bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anaemia: Adaptive Mechanisms and Consequences
Authors: Zarychanski Ryan , Rimmer Emily , Houston Donald S 
Published: April 2013

Abstract

Human life depends on the availability of oxygen and its conversion into energy used by living cells. Reduced oxygen to tissues is referred to as hypoxia, and may result from decreased oxygen delivery or mitochondrial dysfunction. In the setting of tissue hypoxia due to anaemia or other causes, several adaptive and coordinated physiologic processes are initiated to maintain oxygen delivery and limit oxygen consumption. Mechanisms to increase oxygen delivery in the face of anaemia or global hypoxia include the stimulation of erythropoiesis, and increasing cardiac output. Oxygenation availability is further maximised by decreases in the haemoglobin‐oxygen binding affinity, increases in tissue oxygen extraction, and via changes in regional blood flow. Mild to moderate anaemia, especially if chronic, is generally well tolerated given these adaptive processes. In states of inflammation or chronic disease, down regulation of haemoglobin occurs and may represent an important adaptive mechanism.

Key Concepts:

Aerobic metabolism and human life depend on the availability of oxygen.

Anaemia results when the haemoglobin levels are below normal and, if severe, may result in tissue hypoxia.

Adaptive mechanisms exist to compensate for anaemia or other causes of tissue hypoxia so that oxygen delivery is maintained and balanced with oxygen consumption.

A major adaptive mechanism in response to anaemia is to increase production of the growth hormone erythropoietin, leading to the formation of red blood cells.

The anaemia associated with inflammation has features of an adaptive response, is generally well tolerated and rarely requires treatment.
Syphilis: Clinical Aspects
Authors: Wright David J , Norris Steven J , Dhillon Rishi H‐P , Edmondson Diane G 
Published: April 2013

Abstract

Syphilis is a common sexually transmitted disease which, if left untreated, can result in a multiorgan infection. The causative organism is the spirochaete (from the Greek ‘spiral hairs’)

Treponema pallidum

. Other subspecies cause similar diseases such as yaws and pinta but these tend to be less severe and do not cause multisystem morbidity. Syphilis is a classic biphasic illness characterised by an initial skin infection which may be followed years later by involvement of the central nervous system (CNS), skeletal and cardiovascular systems with the great vessel the aorta at particular risk. Congenital transmission can occur and a range of clinical features can afflict the baby. Severe deformities, and even intrauterine death, are associated with transmission late in the pregnancy. Early and appropriate antimicrobial treatment of syphilis in all its guises is therefore of critical importance. Newer imaging techniques have become a useful adjunct in aiding diagnosis, which still relies heavily on serological assays and clinical acumen.

Key Concepts:

Enhancement of infectivity of syphilis and of early syphilitic lesions, in patients with concomitant HIV.

The relapsing nature of syphilis, both in early stages and in the late congenital disease, as in interstitial keratitis and Clutton's joints.

Primary form of syphilis is an early localised primary lesion. The secondary phase is manifested by a systemic disease, whereas the later stages are again localised.

Similarly, early congenital lesions tend to be disseminated, whereas late lesions are localised.

Newer imaging techniques are useful both in diagnosis and for monitoring treatment, especially in those patients with brain and cardiovascular syphilis.
Cell Senescence
In Vitro
Authors: Rattan Suresh IS 
Published: April 2013

Abstract

Cell senescence

in vitro

refers to the multitude of physiological, structural, biochemical and molecular changes that occur progressively during serial subcultivation of normal diploid cells, culminating in the permanent cessation of cell division. The whole duration of serial passaging is considered as the process of cellular ageing, and the end‐stage irreversible growth arrest is termed as replicative senescence. The limited proliferative capacity of normal, diploid and differentiated cells is also known as the Hayflick limit, and the overall phenomenon is called the Hayflick phenomenon. A progressive loss of global
deoxyribonucleic acid (DNA)
methylation and of telomeres is considered to be the critical determinants of the Hayflick limit. However,

in vivo

, it is not the absolute number of senescent cells which is responsible for age‐related impairments, but it is the drift in cell functions occurring during repeated cell division that is relevant to ageing and age‐related diseases. Cell senescence in the body is also considered to be a regulatory mechanism against cancer.

Key Concepts:

Normal, diploid and differentiated cells have a limited division potential, known as the Hayflick limit.

The Hayflick limit can be observed both

in vitro

and

in vivo

, and is both cell type‐specific and species‐specific.

Serial subcultivation of normal cells is accompanied by hundreds of physiological, structural, biochemical and molecular changes, culminating in cellular senescence.

The progressive change in normal cells during serial subcultivation is known as the Hayflick phenomenon, cellular ageing, or replicative senescence.

Cell enlargement, increased cytoskeletal rigidity in terms of polymerisation and cross‐linking, altered cellular responsiveness to stress, accumulation of molecular damage, impaired cellular functions and the reduced activity of maintenance and repair systems are the main changes during cellular ageing.

The senescent phenotype of cells is characterised by the irreversible growth arrest in G0/G1 phase of the cell cycle, which can be bypassed only through cell transformation.

Upregulation of a range of cell cycle check point genes is the hallmark of cellular senescence.

A stochastic and progressive loss of cytosine methylation and of telomeres in genomic DNA appears to be the major factors that limit the cell proliferative ability.

Cellular senescence

in vivo

is considered to be an anticancer mechanism in evolutionary terms.

In the body, it is not the absolute number of senescent cells that is responsible for the age‐related impairments; rather it is the drift in cell functions occurring during repeated cell division that is relevant to ageing and age‐related diseases.
Atomic Force Microscopy
Authors: Galgoczy Roland , Roca‐Cusachs Pere , Alcaraz Jordi 
Published: April 2013

Abstract

Atomic force microscopy (AFM) is a local probe nanotechnique that belongs to the large family of scanning probe microscopies (SPM). It was introduced in 1986, and is the most versatile SPM, because it can be used as an imaging instrument, a force sensor and actuator and as a molecular sensor. AFM enables imaging samples with subnanometer resolution and detecting intermolecular forces as low as a single hydrogen bond. Its high spatial and force resolution, combined with its ability to probe samples in liquid make AFM a very suitable nanotechnique for the life sciences. Accordingly, AFM has been used to examine biological samples embracing all levels of complexity including biomolecules, viruses, prokaryotic and eukaryotic cells and more recently, tissue sections. Moreover, AFM biomedical applications are rising and include their use as a diagnostic tool.

Key Concepts:

AFM is a nanotechnique that allows visualising the surface of biological samples by directly touching them with a mechanical‐based force sensor or cantilever tip.

The essential components of an AFM are a flexible cantilever provided with a sharp tip at its end and a piezoelectric scanner that controls the tip–sample distance.

AFM can be operated in vacuum, air and liquid. The only sample requirements are immobilisation on a flat substrate and a surface roughness smaller than the height of the tip.

The most common modes of operation of AFM as an imaging device are with the tip in either constant or intermitent contact with the sample.

The topography image obtained with AFM is strongly influenced by both the shape and size of the tip and the elastic properties of the sample.

AFM probes can measure intermolecular forces as low as few piconewtons, and apply user‐defined loading forces on the sample surface, thereby acting as a force sensor or actuator.

Using AFM tips with a suitable functionalisation enables probing the specific intermolecular forces involved in molecular recognition events.

The spatial and force range accessible with AFM enables using it to examine biological samples spanning many length scales of biological complexity, from single biomolecules to tissue sections.

Arrays of cantilevers functionalised with specific recognition sites can potentially be used to detect soluble biomarkers in fluid samples of patients at concentrations lower than current diagnostic devices.
Hydrophobic Interaction Chromatography
Authors: Jennissen Herbert P 
Published: April 2013

AbstractHydrophobic interaction chromatography (HIC) involves the separation of protein molecules in their native and biologically active state owing to a differential interaction of these molecules with hydrophobic sites on the surface of a solid support. In the separation process, hydrophobic patches on the protein surface interact with hydrophobic molecules (e.g. alkyl residues) immobilised on the hydrophilic solid phase surface (e.g. agarose). In the paper, a historical overview is followed by a consideration of the biochemical and biophysical mechanisms involved in HIC and a discussion of the critical hydrophobicity method and other approaches to hydrophobic interaction chromatographic methods. A detailed protocol for the individual synthesis of gel libraries for specific needs has been published. The treatise is concluded with a discussion on the predictability of chromatographic results and an outlook into the future.Key Concepts:Positive and negative cooperativity manifests itself by binding isotherms of proteins not governed by the Langmuir equation, that is, a single binding constant but depends on site–site interactions leading to multiple binding constants.Adsorption–desorption hysteresis manifests itself by an adsorption isotherm, which is not retraced by the desorption isotherm, due to conformational changes on the surface, dissipation of entropy and an increase in affinity.Metastability of adsorption states occurs during adsorption–desorption hysteresis and indicates energetically that a local energy minimum exists (i.e. nonequilibrium state) in distinction to the global energy minimum, that is, true equilibrium.Critical hydrophobicity is the threshold hydrophobicity under low salt concentrations (e.g. 50 mM Tris, 150 mM NaCl and pH 7.0) at which the adsorption of a protein can first be measured.A quantised hydrophobicity gradient is a hydrophobicity gradient separated into a library of distinct gels of varying hydrophobicity for determining the critical hydrophobicity.A homologous gel library consists of gels carrying covalently immobilised hydrocarbons (e.g. alkyl residues) comprising a homologous series.The lattice‐site binding function is a protein adsorption isotherm (often showing positive cooperativity) as a function of the surface concentration of immobilised hydrocarbons (e.g. alkyl residues).The bulk ligand binding function is a protein adsorption isotherm on immobilised hydrocarbons (often showing negative cooperativity) as a function of the bulk protein concentration.Predicting chromatographic behaviour from sorption isotherms is a major aim in understanding HIC.Predicting chromatographic behaviour from protein structure is the ultimate aim in understanding and utilising HIC.The critical hydrophobic patch area hypothesis is a method of predicting the chromatographic behaviour of proteins in HIC from protein structure, utilising the area of hydrophobic patches on the surface of proteins.
Chamberland, Charles Edouard
Authors: Harvey Joy 
Published: April 2013

AbstractCharles Chamberland was an associate of Louis Pasteur whose technical skills and inventive mind added significantly to the experimental investigations ofchicken cholera, anthrax, swine erysipelasandrabiesand the development of vaccines produced by the Pasteur Institute. Trained in physics and mathematics rather than biology or medicine, he is credited with the invention of the first laboratory autoclave and the Chamberland–Pasteur porcelain filter. His laboratory of applied microbiology within the Pasteur Institute had the major responsibility for producing commercialanthrax vaccinesand advising satellite Pasteur institutes.
Theorell, Axel Hugo Theodor
Authors: Ljungstrom Olof , Normark Daniel 
Published: April 2013

Abstract
Axel Hugo Theodor Theorell (1903–1982) was a Swedish biochemist and Nobel Prize laureate (1955), who primarily studied enzymatic oxidation processes. He is best known for his work on cell‐respiration oxidation product at the time known as ‘the yellow ferment’, myoglobin, and alcohol dehydrogenases in the liver. In 1936 he became the first director of the section for biochemisty at the newly established Medical Nobel Institute at the Karolinska Institutet (KI), and a full professor at the KI in 1959.
Tiselius, Arne
Authors: Tunlid Anna 
Published: April 2013

Abstract
Arne Tiselius (1902–1971) was a Swedish biochemist who developed electrophoresis and adsorption methods and applied them to the study of proteins and other substances of biological interest. In 1948 he was awarded the Nobel Prize in Chemistry for his research on electrophoresis and adsorption analysis, especially for his discovery of the complex nature of serum proteins. In the following decades several biochemical separation methods were developed at his laboratory at Uppsala University. Tiselius played an active role in Swedish science policy after World War II. He was a member of the Nobel Committee for Chemistry and served as president of the Nobel Foundation.
Hydrophobic Effect
Authors: Lazaridis Themis 
Published: April 2013

AbstractThe term ‘hydrophobic effect’ refers to the poor solubility of nonpolar substances in water compared to organic solvents or to polar substances. The transfer of small nonpolar molecules from the gas phase or organic solvents to water has a characteristic thermodynamic signature: positive free energy, negative enthalpy, large negative entropy and positive heat capacity. This thermodynamic signature can be explained by considering the structure of water around nonpolar substances, which depends on the size and shape of the nonpolar solute. The poor solubility of nonpolar groups in water leads to aggregation of these groups (hydrophobic interaction) and the formation of self‐assembled structures such as miscelles and lipid bilayers. The hydrophobic interaction is also the major contributor to protein folding. The origin of the hydrophobic effect lies in the fact that water interacts with itself much more strongly than it does with nonpolar groups.Key Concepts:The origin of hydrophobicity lies in the strong water–water interactions.The hydrophobic effect is entropic or enthalpic depending on temperature and the geometry of the associating solutes.The characteristics of hydrophobic hydration differ depending on the length scale of the solute.The hydrophobic effect is responsible for the formation of lipid bilayers and the folding of proteins.Interaction between small hydrophobic solutes is in many ways different from transfer to a bulk phase.Most studies find anticooperativity in the interaction between three small nonpolar solutes.Very long‐range attractions between hydrophobic surfaces are probably due to macroscopic phenomena, such as air bubbles.
Electron Cryomicroscopy and Three‐dimensional Computer Reconstruction of Biological Molecules
Authors: Ludtke Steven J , Chiu Wah 
Published: April 2013

AbstractElectron cryomicroscopy (cryo‐EM) single‐particle analysis is a technique for imaging individual molecules or macromolecules under native‐like conditions. When combined with complex computer algorithms, the resulting images can produce a three‐dimensional (3D) structure at resolutions now beyond 4 Å. At these resolutions, the protein backbone can be traced, and in many cases sufficient side chains identified to build a full atomistic model akin to that produced by X‐ray crystallography. Cryo‐EM can also approach problems, which are difficult or impossible for X‐ray diffraction or NMR. For example, cryo‐EM can be used to characterise the structural flexibility/dynamics of large macromolecules, which is not possible via any other current method. Cryo‐EM is also often the method of choice for studying large membrane proteins, which are generally difficult to crystallise. Additional specialised methods exist for 2D crystals or extended structures with helical symmetry.Key Concepts:Owing to the short wavelength of high voltage electrons, it is possible to resolve features at resolutions ∼1000× higher than light microscopes.Liquid specimens cannot be used under the high vacuum of the microscope and must be either frozen in vitreous ice or chemically fixed before imaging.Tens of thousands of randomly oriented 2D images are combined to produce a high‐resolution 3D volumetric structure.
Protein Unfolding and Denaturants
Authors: Konermann Lars 
Published: April 2013

AbstractThe biologically active (native) state of most proteins is characterised by a tightly folded and highly ordered conformation. Denaturants are chemical or physical agents that can induce unfolding of the polypeptide chain. Examples include urea, heat, extremes of pH, as well as some detergents. Unfolded proteins adopt a largely disordered structure. Denaturants can interact directly with the protein, or they can alter the properties of the surrounding aqueous environment. Despite the routine use of denaturants in the biochemical laboratory, the mechanisms whereby these agents destabilise the native state remain poorly understood. Folded protein structures are only marginally stable. As a result, relatively subtle alterations in the physical and chemical properties of the solvent can cause major changes in position of the unfolding equilibrium. This review briefly discusses the most commonly used denaturants, their likely mechanisms of action, as well as some thermodynamic aspects.Key Concepts:The biologically active (native) state N of proteins represents a highly ordered and tightly folded structure.N is in equilibrium with an extensively disordered (unfolded) state U.Denaturing agents (e.g. urea, extremes of pH and temperature) shift the unfolding equilibrium from N to U.The exact mechanism of action remains unclear for most denaturants.The position of the unfolding equilibrium is governed by an interplay of enthalpic and entropic contributions that affect the free energy of unfolding according to ΔG0=ΔH0–TΔS0.The sign and magnitude of ΔG0represents the thermodynamic stability of N; N is stable when ΔG0>0.Unfolding can be triggered by increasing the temperatureT, because U has a higher entropy than N (ΔS0>0).Protein stability measurements are commonly carried out by employing urea or guanidinium chloride‐induced unfolding in conjunction with optical detection.Some proteins adopt semiunfolded structures (intermediates) under mildly denaturing conditions.Protein (un)folding can be studied under equilibrium conditions and in kinetic experiments.
Protein Disulfide Isomerases
Authors: Gilbert Hiram F 
Published: April 2013

AbstractProtein disulfide isomerase(PDI) is a multifunctional protein that facilitates the formation of correct disulfide crosslinks between cysteine residues during the early stages of protein folding and secretion in the endoplasmic reticulum. It is a member of a large family of oxidoreductases that catalyse exchange reactions between thiols and disulfides. PDI is a multidomain protein, consisting of four tandem thioredoxin domains. TheN‐ andC‐terminal thioredoxin domains have catalytic disulfide/dithiol centers while the two internal domains are structural and provide additional interactions with the protein substrates. The catalysis of disulfide formation relies almost entirely on the high reactivity of PDI's active site disulfides. However, the ability to catalyse disulfide isomerisation requires multiple domains. In the cell, PDI's essential activity is the formation of disulfide bonds, but it does catalyse isomerisation.Key Concepts:PDI structure consists of four tandem thiredoxin domains.The ability to form disulfides between cysteines in substrate proteins results from highly reactive active site disulfides.PDI can correct (isomerise) misformed disulfides by reducing incorrect disulfides and reoxidising in a different configuration.The multidomain structure is needed for catalysis of isomerisation but a single catalytic domain is sufficient to catalyse substrate oxidation.In the cell, the essential activity of PDI is its ability to form substrate disulfides.
Genome, Proteome and the Quest for a Full Structure–Function Description of an Organism
Authors: Godzik Adam , Wilson Ian A 
Published: April 2013

AbstractCompletion of the Human Genome Project provided thedeoxyribonucleic acid(DNA) sequence of a human genome – a complete blueprint of our organism. Genomic information is processed intoribonucleic acid(RNA) and then into proteins, which carry out most cellular processes that sustain life. All of these molecules – DNA, RNA and proteins – have unique three‐dimensional shapes, and the atomic details of these shapes, and the inherent information they carry, define their function. Every cell, and ultimately the entire organism, may be viewed as a gigantic three‐dimensional jigsaw puzzle where all of the pieces have to fit together for the whole system to function. Elucidating the shapes of the molecular elements of the cell helps decipher the rules that dictate how they hierarchically form larger objects, such as molecular machines, organelles, cells and organs, how the shapes of individual molecules and their assemblies change on regulation, what changes cause disease and eventually, how they can be repaired or how they can be targeted by drugs.Key Concepts:Genes are coded in a four‐letter code by linear strings of DNA and define sequences and shapes of all downstream products (RNA and proteins).DNA has a limited number of three‐dimensional shapes that it can take (three main forms currently known), but even small variations of these shapes are important for gene regulation and interactions between DNA and other molecules.Products of DNA transcription (RNA) and translation (proteins) have complex but unique three‐dimensional shapes that are defined by their sequence and post‐translational modifications as well as interaction with other molecules.Experimental determination of DNA, RNA and protein three‐dimensional structures by X‐ray crystallography, NMR spectroscopy and other techniques provide a molecular level understanding of the fundamental processes of life.The number of basic shapes (or folds) that RNA and proteins can adopt are limited by steric constraints; however, these numbers are very large as compared to the limited number of DNA shapes – it is now known hundreds (RNA) or thousands (protein) of shapes and (probably) thousands of other shapes are still possible.Regulation of DNA, RNA or protein function often involves changes to their structure and/or dynamics.DNA, RNA and protein molecules form functional networks where neighbours in the network influence and regulate each other. Analyses and simulations of such networks is a subject of systems biology, which ultimately provides a perspective for predictive modelling of biological systems.DNA, RNA and protein molecules can form higher order complexes and assemblies – a process driven by a mutual compatibility of their shapes and/or chemical composition. Such complexes define the many nodes in functional cellular networks.Experimentally determined structures of DNA, RNA and protein complexes and assemblies provide a detailed picture of how regulation of cellular processes is carried out.