Regulation and Organisation in animals

Legal Use of an Animal:

'A vertebrate (minor exceptions) other than man and that experiences pain and suffering (according to scientific evidence)'

UK Animal Welfare Act (AWA) 2006

UK Animals (scientific procedures) Act 1986

4 Major phospholipids, distribution is different between 2 layers = important for communication

Phosphatidylethanolamine

Phosphatidylsenne

Phosphatidylcholine

Sphingomyelin

Phosphatidyllinositol = minor phospholipid

Lipids = 50% mass of membranes. A small animal cell contains 109 lipids. Membrane lipids are either phospholipids, cholesterol or glycolipids.

3 types of communication between cells = Gap Junction, Chemical Messenger (most common), Signalling Molecules

Some signalling molecules pass through the membrane, but most need help from channels, receptors, enzymes, carriers, markers etc. 

• Eicosanoids Retinoids Amines
• Gasses    Steroids
• Purines         Peptides

Most signals need help passing through membranes, only a few don't. Channels, carries, receptors, enzymes, cell adhesion molecules and self identifying markers help.

Phosphatidulinositol => lipid kinases phosphorylate the lipid head, while extracellular signals can activate phospholipases.

Contact dependant signalling requires cells to be in direct contact with one another. Gap junctions are the most intimate and rapid means of communication. Water-filled channels allow small molecules to be exchanged. Most communication is mediated by paracrines that act on cells of a different type in their environment. When the messenger affects cells of the same type it is an autocrine. These are quickly cleared from an area. 

3 classes of cell surface receptor

• G-Protein coupled receptor
• Gated membrane channel receptor
• Enzyme coupled receptor

Protein filamtes = small soluable subunits that spontaneously assemble into large proteins

Contractile bundle (stress fibre), Gel-like network (cell cortex) and Tight parallel bundle (filapodium).

Mechanoreceptors allow organisms to percieve what is happening in the external environment. They are composed of a neurone, socket cell, cuticle and a shaft. 

Mechanosensory neurones in mice express G-Protein coupled receptor MRGPRB4 when detecting stroking.

Pheremones are released to look for a mate, mark territory or signal danger. Olfactory receptors in nose are used to sense pheremones. 

Vomeronasal organ is used to sample urine for mates to see if they are sexually active (Flehmen response).

G-protein coupled receptors sense signalling molecules, all have highly specific structures but all are similar.

Stress=> A generalised, non-specific response to any factor that threatens to/overwhelms the bodies ability to maintain homeostasis. 

Stressor=> Factor/Agent inducing stress. You can have physical, chemical, physiological and psychological/emotional stressors. 

Local temperature changes cause vasodilation or vasoconstriction. Theraputic application to injury takes advantage of this. 

Suddent temp elevation causes initiation of heat shock proteins. They have a role in correct protein folding/refolding. Changes in temp. during development can affect cell and organ structure due to a lack of HSPs. 

Inflammation => innate, non-specific series of events involving certain leukocytes and local vascular changes in response to foreign invasion or tissue damage.

Chemotaxis => directed movement of a cell toward or away from a diffusible chemical.

Physical Stressor => an external challenge to homeostasis.

Psychological stressor => The anticipation that a challenge to homeostasis looms. 

Both physiological and psychological stressors cause fight-or-flight response. Glucocorticoids are metabolised e.g. cortisol. The measure of theses in blood shows how stressed someone is. 

Hypothalamic-Pituitary-Adrenal (HPA) axis is a set of interactions. 

Cortisol increases glucose, amino acids for repair and fatty acids for an alternative fuel in the blood.

Short term stress (transient)

• Metabolic fuel & building blocks available
• Mild/moderate stressors enhance immunity

Long term stress (chronic)

• Adversly affects the cardiovascular function, leads to hypertension & elavated heart rate
• Atherosclerotic plaque formation
• Prolonged immune suppression
• Decresed fertility, increased risk of miscarriage

Socially stressed animals have elevated glucocorticoid levels and enlarged adrenal glands. They also undergo neurobiological change. 

Eukaryotic cells are equipped with mechanisms to survive for a short period of starvation using intracellular protein degredation. 

Autophagy => autophagosomes engulf cell components

Autophagosomes fuse with lysosomes to digest proteins, damaged organelles or disease-causing bacteria. 

Trophectoderm develops into the placenta. Inner cell mass develops into the foetus. These are the blastocyte together. 

Embryonic stem cells were first isolated in 1981 from a mouse. Immunosurgery, mechanical dissociation or laser dissection can be used. 

The cells can be grown in vitro in the presence of leukaemia inhibitory factor and feeder cells. These are pluripotent. Embryonic stem cells are clonogenic, grown indefinatly and give rise to tetramers. 

Diapause => the ability to arrest embryonic development. This allows mating to occur and offspring to be born at optimal times of year.

LIF is a cytokine that mediates cellular pathways that maintains self-renewal in rodents, providing a window of time during development.

• Tipotent : Sufficient to form entire organism
• Pluripotent : Able to form all body cell lineages
• Multipotent : Can form multiple lineages & entire tissue
• Unipotent : Cells can give rise to one cell type

ESCs are unspecialised and can self-renew. They multiply by symmetric division. When differentiated they multiple by assymetric division. 

Expression of specific markers, formation of tetromas and germline chimerism after transfer into a blastocyte are all standard assays of pluripotency. LIF/gp130 triggers a STAT response essential for pluripotency state of ESCs. 

BMP-4 and Wnt are also required to activate Id proteins, Beta-carotenins and SMAD proteins required for SOX2/Oct-4 activity.

Oct-4 is a transcription factor, is expressed maternally and is restricted to blastocyte cells. Expression is directly antagonised by Cdx2, a gene responsible for trophectoderm differentiation. Nanog is another transcription factor expressed in the ICM.

ESCs are derived from ICM, from trophectorderm, primitive endoderm, epiblast and primordial germ cells. 

Fetal stem cells are from cord blood or amniotic fluid. These are stored in liquid nitrogen. Adult stem cells are tissue-specific. Gut scs replenish SI epithelium every 24hrs. 

Spermatogonial scs are derived from mouse testis.

ESCs are unspecialised and can self-renew. They multiply by symmetric division. When differentiated they multiple by assymetric division. 

Expression of specific markers, formation of tetromas and germline chimerism after transfer into a blastocyte are all standard assays of pluripotency. LIF/gp130 triggers a STAT response essential for pluripotency state of ESCs. 

BMP-4 and Wnt are also required to activate Id proteins, Beta-carotenins and SMAD proteins required for SOX2/Oct-4 activity.

Oct-4 is a transcription factor, is expressed maternally and is restricted to blastocyte cells. Expression is directly antagonised by Cdx2, a gene responsible for trophectoderm differentiation. Nanog is another transcription factor expressed in the ICM.

ESCs are derived from ICM, from trophectorderm, primitive endoderm, epiblast and primordial germ cells. 

Fetal stem cells are from cord blood or amniotic fluid. Adult stem cells are tissue-specific.

Embryonic carcinoma cells and embryonic germ cells are isolated from fetal glands. They are pluripotent and share markers with ESCs. 

Human ESCs are derived from preomplantation blastocytes. They are LIF-independant, pluripotent and require activin and FGE. They can be differentiated into a veriety of tissues. Efficiency of differentiation is low but it could be used as a treament for a degenerative disease. 

Adult stem cells are quiescent, so when they divide a transient amplyfying precursor is generated. The precursor undergoes division and has a greater level of cell commitment.

Mesenchymal scs are found in bone marrow and have the potential to divide into chondrocytes, osteoblasts and adipocytes. They can also differntiate into muscle and tendon.

Epidermal scs are a type of kertinocyte. They give rise to interfollicular epidermis, hair follicles and sebaceous glands. 

Applications

• Cell Therapy Study of Early development Cell based drug delivery
• Drug Toxicology Human Disease Model
• Gene Therapy Gene Expression

Model Animals => Mice, Chickens, Frogs, Flies, Nematodes. Similar features of development are called homologies. Aristotle thought of 2 mechanisms :

• Preformation => all parts present from begining (killed off by the cell theory)
• Epigenesis => parts form over time

In 19th/20th century it became clear embryo development is controlled by cell communication. There are several methods of cell signalling. The most common is secretion of diffusible ligands. 

For a cell to recieve a signal is must be competent = have appropriate receptors. Signal transduction => recognise/transmit signals

Morphogen => molecule must induce cells fate in a way directly related to concentration. Therefore, secreted signals generate multiple cell types by diffusing as a gradient across a tissue. Alan Turug describes development of stripes and spots. 

FGFs, Shh, BMPs are important pathways during development. The final outcome is determined by the context the signal is used in. Misregulation of these pathways leads to disease. Analysis of pathways is by:

• Genetics: mutations show how genes affect biochemistry and how they interact
• Biochemistry: radioactive tracers, antibodies or enzymes can be used.

Vertebrates have 25 FGFs & 4 receptors (RTK). FGFs are secreted from signalling centres. It induces dimerisation of the receptor. These then phosphorylise tyrosine = transautophosphorylation.

Phosphorylated receptors form a complex with SH2 and SoS (Son of Sevenless). SoS is a guanine nucleotide exchange factor (GEF). Echanges GDP to Ras for GTP. This activates Ras. 

Active Ras hydrolyses GTR to GDP. It initiates a cascade of protein kinases.

Ras->Raf->Mek->ERK->veriety of targets

In Sevenless, R7 is missing. This gives rough eye phenotype but can be rescused if a compensating mutation is present. This shows relationships between genes in a pathway

Vertebrate homologue of hedgehog protein. it acts through a patched receptor. 

Shh absence => Gli protein is phosphorylated and proteolytically cleaved. A short form enters the nucleus and repressed transcription.

When Shh binds to patched, smoothened is no longer repressed so inactivates kinase proteins. It is normally expressed in limb posterior to specify different parts of the limb

They induce bone formation and are members of the TGF beta-superfamily of signalling molecules.

It consists of type 1 and type 2 receptor subunites. Type 2 phosphorylates type 1 when BMP binds.

Activated receptor phorphorylates R-SMAD which then oligomerises with SMAD-4. This affects gene transcription. 

In the developing neural tube, dorsal cells produce BMP and ventral cells produce Shh. 

Maternal care alters (permenantly) the activity of the glucocorticoid receptor gene in the hippocaripus.

Epigenetics =>The study of mitotically and/or menotically heritable changes in gene functions that cannot be explained by changes in DNA sequence.

Biological memory can be defined as a sustained cellular response to a transient stimulus. 'Reprogramming' or 'dedifferentiation' is a type of memory (epigenetic) erasure of cells. Transferring all the DNA from a differentiated cell into an egg can produce viable offspring.

Clone => population of genetically identical cells or organisms formed by repeated cell division.

Eukaryotic chromosomes consist of repeating protein DNA complexes called nucleosomes. 147bp of DNA are wrapped (2 turns) around proteins called histones.

Euchromatin is the portion of genome available for transcription. Heterchromatin are transcriptionally inactive streches of DNA. Different chromatin states are heritable. DNA methlyation patterns can be inherited. It is an epigenetic signal. 

Genomic imprinting is a phenomenom by which certain genes are expressed in a parent-of-origin specific manner. Imprinted genes remember if they were inherited from the mother or the father.

X-inactivation is an epigenetic process : clonal inheritance of condensed, inactive x chromosome. 

Once inherited the X chromosome stays inactive throughout the lifetime of a female = Epigenetic inheritance.

Epigenetic mechanisms integrate an environmental signal -> Normally nutrition.

Epigenetic memory systems are stable , heritable, reversible, and frequently involve chromatin.

Ecology => The study of interactions between organisms and their environment. Organisms depend on both abiotic and biotic factors for survival. Community ecology is interactions between living organisms in a shared environment:

• Species type
• Species number
• Relative abundace of different species
• Interactions between different species
• Resilience to disturbances

Community interactions are difficult to analyse

You can predict lyme disease rates and oak tree health on the acorn crop. A bumper crop attracts deer and mice to the forest. Mice eat moth pupae so fewer moths eat the oak leaves. Deer have ticks that feed on mice. Ticks bite himans and spread bacteria causing lyme disease. 

Niche => Role of a species in the community and the different factors a species has adapted to for thriving in that community.

• Realised Niche => actual niche occupied by a species in practice. 
• Fundamental Niche => wider potential niche a species could occupy in theory.

The green anole was common in florida untill the brown anole was introduced. The brown anole established itself in the habitat of the green anole, confining the green anole to wetlands and tree leaves. 

Limiting resource = any resource that restricts the niche of a species

• Intra-specific competition - between same species
• Inter-specific competition - between different species

Competitve exclusion principle => two species with identical realised niches cannot coexist. (Can coexist if niches are reduced).

Resource partitioning leads to reduced competition due to different niches of two species. Natural selection favours species avoiding competition for resources. 

Character displacement is divergence in traits between two similar species living in the same habitat. This reduces competition as different traits give species seperate niches. However, this isn't apparent when the species live in different habitats. 

Predation => consumption of a prey species by a predator species. Pursuit and ambush have resulted in natural selection of certain traits. 

Plants cannot escape so have evolved other defence strategies:

• Physical - thorns, bark, leathery/waxy leaves etc.
• Chemical - toxic to herbivores

Some animals have evolved tolerance of toxic chemicals. This reduces competition. They co-evolve distinctive colours and patterns => aposematic colouration.

Prey animals have developed defense strategies through natural selection:

• Physical - speed, quills, shell, group living, flight
• Chemical - toxic, irritant, cryptic colouration for camouflage

Batesian mimicry => species not hunted due to its resemblance of harmful model species

Mullarian mimicry => different harmful species resembling each other

Keystone species - crutial for maintaining community structure and function. Many are apex-predators that control population of other species. Removal of these has DRASTIC effects. 

Symbiosis -> The relationship between two species in a community through co-evolution. One of the symbionts can be harmed, unaffected or benefit. 

• Mutualism = both partners benefit. Obligate (essential for survival of both partners) or facultative (not essential for either partner).
• Commensalism = one partner benefits without affecting the other partner
• Parasitism = parasites benefit and harm host. 2/3 of all species are parasites

Ectoparasits live outside the body of the host. Endoparasites live inside the body of the host.

Wolves were hunted to extiction in many areas which lead to an explosion in herbivore numbers and overgrazing causing dissapearance of plant species. Less plants meant less rodent, predator and scavenger species, and so biodiversity decreased. 

Wolves were reintroduced in some areas which lead to an increase in biodiversity.

Different communities vary greatly in species richness and diversity. 

Evolution => 'Descent with modification' or 'Change in the frequency of genetic traits within populations - over time'.

Nutural selection => Genetic mutations that enhance survival and reproduction and becomes more common in successive generations. (This process can eventually lead to speciation).

Endotherms almost invariably have a body temperature between 35 - 40. Most of the time they live in an environment cooler than their bodies. Fur is an efficient insulator.

• Arctic Hare = 55-70cm, 4-5.5kg, white coat in winter, blue/grey coat in summer, small ears
• Jackrabbit = 50-60cm, 1.4-4kg, brown coat, big ears

Membranes adapt to temperature. Warm-adapted are predominantly SFAs. Cold-adapted contain a high proportion of PUFAs.

Mitochondria are the result of an endosymbiotic event when an ancestral eukaryotic cell engulfed the bacterial acestor.

Non-shivering thermogenesis comes about due to brown adipose tissue found in newborns and hibernating species. There are a high number of mitochondria which cause the brown colour and it is specialised in converting chemical energy into heat. Short cicuiting = without ATP synthesis.

Group structure, sexual behaviour, parent-young interactions, response to humans and other behavioural characteristics are all important when selecting for domestication.

A shift in human culture can provide new ecological niches for those species with favourably adapted characteristics. There was explosive domestication of many forms to serve human culture, as well as selection between species. 

Divergence in domesticated species towards different specialised functions has led to increasing improvment along a straight line for specialised physiological and behavioural function. There has also been development of breeds or verieties by non-functional diversification and imposed reproductive isolation. However, some forms don't response to further selection.

Domestication leads to morphological changes such as decrease in size, change in body proportions, finer hair and flop ears. 

Changes are due to selection pressures and environmental factors.

Ferrel types often revert to the wild form

In commercial pig production, seasonality is overcome.