Propuesta metodológica para desarrollo de modelos de redes neuronales artificiales supervisadas

En Ciencias de la Computación, la adopción disciplinada de métodos y técnicas permite la resolución de problemas. Se presenta una propuesta metodológica para la construcción de Redes Neuronales Artificiales supervisadas integrando a un ciclo de vida de la Ingeniería del Software las fases contempladas en el desarrollo de los mencionados modelos. Se validó en un dominio de la botánica a fin de ilustrar la resolución de problemas del mundo real. Particularmente, se trata desde una perspectiva de innovación educativa para estudiantes de Sistemas de Información, carrera con una fuerte orientación en temas de Ingeniería del Software, quienes como futuros profesionales se insertan en la academia y en las empresas.UNNEArtículo revisado por pare

BubR1 promotes Bub3-dependent APC/C inhibition during Spindle Assembly Checkpoint signaling.

The spindle assembly checkpoint (SAC) prevents premature sister chromatid separation during mitosis. Phosphorylation of unattached kinetochores by the Mps1 kinase promotes recruitment of SAC machinery that catalyzes assembly of the SAC effector mitotic checkpoint complex (MCC). The SAC protein Bub3 is a phospho-amino acid adaptor that forms structurally related stable complexes with functionally distinct paralogs named Bub1 and BubR1. A short motif ("loop") of Bub1, but not the equivalent loop of BubR1, enhances binding of Bub3 to kinetochore phospho-targets. Here, we asked whether the BubR1 loop directs Bub3 to different phospho-targets. The BubR1 loop is essential for SAC function and cannot be removed or replaced with the Bub1 loop. BubR1 loop mutants bind Bub3 and are normally incorporated in MCC in vitro but have reduced ability to inhibit the MCC target anaphase-promoting complex (APC/C), suggesting that BubR1:Bub3 recognition and inhibition of APC/C requires phosphorylation. Thus, small sequence differences in Bub1 and BubR1 direct Bub3 to different phosphorylated targets in the SAC signaling cascade

Simulando problemas en el ciclo lectivo 2013

Se describe una experiencia realizada en el ciclo lectivo 2013 en la asignatura Modelos y Simulación, fundamentada en el Aprendizaje Basado en Problemas y su abordaje con métodos propios de la asignatura. El designio que guía su abordaje es fomentar el pensamiento crítico, resolutivo y mejorar la construcción de conocimientos de los estudiantes enfocándose en la elaboración de posibles soluciones frente a abstracciones de problemas reales y su resolución con métodos de simulación.Palabra(s) clave(s): Modelos y Simulación, Aprendizaje Basado en Problemas, Construcción del conocimiento

Osteogenesis imperfecta: pregled suvremenih spoznaja o radiologiji koštanoga sustava i nove genetske spoznaje

Osteogenesis imperfecta is a genetically and clinically heterogeneous disorder of bone and connective tissue characterized by osteoporosis, fragile bones, hyperextensible joints, dentinogenesis imperfecta, bluish coloration of the sclerae, and adult-onset hearing loss. Medical history, careful physical examination, radiographic features of fractures, and biochemical analysis of skin collagen are the four cornerstones of accurate diagnosis. As osteogenesis imperfecta affects the whole skeleton, radiologic diagnostic features could be seen on any bone at any age of the patient. A radiology specialist should be aware of subtle changes seen on radiographs of axial skeleton (i.e. skull, spine and pelvic bones) and appendicular skeleton (i.e. long and short bones of extremities) as well as of specific osteogenesis features (i.e. “popcorn” calcifications) and difficult differential diagnosis (i.e. hypertrophic callus formation versus osteosarcoma; child abuse fractures versus true osteogenesis imperfecta). About 300 different mutations have been identified within COL1A1 and COL1A2 genes that encode the chains of type I collagen. More than 90% of these are heterozygous single base pair mutations unique to the affected individuals within families. Depending on the location of the mutation within the collagen gene, these produce a variety of clinical pictures which range from mild (OI type 1), lethal (OI type 2) to severely deforming (OI type 3) and mildly deforming (OI type 4). Each of the four types has a common radiologic appearance that helps in establishing the diagnosis. However, recent findings have confirmed that new genes other than type I collagen could be responsible for three new types of OI (OI type 5; OI type 6 and rhizomelic OI). Here we describe the complexity of the phenotype-genotype correlation in OI, and the recently proposed new classification.Osteogenesis imperfecta (OI) je genetski i klinički heterogena bolest kosti i vezivnoga tkiva s odrednicama: osteoporoza; lomljivost kostiju; labavost zglobova, dentinogenesis imperfecta; plavičaste bjeloočnice i nagluhost u odrasloj dobi. Ključ točne dijagnoze su četiri bitna postupka: precizna anamneza; pažljiv fizikalni pregled; uočavanje radioloških značajka prijeloma i promjena kostiju i biokemijska analiza kolagena kože. Uobičajena je podjela na četiri tipa OI: od blagog (tip 1), letalnog (tip 2) do teško deformirajućeg (tip 3) i umjereno deformirajućeg oblika (tip 4). Svaki od četiri tipa ima zasebne radiološke značajke koje pomažu kod postavljanja točne dijagnoze i klasificiranja. Dijagnostičko-radiološki znaci postoje na cijelom mišićno koštanom sustavu od novorođenačke do kasne životne dobi. Za radiologa je važno prepoznati brojne sićušne i specifične promjene na rendgenogramima aksijalnog (lubanja, kralješnica, zdjelica) i apendikularnog (kosti udova) skeleta. Znaci korisni u diferenciranju osteosarkoma prema stvaranju hipertrofičnog koštanog kalusa kod OI i drugi posebni znaci bolesti, primjerice metafizne “popcorn” kalcifikacije, prepoznaju se dobrom radiološkom obradom. Dosad je otkriveno oko 300 različitih mutacija na COL1A1 i COL1A2 genima odgovornima za oblikovanje lanaca kolagena tip I. Klinička slika OI razlikuje se prema mjestu mutacije na genu za kolagen. Nedavni nalazi su potvrdili da i drugi geni, uz kolagen tip 1, mogu biti odgovorni za nastanak tri nova tipa OI: tip 5; tip 6 i rizomelični tip OI. Nadalje, u tekstu je opisana složenost fenotipske i genotipske korelacije, kao i nedavno predložena nova klasifikacija OI

Osteogenesis imperfecta: pregled suvremenih spoznaja o radiologiji koštanoga sustava i nove genetske spoznaje

Osteogenesis imperfecta is a genetically and clinically heterogeneous disorder of bone and connective tissue characterized by osteoporosis, fragile bones, hyperextensible joints, dentinogenesis imperfecta, bluish coloration of the sclerae, and adult-onset hearing loss. Medical history, careful physical examination, radiographic features of fractures, and biochemical analysis of skin collagen are the four cornerstones of accurate diagnosis. As osteogenesis imperfecta affects the whole skeleton, radiologic diagnostic features could be seen on any bone at any age of the patient. A radiology specialist should be aware of subtle changes seen on radiographs of axial skeleton (i.e. skull, spine and pelvic bones) and appendicular skeleton (i.e. long and short bones of extremities) as well as of specific osteogenesis features (i.e. “popcorn” calcifications) and difficult differential diagnosis (i.e. hypertrophic callus formation versus osteosarcoma; child abuse fractures versus true osteogenesis imperfecta). About 300 different mutations have been identified within COL1A1 and COL1A2 genes that encode the chains of type I collagen. More than 90% of these are heterozygous single base pair mutations unique to the affected individuals within families. Depending on the location of the mutation within the collagen gene, these produce a variety of clinical pictures which range from mild (OI type 1), lethal (OI type 2) to severely deforming (OI type 3) and mildly deforming (OI type 4). Each of the four types has a common radiologic appearance that helps in establishing the diagnosis. However, recent findings have confirmed that new genes other than type I collagen could be responsible for three new types of OI (OI type 5; OI type 6 and rhizomelic OI). Here we describe the complexity of the phenotype-genotype correlation in OI, and the recently proposed new classification.Osteogenesis imperfecta (OI) je genetski i klinički heterogena bolest kosti i vezivnoga tkiva s odrednicama: osteoporoza; lomljivost kostiju; labavost zglobova, dentinogenesis imperfecta; plavičaste bjeloočnice i nagluhost u odrasloj dobi. Ključ točne dijagnoze su četiri bitna postupka: precizna anamneza; pažljiv fizikalni pregled; uočavanje radioloških značajka prijeloma i promjena kostiju i biokemijska analiza kolagena kože. Uobičajena je podjela na četiri tipa OI: od blagog (tip 1), letalnog (tip 2) do teško deformirajućeg (tip 3) i umjereno deformirajućeg oblika (tip 4). Svaki od četiri tipa ima zasebne radiološke značajke koje pomažu kod postavljanja točne dijagnoze i klasificiranja. Dijagnostičko-radiološki znaci postoje na cijelom mišićno koštanom sustavu od novorođenačke do kasne životne dobi. Za radiologa je važno prepoznati brojne sićušne i specifične promjene na rendgenogramima aksijalnog (lubanja, kralješnica, zdjelica) i apendikularnog (kosti udova) skeleta. Znaci korisni u diferenciranju osteosarkoma prema stvaranju hipertrofičnog koštanog kalusa kod OI i drugi posebni znaci bolesti, primjerice metafizne “popcorn” kalcifikacije, prepoznaju se dobrom radiološkom obradom. Dosad je otkriveno oko 300 različitih mutacija na COL1A1 i COL1A2 genima odgovornima za oblikovanje lanaca kolagena tip I. Klinička slika OI razlikuje se prema mjestu mutacije na genu za kolagen. Nedavni nalazi su potvrdili da i drugi geni, uz kolagen tip 1, mogu biti odgovorni za nastanak tri nova tipa OI: tip 5; tip 6 i rizomelični tip OI. Nadalje, u tekstu je opisana složenost fenotipske i genotipske korelacije, kao i nedavno predložena nova klasifikacija OI

Comparison of three methods of DNA extraction from human bones with different degrees of degradation

There is a necessity for deceased identification as a result of many accidents and sometimes bones are the only accessible source of DNA. So far, a universal method that allows for extraction of DNA from materials at different stages of degradation does not exist. The aims of this study were: the comparison of three methods of DNA extraction from bones with different degree of degradation and an evaluation of the usefulness of these methods in forensic genetics. The efficiency of DNA extraction, the degree of extract contamination by polymerase chain reaction (PCR) inhibitors and the possibility of determining the STR loci profile were especially being compared. Nuclear DNA from bones at different states of degradation was isolated using three methods: classical, organic phenol–chloroform extraction, DNA extraction from crystal aggregates and extraction by total demineralisation. Total demineralisation is the best method for most cases of DNA extraction from bones, although it does not provide pure DNA. DNA extraction from aggregates removes inhibitors much better and is also a good method of choice when identity determination of exhumed remains is necessary. In the case of not buried bones (remains found outside) total demineralisation or phenol–chloroform protocols are more efficient for successful DNA extraction

Mutations in HNF1A Result in Marked Alterations of Plasma Glycan Profile

A recent genome-wide association study identified hepatocyte nuclear factor 1-α (HNF1A) as a key regulator of fucosylation. We hypothesized that loss-of-function HNF1A mutations causal for maturity-onset diabetes of the young (MODY) would display altered fucosylation of N-linked glycans on plasma proteins and that glycan biomarkers could improve the efficiency of a diagnosis of HNF1A-MODY. In a pilot comparison of 33 subjects with HNF1A-MODY and 41 subjects with type 2 diabetes, 15 of 29 glycan measurements differed between the two groups. The DG9-glycan index, which is the ratio of fucosylated to nonfucosylated triantennary glycans, provided optimum discrimination in the pilot study and was examined further among additional subjects with HNF1A-MODY (n = 188), glucokinase (GCK)-MODY (n = 118), hepatocyte nuclear factor 4-α (HNF4A)-MODY (n = 40), type 1 diabetes (n = 98), type 2 diabetes (n = 167), and nondiabetic controls (n = 98). The DG9-glycan index was markedly lower in HNF1A-MODY than in controls or other diabetes subtypes, offered good discrimination between HNF1A-MODY and both type 1 and type 2 diabetes (C statistic ≥ 0.90), and enabled us to detect three previously undetected HNF1A mutations in patients with diabetes. In conclusion, glycan profiles are altered substantially in HNF1A-MODY, and the DG9-glycan index has potential clinical value as a diagnostic biomarker of HNF1A dysfunction

Toward Male Individualization with Rapidly Mutating Y-Chromosomal Short Tandem Repeats

Peer reviewe

Mps1Mph1 kinase phosphorylates Mad3 to inhibit Cdc20Slp1-APC/C and maintain spindle checkpoint arrests

<div><p>The spindle checkpoint is a mitotic surveillance system which ensures equal segregation of sister chromatids. It delays anaphase onset by inhibiting the action of the E3 ubiquitin ligase known as the anaphase promoting complex or cyclosome (APC/C). Mad3/BubR1 is a key component of the mitotic checkpoint complex (MCC) which binds and inhibits the APC/C early in mitosis. Mps1^Mph1 kinase is critical for checkpoint signalling and MCC-APC/C inhibition, yet few substrates have been identified. Here we identify Mad3 as a substrate of fission yeast Mps1^Mph1 kinase. We map and mutate phosphorylation sites in Mad3, producing mutants that are targeted to kinetochores and assembled into MCC, yet display reduced APC/C binding and are unable to maintain checkpoint arrests. We show biochemically that Mad3 phospho-mimics are potent APC/C inhibitors <i>in vitro</i>, demonstrating that Mad3p modification can directly influence Cdc20^Slp1-APC/C activity. This genetic dissection of APC/C inhibition demonstrates that Mps1^Mph1 kinase-dependent modifications of Mad3 and Mad2 act in a concerted manner to maintain spindle checkpoint arrests.</p></div