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LF205 L10-14


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Alex Rapai


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[Front]


“Eating as an act of ecosystem design”
[Back]


Flavour and nutritional quality of food ingredients are biologically linked to the soil. Consumer choice of flavourful food ingredients will be good for the environment. Consumer value of all produce from a farming system is essential for a robust economy. Modern genetics is essential for adapting new crop and animal varieties for regional production systems.

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LF205 L10-14 - Details

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“Eating as an act of ecosystem design”
Flavour and nutritional quality of food ingredients are biologically linked to the soil. Consumer choice of flavourful food ingredients will be good for the environment. Consumer value of all produce from a farming system is essential for a robust economy. Modern genetics is essential for adapting new crop and animal varieties for regional production systems.
16S rRNA
An essential gene sequence that can be PCR amplified from all bacteria. Mutations have accumulated very slowly in variable (less conserved) regions. Provides a useful taxonomic (phylogenetic) marker because sequence variation will generally vary amongst species, with no affect on fitness. A highly sensitive diagnostic marker to detect Operational Taxonomic Units (OTUs) in DNA extracted from environment samples. Can be quantitative: the number of sequence reads per OTU will indicate the abundance of different species in the environmental sample
The Human Microbiome
Our body is a host for 10-fold more microbial cells than human cells. This microbiota consists of ca. 1000-35000 species. Our microbiota weighs ca 2 kg and plays a controlling role in almost all bodily functions
C. elegans
Signs of ageing: Reduced fertility, feeding, movement, Increased cuticular wrinkling, Increased protein carbonyl, mitochondrial DNA deletions, lipofuscin.
The Dauer Larva
Developmentally arrested alternative third stage larva. Forms in response to high population density (dauer pheromone), high temperature, low food. Non-feeding, buccal cavity sealed, survive on stored food. Live for up to 70 days. Non-ageing: post dauer adults have normal lifespans
Daf mutations
Daf-2, age-1 they switch on the dauer longevity programme in the adult. daf: abnormal in dauer formation. Daf-c: Dauer constitutive. Daf-d: Dauer defective
C. elegans lifespan genes have human homologues!
CE: Human homolog. age-1: Catalytic subunit of phosphatidyl inositol 3-kinase. daf-2: Insulin or IGF-1 receptor. daf-16: FOXO-class forkhead transcription factor (dauer formation).
Insulin/IGF-1 signalling modulates ageing in insects as well as nematodes
Mutations in INR (fly daf-2): mean female lifespan increased by up to 85%. Mutation of chico (insulin receptor substrate), increases lifespan by up to 48%. Implications: Wide evolutionary conservation of the role of insulin/IGF-signalling in the modulation of ageing: a public mechanism of ageing.
Insulin/IGF-1 signalling and ageing in mammals!
Worms, flies: One insulin/IGF-1 receptor. Mammals: insulin receptor, IGF-1 receptor, insulin-receptor-like receptor. Insulin receptor: Mild reduction of function of IR gene: type 2 (non-insulin dependent) diabetes
Polymorphisms in the androgen receptor gene AR, the dopamine receptor gene DRD4, and the 5-HTTLPR VNTR of the serotonin transporter gene might be associated with Life history strategy.
Type 1: Slow LHS, long term Time Orientation (TO). Emphasize behaviours and values that bring benefits in the future. It is associated with delayed sexual initiation. Type 2. fast LHS and short term TO. De-emphasize delay of gratification, risk avoidance, and a strong effort in modern education.
What controls our diet
Religious-nutritional behaviour (Vegetarian or Non-vegetarian diet). Demographic Nutritional changes. Area Specific Deficiencies. Environmental Factors (Tropical or Temperate). House hold Income (less or more expenditure on Quality food).
What role does genetics have for our Nutritional state?
Single cell organisms are able to adjust their metabolic capacity in response to variation in the nutrient supply in the culture medium. In multi-cellular organism, the control of gene expression involves complex interactions of hormonal, neural and nutritional factors.
Evidence for genetic influences: Obesity in Humans
Familial aggregation: familial clustering of obesity in families Twin Studies: greater concordance among MZ twins compared to DZ twins Family Studies: variety of “statistical models” consistent with genetic influences
Nutritional Genomics
How food interacts with genes to increase or decrease risk factors
Potential Benefits
Increased focus on a healthy diet and lifestyle. Motivate positive behaviour change. Increased awareness of risk of certain conditions. Improved health and quality of life. Focus on prevention. Decreased morbidity and premature mortality. Reduced health care costs.
Potential Harms
Attention is drawn away from other modifiable risk factors. Decreased use of other services . False sense of security. Focus on specific nutrients/foods. Ineffective or harmful. Misleading claims.
Consumption of LC-PUFA beneficially affect physiological processes :
Growth, neurological development. Lean and fat mass accretion. Reproduction. Innate and acquired immunity. Infectious pathologies of viruses, bacteria and parasites. The incidence and severity of virtually all chronic and degenerative diseases.
Viral modification
Need to use a virus which replicates by inserting its genes into the host cell's genome. This virus has three genes - A, B and C. Gene A encodes a protein which allows this virus to insert itself into the host's genome. Genes B and C actually cause the disease this virus is associated with. Replace B and C with a beneficial gene. Thus, the modified virus could introduce your 'good gene' into the host cell's genome without causing any disease
Which cells to transform?
Modification of somatic cells by transferring desired gene sequences into the genome. Somatic cells necessary to ensure that inserted genes are not carried over to the next generation
Gene control/regulation
Most viral vectors are unable to accommodate full length human genes containing all of their original regulatory sequences. Human cDNA often used - much regulatory information is lost.
Gene Therapy for Cystic Fibrosis
T is a single gene defect on Chr 7; It is a recessive condition, with heterozygotes being phenotypically normal (suggesting gene dosage effects are not critical); The main pathology is in the lung, which is accessible for treatment; It is a progressive disease with a virtually normal phenotype at birth, offering a therapeutic window
Choices of Vectors
Viral vectors:• Vetrovirus• Adenovirus• Adeno-associated virus• Herpes Simplex Virus
The ideal vector system would have the following characteristics:
(1) an adequate carrying capacity; (2) to be undetectable by the immune system; (3) to be non-inflammatory; (4) to be safe to the patients with pre-existing lung inflammation; (5) to have an efficiency sufficient to correct the cystic fibrosis phenotype; (6) to have long duration of expression and/or the ability to be safely re-administered.
Mode of delivery
The instillation of large volumes of vector-containing fluid into the lung via the nose. However, 1. this mode of delivery poses safety problems because of the potential for aspiration. 2. In addition, the instillation of large volumes of fluid leads to enhanced alveolar exposure, as a result of bulk flow into the lung parenchyma. This exposure is undesirable because it may induce adverse reactions. 3. At the same time, it is likely that airway epithelial cells, rather than alveolar epithelial cells, are the appropriate target for CFTR gene transfer
Aerosolized vectors
Another mode of lung delivery for vector-containing fluid is by oral inhalation of aerosolized vectors. However, aerosolization of a fluid is typically achieved by means of a nebulizer, and most nebulizers have been designed to generate small particles. This is because they have been developed to deliver drugs to treat patients with asthma, and in asthma the target region of the lungs is often the peripheral airways.
Improvement of aerosol delivery
One way to avoid alveolar deposition is to generate a large droplet aerosol. Improve target specificity using a spray device that is inserted into a bronchoscope. Research suggests that spray delivery of the vector could provide a means of targeting the larger, central airways, avoiding deposition in the smaller airways and alveolar region, which is more likely with nebulizers that generate small aerosol particles.
Current treatment
Modern treatment now includes 1. the intake of digestion enzymes, nutritional supplements, 2. percussion and postural drainage of the lungs, improved antibiotics 3. inhalation of aerosols containing medication.
Cystic fibrosis gene therapies being tested
“Crippled” adenovirus selected (non-integrating, replication defective, respiratory virus) – Gene therapy trials – 3 Research teams, 10 patients/team. 2 teams administered virus via aerosol delivery into nasal passages ad lungs. 1 team administered virus via nasal passages only. Only transient expression observed →because adenovirus does not integrate into genome like retroviruses
Problems with Gene Therapy
Short Lived, Immune Response, Viral Vectors, Multigene Disorders, May induce a tumor.
How are plants targeted?
A particle gun is used to shoot small bits of metal coated with the gene into the plant.
General Ethical Concerns
Benefits of medical genomics will be expensive—potential to exacerbate inequalities in health and health care. There are limited incentives for for-profit entities to focus on health problems of developing countries. Traditional ethical issues are different because of the nature of genetic information and the social, economic, political, and cultural contexts of developing countries.
Ethical considerations in research into genetic influences of behaviour
Research in human genetics aims to identify particular genes involved in hereditary diseases or mental disorders. This kind of research may pose risks to participants because of the link between genetic heritage and people’s life. Genetic information obtained from such research can also be problematic for the participants family. How might knowing about someone’s personal genetic information affect the individual and how that person is perceived and treated by others? How might genetic information affect minority group members? If misused, genetic information can be stigmatizing and may affect peoples ability to get jobs or insurance.