y‐linked sex‐determining factor) and the SOX, TCF‐1 and LEF‐1 transcription factors.

Unlike canonical HMG proteins, these other HMG domain proteins have specific, important and well‐defined biological roles, particularly in embryonic development.
Nuclear Transfer from Cell Lines
Authors: Wells David N 
Published: March 2010

Abstract

The production of cloned animals following nuclear transfer, using somatic cells grown in culture, represents a remarkable feat of developmental biology. It demonstrates the potential of a differentiated nucleus to be reprogrammed back to an embryonic state when exposed to a suitable cytoplasmic environment, such as that of an oocyte. It involves fundamental changes to the patterns of DNA (
deoxyribonucleic acid
) methylation and chromatin modification imposed on a specialized nucleus to enable the precise temporal‐spatial sequence of gene expression necessary for normal embryogenesis. However, reprogramming is often incomplete with the development going astray, resulting in a continuum of embryo, fetal and post‐natal mortality. The majority of the clones that do survive to adulthood, and their sexually derived progeny, do, however, appear normal. This provides encouragement for the practical applications of nuclear cloning in the fields of agriculture, animal conservation and biomedicine.

Key concepts:

The cytoplasm of mature oocytes and young zygotes has the potential to reprogramme the epigenetic state and pattern of gene expression of somatic donor cells back to that of an embryo, to enable the creation of a cloned animal.

Undifferentiated embryonic blastomeres result in greater animal cloning efficiency but practically all somatic cell types are equally difficult to reprogramme.

Faulty reprogramming compromises subsequent development and is associated with serious animal welfare concerns affecting the acceptability of the current procedures in food‐producing species.

In cattle, approximately 50% of nuclear transfer embryos derived from somatic cells that are transferred to surrogate females may initiate pregnancies, but only 15% produce calves with ultimately 10% resulting in healthy adult clones. The cloning efficiencies in most other species are less than this.

Any epigenetic errors that may persist in surviving clones appear to be reset through gametogenesis and are not transmitted to progeny following sexual reproduction.

Cloning can be used in agriculture to multiply high‐value breeding animals to effectively disseminate genetic gain.

Somatic cell cloning is a valuable reproductive tool to resurrect genetically superior livestock after slaughter, accidental death, injury or disease to avoid the lost of valuable genotypes.

The milk and meat from surviving cloned livestock has similar composition to that produced from conventional livestock and is safe to consume.

Nuclear transfer is a valuable method to produce transgenic livestock from genetically modified cells for specific agricultural and biomedical applications.

The controversy over the use of human somatic cell nuclear transfer to generate patient‐specific embryonic stem cells for regenerative medicine has abated after the revelation that somatic cells can be directly reprogrammed into induced pluripotent stem cells
in vitro
, signalling the latest revolution in this field.
Nuclear Magnetic Resonance (
NMR
) Spectroscopy: Structure Determination of Proteins and Nucleic Acids
Authors: Greenbaum Nancy , Ghose Ranajeet 
Published: March 2010

Abstract

Nuclear magnetic resonance (NMR) spectroscopy is a powerful biophysical technique that facilitates determination of the three‐dimensional structure and interactions of proteins and nucleic acids in solution. A set of NMR experiments identifies spectral signatures corresponding to specific atoms on individual residues in the molecule and determines their order in the primary sequence. Distance and angular relationships are subsequently measured and utilized to supplement standard force‐fields used in molecular dynamics (MD)‐based protocols to obtain high‐resolution structural models. Structure determination is aided by molecular biology and biochemistry to generate samples optimally labelled with NMR‐active isotopes; by improvement in the design of NMR instrumentation to allow spectral signatures to be recorded with high sensitivity; by development of efficient techniques to manipulate nuclear spins at the quantum level; and by generation of advanced computer algorithms that allow rapid processing, manipulation and storage of large quantities of NMR data.

Key Concepts:

Solution NMR is an excellent spectroscopic technique for the determination of the three‐dimensional structure of biomolecules at near‐physiological conditions.

The abundance of chemical and structural information available from NMR spectra derives from the ability to selectively manipulate specific nuclei by customizable sequences of radio‐frequency pulses in a large static magnetic field.

NMR signals report on the variety of chemical environments experienced by nuclei in biomolecules through unique spectral signatures.

The repertoire of information‐rich NMR experiments has been expanded by the ability to enrich biomolecules with NMR‐active nuclei taking advantage of advances in molecular biology and biochemistry.

Nuclear spins in biomolecules form magnetically coupled networks, with characteristic spectral profiles that can be manipulated to extract angular, orientational and distance information for calculation of three‐dimensional structural models.
Bell's Palsy
Authors: Gilchrist James M 
Published: March 2010

Abstract

Bell's palsy is an idiopathic neuropathy of the facial nerve, meaning there is no known cause. It was first described in the medical literature in 1821 and is the most common cause of facial neuropathy. It usually presents as acute, weakness of one side of the entire face. This is in contrast to facial weakness from a cerebral hemisphere stroke which spares the forehead muscles of the face. Increased loudness and decreased taste on the affected side are also common, as are numbness and pain. Loss of hearing, ringing in the ears, problems with speech or swallowing or weakness elsewhere should provoke looking for another diagnosis than Bell's palsy. The chance of full recovery is excellent but the use of steroids within three days of onset, especially in patients with moderate or severe weakness, improves the chance of full recovery even further. The use of antiviral agents should probably be limited to those patients with severe weakness, or with evidence of herpes zoster infection in the ear or mouth (Ramsay Hunt syndrome).

Key concepts

Bell's palsy is the most common cause of facial neuropathy.

It is defined as idiopathic facial neuropathy.

It has as excellent prognosis, with 85% of patients having recovery by 6 months.

Steroids given within 3 days of onset improve the chance of recovery even further.

The facial nerve travels a long and bending path, which is why so many diseases can affect it.

Facial neuropathy causes weakness of the entire side of the face versus cerebral hemisphere stroke which spares the forehead muscles.

There is mounting evidence to support the hypothesis that Bell's palsy in most patients is caused by reactivation of herpes simplex virus in the geniculate ganglion.
Stanier, Roger Yate
Authors: Oren Aharon 
Published: March 2010

Abstract

Roger Stanier (1916–1982), a Canadian‐born microbiologist, who worked at the University of Berkeley, California and at the Institut Pasteur, Paris, and became renowned for his studies on the bacterial degradation of aromatic compounds and the taxonomy and physiology of cyanobacteria and as the author of
The Microbial World
, the major textbook of general microbiology in the 1960–1980s.
Graphite Furnace Atomic Absorption Spectrometry
Authors: Holcombe James A. , Borges Daniel L. G. 
Published: March 2010

AbstractGraphite furnace atomic absorption spectrometry (GFAAS) is also known as electrothermal atomization atomic absorption spectrometry (ETAAS). It is an atomic spectroscopic technique in which a small sample is placed inside a graphite tube that is then resistively heated to accomplish sample desolvation (for liquid samples), ashing or charring (to decompose the sample and volatilize some of the matrix), and finally atomization. Typically, the light from a line source characteristic of the element being determined is passed longitudinally through the tube and the absorbance resulting from the presence of free analyte atoms in the gas phase is measured. A continuum source and high‐resolution spectrometer can accomplish a similar objective. The absorbance signal is transient in character, lasting approximately 1–5 s, and the area under this transient peak is generally used in the construction of a calibration curve. Modern instrumentation provides high levels of automation with capabilities of background correction as well as routine methods of sample analysis, for example quality assurance/quality control (QA/QC), standard additions, matrix modification, etc. Since the technique was first introduced in 1969, a lot of progress has been made in understanding the processes occurring within the graphite tube atomizer that ultimately produces the absorbance signal. An understanding of the free atoms formation process has facilitated the application of the technique to the analysis of a variety of complex samples.Graphite furnace (also known as an electrothermal atomizer or ETA) atomic absorption is generally considered an ultratrace and microtrace analytical technique with limits of detection (LODs) in the low picogram range, precision of a few percent (relative standard deviation), and a dynamic range of about three orders of magnitude. In addition to its excellent sensitivity, it is unique in its ability to handle microsamples including aqueous solutions, viscous liquids, slurries, and even solids. In general, there is considerable literature detailing methods and procedures for the determination of a variety of analytes in complex matrices that can be used by the analyst to apply the approach to new, complex analytical needs. When used correctly, this analytical tool can provide precise, accurate analysis for a wide range of sample types.
Atmospheric‐Pressure Solid Analysis Probe (ASAP)
Authors: McEwen Charles N. 
Published: March 2010

AbstractThe atmospheric sample analysis probe (ASAP) is a simple but powerful direct method for the rapid analysis of a wide variety of materials. The method uses standard ion sources provided on commercial mass spectrometers without interfering with the intended operation. In addition to a fundamental description of the ASAP method, material characterization examples, including synthetic compounds, drugs, tissue, polymers, and petroleum, are presented.
Neutron Radioscopy: Industrial and Scientific Applications
Authors: Hickner Michael A. , Hussey Daniel S. 
Published: March 2010

AbstractNeutron imaging is a precise measurement tool for water content in proton exchange membrane fuel cells (PEMFCs), enabling the direct measurement of the water distribution in standard, commercially viable fuel cell hardware. In the last 5–7 years, neutron imaging has proven to be an invaluable tool in fuel cell research and has provided information inaccessible by any other measurement technique. The unique aspects of imaging real fuel cells are due to the large neutron scattering cross section from hydrogenous liquids, combined with the relatively small scattering cross section from many common metals and other materials of construction. Neutron‐imaging instruments are simple in design, and high‐resolution digital neutron‐imaging detectors (down to 20 µm) are routinely available at many neutron‐imaging facilities. One drawback of neutron imaging is that a high flux neutron beamline is required, and only 6–10 facilities in the world are currently equipped to do these types of measurements. The majority of this article discusses the uses of neutron imaging to investigate water transport phenomena in PEMFCs, including optimal channel design, effects of thermal gradients, and material property effects on liquid water retention. In addition, examples are given of neutron tomography applied to the study of other hydrogen‐based energy storage systems — metal hydride storage beds and alkaline batteries.
Analytical Ultracentrifugation
Authors: Schuck Peter , Balbo Andrea , Brown Patrick H. , Zhao Huaying 
Published: March 2010

Abstract
Analytical ultracentrifugation is a powerful and very versatile technique for the study of particles in solution ranging from sub‐nanometers to micrometers in size. It allows the characterization of their size or size distribution, low‐resolution (hydrodynamic) shape, density, and solvation properties, and, in some cases, composition and attractive or repulsive interactions. For single‐ or multicomponent systems with reversible chemical reactions, the number and stoichiometry of complexes, the timescale of their interconversion, as well as binding constants from nanomolar to millimolar range can be determined. Analytical ultracentrifugation is based on first principles and has a long history of theoretical and practical development. This present article provides an introduction of the theoretical concept, the instrumentation, and considerations for conducting experiments and data analysis.
Quantitative Imaging of Membrane Mechanics with Molecular Resolution
Authors: Dong Mingdong , Sahin Ozgur 
Published: March 2010

Abstract
Atomic force microscope (AFM) is a powerful tool to study the surface morphology of biological samples. High‐resolution topographical images allow visualization of nanomaterials and characterization of nanostructures to understand functional properties in detail. However, in general, morphology is not sufficient to link structure and function of materials and biomolecules. Complementary information on optical, electronic, mechanical, thermal, chemical, and magnetic properties with nanometer‐scale spatial resolution can be extremely helpful. Recently, progress has been made in the measurement and characterization of dynamic nanomechanical properties with high spatial resolution using specially designed AFM cantilevers. High‐resolution mechanical measurements can be particularly useful in providing insights into biological membranes, because these membranes comprise biomolecules whose mechanical properties are tailored to assist their biological function. With this perspective, we review the recently developed experimental technique and its applications in quantitative imaging of membrane mechanics.