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Estudo funcional de variantes estruturais da hemoglobina humana

2009· dissertation· pt· W1006583568 on OpenAlexaboutno aff
Susan E. Jorge

Bibliographic record

Venuenot available
Typedissertation
Languagept
FieldMedicine
TopicHemoglobinopathies and Related Disorders
Canadian institutionsnot available
Fundersnot available
KeywordsMolecular biologyBiology

Abstract

fetched live from OpenAlex

A hemoglobina (Hb), pigmento respiratorio de todos os organismos vertebrados, encontra-se em elevadas concentracoes nas hemacias e e responsavel pelo transporte de O2 dos pulmoes para os tecidos. A Hemoglobina humana constitui-se de dois pares de cadeias polipeptidicas (globinas), cada qual envolvendo um grupo prostetico heme, que se liga reversivelmente ao O2. Mais de 1000 variantes estruturais da Hb humana ja foram descritas, parte delas relacionada a manifestacoes clinicas importantes. Algumas variantes apresentam alteracao funcional, que se traduz em afinidade modificada pelo O2. Quando elevada, ha uma producao compensatoriamente maior de hemacias, levando a policitemia; quando diminuida, resulta em cianose. O Laboratorio de Hemoglobinopatias do Departamento de Patologia Clinica da FCM/UNICAMP e um dos laboratorios de referencia no pais, tendo identificado, ate o momento, 12 hemoglobinas novas e 51 variantes raras. Destas, as variantes novas Hb Hb Boa Esperanca (?16 Lys?Thr), Hb Itapira (?30 Glu?Val), Hb Bom Jesus da Lapa (?30 Glu?Ala), Hb Olinda [s22 (b4) -25 (b7)], Hb Caruaru (s 122 Phe?Ser) e Hb S-Sao Paulo (s6 Glu?Val ; s65 Lys?Glu) foram aqui caracterizadas funcionalmente, assim como as variantes raras Hb Iwata (a87 His??Arg), Hb Sunshine Seth (?94 Asp?His), Hb Deer Lodge (s2 His?Arg), Hb Deer Lodge (s2 His??Arg) + Hb S (s6 Glu??Val), Hb G-Siriraj (s7 Glu??Lys), Hb G-Siriraj (s7 Glu??Lys) e Hb C (s6 Glu??Lys) em associacao, Hb M-Saskatoon (s63 His??Tyr), Hb Redondo (s92 His? Asn), Hb Koln (s98 Val??Met), Hb Coimbra (s99 Asp??Glu) e Hb Dhonburi (s126 Val?Gli)+ Btal. O metodo analitico empregado foi descrito por Rossi-Fanelli & Antonini (1958), e analisa espectrofotometricamente o comportamento da Hb frente a conhecidas pressoes parciais de oxigenio (pO2), possibilitando a medida de afinidade (p50), da constante de Hill (n), que verifica o fenomeno de cooperatividade entre as cadeias globinicas para ligacao do O2, o efeito Bohr (que indica facilidade na ligacao Hb-O2 conforme e elevado o pH do meio), bem como a interacao com o Inositol Hexafosfato (IHP), um fosfato polianion que dificulta a ligacao entre a Hb e o O2. A excecao das Hbs Itapira e Bom Jesus da Lapa, em concentracoes reduzidas nos hemolisados, todas as demais apresentam afinidade alterada pelo oxigenio. Como complementacao ao estudo funcional, as Hbs Caruaru e Sao Paulo tambem foram submetidas a analise por dinâmica molecular, atraves dos programas VMD (Visual Molecular Dynamics), com dados inseridos nos softwares CHARMM (Chemistry at Harvard Molecular Mechanics) e NAMD (Nanoscale Molecular Dynamics). As demais variantes tiveram sua analise estrutural individualizada feita atraves da visualizacao de estruturas nativas depositadas no Protein Data Bank, para melhor compreensao da relacao entre o aminoacido substituido e a funcao proteica alterada. Deste modo, foi possivel estabelecer correlacoes entre a estrutura e a funcao e inferir sobre as manifestacoes clinicas resultantes da presenca destas heme proteinas anomalas, ilustrando-se assim a importância desses estudos para a completa caracterizacao das variantes Abstract

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)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.003
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.012
GPT teacher head0.271
Teacher spread0.259 · 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 designObservational
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".

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Citations1
Published2009
Admission routes1
Has abstractyes

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