bluuebunny/crossref_metadata_2025_split huggingface dataset:
Filoviruses: Ebola, Marburg and Disease
Authors: Groseth Allison , Hoenen Thomas , Eickmann Markus , Becker Stephan 
Published: April 2013

Abstract

Ebola and Marburg viruses belong to the family of filoviruses and cause severe haemorrhagic fevers in humans and nonhuman primates. Since their discovery in 1967, during outbreaks in Germany and former Yugoslavia originating with nonhuman primates imported from Uganda, they have been responsible for numerous disease outbreaks in Africa. Ebola has also been implicated in massive die‐offs of great apes and in recent years there have been several cases of imported Marburg infections into Europe and North America. Filoviral haemorrhagic fevers (FHF) are severe diseases with case fatality rates of up to 90%. Currently, there is neither a licensed vaccine nor a specific therapy available. Although experimental vaccines and treatments have shown promise in nonhuman primates, at the present time supportive therapy and prevention of disease transmission through rigorous case management and patient isolation are the only means available to combat FHF.

Key Concepts:

Human pathogenic filoviruses (Ebola and Marburg viruses) are found in Africa, whereas
Reston ebolavirus
, which is nonpathogenic to humans, originates in the Philippines, where it is found in both nonhuman primates and pigs.

Although the absolute number of filoviral haemorrhagic fever cases is low when compared to other diseases, the severe disease picture and high case fatality rates have led to a high public profile of filoviral haemorrhagic fevers.

Imported nonhuman primates have been the cause of outbreaks of filoviral haemorrhagic fever in Europe and North America, both among humans and nonhuman primates. Tourism has also resulted in several imported infections during the last years.

Bats represent the most likely reservoir for filoviruses.

The pathophysiology of filoviral haemorrhagic fevers involves vascular dysfunction, impairment of the immune system and massive dysregulation of cytokine production.

Death is caused by multiple organ failure as result of a syndrome resembling septic shock.

Experimental treatments and vaccines in nonhuman primates exist, but are not licensed for use in humans.

Currently the only measures to combat filovirus infections are supportive therapy and patient isolation.
Leptospirosis
Authors: Sitprija Visith , Tantawichien Terapong 
Published: April 2013

Abstract

Leptospirosis is an important zoonotic disease caused by pathogenic spirochaetes of the genus

Leptospira

. Because of rapid global communication the disease has been recognised as an emerging zoonosis that occurs in both developing and developed countries although it is considered as a tropical disease. Typically, leptospirosis is characterised by a sudden onset of fever, chills, jaundice, myalgia and renal failure. The disease can be subclinical. Pathophysiology of leptospirosis involves bacterial invasion, haemodynamic changes and immune response. Hypotension is a common clinical sign which may precede pulmonary symptoms and acute renal failure. Pulmonary haemorrhage is life threatening. The mortality rate of leptospirosis varies from minimal to 16%. Penicillin remains the drug of choice in leptospirosis. Cephalosporins and doxycycline are satisfactory alternatives.

Key Concepts:

Leptospirosis is a zoonotic disease caused by pathogenic leptospires.

Rodents, because of their alkaline urine, serve as an important reservoir for leptospires.

Leptospires enter the host through a break in the skin or through intact mucous membrane and spread through the blood stream to all organs within 48 h.

Bacterial clearance is by phagocytosis and humoral mechanism.

Organ injury is the results of inflammation induced by leptospire invasion, LPS, enzymes and outer membrane proteins.

Through activation of Toll‐like receptors on host cells by outer membrane proteins and LPS proinflammatory cytokines and vasoactive mediators are released.

Systemic vasodilatation, renal vasoconstriction and increased capillary permeabliity are the basic haemodynamic response to proinflammatory cytokines and vasoactive mediators that causes hypotension and decreased renal blood flow.

Pulmonary haemorrhage and acute respiratory distress syndrome caused by endothelial injury represent severe leptospirosis.

Renal failure in leptospirosis, due to tubular necrosis, is catabolic in type and may be associated with cholestatic jaundice.

Hypokalaemia and hypomagnesaemia with hyperkaliuria and hypermagnesuria due to renal tubular dysfunction are commonly observed.
Transcriptional Gene Regulation in Eukaryotes
Authors: Latchman David S 
Published: April 2013

Abstract

Regulation of gene transcription is the primary means by which gene expression is controlled to produce different proteins in different cell types or in response to different stimuli. This process is controlled by transcription factors that belong to specific families which are defined on the basis of the different protein domains used to bind to
deoxyribonucleic acid
(DNA). Many transcription factors contain specific activation domains which allow them to activate transcription. In contrast, other transcription factors repress transcription either directly or indirectly by interfering with positively acting factors. Moreover, DNA‐binding transcription factors can also interact with one another and with non‐DNA‐binding coactivators and corepressors so allowing an individual transcription factor to differentialy regulate different genes. In turn, transcription factors are themselves regulated by controlling either their synthesis or by activating them from a pre‐existing inactive state by mechanisms such as ligand binding, phosphorylation or dissociation of an inhibitory protein. These mechanisms allow cellular differentiation events or specific signals to regulate gene expression by altering the synthesis and/or activity of individual transcription factors and thereby altering the expression of their target genes.

Key Concepts:

Regulation of the transcription of DNA into RNA is the key event controlling gene expression.

Transcription is regulated by specific proteins called transcription factors.

Many of these factors act by binding to specific DNA sequences in gene promoters or enhancers.

Transcription factors bind to the DNA via specific DNA‐binding domains which differ between different transcription factor families.

Following DNA binding, some factors activate transcription via specific activation domains.

Other transcription factors can repress transcription either directly or indirectly by interfering with the action of positively acting factors.

In order to regulate gene transcription, transcription factors are themselves regulated by controlling either their synthesis or their activity.

The rate of transcription of a particular gene is therefore determined by the balance between the levels/activity of the activating and inhibitory transcription factors which act on it.
Clonal Isolation and Plating Efficiency
Authors: Martin Bernice M 
Published: April 2013

Abstract

Viable cultures of cells that were initiated from single cells can be obtained. However, both the isolation of the single cell of interest and the ability to promote proliferation of this cell present challenges. Selection of the single cell can be achieved in a number of ways. Among the methods discussed are a direct approach (cloning cylinders or discs), a theoretical approach (limiting dilution) and isolation using cell sorters. Any of these approaches can be combined with a pre‐seeding technique that will enrich the population of the desired cells in the culture. A number of techniques to address the second challenge, cell proliferation, are also addressed. These include the use of culture ware with a small growth area, increasing the likelihood of cell attachment, the enrichment of the culture medium and the use of feeder layer cells. Because cells differ widely in their characteristics, a combination of techniques can be used.

Key Concepts:

Cloned cells in culture are derived from a single cell.

Each of the cells in a clone should have identical characteristics.

Selection of cells for cloning may be aided by fluorescent molecules and FACS.

The survival and proliferation of the cells that form clones require special conditions.
Differentiation of Somatic Cells, Stem Cells and Stem Cell Variants:In VitroModels
Authors: Danilenko Michael , Coffman Frederick D , Studzinski George P 
Published: April 2013

AbstractBecause conditions of culturein vitrocannot be identical to those in the living system, cell lines culturedin vitroare referred to as ‘model systems’. Not all cell types are capable of differentiationin vitro. Stem cells are of various types, including embryonic stem cells (ESC), mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), cancer/leukaemia stem cells (CSCs/LSCs),etc.Procedures for studying differentiation in model systems depend on the type of culture that can be employed. Techniques employed include liquid suspension cultures, monolayer cultures and complex culture systems involving semisolid matrices or liquid overlay methods. Cells derived from various tissues can be maintained in culture known as ‘primary culture’. Only a rare human cell in a culture can undergo changes in its molecular machinery known as ‘immortalisation’ which allow it to propagate indefinitely. Recent developments include systems optimised for stem cell differentiation. Suchin vitroculture techniques have applications to the study of differentiation in basic research and clinical applications.Key Concepts:Mammalian cells derived from many tissues, the subject of this article, can propagate outside of the body.Stem cells can differentiate, but provide a reservoir for development of functional cells of various types which is known as ‘lineage expansion’.Stem cells give rise to progenitor cells (PCs) which can differentiate into mature cells, but have a limited repertoire of lineages of differentiation.Mature cells can be induced to have the capabilities of stem cells and PCs by introduction of four or less transcription factors (TFs), for example, Oct4, Sox2, Klf4 and c‐Myc, under defined conditions.The cell environment – other cells, extracellular material – can favour lineage expansion into mature, functional cells and is called a ‘niche’.
Use of Animal Cells and Display Methods for the Production of Human Monoclonal Antibodies
Authors: Tomimatsu Kosuke , Teruya Kiichiro , Shirahata Sanetaka 
Published: April 2013

Abstract

Human monoclonal antibodies have great potential for use in the treatment of various human diseases. An

in vitro

immunisation protocol using human peripheral blood mononuclear cells (PBMCs) was developed to generate human antigen‐specific antibodies. After antigen sensitisation of PBMCs

in vitro

, B cells producing antigen‐specific antibody can be propagated within a week. Heavy and light chain variable region genes were easily amplified from these

in vitro

immunised PBMCs. After generating a combinatorial phage library, antigen‐specific clones were selected by panning rounds. Next, the variable region genes of heavy and light chains of these selected clones were combined with human IgG constant region genes to produce human IgG‐type antibody in mammalian cells. This

in vitro

immunisation method will be applied widely for the production of human monoclonal antibodies for therapeutics by combination with several display methods.

Key Concepts:

In vitro
immunisation method can be used to induce B cells producing antigen‐specific human monoclonal antibodies from human peripheral lymphocytes.

Phage display method can be used to efficiently generate antigen‐specific human monoclonal antibodies.

The combined use of
in vitro
immunisation and phage display methods is beneficial to efficiently establish recombinant animal cells producing antigen‐specific human monoclonal antibodies from a relatively small library.
Pore‐forming Toxins
Authors: Dalla Serra Mauro , Tejuca Martínez Mayra 
Published: April 2013

AbstractPore‐forming toxins (PFT) are proteins able to produce well‐structured holes in target cell membrane. They have a very broad taxonomic distribution being produced from bacteria to mammals. Depending on the secondary structure of the membrane‐spanning region, these proteins are categorised into two classes: α‐PFT and β‐PFT. The pore structure of representative members of each class will be described. These proteins can be also classified according to their pore structure:barrel‐staveandtoroidalprotein–lipid pore. In thebarrel‐stavepore the protein molecules provide a continuous interface between the core of the bilayer and the channel lumen, whereas in thetoroidalprotein–lipid pore both polypeptide chains and polar phospholipid headgroups are involved in the building of pore walls. The stoichiometry and the pore diameter depend on the protein, thus the channels can allow leakage of ions, adenosine triphosphate (ATP), proteins and even bacteria. Attacked cells trigger different responses, some promoting recovery of membrane integrity, others transition to a low‐energy‐consumption state, in addition to inflammatory responses and changes in gene transcription.Key Concepts:Pore‐forming toxins are proteins produced from bacteria to mammals.Pore‐forming toxins are classified as α‐PFT and β‐PFT, according to the structure adopted by the transmembrane region.Pores are nanometre funnel‐like holes that permit the passage of water, ions and small molecules through cell membranes.PFT form two types of pores, the barrel‐stave and the toroidal protein–lipid pore.Cells react to pore formation, repair the damage and survive.
Capillary Electrophoresis
Authors: Righetti Pier Giorgio , Guttman András 
Published: April 2013

Abstract

Capillary electrophoresis is an electric field‐mediated microseparation technique that utilises narrow‐bore fused‐silica capillaries (10–100 μm) and high applied electric fields (100–1000 V/cm) enabling short analysis times with high separation efficiency and excellent resolution, whereas the narrow bore capillary readily dissipates the generated Joule heat. The main separation modes of capillary electrophoresis are capillary zone electrophoresis (CZE), micellar electrokinetic chromatography (MEKC), capillary isoelectric focusing (cIEF), capillary gel electrophoresis (CGE) and capillary electrochromatography (CEC). As a truly orthogonal method to high‐performance liquid chromatography (HPLC), capillary electrophoresis is recently gaining high importance in the pharmaceutical, biotechnology and biomedical industries, especially for the analysis of protein therapeutics.

Key Concepts:

Capillary electrophoresis (CE) is a truly orthogonal separation method to chromatography‐based techniques.

CE is a fully automated approach to electrophoresis.

The narrow bore capillaries used in CE enable application of high separation voltages without significant heat generation.

Electroendoosmotic flow (EOF) generates a bulk fluid flow within the narrow bore capillary and therefore one of the driving forces of CE analysis.

The main separation modes of CE are: Capillary zone electrophoresis (CZE) separation is based on free solution mobility; micellar electrokinetic chromatography (MEKC) utilises partitioning of hydrophobic analytes within charged micelles; capillary gel electrophoresis (CGE) applies sieving polymers for size separation of macromolecules; and capillary isoelectric focusing (cIEF) separates amphoteric analytes based on their charge states; and capillary electrochromatography (CEC) based on the interplay between electric field and chromatography‐mediated separations.

CE is one of the emerging separation techniques in the biotechnology, biopharmaceutical and biomedical industries.

Microfluidics devices integrate the concept of CE with fluidics sample manipulation such as on chip sample preparation.
Macromolecular Structure Determination: Comparison of X‐ray Crystallography and
NMR
Spectroscopy
Authors: Krishnan VV , Rupp B 
Published: April 2013

Abstract

X‐ray crystallography and nuclear magnetic resonance (NMR) spectroscopy are the most powerful and predominant techniques used to experimentally determine the three‐dimensional structures of biological macromolecules at near atomic resolution. X‐ray diffraction (XRD) studies require a crystalisable protein, whereas NMR is suitable for macromolecules in solution. XRD has no size limitations and provides the most precise atomic detail, whereas information about the dynamics of the molecule may be limited. NMR excels in cases where no protein crystals can be obtained and it provides solution state dynamics, but in turn delivers lower resolution structures and is in general limited to molecular weights below approximately 50 kDa. The two techniques can deliver complementary information. Approximately 90% of the experimentally determined macromolecular structures deposited in Protein Data Bank are crystal structures, with NMR dominating the <10 kDa molecular weight range.

Key Concepts:

XRD and NMR are complimentary structure determination methods.

XRD has no size limitations and provides the most precise atomic detail, whereas information about the dynamics of the molecule may be limited.

NMR excels in cases where no protein crystals can be obtained and it provides solution state dynamics, but in turn delivers less detail and in general practice is limited to molecular weights below approximately 50 kDa.
Bergström, Sune
Authors: Ljungström Olof , Normark Daniel 
Published: April 2013

Abstract
Sune Bergström (1916–2004) was a Swedish biochemist and Nobel Prize laureate (1982) for his work on the compounds known as prostaglandins widely distributed in living organisms. Other work dealt with the biosynthesis and metabolism of bile acids. Bergström was dean during1963–1966 and president 1969–1977 of the Karolinska Institutet in Stockholm and chairman of both the board of the Nobel Foundation 1975–1987 and WHO Advisory Committee on Medical Research 1977–1982.
Calorimetry
Authors: Emerson Joseph P , Le Vu H , Lewis Edwin A 
Published: April 2013

AbstractIn biology, particularly in studies relating the structure of biopolymers to their functions, two of the most important questions are: (1) how tightly does a small molecule bind to a specific interaction site? and (2) if the small molecule is a substrate and is converted to a product, how fast does the reaction take place? Because almost any chemical reaction or physical change is accompanied by a change in heat or enthalpy, an isothermal titration calorimeter is an ideal instrument to measure either how much of a reaction has taken place or the rate at which a reaction is occurring. In contrast to optical methods, calorimetric measurements can be done with reactants that are spectroscopically silent (a chromophore or fluorophore tag is not required), can be done on opaque, turbid or heterogeneous solutions (e.g. cell suspensions) and can be done over a range of biologically relevant conditions (temperature, salt, pH,etc).Key Concepts:Almost all chemical reactions are accompanied by a change in heat or enthalpy.Calorimetry can determine the complete set of thermodynamic parameters that characterise binding reactions, for example K, ΔG°, ΔH°, ΔS° and ΔCp.Binding reactions are typically pH, salt and temperature dependant.
Protein Structure Prediction
Authors: Roy Ambrish , Zhang Yang 
Published: April 2013

Abstract

The goal of protein structure prediction is to estimate the spatial position of every atom of protein molecules from the amino acid sequence by computational methods. Depending on the availability of homologous templates in the PDB library, structure prediction approaches are categorised into template‐based modelling (TBM) and free modelling (FM). While TBM is by far the only reliable method for high‐resolution structure prediction, challenges in the field include constructing the correct folds without using template structures and refining the template models closer to the native state when templates are available. Nevertheless, the usefulness of various levels of protein structure predictions have been convincingly demonstrated in biological and medical applications.

Key Concepts:

Evolution is a general principle to guide protein structure and function predictions.

Proteins of similar sequence have similar 3D structure.

Function of protein is decided by the 3D structure.

TBM using homologous templates has the highest accuracy.

Template structure can be refined by combining multiple templates.

Current physics‐based
ab initio
folding can only fold small proteins.

Threading is an efficient tool for detecting distantly homologous templates.

Membrane protein structure prediction is challenging due to the lack of templates.

Disordered regions exist in protein which does not possess stable structure but has important function implications.
History of Cancer Research
Authors: Morange Michel 
Published: April 2013

AbstractHistory of cancer research has always been closely linked with the history of biology. The rise of the cell theory in the middle of the nineteenth century led to a unified conception of cancer, and to a dramatic change in the description of this disease, as well as in its diagnosis and prognosis. Cancer research has been revitalised during the last three decades through the development and transformations of molecular biology. Cancer results from the accumulation of mutations in oncogenes (genes stimulating cell proliferation) and tumour‐suppressor genes (genes limiting cell growth). At least six mutations are necessary for the formation of a tumour. Drugs specifically targeted against these molecular actors of cancer are progressively finding their place in chemotherapy. Simultaneously, new systemic and evolutionary visions of cancer are slowly emerging.Key Concepts:Cancer has always been at the forefront of biological research.Molecular biology has profoundly transformed the vision of cancer.A succession of somatic mutations is required for the formation of a tumour.Drugs specifically targeted against the products of oncogenes are progressively entering into clinics.The growth and expansion of a tumour is seen now as an evolutionary process.In systems biology, cancer is seen as a new functional state of the cell.Epigenetic modifications might play a role in the formation of tumours.The role of cancer stem cells in the development of tumours is still discussed.