Unit 2 - Week 2 - Amankwah, Loh 3 and 4, and McCrone Flashcards
When should a baby start smiling? Laughing?
2 months; 4 months
When does a baby start to sit and reach for things?
6 months
When do babies generally start walking?
12 months. Crawling by 9 months
At what age does a baby know its age and sex?
3 years
At what age should a child toilet alone?
4 years
At what age does a baby understand object permanence?
9 months, along with saying Mama, Dada, and clapping and crawling
True or False: Newborns cry to communicate their needs.
True
When a patient presents with abdominal pain, you want to know:
Onset and duration Character Associated symptoms Relationship factors Stool characteristics Urine characteristics Medications Other things you will want to know are the patient’s Past Medical History, past surgical history, family history and social.
Inspect the abdomen for the following:
Skin characteristics
Venous return patterns
Symmetry
Surface motion
Inspect abdominal muscles as patient raises head to detect presence of the following:
Masses
Hernia
Separation of muscles
Auscultate with stethoscope diaphragm for the following:
Bowel sounds
Friction rubs over liver and spleen
Bruits over aorta and renal and femoral arteries
What are the primary roles of chaperones?
To prevent misfolding, mainly in large multimeric proteins that might need help to fold, and to prevent aggregation. Some hsp’s have recently been shown to pull apart aggregating proteins!
When are hsp’s upregulated? Give one example.
Fever, high temperature
What is the function of Hsp70?
To help bind to proteins during translation into the ER. They help folding at the synthesis stage.
What is the function of Hsp60?
When translation is finished, the protein goes inside the Hsp60 double donut, and the cap (GroES) comes on, and isolated the protein for folding. If it fails, the protein is spit back out into the ER lumen. This can be a cyclical process.
What are the proposed mechanisms of GroEL/GroES?
It pulls the protein inside (isolation), then upon the closing of the box, the inside residues change to allow the protein to unfold and/or attempt to fold, and functions by confinement to allow the protein space and time to fold correctly. Hps60
For what diseases are protease inhibitors in clinical trials
HIV
Cancer
Cardiovascular disease
What is the minimum number of ubiquitins needed for degradation signal?
4
Covalent ligation of ubiquitin is a reaction that requires:
ATP
Ubiquitin typically attaches to the side chain of what residue?
Lysine
What three enzymes target proteins for destruction?
E1 –> activates ubiquitin
E2 –> transfers activated ubiquitin to target-E3 complex
E3 –> catalyzes final transfer of ubiquitin
What happens in the proteasome?
The proteasome, 26S, attaches to the polyubiquitinated protein, chaperones are thought to unfold the protein, the ubiquitins get unfolded and recycled, and the protein is cleaved into 3-30 aa peptides, which can then be used for MHC I presentation (back through ER), or further cleaved by free endo/exopeptidases in the cytoplasm.
p53 encodes its own:
E3 ligase
In cancer, how can the ubiquitin-proteasome pathway be influenced?
Increased degradation of tumor suppressors, ie p53, p27
What is an example of the ubiquitin-proteasome pathway’s influence on neurodegenerative diseases such as HD, AD, and Parkinson’s?
Accumulated ubiquitinated proteins have been observed in plaques, contributing to the aggregations, ie Lewy Bodies (Parkinson’s)
What is the major problem in CF, having to do with the ubiquitin-proteasome pathway?
The mutation in deltaF508 causes extended misfolding of the Chloride channel, which after time, gets shunted to the ubiquitin-proteasome pathway, even though those proteins, should they make it into the cell membrane, are partially functional, when they make it there.
What are the three mechanisms of protein formation failure?
- Direct knockout - correct structure but, due to a mutation, no function (missing aa’s necessary)
- Destabilization - protein cannot fold
- Toxic conformation - protein now has new, wrong fx due to mutation, or is driven to fold incorrectly.
The glu to val mutation in sickle cell anemia is an example of what protein formation failure?
Toxic conformation
Known as “the guardian of the genome,” this protein transcription factor activates target proteins that participte in cell-cyle arrest or apoptosis.
p53
What is the most frequently mutated protein in cancer, accounting for nearly 30,000 mutations catalogued to date, and the point mutations of which are found in nearly 50% of tumors?
p53
