The cell-autonomous role of phosphatase orphan 1 in skeletal tissue development
Bibliographic record
Abstract
Introduction.Phosphatase orphan 1 (PHOSPHO1) is a member of the haloacid dehalogenase (HAD) superfamily of Mg +2 -dependent hydrolases, which shows high affinity to phosphocholine and phosphoethanolamine.This intracellular enzyme is highly expressed in mineralized tissues.Global deficiency of PHOSPHO1 in phospho1-/-mice leads to skeletal abnormalities, osteomalacia, scoliosis, and spontaneous fractures.Objective.This manuscript aims to investigate whether the osteoblast-specific restoration of Phospho1 expression in Phospho1-/mice will prevent skeletal abnormalities and improve the mechanical properties of their bones.Methods.We constructed a Col1a1-Phospho1 transgene in which a 2.3 kb proximal Col1a1 promoter drives the osteoblast-specific transgene expression.A total of 5 transgenic lines were generated.Transgene expression was confirmed by semi-quantitative PCR.Phosph01-/-;Col1a1-Phospho1 mice were generated to examine bone mineralization status, bone volume over tissue volume, as well as osteoblast and osteoclast numbers by histomorphometry.Finally, bone mechanical properties were examined using the3-point bending test.Results.Semi-quantitative PCR analyses showed that out of five founders, only one expressed osteoblast-specific Phospho1.Histological analyses showed normal osteoid volume in Phospho1-/--;Col1a1-Phospho1 mice.This reduction of the osteoid volume improves the biomechanical properties of bones in Phospho1-/-;Col1a1-Phospho1 mice, as shown by the 3-point bending test.Overall, there was a reduction in skeletal deformities, as all the bone histomorphometric parameters became comparable to those of wild type mice."O my Lord! expand me my breast; Ease my task for meand remove the impediment from my speech So they may understand what I say" [The Holy Quraan, Taa-Haa: 25-28] I would like to first express my sincere thanks to my supervisor Dr. Monzur Murshed for his guidance throughout my Master's degree and for helping me develop as a researcher in the field of skeletal biology.Your passion for science is inspiring and your patience with students has been much appreciated over the years.I will carry with me all that I have learned as your student throughout my future scientific endeavours.I would like to thank my supervisory committee members, Dr. Mari Kartinen and Dr. Laura Stone.I am extremely fortunate to have had the opportunity to work with this group of dedicated colleagues.My gratitude and appreciation also goes to past and present members of my lab, especially Dr. Jingjing Li, Juliana Marulanda, Sharifa Alebrahim, Garthiga Manickan, Abhinav Parashar, HaithamAlagori and Jobran Moshi Michelle Berkvens.My thank goes to Dr. Hadil Al-Jallad for her unconditional emotional
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".