Jochen Walter Webinar July 2014
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Webinar presentation made by Dr. Jochen Walter, July 8, 2014 - http://www.alzforum.org/webinars/mutations-impair-trem2-maturation-processing-and-microglial-phagocytosis
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Snp
SNPs are found in
coding and (mostly) noncoding regions.
Occur with a very high frequency
about 1 in 1000 bases to 1 in 100 to 300 bases.
The abundance of SNPs and the ease with which they can be measured make these genetic variations significant.
SNPs close to particular gene acts as a marker for that gene.
SNPs in coding regions may alter the protein structure made by that coding region.
A SNP is defined as a single base change in a DNA sequence that occurs in a significant proportion (more than 1 percent) of a large population. Sequence genomes of a large number of people
Compare the base sequences to discover SNPs.
Generate a single map of the human genome containing all possible SNPs => SNP maps
Gene therapy of genetic disorders like hepatitis, neuroblastoma, thalassemia
Gene therapy is the modern techniques of treatment of various diseases and disorders.
Gene therapy is the introduction of genes into existing cells to prevent or cure a wide range of diseases.
It is a technique for correcting defective genes responsible for disease development.
Inactivating, or “knocking out,” a mutated gene that is functioning improperly.
The first approved gene therapy experiment occurred on September1990 in US, when Ashanti DeSilva was treated for ADA-SCID.
Under the direction of William French Anderson, at the National Institutes of Health (NIH),
ROLE OF NETosis IN PATHOLOGICAL AND TOXICOLOGICAL CONDITIONS.
NETosis is one of the unique mechanism exhibited by Neutrophils for neutralizing invaded pathogens.
TDP-43 shapeshifts to encipher FTD severity
By: Edward M. Barbieri and James Shorter
TDP-43 forms cytoplasmic aggregates in degenerating neurons of frontotemporal dementia (FTD) patients.
Laferrière et al. now establish that TDP-43 assemblies from distinct FTD subtypes have different structures,
neurotoxicities, and seeding activities, which correlate with FTD severity. Thus, distinct pathological TDP-43
assemblies akin to prion strains might underpin distinct FTD subtypes.
Single nucleotide polymorphism
Single Nucleotide Polymorphism (SNP)
Polymorphism is a generic term that means 'many shapes‘. It is the ability to appsear in different form .
A single nucleotide polymorphism (SNP) is a DNA sequence variation occurring when a single nucleotide - A, T, C, or G - in the genome differs between members of a species (or between paired chromosomes in an individual).
For example, two sequenced DNA fragments from different individuals, AAGCCTA to AAGCTTA, contain a difference in a single nucleotide. For a variation to be considered a SNP, it must occur in at least 1% of the population.
CHARACTERISTICS OF SNP
• In human beings, 99.9 percent bases are same.
• Remaining 0.1 percent makes a person unique.
• Different attributes / characteristics / traits
• How a person looks, diseases he or she develops.
These variations can be:
Harmless (change in phenotype)
Harmful (diabetes, cancer, heart disease, Huntington's disease, and hemophilia )
Latent (variations found in coding and regulatory regions, are not harmful on their own, and the change in each gene only becomes apparent under certain conditions e.g. susceptibility to lung cancer)
TYPES OF SNP
NON-CODING REGION
A segment of DNA that does comprise a gene and thus does not code for a protein .
CODING REGION
Regions of DNA/RNA sequences that code for proteins
Synonymous
A SNP in which both forms lead to the same polypeptide sequence is termed synonymous
(sometimes called a silent mutation).
Non synonymous
If a different polypeptide sequence is produced they are non synonymous . A non synonymous change may either be missense or nonsense, where a missense change results in a different amino acid, while a nonsense change results in a premature stop codon.
SNP Applications
• Gene discovery and mapping
• Association-based candidate polymorphism testing
• Diagnostics/risk profiling
• Response prediction
• Homogeneity testing/study design
• Gene function identification
Gene therapy
Gene therapy , Nucleic acids , GENES , ADA-SCID(Severe combined immunodeficiency) , APPROACHES IN GENE THERAPY : Types of gene therapy , somatic gene therapy , germ line gene therapy , Gene modification , gene replacement , gene correction , gene augmentation , Gene transfer methods , viral gene transfer (biological) , non viral gene transfer : physical method ,chemical method , retrovirus vector system , adenovirus vector system , Adeno associated virus vector , Herpex simplex virus vector , Electroporation , Microinjection , Gene Gun , Calcium phosphate mediated DNA transfer , Liposome mediated gene transfer , Potential target diseases for Gene Therapy , GENE THERAPY USED TO TREAT TYPE I DIABETES , GENE THERAPY FOR CANCER TREATMENT , PARKINSON’S DISEASE , GENE THERAPY TREATMENT FOR ADA-SCID , GENE THERAPY FOR CYSTIC FIBROSI S, HEMOPHILIA , BLINDNESS
Gene therapy , Nucleic acids , GENES , ADA-SCID(Severe combined immunodeficiency) , APPROACHES IN GENE THERAPY : Types of gene therapy , somatic gene therapy , germ line gene therapy , Gene modification , gene replacement , gene correction , gene augmentation , Gene transfer methods , viral gene transfer (biological) , non viral gene transfer : physical method ,chemical method , retrovirus vector system , adenovirus vector system , Adeno associated virus vector , Herpex simplex virus vector , Electroporation , Microinjection , Gene Gun , Calcium phosphate mediated DNA transfer , Liposome mediated gene transfer , Potential target diseases for Gene Therapy , GENE THERAPY USED TO TREAT TYPE I DIABETES , GENE THERAPY FOR CANCER TREATMENT , PARKINSON’S DISEASE , GENE THERAPY TREATMENT FOR ADA-SCID , GENE THERAPY FOR CYSTIC FIBROSI S, HEMOPHILIA , BLINDNESS
Nucleic acid based therapeutic drug delivery system
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Carlos Cruchaga Webinar July 2014
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Joseph El Khoury Webinar July 2014
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Snp
SNPs are found in
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Occur with a very high frequency
about 1 in 1000 bases to 1 in 100 to 300 bases.
The abundance of SNPs and the ease with which they can be measured make these genetic variations significant.
SNPs close to particular gene acts as a marker for that gene.
SNPs in coding regions may alter the protein structure made by that coding region.
A SNP is defined as a single base change in a DNA sequence that occurs in a significant proportion (more than 1 percent) of a large population. Sequence genomes of a large number of people
Compare the base sequences to discover SNPs.
Generate a single map of the human genome containing all possible SNPs => SNP maps
Gene therapy of genetic disorders like hepatitis, neuroblastoma, thalassemia
Gene therapy is the modern techniques of treatment of various diseases and disorders.
Gene therapy is the introduction of genes into existing cells to prevent or cure a wide range of diseases.
It is a technique for correcting defective genes responsible for disease development.
Inactivating, or “knocking out,” a mutated gene that is functioning improperly.
The first approved gene therapy experiment occurred on September1990 in US, when Ashanti DeSilva was treated for ADA-SCID.
Under the direction of William French Anderson, at the National Institutes of Health (NIH),
ROLE OF NETosis IN PATHOLOGICAL AND TOXICOLOGICAL CONDITIONS.
NETosis is one of the unique mechanism exhibited by Neutrophils for neutralizing invaded pathogens.
TDP-43 shapeshifts to encipher FTD severity
By: Edward M. Barbieri and James Shorter
TDP-43 forms cytoplasmic aggregates in degenerating neurons of frontotemporal dementia (FTD) patients.
Laferrière et al. now establish that TDP-43 assemblies from distinct FTD subtypes have different structures,
neurotoxicities, and seeding activities, which correlate with FTD severity. Thus, distinct pathological TDP-43
assemblies akin to prion strains might underpin distinct FTD subtypes.
Single nucleotide polymorphism
Single Nucleotide Polymorphism (SNP)
Polymorphism is a generic term that means 'many shapes‘. It is the ability to appsear in different form .
A single nucleotide polymorphism (SNP) is a DNA sequence variation occurring when a single nucleotide - A, T, C, or G - in the genome differs between members of a species (or between paired chromosomes in an individual).
For example, two sequenced DNA fragments from different individuals, AAGCCTA to AAGCTTA, contain a difference in a single nucleotide. For a variation to be considered a SNP, it must occur in at least 1% of the population.
CHARACTERISTICS OF SNP
• In human beings, 99.9 percent bases are same.
• Remaining 0.1 percent makes a person unique.
• Different attributes / characteristics / traits
• How a person looks, diseases he or she develops.
These variations can be:
Harmless (change in phenotype)
Harmful (diabetes, cancer, heart disease, Huntington's disease, and hemophilia )
Latent (variations found in coding and regulatory regions, are not harmful on their own, and the change in each gene only becomes apparent under certain conditions e.g. susceptibility to lung cancer)
TYPES OF SNP
NON-CODING REGION
A segment of DNA that does comprise a gene and thus does not code for a protein .
CODING REGION
Regions of DNA/RNA sequences that code for proteins
Synonymous
A SNP in which both forms lead to the same polypeptide sequence is termed synonymous
(sometimes called a silent mutation).
Non synonymous
If a different polypeptide sequence is produced they are non synonymous . A non synonymous change may either be missense or nonsense, where a missense change results in a different amino acid, while a nonsense change results in a premature stop codon.
SNP Applications
• Gene discovery and mapping
• Association-based candidate polymorphism testing
• Diagnostics/risk profiling
• Response prediction
• Homogeneity testing/study design
• Gene function identification
Gene therapy
Gene therapy , Nucleic acids , GENES , ADA-SCID(Severe combined immunodeficiency) , APPROACHES IN GENE THERAPY : Types of gene therapy , somatic gene therapy , germ line gene therapy , Gene modification , gene replacement , gene correction , gene augmentation , Gene transfer methods , viral gene transfer (biological) , non viral gene transfer : physical method ,chemical method , retrovirus vector system , adenovirus vector system , Adeno associated virus vector , Herpex simplex virus vector , Electroporation , Microinjection , Gene Gun , Calcium phosphate mediated DNA transfer , Liposome mediated gene transfer , Potential target diseases for Gene Therapy , GENE THERAPY USED TO TREAT TYPE I DIABETES , GENE THERAPY FOR CANCER TREATMENT , PARKINSON’S DISEASE , GENE THERAPY TREATMENT FOR ADA-SCID , GENE THERAPY FOR CYSTIC FIBROSI S, HEMOPHILIA , BLINDNESS
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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Physiology of Special Chemical Sensation of Taste
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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