bluuebunny/crossref_metadata_2025 huggingface dataset:
Moderate topsoil erosion rates constrain the magnitude of the erosion-induced carbon sink and agricultural productivity losses on the Chinese Loess Plateau
Authors: Zhao J. , Van Oost K. , Chen L. , Govers G.
Published: September 2015

Abstract. Despite a multitude of studies, erosion rates as well as the contribution of different processes on Chinese Loess Plateau (CLP) remain uncertain. This makes it impossible to correctly assess the impact of conservation programs and the magnitude of the erosion-induced carbon sink. We used a novel approach, based on field evidence, to reassess erosion rates on the CLP before and after conservation measures were implemented. Our results show that the current average topsoil erosion rate is 3–9 times lower than earlier estimates suggested: most sediments are mobilised by gully erosion and/or landsliding. Under 2005 conditions, the combination of topsoil erosion, gully erosion and landslides mobilised 0.81 ± 0.23 Gt yr−1 of sediments and 4.77 ± 1.96 Tg yr−1 of soil organic carbon (SOC): the latter number sets the maximum magnitude of the erosion-induced carbon sink, which is ca. 4 times lower than other recent estimates suggest. The sediment fluxes we calculate are consistent with sediment yields measured in the Yellow River. The conservation programs implemented from the 1950s onwards reduced topsoil erosion from 0.51 ± 0.13 to 0.30 ± 0.08 Gt yr−1 while SOC mobilisation was reduced from 7.63 ± 3.52 to 4.77 ± 1.96 Tg C. Prior to 1950, a geomorphological equilibrium existed whereby the amount of sediment and carbon exported to the Bohai sea was similar to the amount of sediment eroded on the CLP, so that the erosion-induced carbon sink nearly equalled the amount of mobilised SOC. Conservation efforts and reservoir construction have disrupted this equilibrium and most eroded sediments and carbon are now stored on land where part of the SOC may decompose, thereby potentially lowering the strength of the erosion-induced carbon sink. Despite the fact that average topsoil losses on the CLP are still relatively high, the current level of topsoil erosion on the CLP is no major threat to the agricultural productivity of the area, mainly because fertilizer application has dramatically increased since 1980. Assessing the human impact on agricultural ecosystems at larger scales requires a careful identification and quantification of the processes involved: by doing so for the CLP we have shown that current perceptions regarding the intensity of soil erosion and its effects (both negative and positive) need to be revised.
Subsurface flow mixing in coarse, braided river deposits
Authors: Huber E. , Huggenberger P.
Published: September 2015

Abstract. Coarse, braided river deposits show a large hydraulic heterogeneity at the metre scale. One of the main depositional elements found in such deposits is a trough structure filled with open-framework–bimodal gravel couplet cross-beds. Several studies investigated the impact of the highly permeable open-framework gravel texture mainly in terms of concentration breakthrough curves. However, although the trough fills are expected to be significant mixing agents for the subsurface flow, their impact on the three-dimensional flow field has not draw much attention. This study aims to evaluate the subsurface flow mixing caused by overlapping trough fills embedded in a poorly-sorted gravel matrix. Below the river bed of the Tagliamento River (northeast Italy), trough fills were identified with ground-penetrating radar (GPR) probing. Based on field observations of coarse, braided river deposits, a simple three-dimensional geometrical model with associated hydraulic properties was fitted to the interpreted GPR reflectors. Then, steady-state subsurface flow and advective transport simulations were performed on the small-scale, high-resolution model (size: 45 m × 50 m × 10.26 m). The impact of trough fills on the flow field is visualised by the injection of a conservative tracer at three different depths.
Burning management in the tallgrass prairie affects root decomposition, soil food web structure and carbon flow
Authors: Shaw E. A. , Denef K. , Milano de Tomasel C. , Cotrufo M. F. , Wall D. H.
Published: September 2015

Abstract. Root litter decomposition is a major component of carbon (C) cycling in grasslands, where it provides energy and nutrients for soil microbes and fauna. This is especially important in grasslands where fire is a common management practice and removes aboveground litter accumulation. In this study, we investigated whether fire affects root decomposition and C flow through the belowground food web. In a greenhouse experiment, we applied 13C-enriched big bluestem (Andropogon gerardii) root litter to intact tallgrass prairie soil cores collected from annually burned (AB) and infrequently burned (IB) treatments at the Konza Prairie Long Term Ecological Research (LTER) site. Incorporation of 13C into microbial phospholipid fatty acids and nematode trophic groups was measured on six occasions during a 180-day decomposition study to determine how C was translocated through the soil food web. Results showed significantly different soil communities between treatments and higher microbial abundance for IB. Root decomposition occurred rapidly and was significantly greater for AB. Microbes and their nematode consumers immediately assimilated root litter C in both treatments. Root litter C was preferentially incorporated in a few groups of microbes and nematodes, but depended on burn treatment: fungi, Gram-negative bacteria, Gram-positive bacteria, and fungivore nematodes for AB and only omnivore nematodes for IB. The overall microbial pool of root litter-derived C significantly increased over time but was not significantly different between burn treatments. The nematode pool of root litter-derived C also significantly increased over time, and was significantly higher for the AB treatment at 35 and 90 days after litter addition. In conclusion, the C flow from root litter to microbes to nematodes is not only measurable, but significant, indicating that higher nematode trophic levels are critical components of C flow during root decomposition which, in turn, is significantly affected by fire management practices. Not only does fire affect the soil community and root decomposition for Konza Prairie LTER soils, but the lower microbial abundance, greater root turnover, and the increased incorporation of root litter C by microbes and nematodes for AB suggests that tallgrass prairie management through annual burning increases root litter-derived C flow through the soil food web.
The Acquisition of Preposition Stranding and Pied Piping in Interrogatives by Arab Jordanian EFL Speakers
Authors: Almahammed Yazan Shaker , Ariff Tun Nur Afizah Zainal , Sidek Harison Hanisa Mohd
Published: September 2015

The current study aimed primarily at investigating the acquisition of preposition stranding and pied piping by Jordanian EFL speakers. As secondary purposes, the study attempted to supply convincing accounts for the occurrence of preposition stranding and pied piping based on previous literature carried out on this area of language. The study also sought to show any instances of Null preposition phenomenon as acquiring preposition stranding and pied piping. In collecting the data needed for the study, grammaticality judgment and correction task was employed. The task consisted of 21 sentences; 15 of which were incorrect as a result of absence of prepositions and 6 were correct. 355 Jordanian EFL students from ten universities took part in this study. The results of the study indicated that, there were no statistical significant difference between the use of preposition stranding and pied piping among the respondents. More specifically, the respondents produced nearly equal rates of preposition stranding and pied piping. In addition, the results showed that transfer from Arabic is the best possible account for use of pied piping since both Arabic and English permit pied piping in interrogative clauses. In contrast, the frequent emergence of preposition stranding can be justified by salience factor. Lastly, the results revealed a strong evidence for the presence of Null preposition in the language of Jordanian EFL speakers. 
Cognitive Enhancement and Anthropotechnological Change
Authors: Lemmens Pieter ,   Philosophy Documentation Center
Published: September 2015

Abstract: This article focuses on cognitive enhancement technologies (CET) and their possible anthropological implications, and argues for a reconsideration of the human-technology relation so as to be able to better understand and assess these implications. Current debates on cognitive enhancement (CE) consistently disregard the intimate intertwinement of humans and technology as well as the fundamentally technogenic nature of anthropogenesis. Yet, an adequate assessment of CET requires an in-depth and up-to-date re-conceptualization of both. Employing insights from the work of Bernard Stiegler, this article proposes an organology and pharmacology of CE. What is typical about new CET is their interiorizing nature, which can be expected to fundamentally reshape organological configurations. Starting from the premise that CE is a phenomenon that predominantly unfolds within the current conjuncture of cognitive capitalism, I will present the issue of cognitive proletarianization as being of crucial importance for considering CE. I conclude by providing some methodological guidelines for the development of a positive pharmacology of CET and by suggesting that CET should be considered as technologies of the self sensu Michel Foucault.
Acute‐Phase Proteins
Authors: Raynes John G
Published: September 2015

Acute‐phase proteins (APPs) form part of the systemic acute‐phase response which accompanies inflammation. Their primary site of synthesis is the hepatocyte in response to interleukin‐6 and other inflammation‐associated cytokines. Clinically, APPs such as C‐reactive protein provide a useful indicator of the extent of inflammation responding most intensely in severe cases such as sepsis, but showing some response in even mild inflammatory insults or stress. Functions of APPs are still poorly defined but are largely homeostatic and diverse including innate protective immune roles, transport functions, protease inhibition, clotting and metabolic functions. Hepatocytes upregulate secretory pathway networks to allow an increased synthetic activity, although some proteins are actively downregulated. Evidence has mounted to show the importance of APPs for protection of the host.

Key Concepts

Acute‐phase proteins are increased in response to inflammatory stimuli within 12–72 h.

Functions include direct innate recognition, innate immune response in control of inflammation and immunity, transport of a variety of metabolic and micronutrient factors, enzymes and proteins involved in clotting and thrombosis and so on.

Hepatocytes are the main source of acute‐phase proteins.

Induction is mainly through transcriptional control through STAT3 and other factors.

Concentrations return to normal when inflammation subsides and thus they provide a useful rapidly responding clinical marker of inflammation.

Some proteins have increased synthesis to replace that consumed (e.g. complement or clotting components) others are required to fulfil new requirements (e.g. lipocalin‐2).

The acute‐phase proteins should be viewed as an important part of the overall systemic response to inflammation (acute‐phase response).
Complement: Classical and Lectin Pathways
Authors: Thielens Nicole M , Gaboriaud Christine , Thiel Steffen
Published: September 2015

The classical and lectin pathways of complement are major recognition systems of innate immunity that are found in mammals and other animal species. By means of several multimolecular proteases, each comprising a recognition protein and a protease component, pathogens and other targets are detected and thereby trigger proteolytic reactions. The classical pathway is initiated by C1, a complex of the recognition molecule C1q and two associated enzymes, C1r and C1s, whereas the lectin pathway is initiated by carbohydrate recognition molecules (mannan‐binding lectin (MBL) or one of the three ficolins or collectin‐LK) in complex with another set of enzymes, MBL‐associated serine proteases (MASPs). Both pathways converge to the formation of C3 convertase, a complex protease that cleaves C3, the central component of the complement system. Proteolytic cleavage of C3 generates a series of fragments and elicits various effector mechanisms, including inflammation and phagocytosis. These mechanisms contribute to the elimination of pathogenic microorganisms and altered host cells from blood and tissues and modulate the adaptive immune response.

Key Concepts

C1q, MBL, CL‐LK and ficolins are pattern‐recognition molecules able to sense motifs on pathogens and altered self‐cells.

C1q is a major sensor of apoptotic cells and regulator of immune tolerance.

Proteolytic cleavage of C3 is pivotal for amplification of the complement response and labelling of the target particles.

Target recognition, proteolysis and complex formation generate conformational changes that underlie complement functioning.

Complement activation and activity are tightly regulated to avoid noxious side‐effects on normal host cells and tissues.
Inflammatory Mediators
Authors: Alvine Travis D , Knopick Peter L , Nilles Matthew L , Bradley David S
Published: September 2015

Cytokines and chemokines are soluble inflammatory mediators that are naturally produced during an inflammatory response. The type of immune response (pro‐ or anti‐inflammatory, cell mediated or humoral) elicited by these molecules largely depends on the initial cytokines released in response to bodily injury or pathogen invasion. The characteristic signs of inflammation: redness, swelling, heat and pain are the result of coordinated, intricate signalling responses by these soluble mediators that primarily facilitate cellular infiltration to the site of infection. The nature of the immune response is further complicated by the fact that several cytokines can promote both pro‐ and anti‐inflammatory responses. Although cytokines and chemokines are often effective at resolving inflammation, aberrant cytokine and chemokine signalling have been shown to contribute to many autoimmune diseases.

Key Concepts

Fine‐tuned immune signalling is critical for resolution of potentially harmful stimuli.

Inflammatory mediators are the molecules responsible for immunological homeostasis.

Cytokines and chemokines link the innate and adaptive immune systems.

Inflammatory mediators regulate physiological processes distinct from the immune system.

Cytokines and chemokines are powerful signalling proteins.

Arachidoic acid is synthesised into prostaglandins and leukotrienes.

Activation of the complement system yields anaphylatoxin production.
Hepatitis
E
Virus
Authors: Lhomme Sebastien , Abravanel Florence , Chapuy‐Regaud Sabine , Dubois Martine , Mansuy Jean‐Michel , Peron Jean‐Marie , Alric Laurent , Rostaing Lionel , Kamar Nassim , Izopet Jacques
Published: September 2015

The hepatitis E virus (HEV) infection is a worldwide disease. HEV is usually responsible of an acute self‐limiting infection, but pregnant women and patients with preexisting liver disease can suffer from severe forms. HEV infections can lead to chronic hepatitis and cirrhosis in immunocompromised patients. Extrahepatic manifestations can also occur. In developing countries, HEV is transmitted via contaminated water. In developed countries, transmission is zoonotic due to consumption of uncooked or undercooked infected meat and direct contact with infected animals. Transfusion‐transmitted HEV infections were also described. HEV infections are diagnosed by detecting anti‐HEV antibodies in the serum. In immunocompromised patients, detecting HEV RNA in the blood or faeces is needed. A 3‐month course of ribavirin is effective for treating chronic infection: a sustained virologic response occurs in 78% of patients. Vaccine has been recently licensed for use in China and provides protection against hepatitis E for up to 4.5 years.

Key Concepts

The hepatitis E virus infection is a worldwide disease.

Animal reservoir is responsible for autochthonous HEV infection in developed countries.

Chronic infections are possible in immunocompromised patients.

Treatment of choice for chronic HEV infections is a 3‐month course of ribavirin.

Vaccine afforded a sustained protection.
Picornaviruses
Authors: Rowlands David J
Published: September 2015

The name picornavirus is derived from
pico
for small and ribonucleic acid (RNA), denoting the chemical nature of the genome. Virions are nonenveloped icosahedral particles approximately 30 nm in diameter. The capsid is constructed from 60 copies of each of four structural proteins, which account for 70% of the particle mass and enclose the single‐strand genome of 7500–8500 nucleotides. The positive‐strand genome acts directly as a messenger RNA to template a single polyprotein product. This is subsequently processed by virally encoded proteases into mature active proteins. Several intermediate products have distinct functions to the final fully processed proteins. Replication of the genome is initiated by an uridylated peptide and proceeds via a negative‐strand intermediate template. Picornaviruses are among the smallest pathogens of vertebrates and are responsible for many important diseases in humans and animals.

Key Concepts

There are effective vaccines against polio, hepatitis A and foot‐and‐mouth disease viruses. In addition, movement control and slaughter is used to control foot‐and‐mouth disease. There are no licensed drugs for picornavirus infections.

Genome sequence comparisons have replaced biological and biophysical comparisons as the bases for classification within the family.

Picornavirus particles comprise 60 copies each of four structural proteins, which form a quasi‐T1 icosohedral capsid encasing the single‐strand RNA genome.

The picornavirus RNA genome functions as a messenger RNA to template the synthesis of a single polyprotein, which is posttranslationally processed by viral proteases.

Picornaviruses bind to cell‐specific surface receptors, and this interaction is an important factor in determining host and tissue specificity of each virus.

Picornaviruses cannot gain entry to cells by membrane fusion, as is the case for enveloped viruses, and require special mechanisms to breach cellular membranes and safely deliver the genome into the host cell.

Genome replication occurs in association with virus‐modified cellular membranes. Viral RNA templates complementary negative‐strand molecules, which in turn template multiple positive‐strand copies. The synthesis of all RNA molecules is initiated by an uridylated peptide primer.

The mechanisms of transmission of infection play key roles in the epidemiology of picornavirus infections.

Picornaviruses are responsible for a wide range of clinical diseases resulting from multiple factors such as receptor specificity, tissue‐specific susceptibility, virulence and the mechanisms of transmission.
Neutrophils
Authors: Borregaard Niels
Published: September 2015

Production of neutrophils occupies almost two third of the activity in bone marrow. Production and release are governed by the level of granulocyte‐colony‐stimulating factor and by chemokines that provide either retention signals or release signals. Circulating neutrophils are directed to sites of infection by endothelial cells in postcapillary venules at sites of infection. The endothelial cells capture by‐passing neutrophils and guide the neutrophils across the endothelial cell layer. The neutrophils then migrate towards the invading microbes guided by signals produced by the microbes and sensed by the neutophils. Killing of microbes takes place largely in a phagocytic vacuole created by uptake of the microbes and fusion of granules with the membrane surrounding the microbes taken up. Here, killing is effectuated by granule proteins and by bactericidal reactive oxygen metabolites created by the neutrophil respiratory burst activity. Thereafter, the neutrophil may undergo apoptosis and become phagocytosed by macrophages or undergo NETosis with extrusion of nets of DNA that may limit bacterial spread.

Key Concepts

Production of neutrophils is quantitatively the most important activity in the bone marrow.

Endothelial cells that are activated by local infection/inflammation capture by‐passing neutrophils and guide them to the site of infection.

Bacteria are taken up by neutrophils into a phagocytic vacuole created by the plasma membrane which wraps around the ingested microbes and fuses with granules.

Killing is effectuated by a combination of exposure of microorganisms to highly reactive oxygen species generated by neutrophils in the phagocytic vacuole and by bactericidal proteins stored in granules and liberated to the phagocytic vacuole.

Death of neutrophils by apoptosis regulates the production of neutrophils by a feedback loop that tunes production of G‐CSF according to the rate of apoptosis.

Death by NETosis involves extrusion of DNA associated with antimicrobial peptides. This may provide defence against spread of microorganisms.
Antigen Processing
Authors: Gardiner Gail J , Deffit Sarah N , Blum Janice S
Published: September 2015

Antigen presentation is an important mechanism by which the immune system recognises infection and maintains self‐tolerance. In order to effectively present antigens to T lymphocytes, intracellular enzymes degrade antigenic macromolecules into short fragments, which then bind major histocompatibility complex class I and class II molecules, or alternatively nonpolymorphic major histocompatibility complex class Ib molecules. This process of fragmentation is known as antigen processing and is shaped by the specificity of the enzymes involved as well as the intracellular compartments where processing takes place. Key players in antigen processing include cytoplasmic enzymes such as the proteasome and calpain, as well as cysteine cathepsins, aspartyl proteases, NADPH oxidase and GILT, which all reside in acidic vacuolar compartments. The trafficking of antigens to different intracellular compartments influences the sequence of processing and the selection of antigenic epitopes, which are displayed on the cell surface to promote immune activation or tolerance.

Key Concepts

Trafficking of antigens into proper compartments affects the degradation and availability of epitopes for both MHC‐I and MHC‐II presentation.

Proteasome activity affects MHC‐I peptide generation and endogenous cytoplasmic peptide generation for MHC‐II.

ROS production by NADPH oxidase can affect MHC‐I cross‐presentation and MHC‐II presentation.

Cathepsin activity, which is regulated by endosomal pH, generates peptides for MHC‐I cross‐presentation and MHC‐II presentation.

The reduction of disulphide bonds by GILT affects availability of epitopes for MHC‐II presentation.

While homologous to MHC‐I, nonclassical MHC‐Ib acquire antigens processed in acidic compartments much like MHC‐II.
Immunodeficiency, Primary: Affecting the Adaptive Immune System
Authors: Vihinen Mauno
Published: September 2015

Primary immunodeficiency (PID) is an intrinsic defect of the immune system. Patients with PID have increased susceptibility to recurrent and persistent infections, and they may also have autoimmune and cancer‐related symptoms. PIDs are mainly rare hereditary disorders of the immune system which often have serious consequences. Infections are the hallmarks of PIDs. Clinical descriptions have already been made for about 250 PIDs, for which approximately 200 genetic aetiologies have been described. There are several different mechanisms behind PIDs. Some PIDs affect T‐ or B‐cell functions, and when both cell types are affected, it leads to severe combined immunodeficiencies (SCIDs). Other PIDs affect major histocompatibility complex, antibody production, lymphocyte apoptosis, phagocytosis, complement cascade or the innate immune system. PIDs are a constantly growing group of mainly rare diseases that help to understand how the complex immune system is composed, acting and regulated.

Key Concepts

Adaptive immunity is a specific and long‐lasting response of lymphocytes to antigens.

Combined immunodeficiency affects both B and T cells.

Lymphocytes are white blood cells including B and T cells.

Signal transduction is a process by which a cell converts one kind of signal or stimulus into another. In a signalling cascade, an extracellular signal interacts with a cell surface receptor, which leads to a change in the level of a second messenger and ultimately a change in the cells functioning.
Typing for Transplantation Antigens and Their Genes
Authors: Briggs David , Jobson Shirley
Published: September 2015

Safe and effective clinical transplantation requires human leucocyte antigen (
HLA
) typing of donors and recipients. Various immune diseases are associated with particular
HLA
types and
HLA
typing can be of diagnostic value. Finally,
HLA
typing is used increasingly in peptide vaccine design for cancer treatment.
HLA
typing is now carried out at the
DNA
level, which allows testing ranging from high resolution (i.e.
DNA
sequencing) to low resolution (which defines broadly related allele groups). The clinical application dictates the required resolution and therefore the method. Successful haematopoietic stem cell transplantation usually depends on exact
HLA
matching and therefore the higher resolution of testing, while for solid organ transplantation, lower resolution testing is generally sufficient. Current
DNA
testing methods rely on a polymerase chain reaction stage to either generate target
DNA
for analysis or generate sufficient specific
DNA
to detect directly. A systematic nomenclature for
HLA
has been developed and refined to account for the different methods of testing and the extreme genetic variability of the
HLA
system. The latest approaches to
HLA
typing use next generation sequencing (
NGS
) and, although not yet in widespread use in H&I laboratories, these may well provide definitive HLA typing for all applications in the near future.

Key Concepts

There are two classes of HLA with multiple members of each class (A, B and C for Class I and DR, DQ and DP for Class II).

HLA proteins are determined by the most polymorphic genes in humans – over 12 000 known alleles that determine nearly 9000 genetically different proteins (allotypes).

An HLA allele is defined by its entire DNA sequence. There is much sharing of certain polymorphic sequences between different alleles.

HLA nomenclature is complex but systematic.

Serological typing, the first approach used for HLA, discriminates alleles poorly because of the lack of a full range of antibodies.

Rapid HLA typing is currently best achieved using allele‐specific PCR, whereby DNA primers are used to discriminate between selected sequences in different alleles.

Typing using DNA probes to discriminate between sequences in different alleles is cost‐effective for large‐scale clinical testing.

The highest resolution of HLA typing requires genomic DNA sequencing.

Low‐resolution typing can give ambiguous results in heterozygotes (i.e. various allele combinations).
Complement: Measurement
Authors: Morgan Bryan Paul
Published: September 2015

Complement comprises more than 30 proteins present in plasma, other biological fluids and on cell surfaces that collaborate in the host defence against infection. The components of the pathway interact in a sequential manner to efficiently label pathogens; self‐cells are protected by plasma and membrane regulators, and cells bind and respond to products of activation through specific membrane receptors. Measurement of complement components, activation products and activity can be clinically useful in several situations: first, where there is a suspicion of a complement deficiency; second, where complement activation is suspected in a disease and third, to monitor effect of a therapeutic intervention on complement activation or activity. This article describes methods for measuring levels of complement proteins, activation products and complement activity in biological fluids and discusses recent developments in the field. In particular, the interindividual variability in complement activity is described and the relevance of this inherited ‘complotype’ on disease susceptibility discussed. The advent of effective anticomplement drugs, already in clinical use in several disease areas, opens a new area in which effective measurement of complement will be an essential requirement.

Key Concepts

Correct sample collection and storage is essential for effective measurement of complement.

Functional assays of complement haemolytic activity provide the best screen for suspected deficiencies.

Immunochemical measurement of circulating complement components and activation fragments can be performed by commercial assays, nephelometric, turbidimetric or ELISA.

Pathway‐specific and individual component‐specific functional assays of complement activity are required to detect deficiencies that do not affect immunochemical levels.

Functional complement assays are highly dependent on the choice of target cell and buffer composition, particularly the presence of calcium and magnesium ions.

Modern structural analyses and biosensor assays allow an in‐depth analysis of the affinity and kinetics of complement component interactions that reveals the impact of mutations and polymorphisms.

National and international quality control of complement assays has been lacking in the past and is required for meaningful interlaboratory comparisons.
Eosinophilia and the Hypereosinophilic Syndrome
Authors: Hsieh Fred H
Published: September 2015

The eosinophilic granulocyte is involved in the pathogenesis of diverse inflammatory processes, some of which may be beneficial to the host, such as in host defence against parasitic infection, and others are implicated in disease. In addition to being associated with allergic and atopic disease, eosinophilia can be seen in multiorgan system disorders, such as with rheumatologic and hematologic diseases, and can also be associated with single‐organ system disease involving the lungs, the heart, skin and soft tissues, and the gastrointestinal tract. Hypereosinophilia is characterised by the prolonged elevation of the peripheral blood eosinophil count, and the hypereosinophilic syndrome (HES) refers to a group of disorders marked by hypereosinophilia with multisystem target organ damage. The molecular pathogenesis of selected clonal and secondary HESs has been identified, and recognition of specific molecular defects can help to guide specific treatment approaches.

Key Concepts

The eosinophil is a myeloid lineage granulocyte derived from the hematopoietic stem cell.

Interleukin‐5 is the key cytokine involved with eosinophil lineage commitment, development, expansion, homing and activation.

Eosinophils produce a diverse array of mediators but there are at least four specific mediators unique to eosinophils – eosinophil cationic protein, eosinophil‐derived neurotoxin, eosinophil peroxidase and major basic protein.

A vast array of human diseases is associated with eosinophilia, including single‐organ system involvement and multisystem involvement.

The hypereosinophilic syndrome (HES) is defined by having a peripheral blood eosinophilia >1500 cell/μL for at least 1 month, with evidence of eosinophil‐dependent target organ damage, and all other aetiologies of eosinophilia excluded.

The myeloproliferative variant HES is characterised by abnormal PDGFRA signalling and is markedly sensitive to tyrosine kinase inhibitors targeting PDGFRA.

The lymphocytic variant HES is a reactive eosinophilia driven by clonal, nonmalignant T cells with abnormal immunophenotype secreting high concentrations of eosinophilpoietins such as IL‐5.
Atopy and Asthma
Authors: Yates Anne B , deShazo Richard D
Published: September 2015

Atopy is the genetic propensity to develop an immunoglobulin E antibody response to common allergens. The most common clinical manifestations of atopy are allergic rhinitis, asthma and atopic dermatitis. Asthma is a complex disorder of the airways, involving airway hyperresponsiveness, airflow obstruction that is at least partially reversible, and inflammation of the airways. Although atopy has been identified as the strongest predisposing factor for the development of asthma, not all asthma is allergic in nature. The overall prevalence of asthma has been increasing worldwide for the last few decades, and continues to increase globally. Guidelines for the evaluation and treatment of asthma were developed in the early 1990s, and are revised periodically as research into effectiveness of available medications emerges, and development of new therapies arise.

Key Concepts

Immunoglobulin E (IgE), produced by atopic individuals, plays a key role in allergic disorders, with atopic asthma being a prime example of IgE‐mediated inflammation.

Asthma is a common but complex disorder of the airways, involving variable and recurrent symptoms, airway obstruction, inflammation and bronchial hyperresponsiveness.

Symptoms of asthma include coughing, wheezing, shortness of breath and feelings of chest tightness or pain with breathing.

Numerous comorbidities may complicate and exacerbate asthma.

Onset of asthma usually begins early in life, although adult‐onset of asthma may occur.

Genetic predisposition and environmental factors play a role in the development of asthma.

The diagnosis of asthma depends on the appropriate historical symptoms, physical examination, objective measurement of lung function and response to bronchodilator.

Treatment of asthma centres around control of chronic inflammation, avoidance of triggering factors and treatment of acute bronchospasm when needed.

Asthma severity is stratified based on factors regarding symptom frequency and severity, occurrence of nocturnal symptoms, frequency of short‐acting beta‐agonist use, interference with normal activity and objective measurement of pulmonary function. Risk assessment includes frequency of systemic corticosteroid use, and frequency and severity of asthma exacerbations.

Individuals over 65 may have a decreased perception of breathlessness and air hunger. Therefore, the use of clinical symptoms to diagnose and treat seniors may underestimate the severity of airways obstruction.
C
uvier,
G
eorges
Authors: Rudwick Martin JS
Published: September 2015

Georges Cuvier (1769–1832) was a distinguished French comparative anatomist, palaeontologist and civil servant. He defined major groups of animals (now
phyla
) with distinct kinds of anatomy; he showed that many fossil vertebrate species are distinct from any known alive, and he thereby helped establish the reality of extinction as a natural process; and he pioneered the reconstruction of individual fossil species and of the history of life as a whole. He regarded the origins of species and episodes of mass extinction as natural events, but was reluctant to speculate on their causes.
Ageing and the Immune System
Authors: Aspinall Richard , Lang Pierre Olivier
Published: September 2015

Recognising invading foreign organisms, preventing their spread and ultimately clearing them from the body throughout life is the central role of the immune system. In a healthy adult, the immune system is composed of approximately 10
12
cells which interact with each other to produce both effector molecules and cells which defend the tissues of the body against potential pathogens.

Unfortunately, like all biological systems, there is normal wear and tear, and with advancing age, the immune system shows a gradual loss of function. However, because each individual differs in their genetic makeup and has been exposed to a different range of environmental factors, this functional decline is not uniform and predictable. There is no certain age at which this process begins and no defined pathway or identifiable sequence of loss of function. The result is considerable variation within the aged population in the ability of an individual to respond productively to potential pathogens and vaccines. Current work is directed at mapping the changes in the immune system with age with a view to identifying any common triggers of deterioration in function. This in turn might lead to an opportunity to reverse the degradation process and thus to extend the period of fully effective protection.

Key Concepts

Low‐grade systemic inflammation is a feature which characterises the ageing process in many individuals.

Evidence from epidemiology studies shows that the susceptibility to infectious diseases increases with age.

Studies on responses to vaccines reveal that many older individuals fail to produce the responses seen in younger individuals, which is associated with protection from the disease.

Some change in the function of cells of the innate immune system (NK cells, neutrophils, macrophages and dendritic cells) has been noted in a number of older individuals.

All older individuals show an accumulation of fat in the primary lymphoid organs, which is associated with functional decline and a reduction in their ability to produce new lymphocytes.

The thymus atrophies with age, and there is a reduction in the areas of active thymopoeisis and in the output of naïve T cells.

The area of active (red) bone marrow declines with age, and the number of naïve B cells emerging from the marrow shows a reduction with age.

A successful T cell‐mediated immune response results in the generation of both T and B memory cells, and as survival depends on successful responses, there is an increase in the number of memory cells with age.

Infections with persistent viruses such as the human herpes virus group can lead to the expansion of specific clones amongst which are cells at, or close to, their replicative limit.

The expansion of some clones within the memory cell pool may also be linked with the loss of other clones and the appearance of ‘holes’ in the repertoire.
Hereditary Breast Cancer Syndromes: Molecular Pathogenesis and Diagnostics
Authors: Vos S , Van der Groep P , Van der Wall E , Van Diest Paul J
Published: September 2015

Breast cancer is a major cause of morbidity and mortality worldwide. Approximately, 20% of breast cancer cases are due to a familial predisposition. Most of these familial breast cancers are due to mutations in well‐known genes linked to breast cancer, such asBRCA1,BRCA2,TP53,CHEK2,PTEN,CDH1,STK11/LKB1,RAD50,BRIP1andPALB2. Some of these cancers are, however, due to (a combination of) mutations in lower penetrance genes or some cancers show no relationship with known susceptibility genes. In this article, we describe the function of recently known breast cancer susceptibility genes, the molecular pathogenesis and the histopathology of these hereditary breast cancer syndromes. This may provide a better understanding and classification of hereditary breast cancer and may offer tools for better diagnosis and selection of patients sensitive to specific targeted therapies.

Key Concepts

Breast cancer is the most frequent cancer diagnosed in women worldwide.

In 5–10% of total breast cancer cases, there is familial breast cancer susceptibility.

Hereditary breast cancer is familial breast cancer with a clear Mendelian inheritance pattern.

Breast cancer susceptibility genes can be divided into high‐, intermediate‐ and low‐risk genes, of which the high‐risk genesBRCA1andBRCA2are the best known.

Breast cancer susceptibility genes mostly involve DNA repair mechanisms.

The discovery of breast cancer susceptibility genes has improved our knowledge of breast carcinogenesis, including the morphological, immunohistochemical and molecular characterisation of familial breast cancer.

Moreover, knowledge of the biological processes underlying familial breast cancer offers tools for cancer screening, prevention and management.
Chromosomal Rearrangements in Primates
Authors: Ruiz‐Herrera Aurora
Published: September 2015

Primates are characterised by the non‐specialist nature of their morphological features that, together with the plasticity of their behaviours, have allowed them to exploit a wide variety of ecological niches. The study of the mechanisms involved in karyotype evolution in Primates is fundamental to our understanding of mammalian genome organisation and its role in adaptation. The combined use of comparative genomics and molecular cytogenetics has contributed to the finer dissection of chromosomal rearrangements in Primates, providing new insights into the dynamics of genome reshuffling that characterise this group. These approaches have permitted the characterisation of large‐scale genomic changes (i.e. inversions, fusions, fissions and translocations) as well as the chromosomal regions involved. This has contributed to refine Primate genomic architecture and evolutionary relationships among species. Here the different evolutionary patterns that have been described in Primates will be investigated together with the most plausible hypotheses for ancestral karyotypes that have been inferred for each specific lineage.

Key Concepts

Primates are classified into six major groups: lemurids, lorisids, tarsiers, New‐World monkeys, Old‐World monkeys and apes.

The diversity of Primate species is exemplified by the variety of diploid numbers that characterise the group, ranging from 2n = 16 (i.e.
Callicebus lugens
) to 2n = 72 (i.e. some
Cercopithecus
species).

Comparative chromosomal studies among species are now possible, thanks to the combined use of different methodological approaches such whole‐genome comparative studies and FISH using either whole‐chromosome paintings or DNA‐specific probes.

Chromosomal evolution within Primates is highly intricate, as each major taxonomic group has followed a different pattern of reorganisations.

The family Hominidae, which includes orang‐utans, gorillas, chimpanzee and humans, has suffered few large‐scale chromosomal reorganisations since their common ancestor, most of them being lineage‐specific inversions.

Lesser apes are characterised by an extremely high rate of chromosomal reshuffling, including lineage‐specific fissions, fusions, inversions and translocations.

The group Catarrhini shows a general pattern of moderate rate of chromosomal changes, whereas Platyrrhini represents a highly diverse group with diploid numbers ranging from 2n = 16 in
Callicebus
to 2n = 62 in
Lagothrix
, in which inter‐ and intra‐specific chromosomal reorganisations are abundant.

The general view is that the putative karyotype of the last common ancestor of Primates consists of 50 chromosomes, with the following homologies with human chromosomes: 1, 2p‐q, 2q, 3/21, 4, 5, 6, 7b, 7a/16p, 8, 9, 10p, 10q, 11, 12a/22a, 12b/22b, 13, 14/15, 16q, 17, 18, 19p, 19q, 20, X and Y.
TGF‐β in the Immune Response
Authors: Nakatsukasa Hiroko , Tu Eric , Chia Cheryl Pei Zhi , Chen WanJun
Published: September 2015

Transforming growth factor‐β (TGF‐β) is a highly evolutionally conserved cytokine that is critical for embryogenesis, cancer and matrix formation and immune responses. Three distinct isoforms, TGF‐β1, 2 and 3, are found in mammals. TGF‐β is secreted by immune and nonhematopoietic cells and acts on virtually all cell types through ubiquitously expressed receptors, which transduce the TGF‐β signal through canonical Smad‐dependent pathway and noncanonical Smad‐independent pathways. In particular, TGF‐β plays a crucial role in immune tolerance and maintains immune homeostasis by inhibiting proliferation, differentiation, activation and effector function of immune cells. On the other side of the coin, TGF‐β can display proinflammatory properties, depending on the context. The more complete understanding of the various functions of TGF‐β in the immune system, especially in tolerance, will enable us to design more specific and effective therapies for immune disorders.

Key Concepts

TGF‐β is a multifunctional cytokine that mainly suppresses immune responses to maintain immune homeostasis.

TGF‐β signalling is transduced via not only its unique protein, Smad, but also via Smad‐independent pathways.

T cells are the major targets of TGF‐β in immune system and its activation/proliferation, apoptosis and differentiation are regulated by TGF‐β.

TGF‐β is a key mediator for the regulation of autoimmune diseases.
H
enipaviruses
Authors: Aljofan Mohamad
Published: September 2015

Henipaviruses are the deadliest human pathogens of the
Paramyxoviridae
family. The genus
Henipavirus
includes two closely related, zoonotic, and highly pathogenic paramyxoviruses, Nipah virus (NiV) and Hendra virus (HeV), which cause high morbidity and mortality in animals and humans. There are no approved therapeutics to treat or prevent henipavirus infections in humans. The bat species
Pteropus
are the natural reservoir of henipaviruses, and zoonotic transmission can occur directly or through an intermediate host; horses for HeV and pigs for NiV. The unavailability of a treatment for these infections, the recent detection of HeV antibodies in family pets and the emergence of NiV infections in new geographic areas (Philippines) are an illustration of the risk that these viruses possess and their momentum of becoming a global threat. Unless an effective therapeutic against these viruses is developed, they will continue to emerge and cause significant challenges and threats in the coming years.

Key Concepts

The newly established genus
Henipavirus
of
Paramyxoviridae
family has three members Hendra, Nipah and Cedar viruses.

Fruit bats of the genus
Pteropus
have been identified as the natural reservoir for henipaviruses.

Both Nipah and Hendra viruses are highly pathogenic agents that cause acute encephalitis and respiratory illness with high mortality rate in humans, pigs and horses.

There is no approved therapeutics for the treatment of henipaviruses, and they continue to pose a threat in Australia (Hendra virus) and East and Southeast Asia (Nipah virus) with a great potential to spread beyond these regions.

M 102.4 is an experimental monoclonal antibody that targets the viral entry stage of
Henipavirus
and was proven to treat henipavirus infections in animals.
J
ean
B
rachet (1909–1988)
Authors: Rheinberger Hans‐Jörg
Published: September 2015

This article gives a short account of the work and life of the Belgian molecular embryologist and cytologist Jean Brachet (1909–1988). Jean Brachet was born in Belgium and educated as a physician at the Free University of Brussels. Still while studying, he started to do cytological experiments in the laboratory of Albert Dalcq, looking into the cellular distribution of nucleic acids (DNA (deoxyribonucleic acid) and RNA (ribonucleic acid)). During the 1940s, he established, together with his colleagues Raymond Jeener and Hubert Chantrenne, and under difficult political and material circumstances, the view that RNA is implicated in protein synthesis. Moreover, he identified the cellular granules then called microsomes (today's ribosomes) as the sites of the fabrication of proteins. After the Second World War, he became the leading figure of the Brussels (Rouge Cloître) school of molecular biology. Together with Adrienne Ficq, he developed a potent method of cyto‐autoradiography. On a science policy level, he was instrumental in establishing molecular biology in Belgium and in creating the European Molecular Biology Organization and Laboratory. Throughout his life, Brachet's experimental efforts aimed at understanding organismic development at a molecular level.