bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterochrony
Authors: Horder Tim
Published: April 2013

Heterochrony has often been proposed as a leading mechanism for macroevolutionary change in morphology of organisms, based simply on a relative shift in the timing of events during embryonic development in the evolving organisms. Its most recent formulation was in Gould's ‘clock model’. Such timing shifts were seen as being controlled genetically (by ‘rate genes’) or by hormones (such as thyroxine). Heterochrony has much in common with the concept of allometry. The concept originated in the context of the idea of recapitulation where embryonic development was interpreted as a repetition of the organism's evolutionary history but in accelerated form; deviations from this recapitulation were identified as instances of heterochrony. In a later version used to explain macroevolutionary change (paedomorphosis), a new adult morphology is derived from ancestral larval forms by truncation of ancestral adult stages. However, it is difficult to see how genuine structural novelty can be explained, given that timing changes during development can in themselves do no more than redeploy preexisting characters. The explanatory value of the concept of heterochrony is increasingly questioned; at best it only indirectly relates to, or identifies, specific underlying mechanisms. It is in effect a form of redescription.

Key Concepts:

The extension across time of stages and component events in embryonic development is an inherent feature because development involves a cumulative succession of cell multiplication and differentiative processes, all starting from the single cell stage of the egg.

The controversial concept of heterochrony attempts to characterise a mechanism controlling variations in developmental timing of the embryo or its component parts, which could potentially mediate and explain the evolution of new morphologies.

Neoteny is a paradigm example of heterochrony, in which the adult morphology of a species is thought to be derived from the larval form of an ancestral species whose adult form is lost, perhaps by abandonment of the preexisting developmental events of metamorphosis.

It has been proposed that a heterochronic process such as neoteny could be the basis for major innovations of new taxa (macroevolution); in a form of heterochrony termed paedomorphosis, a new body plan can be established by elaboration of a larval morphology rather than being restricted to modifications to the preexisting adult body plan.
Genetic Load
Authors: Whitlock MC , Davis B
Published: April 2013

Genetic load is the reduction in the mean fitness of a population relative to a population composed entirely of individuals having optimal genotypes. Load can be caused by recurrent deleterious mutations, genetic drift, recombination affecting epistatically favourable gene combinations, or other genetic processes. Genetic load potentially can cause the mean fitness of a population to be greatly reduced relative to populations without sources of less fit genotypes. Mutation load can be difficult or impossible to measure. Many species have mutation rates low enough that substantial genetic load is not expected, but for others, such as humans, the mutation rate may be great enough that load can be substantial. In extremely small populations, drift load, caused by the fixation by drift of weakly deleterious mutations, can threaten the probability of persistence of the population. Migration from other populations adapted to different local conditions can bring in locally maladapted alleles, resulting in migration load.

Key Concepts:

Genetic load is the reduction in mean fitness of a population caused by some population genetic process.

Mutation load is the reduction in fitness caused by recurrent deleterious mutations.

Mutation load may be as great as 95% for the human population.

Drift load is the reduction in mean fitness caused by genetic drift. In extreme cases, deleterious alleles can reach a frequency of one in a population because of genetic drift.

Genetic load can also be caused by recombination breaking up beneficial combinations of alleles, segregation reducing the frequency of fit heterozygotes, or migration bringing less fit alleles into a local population.
Malaria
Authors: Bannister Lawrence H , Sherman Irwin W
Published: April 2013

Malaria is a disease of the blood resulting from infection by protozoan parasites of the genus
Plasmodium
, transmitted by female Anopheline mosquitoes. Five species of
Plasmodium
infect humans,

Plasmodium falciparum

,

Plasmodium vivax

,

Plasmodium ovale

,

Plasmodium malariae

and

Plasmodium knowlesi

. The parasite life cycle includes stages in the mosquito and in human liver cells and red blood cells, which they penetrate and feed on.

Plasmodium falciparum

is the main cause of malaria deaths, especially of young African children. Cerebral malaria, renal and pulmonary failure are major pathologies. Frequent infections gradually confer immunity over several years, but this is rarely complete. Many antimalarial drugs are available for prophylaxis and treatment, but emerging parasite resistance limits their use. Several vaccines are being tested, with some moderate success. Efforts to control malaria include breeding grounds drainage, insecticide sprays and use of insecticide‐impregnated bednets. With the help of several major global initiatives, there are reports of significant reductions of malaria cases.

Key Concepts:

Malaria is a disease caused by infection of red blood cells (erythrocytes) by protozoan parasites of the genus
Plasmodium.

Malaria is a major global disease affecting many millions worldwide and causing up to a million or more deaths a year, mostly children under 5 years in sub‐Saharan Africa.

Malaria is caused by five species of
Plasmodium
, the most lethal being
Plasmodium falciparum
.

Malaria parasites are transmitted to humans by the bite of infected female mosquitoes, and then the parasite multiplies first in the liver and later in the bloodstream before passing back to the mosquito as it feeds.

Malaria has many symptoms, which include cyclic episodes of fever, the frequency depending on malaria parasite species.

Severe malaria is frequently fatal if not treated rapidly.

The pathology of malaria is related to blood infections, either by destroying erythrocytes or by blocking small blood vessels (sequestration) as occurs in cerebral malaria.

Acquired immunity builds up gradually and its maintenance depends on repeated infections; innate immunity is often associated with genetic diseases of the blood.

Numerous antimalarial drugs have been developed including those related to quinine and more recently artmesinin, but parasites have developed resistance to most of these in some parts of the world; several vaccines are now under trial.

Other efforts to control malaria include elimination of mosquitoes and draining their breeding grounds plus the use of insecticide‐impregnated bednets to minimise transmission.
Leishmaniases
Authors: Chang Kwang Poo
Published: April 2013

Leishmaniases are parasitic diseases, which are transmitted by the blood‐sucking sand flies as the vectors. These diseases are largely zoonotic, but considered as anthroponotic in some endemic sites. The reservoir animals include canines, rodents, edentates and other wild animals. A spectrum of clinical manifestations is associated with these diseases, ranging from self‐healing cutaneous lesions to facial mucocutaneous disfiguration to visceralization with fatal consequence. According to the World Health Organisation, there are 12 million cases of these diseases in approximately 90 countries with an annual incidence of approximately 2 million. Treatment of leishmaniases depends on very few drugs for chemotherapy, which are either expensive or toxic and have lost effectiveness due to drug‐resistance. The causative agents are the trypanosomatid protozoa
Leishmania
, widespread in tropical and subtropical areas. Intraphagolysosomal parasitism of macrophages by these parasites is a key feature in considering molecular mechanisms of their virulence relevant to developing effective drugs and vaccines needed.

Key Concepts:

Trypanosomatid protozoa in the genus of
Leishmania
cause Leishmaniases.

They have evolved mechanisms to live in macrophage endosomes/lysosomes.

The diseases are wide‐spread mainly in tropical and subtropical areas of the world.

The diseases are largely zoonotic and transmitted by blood‐sucking sand flies.

Reservoirs include domestic and wild animals, for example, canines, rodents & edentates.

Clinically, there are cutaneous, mucocutaneous and visceral Leishmaniasis.

The clinical spectrum results from host immunopathology to
Leishmania
infection.

Chemotherapy relies on toxic drugs and loses its effectiveness to drug‐resistance.

Drug development programs by targeting unique parasite enzymes are very few.

Control programs include the use of anti‐vector pesticide/repellents.
Eimeria
Authors: Duszynski Donald W
Published: April 2013

The protist phylum Apicomplexa Levine, 1970, comprises >4000 described species, all obligate parasites, that infect a wide range of vertebrates and invertebrates. Within the phylum, the genusEimeriaSchneider, 1875, (Family Eimeriidae) is the mostspecioselineage (>1800 species) of intracellular parasites found in all classes of vertebrates and some invertebrates. All eimerians have direct life cycles that include both asexual (merogony) and sexual (gamogony) reproduction, the latter resulting in the production of resistant propagules, the oocysts, which are discharged into the environment by the infected host. Endogenous development usually occurs in epithelial or endothelial cells of the intestine or in related structures (e.g. gall bladder, bile ducts, renal tubular epithelium, esophageal epithelium, oviduct epithelium uterine wall epithelium, etc.). Some eimerian species are highly pathogenic, especially in domesticated animals, but some also in wild animal species.

Key Concepts:

Within the coccidia proper, the Family Eimeriidae comprises about 15 genera, includingEimeria; all are obligate intracellular parasites known to infect every animal group which has been examined for them.

Untapped Biodiversity: The genusEimeria, with >1800 described forms, may be the most speciose group of parasites on Earth, but it has been little studied in the Earth's app. 62 150 vertebrate species.

It can be estimated that 98.6% (or more) of the coccidian parasites of vertebrates are yet to be discovered, based on what we know through 2010.

Our knowledge of the biodiversity of life on Earth is still badly incomplete, especially of the microbes that inhabit the seas, the soils and the bodies of ‘higher’ organisms that live in and on them.

Parasitologists, and most other biologists in general, agree that parasites represent a large proportion of all living species and may, in fact, far exceed the total number of all ‘free‐living’ forms.

As human population increases and agricultural development continues to shrink/fragment natural ecosystems, food webs will be disrupted and new and more virulent strains of coccidia may be expected, especially when exacerbated by environmental stressors (pollution), global climate change and invasion of new parasites from edge‐dwelling hosts.
Entamoeba
and
Entamoeba histolytica
Authors: Pritt Bobbi S , Clark C Graham
Published: April 2013

Entamoeba
species are unicellular eukaryotes that parasitise all classes of vertebrates and some invertebrates. Only three species of
Entamoeba
have been proven to cause disease and sometimes death in their hosts:

Entamoeba histolytica

, a parasite of humans,

Entamoeba nuttalli

, a parasite of nonhuman primates and

Entamoeba invadens

, a parasite of reptiles. Other species appear to live as commensals in their hosts and do not cause evident disease. Amoebiasis is defined as infection with

E. histolytica

regardless of symptoms. Most cases of amoebiasis are asymptomatic, but

E. histolytica

can rarely cause intestinal or disseminated disease. Identification of

E. histolytica

is complicated by the existence of two morphologically identical amoebae that may also colonise the human intestinal tract,

Entamoeba dispar

and

Entamoeba moshkovskii

, neither of which are thought to cause disease.
Entamoeba
spp. are commonly studied to gain further insight into protozoal evolution, amoeboid locomotion and cell‐killing ability, among other topics.

Key Concepts:

Entamoeba
species are unicellular eukaryotes in the supergroup Amoebozoa.

Entamoeba
species parasitise all classes of vertebrates and some invertebrates.

The life cycle of most
Entamoeba
species consists of a motile, feeding and reproductive trophozoite stage and an environmentally resistant cyst stage responsible for transmitting the infection.

Most
Entamoeba
species do not cause disease in their host and are considered commensal organisms.

Entamoeba histolytica

infection is referred to as amoebiasis regardless of whether or not symptoms are present.

Most infections with

E. histolytica

in humans are asymptomatic, but

E. histolytica

can rarely cause dysentery or disseminated disease and is associated with significant human morbidity and mortality worldwide.

Diagnosis and epidemiologic studies of

E. histolytica

are complicated by the presence of morphologically identical amoebae in human faeces.

Entamoeba
species are studied to gain insights into aspects of biology, including human disease, parasitism, evolution, cell locomotion and cell‐killing mechanisms.
Vorticella
Authors: Buhse Howard E , McCutcheon Suzanne M , Clamp John C , Sun Ping
Published: April 2013

Many species of the genusVorticellaare common ciliates living in many types of aquatic habitats. Their distinctive, contractile stalk anchors the unicellular body to a substrate. Contraction of the cell is calcium‐driven and independent ofadenosine triphosphate(ATP), relying on the presence of calcium‐binding proteins. A coupled mechanochemical model accounts for the coiling of an elastic stalk and the binding of calcium to the calcium‐binding proteins. Stalk elongation is driven by elastic energy stored in the coiled stalk and the rate of elongation is controlled by calcium dissociation from calcium‐binding proteins and its re‐sequestration into internal stores. Recently, the taxonomic status of the subclass Peritichia has changed radically based on molecular studies. The former order Mobilida was removed from the subclass and elevated to the level of a separate subclass. Phylogenetic studies using small subunitribosomal ribonucleic acid(ssu rRNA) and internal transcribed spacer (ITS) sequences place the Peritrichia closer to the subclass Hymenostomatia and the Mobilia closer to the subclass Peniculia.

Key Concepts:

Contractility inVorticellarelies on a calcium‐driven, ATP‐independent system that depends on calcium‐binding proteins.

Vorticellacan be used as a bio‐indicator for the evaluation of polluted waterways.

Vorticellaand similar filter‐feeding ciliates are used to clarify sewage in waste treatment plants.

Vorticellais a useful organism for the study of exocytosis by examining production and release of granules that form the extracellular matrix of the stalk and the adhesive pad.

Vorticellastalk contraction and relaxation is dependent of the presence or absence of calcium ions, this property can be exploited in a microelectromechanical system (MEMS) to perform linear work generated by spasmonemal contraction and controlled by calcium levels.

Chemical analysis of the sticky material that anchors the stalk ofVorticellafirmly to its substrate could result in the identification of a new type of adhesive material that sets in water.
Plant Nuclear Genome Composition
Authors: Heslop‐Harrison JS (Pat) , Schmidt Thomas
Published: April 2013

The plant nuclear genome consists of
deoxyribonucleic acid
(DNA) divided among the chromosomes within the cell nucleus. Plant genomes contain coding and regulatory sequences for genes and repetitive DNA. They are evolutionarily dynamic and analysis provides insights into the evolution of genes and genomes, supporting studies of species phylogeny and plant breeding. The amount of DNA present in plant genomes, nearly constant within one species, varies over some 2300 times between species; the majority of the difference is accounted for genome duplication, or by various classes of repetitive DNA which may be dispersed widely along chromosomes or located in arrays at a small number of loci. Bioinformatics and genome sequence analysis show conservation of many gene sequences across all plants. Repetitive DNA motifs may be conserved over large taxonomic groupings or evolve rapidly. Repetitive DNA plays an important role as a structural component of plant chromosomes (e.g. telomeres and centromeres) and affects gene regulation.

Key Concepts:

Plant nuclear genome sizes, constant in a species, vary from 60 000 000 base pairs of DNA (written as 60 Mbp) to 150 000 Mbp, a range of 2300 times.

The DNA of plant nuclear genomes is wrapped around the histone proteins to form nucleosomes, and the resulting chromatin is organised into linear chromosomes with characteristic numbers, sizes and morphology in each species.

Genomes contain coding sequences, typically for 25 000–40 000 genes, and regulatory sequences, as shown by genome sequencing and bioinformatics.

Size variation comes from polyploidisation, genome or chromosome duplication, and particularly amplification of DNA motifs to give repetitive DNA.

Repetitive DNA consists of sequences that amplify via RNA intermediates (retrotransposons), through copying and reinsertion of DNA (DNA transposable elements), or other mechanisms (satellite and microsatellite DNA).

Some repetitive DNA encodes genes, in particular the 45S and the 5S ribosomal RNA genes (rDNA); other repetitive DNA has structural roles at the telomeres or chromosomal ends and the centromeres where chromosomes attach to microtubules during segregation. In most species, much of the repetitive DNA has no known function.
Plant Breeding and Crop Improvement
Authors: Caligari Peter DS , Forster Brian P
Published: April 2013

To respond to the increasing need to feed the world's population, standing in 2011 at 7 billion and predicted to reach 9 billion by 2050, as well as an ever greater demand for a balanced and healthy diet, there is a continuing need to produce improved new cultivars of plants, particularly crop plants. Land available for crop production is limited, with much of the world's best soils already in use and others protected, for example, for environmental concerns. The demand for food brings marginal lands into play for which stress tolerant crops need to be developed. Climate variation is yet another challenge breeders have to respond to. In short, more food, fibre, fuel and forage need to be produced per unit of land. The strategies used to meet these demands are increasingly based on our knowledge of relevant science, particularly genetics and reproductive biology. Success is gained by a multidisciplinary understanding and the deployment of relevant science and technology.

Key Concepts:

Plant breeders must have access to genetic variation in crop species.

Plant breeders must be equipped with the tools to respond quickly to new demands by developing accelerated breeding techniques and the ability to screen for traits of interest rapidly among progeny.

Yield and yield stability remain the top priorities for breeders.

Increasing production of plant products is essential for food, feed and fibre for the increasing World population.

Breeders must be visionary in planning for requirements in the future, at least 7–20 years ahead, as this is the timescale from initiating the breeding programme to releasing cultivars.
Mice as Experimental Organisms
Authors: Merlo Giorgio , Altruda Fiorella , Poli Valeria
Published: April 2013

The mouse is extensively used as a model system to reproduce human diseases in a mammalian system, and to consequently allow to examine the molecular and pathogenic features of the disease in a context that is as close as possible to the human being. The use of the mouse has been particularly useful in three large areas of experimental pathogenesis: (1) classic monogenic diseases, (2) cancer development and progression and (3) developmental genetics and congenital pathologies. In each of these areas, significant progress has been made in recent years. Here, after a short introduction to the biology of the mouse and its history as a model organism, we summarise the current status of genetic manipulation of the mouse genome, provide an overview of current knowledge and illustrate some recent advancements.

Key Concepts:

The mouse is a model of choice to study human disease because is relatively easy to handle while being surprisingly similar to humans.

The mouse and human genomes share considerable homology.

The pluripotency of early embryonic cells is the basis of the possibility to manipulate the mouse genome and obtain animals carrying specific mutations.

Current methodology consent to modify the mouse genome in several ways, including conventional, dynamic and inducible mutations.

Mouse models of human genetic diseases provide an ideal basis for studying the pathogenic mechanism and testing innovative therapies.

Key concept in cancer initiation and progression have been established thanks to mouse models.

Experimentally, we can use the mouse to visualise complex processes (cell communication, differentiation fate and embryonic development) in a mammalian system.

Embryonic development of Vertebrates is highly conserved, reflecting extensive genome conservation.

Pluripotency is also achieved by reprogramming of somatic cells; this has great implication for biology of stem cells and possible innovative therapies.
Pollen: Structure and Development
Authors: Borg Michael , Twell David
Published: April 2013

Pollen grains contain the highly reduced haploid microgametophyte generation in seed plants that establishes the male germline during sexual reproduction. Pollen protects the germline from environmental injury, promotes gamete dispersal and ensures delivery of a pair of sperm cells to the female gametesviathe pollen tube. Microgametogenesis is initiated from haploid microspores that undergo one or more asymmetric mitotic divisions followed by differentiation to form a tube cell and a pair of sperm cells. Knowledge of the molecular mechanisms governing microgametogenesis has advanced rapidly through genetic analysis of mutants that disturb cellular patterning and gamete specification in flowering plants and through the application of genome‐wide transcriptomic studies. Recent evidence also supports a diverse and significant role for functional small RNA pathways and epigenetic regulation during microgametogenesis. Together these advances are helping to establish models of the gene regulatory networks governing gametophyte development and gamete specification.

Key Concepts:

Pollen grains harbour the haploid microgametophytes of seed plants (spermatophytes) that deliver twin sperm cells to the female gametophyteviathe pollen tube.

Pollen contains high levels of stored transcripts and protein for use during germination and pollen tube growth.

The complexity of haploid gene expression is reduced during pollen development and is accompanied by a relative increase in the expression of pollen‐specific transcripts.

Sperm cells possess a reduced but extensive transcriptome that has a relatively high number of sperm cell‐specific transcripts.

Formation of the male germline results from microtubule‐dependent asymmetric division of a progenitor microspore.

Ubiquitin‐mediated proteolysis is essential for germline cell cycle progression.

Male germline specification involves the coordination of cell cycle and differentiation by the germline‐specific transcription factor DUO1.

Multiple small RNA pathways function in the microgametophyte to control gene expression, transposon activity and fertilisation.
Meristems
Authors: Green Kirsten A
Published: April 2013

A central feature of plant development is the continuous generation of organs throughout the lifespan of the plant. In the region designated the meristem, undifferentiated cells are maintained throughout the life cycle of the plant, providing a source of cells from which plant organs are derived. Cells that are differentiating as they are channelled toward a particular developmental fate also reside in the meristem, as do the resultant organ primordia. The meristem is a self‐renewing structure and its stem cell population is maintained at a near constant number despite the perpetual mobilisation of differentiating cells into organogenesis. The meristem's capacity to balance continuous differentiation of cells while replenishing the pool of undifferentiated, pluripotent cells is tightly controlled by a very complex and overlapping network of regulatory pathways.

Key Concepts:

Plants, unlike animals, have the capacity to generate new organs post‐embryonically, throughout the lifespan of the plant.

Shoot and root apical meristems have the capacity to balance perpetual differentiation of cells while maintaining a population of undifferentiated stem cells.

Because fates of meristematic cells are determined by their relative positions, they must be in continuous communication with their neighbouring cells.

Signals can be transmitted from more mature cells to initial cells to specify the pattern of meristem differentiation.

The number of stem cells in meristems is remarkably constant despite the continuous recruitment of differentiating cells into organs.

InArabidopsisshoot meristems, a feedback loop between WUSCHEL and the CLAVATA signalling pathway is crucial for specifying and maintaining the stem cell niche in the shoot apex.

Within their niche boundaries, stem cells remain in an undifferentiated state in response to positional cues from neighbouring cells while cells displaced from the niche begin the process of differentiation.
Plant Biomechanics
Authors: Vincent Julian FV
Published: April 2013

The mechanical design of plants is based on the tensile properties of cellulose molecules which combine to form stiff nanofibrils from which the wall surrounding all plant cells is mainly constructed. Simple plants such as liverworts are made from few cell types and rely for their stiffness on the osmotically maintained pressure (turgor) of water inside the cell reacting against the stiff cellulose. As plants evolved and grew towards the light they developed larger fibres which transmit the forces more effectively and convert the plant into a complex pre‐stressed structure, but still largely dependent on water pressure for its rigidity. Increased structural complexity leads to increased fracture resistance and durability. Lignin glues the nanofibrils together so that the fibres, and then the cell walls in general, can take compressive forces, and tall herbs and trees evolve. Some plants (lianas, creeping herbs, Spanish moss, etc.) can grow large relying on simple tension under gravitation.

Key Concepts:

Cellulose is the commonest, and most technically most useful and important, biological fibre‐forming molecule.

The cell wall is a composite material of fibres in a matrix.

Since the plant cell wall is a relatively open fibrous structure, it is very difficult to ascribe unique mechanical properties to it. This variability gives it adaptability.

Intrinsically plants move slowly using turgor, but they can move quickly by storing elastic energy over time and releasing it suddenly. This is called
power amplification.

The more cells, the more tissue types are possible and the plants can be larger and more adaptive.

Cellulose is distributed nonuniformly in a way that maximises its effectiveness.

Lignified tissues are mostly dead and so are simple prototypes for biomimetics.
Plant Tissues
Authors: Hülskamp Martin , Schnittger Arp
Published: April 2013

Higher plants are organized into three tissue layers: the epidermis, the ground tissue and the vascular system. The three tissue layers are established in the meristems and they are largely maintained as separate tissues throughout plant development. The L1 layer forms the epidermis responsible for plant protection and gas exchange. The L2 layer develops into subepidermal tissues generating most photosynthetically active tissues. The L3 layer generates the vascular system required for long‐distance transport of water and metabolites. Despite the clonal origin the differentiation of cells depends on the developmental context. Experiments in which single tissue layers were genetically manipulated revealed the relative importance for overall plant growth and development for each tissue layer. Central questions are: which layer determines the shape of organs, how are the cell division rates coordinated among the different tissue layers, how can the different cell layers communicate with each other and in particular what is the importance of hormonal control? The current knowledge of the underlying molecular principles are discussed.

Key Concepts:

Plant organs develop from three meristematic layers that are largely kept separate throughout development because of the periclinal division patterns.

The outermost meristematic L1 layer forms the epidermis that serves as a protection shield against the environment and regulates the gas exchange.

The second meristematic L2 layer generates the ground tissue which may adopt various functions including photosynthesis, storage, reproduction and mechanical support.

The innermost meristematic L3 layer produces the vascular system that governs the long‐distance water and metabolite transport.

Each tissue layer has distinct roles in the regulation of organ shape, cell division rates that seem to be dependant on the genetic pathway and the plant species.

Intercellular communication is mediated by receptor ligand systems and controlled transport through plasmodesmata.
Mesophyll
Authors: Pyke Kevin
Published: April 2013

Cells of the mesophyll make up the bulk of internal leaf tissue and are the major site of photosynthesis in a plant by virtue of containing large populations of chloroplast organelles. The differentiation of the mesophyll and its coordinated expansion is important to leaf function because light interception by chloroplasts and gas exchange in the internal airspaces of the leaf are crucial to optimise rates of photosynthesis. In dicotyledonous leaves there are two types of mesophyll cell; palisade mesophyll and spongy mesophyll. Palisade mesophyll cells are elongate and form a layer beneath the upper epidermis, whereas spongy mesophyll cells are internal to the lower epidermis. Mesophyll cells in monocotyledonous leaves are often highly lobed. All mesophyll cells contain large populations of chloroplasts, which enable the leaf to carry out photosynthetic carbon assimilation.

Key Concepts:

In dicotyledonous leaves there are two types of mesophyll cells, palisade mesophyll and spongy mesophyll.

Palisade mesophyll cells form a layer beneath the upper epidermis whereas spongy mesophyll cells are internal to the lower epidermis.

In monocotyledonous leaves, mesophyll cells are not differentiated into two types according to position in the leaf, although those cells circling the vascular tissue form a distinct cell‐type called the bundle sheath cell.

Mesophyll cells in monocotyledonous leaves are often highly lobed.

Mesophyll cells originate from the L2 and L3 layers of the shoot apical meristem.

A major role of leaf mesophyll cells is to contain large populations of chloroplasts, which carry out photosynthetic carbon assimilation facilitating plant growth.
Parenchyma
Authors: Pruyn Michele L , Spicer Rachel
Published: April 2013

In plants, parenchyma refers to a tissue composed of living cells, usually having only thin, primary cell walls and varying widely by morphology and metabolism. Parenchyma in the primary plant body often occurs as a continuous mass, such as in the cortex or pith of stems and roots, the mesophyll of leaves and the flesh of fruits. In vascular tissue parenchyma cells form axial strands that run along the length of the plant body and, where secondary growth occurs, in radial files that run from the outer tissues towards the pith. The unifying characteristic of all parenchyma cells is that they are living at maturity and capable of cell division, giving them important roles in regeneration and wound healing. Other key functions of these cells include photosynthesis, storage, secretion and transport.

Key Concepts:

Parenchyma refers to both a cell type and a simple tissue and is found within all three tissue systems of vascular plants: the dermal, ground (fundamental) and vascular tissue systems.

Parenchyma functions are diverse and dependant on both location within the plant and morphological specialisation.

Parenchyma forms the bulk of plant ground tissue, where they may be specialised to function in photosynthesis, storage, or transport.

Parenchyma is integral to vascular tissue, where it provides a route of exchange for materials within and between the xylem and the phloem.

Parenchyma is composed of living cells that retain the ability to divide and hence play a key role in several developmental processes, as well in plant response to wounding.
Chronic Obstructive Pulmonary Disease
Authors: Stockley RA
Published: April 2013

Chronic obstructive pulmonary disease is a group of conditions characterised by the presence of persistent airflow obstruction during expiration, primarily owing to narrowing of the smaller airways. Its prevalence is increasing and soon it will be the third most common cause of illness and death worldwide. The condition is a slowly progressive one punctuated by acute episodes of deterioration (exacerbations) and there is currently no specific therapy confirmed to slow the progression. The underlying pathophysiology is believed to be uncontrolled inflammation owing to a combination of genetic and environmental factors. Although classically associated with smoking, increasing pollution in the industrialised world and the burning of biomass fuels indoors in the third world also influences its prevalence.

Key Concepts:

COPD is a group of conditions in which airflow obstruction cannot be fully reversed.

The pathophysiology is owing to uncontrolled inflammation in the lung.

COPD is associated with an increased risk of co‐morbidities such as arteriosclerosis, type II diabetes and osteoporosis probably as a result of common inflammatory processes.

Thoracic imaging is being increasingly used to identify different pathological processes that contribute to COPD.

Large clinical trials of inhaled therapy have demonstrated a reduction in the number of acute episodes of deterioration and possibly mortality.
Immune Haemolytic Anaemia
Authors: Packman Charles H
Published: April 2013

The immune haemolytic anaemias comprise a set of diseases characterised by shortened red blood cell survival (haemolysis) mediated by the action of antibodies and serum complement. The haemolysis is evidenced by a raised reticulocyte count in the absence of blood loss. Activity of the immune system is diagnosed by the presence of antibody or fragments of complement components (mainly C3 and C4) on the red blood cell surfaces by means of the direct antiglobulin test. Pathogenic antibodies may bind optimally at either 37°C (warm autoimmune haemolytic anaemia) or at 4°C (cold agglutinin disease). Drugs may also cause immune haemolysis either by induction of drug‐dependent antibodies to red blood cells or by induction of autoantibodies.

Key Concepts:

The immune haemolytic anaemias are characterised by shortened red blood cell survival mediated by the action of antibodies and complement.

The key laboratory finding is the demonstration of antibody or complement on red blood cells by means of the direct antiglobulin (Coombs) test.

Antibodies may bind optimally at body temperature (37°C; warm antibody autoimmune haemolytic anaemia) or at 4°C (cold agglutinin disease).

Autoimmune haemolytic anaemia is most often idiopathic, but some cases occur in association with other diseases, most commonly a lymphoma or systemic lupus erythematosus.

Drugs may cause antibody binding to red blood cells by three distinct mechanisms. Nowadays, the most common offending drugs are second and third generation cephalosporins.

Treatment options include glucocorticoids and splenectomy (warm antibody autoimmune hemolysis); rituximab (warm antibody autoimmune haemolysis and cold agglutinin disease); and removal of the offending drug (drug‐immune haemolytic anaemia).

Transfusion should not be withheld from patients with symptomatic anaemia while awaiting a response to other treatments.
Chronic Lymphocytic Leukaemia
Authors: Dearden Claire
Published: April 2013

Chronic lymphocytic leukaemia (CLL) results from the expansion of a clone of CD5
+
B lymphocytes with distinct morphology and membrane antigens. The clinical course is variable and is determined by the stage of the disease. A number of serum, immunological and genetic markers are important determinants of prognosis. Treatment is only indicated in symptomatic patients with active disease. Initial therapy for fit patients is usually with combination chemoimmunotherapy, whereas single alkylating agents continue to be used for those unable to tolerate more intensive treatments. The presence of
TP
53 deletion, detected by fluorescence

in situ

hybridisation (FISH) analysis, predicts for poor response to conventional treatments and should be assessed in all patients before initiating therapy so that an alternative regimen can be selected. A number of new agents have shown activity in CLL.

Key Concepts:

CLL results from an expansion of clonal CD5
+
CD19
+
Blymphocytes with a unique diagnostic immunophenotype.

The clinical course of CLL is highly variable with some patients surviving decades without treatment, whereas others may die within 3–5 years of diagnosis.

Clinical stage and new laboratory markers give prognostic information. Patients whose CLL cells harbour
TP
53 deletions or mutations have a particularly poor outcome.

Patients with early stage asymptomatic disease do not require treatment.

Combination chemoimmunotherapy is recommended for fit patients with no
TP
53 abnormality.

Single agent alkylator therapy (chlorambucil or bendamustine) is suitable for less fit patients.

A number of newer agents are now available for management of relapsed/refractory patients.

Where possible patients should be treated within a clinical trial.

Allogeneic transplantation should be considered for younger fit patients with high‐risk disease.

Care in the prevention and management of infections is crucial.
Chronic Myeloid Leukaemia
Authors: Mughal Tariq I , Goldman John M
Published: April 2013

Chronic myeloid leukaemia (CML) is a clonal BCR–ABL1‐positive myeloproliferative disorder that results from an acquired genetic change in a single pluripotential haematopoietic stem cell. Although CML is rare, the lessons learned from unravelling its molecular biology over the past three decades have resulted in successful treatment for patients and also in a major paradigm shift in cancer medicine in general. Today many forms of cancer are being treated with drugs that target various molecular abnormalities known to play a role in the pathogenesis of the candidate disease. For CML patients, the introduction of the original tyrosine kinase inhibitor (TKI), imatinib mesylate, in 1998 was an important therapeutic milestone with most patients achieving a complete cytogenetic response and prolongation of survival compared with the previous therapies other than allogeneic stem cell transplantation (allo‐SCT). A small minority of patients were also able to achieve a complete molecular remission (CMR). With the more recent introduction of the second generation TKIs, dasatinib and nilotinib, the treatment results for the newly diagnosed patient in chronic phase (CP) seem even better, in particular the number of patients achieving CMR. Allo‐SCT is increasingly being offered when patients fail at least two lines of TKIs, except for children, where some specialists feel, it is appropriate to offer SCT as first or second line therapy. Efforts are also made to assess the potential for immunotherapy and other novel drugs, such as ponatinib, targeting specific subgroups of patients, for example, those with a mutant T315I clone have been developed.

Key Concepts:

Concept of targeted therapy in cancer medicine.

Molecular pathogenesis of CML in CP: a single pathogenetic abnormality.

Imatinib as a paradigm for successful molecularly targeted therapy.

Second and third generation tyrosine kinase inhibitors: successes and challenges.

Role of allogeneic stem transplantation in the era of the second generation TKI.
Bacterial Meningitis
Authors: Hemsley Carolyn , McGregor Alastair
Published: April 2013

Bacterial meningitis is bacterial infection of the cerebrospinal fluid within the subarachnoid space. It can be broadly divided into acute or chronic meningitis and community‐acquired or healthcare‐associated (nosocomial) meningitis. Each entity is associated with a particular pattern of infecting organisms, presentation, management and outcome. Acute bacterial meningitis is the commonest and, arguably, the most important. The epidemiology of acute bacterial meningitis is evolving worldwide, primarily driven by changing immunisation schedules. A wide variety of organisms have been associated with acute bacterial meningitis, but the majority of cases are caused by a handful of organisms (Streptococcus pneumoniae,Neisseria menigitidis, Group B streptococcus,Haemophilus influenzaeandListeria monocytogenes). Chronic bacterial meningitis is less common and is usually caused byMycobacterium tuberculosis. Bacterial meningitis is a medical emergency requiring prompt diagnosis and treatment as mortality approaches 100% if left untreated. Even with treatment there is a significant mortality rate and long‐term neurological sequelae are common.

Key Concepts:

The frequency and aetiology of bacterial meningitis varies according to multiple factors but most importantly patient age, geographical region and social setting.

The incidence and commonest aetiological agents of bacterial meningitis have altered over the last two decades with the introduction of Hib, pneumococcal and menigococcal vaccines.

The triad of fever, meningitis and altered mental state is not universally present but the absence of any of these features usually excludes a diagnosis of meningitis.

Early antibiotics administration is crucial to achieving a good outcome.

CSF examination is the most valuable diagnostic investigation.

Empiric treatment for tuberculous meningitis should be commenced on clinical suspicion alone and should not wait for microbiological confirmation.

Coadministration of glucocorticoids with antituberculous therapy reduces both morbidity and mortality from TBM.
Filoviruses: Ebola, Marburg and Disease
Authors: Groseth Allison , Hoenen Thomas , Eickmann Markus , Becker Stephan
Published: April 2013

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

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.