bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mice as Experimental Organisms
Authors: Merlo Giorgio , Altruda Fiorella , Poli Valeria 
Published: April 2013

AbstractThe 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

AbstractPollen 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

AbstractA 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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

AbstractChronic 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

Abstract

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

Abstract

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

Abstract

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

AbstractBacterial 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.