MétaCan
Menu
Back to cohort
Record W2745817264 · doi:10.1016/j.molmet.2017.08.006

Disruption of the homeodomain transcription factor orthopedia homeobox ( Otp ) is associated with obesity and anxiety

2017· article· en· W2745817264 on OpenAlex
Lee Moir, Elena G. Bochukova, Rebecca Dumbell, Gareth Banks, Rasneer Sonia Bains, Patrick M. Nolan, Cheryl L. Scudamore, Michelle Simon, Kimberly A. Watson, Julia M. Keogh, Elana Henning, Audrey E. Hendricks, Stephen O’Rahilly, Inês Barroso, Adrienne E. Sullivan, David C. Bersten, Murray L. Whitelaw, Susan Kirsch, Elizabeth Bentley, I. Sadaf Farooqi, Roger Cox

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueMolecular Metabolism · 2017
Typearticle
Languageen
FieldPsychology
TopicNeuroendocrine regulation and behavior
Canadian institutionsHospital for Sick Children
FundersNIHR Cambridge Biomedical Research CentreMedical Research CouncilNational Institute for Health and Care ResearchWellcome TrustWellcome
KeywordsHomeoboxTranscription factorHNF1BHomeobox A1EMX2AnxietyObesityHomeobox protein Nkx-2.5BiologyGeneticsEndocrinologyMedicineGenePsychiatry

Abstract

fetched live from OpenAlex

OBJECTIVE: Genetic studies in obese rodents and humans can provide novel insights into the mechanisms involved in energy homeostasis. METHODS: In this study, we genetically mapped the chromosomal region underlying the development of severe obesity in a mouse line identified as part of a dominant N-ethyl-N-nitrosourea (ENU) mutagenesis screen. We characterized the metabolic and behavioral phenotype of obese mutant mice and examined changes in hypothalamic gene expression. In humans, we examined genetic data from people with severe early onset obesity. RESULTS: mice exhibit increased food intake, weight gain, and anxiety when in novel environments or singly housed, phenotypes that may be partially explained by reduced hypothalamic expression of oxytocin and arginine vasopressin. R108W affects the highly conserved homeodomain, impairs DNA binding, and alters transcriptional activity in cells. We sequenced OTP in 2548 people with severe early-onset obesity and found a rare heterozygous loss of function variant in the homeodomain (Q153R) in a patient who also had features of attention deficit disorder. CONCLUSIONS: OTP is involved in mammalian energy homeostasis and behavior and appears to be necessary for the development of hypothalamic neural circuits. Further studies will be needed to investigate the contribution of rare variants in OTP to human energy homeostasis.

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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.477
Threshold uncertainty score0.465

Codex and Gemma teacher scores by category

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

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.

Opus teacher head0.018
GPT teacher head0.282
Teacher spread0.264 · 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