We noted you are experiencing viewing problems
-
Check with your IT department that JWPlatform, JWPlayer and Amazon AWS & CloudFront are not being blocked by your network. The relevant domains are *.jwplatform.com, *.jwpsrv.com, *.jwpcdn.com, jwpltx.com, jwpsrv.a.ssl.fastly.net, *.amazonaws.com and *.cloudfront.net. The relevant ports are 80 and 443.
-
Check the following talk links to see which ones work correctly:
Auto Mode
HTTP Progressive Download Send us your results from the above test links at access@hstalks.com and we will contact you with further advice on troubleshooting your viewing problems. -
No luck yet? More tips for troubleshooting viewing issues
-
Contact HST Support access@hstalks.com
-
Please review our troubleshooting guide for tips and advice on resolving your viewing problems.
-
For additional help, please don't hesitate to contact HST support access@hstalks.com
We hope you have enjoyed this limited-length demo
This is a limited length demo talk; you may
login or
review methods of
obtaining more access.
Printable Handouts
Navigable Slide Index
- Introduction
- The carbonic anhydrase (CA) reaction
- The first known inherited CA deficiency syndrome
- First feature: bone fracture and osteopetrosis
- The reasons for suspecting it was a new disease
- Second feature: renal tubular acidosis (RTA)
- Third feature: cerebral calcification
- What enzyme deficiency produce such defects?
- Patterns of erythrocyte CA I and CA II
- My first paper on carbonic anhydrases
- Osteopetrosis/RTA always true for CA II-deficiency
- 16 structural gene mutations in CA II-deficiency
- The proposed roles of CA II and CA IV
- How do we explain cerebral calcification?
- 1983: 50-year anniversary symposium
- How was carbonic anhydrase discovered?
- Purified enzyme was found to contain zinc
- 1945 - 1960: the middle years
- 1960 - 1980: the protein era
- Other CA family members known by 1983
- Why six enzymes for such a simple reaction?
- Partial answer: compartmentalization
- 260-amino acid CA domain is common to all CAs
- N-terminal a.a sequences of catalytic human CAs
- C-terminal a.a sequences of catalytic human CAs
- CA-related proteins (CARPs)
- Why was CA IV of special interest?
- CA IV in the lumen of the proximal renal tubules
- Immunofluorescent labeling of CA IV
- Cartoon of the CA IV-membrane interaction
- Back to the American family with CA II-deficiency
- What CA IV does in your proximal tubules
- How to prove it? find a CA IV deficient patient
- On to the mouse!
- Mouse knockout has no kidney phenotype
- CA IV and CA XIV in kidney proximal tubules
- Wrong predicted CA IV deficiency phenotype
- Summary of CA IV and CA XIV findings in kidney
- Confocal laser scanning images of CA XIV
- CA XIV enrichment in specific membrane domains
- CA XIV is the membrane CA in the retina
- CA IV and XIV knockout mice
- We thought we were finished with CA IV...
- South African family with retinitis pigmentosa
- What is retinitis pigmentosa (RP)?
- What does the retina look like in RP?
- Rhodopsin mutations and retinal disorders
- Predicted R14W mutation effect on CA IV protein
- Could we find a precedent?
- CA IV is absent in the retina
- CA IV is highly expressed in the choriocapillaris
- A working hypothesis for RP17
- What is the UPR?
- How does the UPR help the cell handle ER stress
- R14W mutant CA expression in COS-7 cells
- R14W mutation reduces-steady state level
- Turnover of R14W and wild-type CA IV protein
- R14W mutation and induction of ER proteins
- R14W CA IV-induced ER stress and apoptosis
- R14W CA IV induces upregulation of CHOP
- R14W CA IV induces Annexin V / TUNEL staining
- Apoptosis-inducing signal sequence in CA IV
- So what? good question!
- If RP17 is a protein folding disease...
- Acetazolamide and R14W CA IV degradation rate
- PBA and R14W CA IV biosynthesis and stability
- Will CA inhibitors reduce UPR gene upregulation?
- Chemical chaperones and apoptosis protection
- Summary
- Future studies
- Immunofluorescence of transgenic retina
- TUNEL staining of retina from control mouse
- R14W CA IV transgenic mouse retina staining
Topics Covered
- Carbonic anhydrase deficiencies
- History of the disease
- Roles of CA II and IV in disease
- Sulfonamide inhibitors for treatment of some disorders
- Characterization of CA isozymes
- CA IV discovery and function
- Mouse knockout models of CA deficiencies
- CA IV, unfolded protein response and retinitis pigmentosa
- ER stress and apoptosis in the choriocapillaris
- Chemical chaperones and treatment of retinitis pigmentosa
- Future studies
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Sly, W. (2007, October 1). Genetic disorders of carbonic anhydrases II and IV [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 1, 2024, from https://doi.org/10.69645/IPNX7682.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. William Sly has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.