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Record W4403507148 · doi:10.1101/2024.10.14.618278

Apoptosis is increased in cortical neurons of female Marfan Syndrome mice

2024· preprint· en· W4403507148 on OpenAlexaff
Mitra Esfandiarei, Faizan Anwar, Manogna Nuthi, Alisha Harrison, Mary Eunice Barrameda, Tala Curry, Kasey Pull, Theresa Currier Thomas, Nafisa M. Jadavji

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2024
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicConnective tissue disorders research
Canadian institutionsCarleton UniversityUniversity of British Columbia
FundersNational Institutes of Health
KeywordsMarfan syndromeApoptosisCortical neuronsNeuroscienceInternal medicineBiologyMedicineGenetics

Abstract

fetched live from OpenAlex

Abstract Marfan Syndrome (MFS) is an autosomal dominant genetic disorder that affects connective tissue throughout the body due to mutations in the FBN1 gene. Individuals with MFS display symptoms in different organs, particularly in the vasculature, but the mechanisms of this multi-system dysfunction are still under investigation. There is still a gap in our understanding of the impact of monogenic connective tissue aberrations on the brain. This study aims to determine the impact of MFS on neurodegeneration, in cortical brain tissue of male and female MFS mice. Brain tissue of 6-month-old female and male mice with the FBN1 C1041G/+ mutation and wildtype litter mates was collected and stained for active caspase-3 (ac3), brain derived neurotrophic factor (BDNF), and neuronal nuclei (NeuN) or with TUNEL and DAPI. Data revealed increased levels of ac3 in neurons within the sensory and motor cortical areas of female MFS mice compared to sex- and age-matched controls. We confirm increased levels of apoptosis in MFS mice using TUNEL staining within the same brain areas. We also report increased levels of neuronal BDNF levels in cortical brain tissue of male and female MFS mice. These results indicate a heightened susceptibility for neurodegeneration in the mouse model of MFS. Significance Statement The study revealed that female mice with a FBN1 C1041G/+ mutation have more apoptotic neurons in sensory and motor cortical brain tissue compared to wildtype litter mates.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.004
Threshold uncertainty score0.013

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0020.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0040.001

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.

Opus teacher head0.015
GPT teacher head0.259
Teacher spread0.244 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations1
Published2024
Admission routes1
Has abstractyes

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