74 research outputs found
Retinal pigment epithelium degeneration caused by aggregation of PRPF31 and the role of HSP70 family of proteins
Background
Mutations in pre-mRNA splicing factor PRPF31 can lead to retinitis pigmentosa (RP). Although the exact disease mechanism remains unknown, it has been hypothesized that haploinsufficiency might be involved in the pathophysiology of the disease.
Methods
In this study, we have analyzed a mouse model containing the p.A216P mutation in Prpf31 gene.
Results
We found that mutant Prpf31 protein produces cytoplasmic aggregates in the retinal pigment epithelium and decreasing the protein levels of this splicing factor in the nucleus. Additionally, normal protein was recruited in insoluble aggregates when the mutant protein was overexpressed in vitro. In response to protein aggregation, Hspa4l is overexpressed. This member of the HSP70 family of chaperones might contribute to the correct folding and solubilization of the mutant protein, allowing its translocation to the nucleus.
Conclusions
Our data suggests that a mechanism haploinsufficiency and dominant-negative is involved in retinal degeneration due to mutations in PRPF31. HSP70 over-expression might be a new therapeutic target for the treatment of retinal degeneration due to PRPF31 mutations.This project has been financed through a) The ISCIII (Miguel Servet-I, 2015), co-financed by the European Regional Development Fund (ERDF), No CP15/00071. b) The European Union’s Horizon 2020 research and innovation program, under grant agreement No 634479. c) Regional Ministry of Economy, Innovation and Science of the Junta de Andalucía, No P09-CTS-04967.info:eu-repo/semantics/publishedVersio
Estimación del sexo a partir del diámetro de la cabeza humeral y femoral en poblaciones mexicanas de época prehispánica y contemporánea
In bioarchaeology and forensic anthropology the most reliable skeletal element for sex estimation is the pelvis; nevertheless, when it is missing, other postcranial elements must be used. The main goal of this research is to provide sectioning points for sex assessment from humeral and femoral head diameters for three prehispanic and two contemporary Mexican populations. Using a sliding caliper, a total of 386 (45.3% female and 54.6% male) humeral and femoral head diameters were recorded. The sectioning point was calculated as the mean between sexes, and univariate independent sample t-tests were performed to test significant differences between sexes. The results demonstrate significant sexual differences in all populations and high percentages of correct sex classification (90%-94%). We conclude that the proposed cut-off points can be used as an alternative for sex estimation in Mexican populations, in contexts with incomplete skeletons and/or fragmented bones.Tanto en bioarqueología como en antropología forense, la pelvis es el elemento óseo con mayor confiabilidad para la estimación sexual; no obstante, cuando no está presente, otros elementos deben ser utilizados. Es por ello que el objetivo principal de este trabajo es proveer puntos de corte para estimar el sexo a partir del diámetro de la cabeza del húmero y del fémur, en poblaciones mexicanas (tres prehispánicas y dos contemporáneas). Utilizando el compás de corredera, se midió un total de 386 (45,3% femeninos y 54.6% masculinos) diámetros de la cabeza humeral y femoral. Los resultados demuestran diferencias estadísticamente significativas entre sexos en todas las poblaciones y altos porcentajes de clasificación sexual correcta (90%-94%). Por lo tanto, concluimos que los puntos de corte propuestos pueden ser utilizados como una alternativa para la estimación sexual, para la población mexicana, en contextos con esqueletos incompletos y/o huesos fragmentados.Asociación de Antropología Biológica Argentin
Reconstructing the impact of human activities in a NW Iberian Roman mining landscape for the last 2500 years
This article was made available through the Brunel Open Access Publishing Fund.Little is known about the impact of human activities during Roman times on NW Iberian mining landscapes beyond the geomorphological transformations brought about by the use of hydraulic power for gold extraction. We present the high-resolution pollen record of La Molina mire, located in an area intensely used for gold mining (Asturias, NW Spain), combined with other proxy data from the same peat core to identify different human activities, evaluate the strategies followed for the management of the resources and describe the landscape response to human disturbances. We reconstructed the timing and synchronicity of landscape changes of varying intensity and form occurred before, during and after Roman times. An open landscape was prevalent during the local Late Iron Age, a period of relatively environmental stability. During the Early Roman Empire more significant vegetation shifts took place, reflected by changes in both forest (Corylus and Quercus) and heathland cover, as mining/metallurgy peaked and grazing and cultivation increased. In the Late Roman Empire, the influence of mining/metallurgy on landscape change started to disappear. This decoupling was further consolidated in the Germanic period (i.e., Visigothic and Sueve domination of the region), with a sharp decrease in mining/metallurgy but continued grazing. Although human impact was intense in some periods, mostly during the Early Roman Empire, forest regeneration occurred afterwards: clearances were local and short-lived. However, the Roman mining landscape turned into an agrarian one at the onset of the Middle Ages, characterized by a profound deforestation at a regional level due to a myriad of human activities that resulted in an irreversible openness of the landscape. © 2014 The Authors
Evidence for association between structural variants in lissencephaly-related genes and executive deficits in schizophrenia or bipolar patients from a Spanish isolate population
There is evidence for an association between structural variants in genes for lissencephaly, which are involved in neuronal migration, and prefrontal cognitive deficits in schizophrenia and bipolar patients. On the basis of these intriguing findings, we analyzed 16 markers located in the lissencephaly critical region (LCR in chromosome 17p13.3) in 124 schizophrenic, 56 bipolar, and 141 healthy individuals. All recruits were from a Spanish population isolate of Basque origin that is characterized by low genetic heterogeneity. In addition, we examined whether structural genomic variations in the LCR were associated with executive cognition. Twenty-three patients (12.8%), but none of the controls, showed structural variants (deletions and insertions) in either of two markers related with lissencephaly (D17S1566 on tumor suppressor gene TP53: tumor protein p53 and D17S22 on SMG6 gene: Smg-6 homolog, nonsense mediated mRNA decay factor- Caenorhabditis elegans). These patients performed significantly worse in the Wisconsin Card Sorting Test-Categories in comparison with patients without such variations in lissencephaly-related genes. The presence of structural variants was related to completed categories, and accounted for 10.7% of the variance (P= 0.001). Finally, logistic regression showed that poor Wisconsin Card Sorting Test-Categories performance was the only predictor of belonging to the positive LCR variations group. These new findings provide further evidence for the association between some lissencephaly-related genes and both schizophrenia and bipolar disorder, and influence on frontal executive functioning. © 2008 Wolters Kluwer Health|Lippincott Williams & Wilkins.FIS-MSC PI051293, AstraZeneca, Spanish Ministry of Health, Instituto de Salud Carlos III, Ciber en Salud Mental (CIBER-SAM) GV2005-303.Peer Reviewe
Mutations in TP53 and JAK2 are independent prognostic biomarkers in B-cell precursor acute lymphoblastic leukaemia
[EN]Background:
In B-cell precursor acute lymphoblastic leukaemia (B-ALL), the identification of additional genetic alterations associated with poor prognosis is still of importance. We determined the frequency and prognostic impact of somatic mutations in children and adult cases with B-ALL treated with Spanish PETHEMA and SEHOP protocols.
Methods:
Mutational status of hotspot regions of TP53, JAK2, PAX5, LEF1, CRLF2 and IL7R genes was determined by next-generation deep sequencing in 340 B-ALL patients (211 children and 129 adults). The associations between mutation status and clinicopathological features at the time of diagnosis, treatment outcome and survival were assessed. Univariate and multivariate survival analyses were performed to identify independent prognostic factors associated with overall survival (OS), event-free survival (EFS) and relapse rate (RR).
Results:
A mutation rate of 12.4% was identified. The frequency of adult mutations was higher (20.2% vs 7.6%, P=0.001). TP53 was the most frequently mutated gene (4.1%), followed by JAK2 (3.8%), CRLF2 (2.9%), PAX5 (2.4%), LEF1 (0.6%) and IL7R (0.3%). All mutations were observed in B-ALL without ETV6-RUNX1 (P=0.047) or BCR-ABL1 fusions (P<0.0001). In children, TP53mut was associated with lower OS (5-year OS: 50% vs 86%, P=0.002) and EFS rates (5-year EFS: 50% vs 78.3%, P=0.009) and higher RR (5-year RR: 33.3% vs 18.6% P=0.037), and was independently associated with higher RR (hazard ratio (HR)=4.5; P=0.04). In adults, TP53mut was associated with a lower OS (5-year OS: 0% vs 43.3%, P=0.019) and a higher RR (5-year RR: 100% vs 61.4%, P=0.029), whereas JAK2mut was associated with a lower EFS (5-year EFS: 0% vs 30.6%, P=0.035) and a higher RR (5-year RR: 100% vs 60.4%, P=0.002). TP53mut was an independent risk factor for shorter OS (HR=2.3; P=0.035) and, together with JAK2mut, also were independent markers of poor prognosis for RR (TP53mut: HR=5.9; P=0.027 and JAK2mut: HR=5.6; P=0.036).
Conclusions:
TP53mut and JAK2mut are potential biomarkers associated with poor prognosis in B-ALL patients.European Commision (EC). Funding FP7/SP1/HEALTH. Project Code: 30624
Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)
This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe
POR UNA CULTURA DE PAZ: UNA MIRADA DESDE LAS CIENCIAS DE LA CONDUCTA
En
virtud
de
lo
anterior,
los
estudiosos
de
las
ciencias
de
la
conducta
de
la
Universidad
Autónoma
del
Estado
de
México,
ante
la
persistencia
y
proliferación
de
estos
hechos
en
diversas
partes
del
Mundo
y
de
nuestro
país
en
particular, se
convocó
a
los
estudiosos
interesados
y
a
la
sociedad
en
general
a
presentar
trabajos
para
analizar,
debatir
y
proponer
estrategias
de
acción
y
dirección,
que
fortalezcan
una
convivencia y bienestar con sentido humanista para una cultura de paz.
El
presente
texto
es
producto
de
esta convocatoria
que
recoge
los
trabajos
de
los
interesados
en
la
temática,
de
diferentes
países
(España,
Argentina,
Cuba,
Brasil,
Costa
Rica
y
México)
retomando
con
ello
sus
experiencias
relativas
al
estudio,
análisis,
comprensión
e
instrumentación
de
la
cultura
de
paz
en
los
distintos
ámbitos
institucionales
en
los
que
participan:
educativo,
salud,
penitenciario,
social,
laboral,
familia,
alimentario,
psicológico,
por
mencionar
algunos.
El
presente
libro,
propicia
un
espacio
de
reflexión,
diálogo
y
posicionamiento
de
las
ciencias
de
la
conducta
para
la
apropiación,
análisis,
debate
y
propuestas
que
fortalezcan
una
cultura
de
paz
a
través
de
la
convivencia
y
el
bienestar
social
con
sentido
humanista.
El
sistema
económico
neoliberal
y
el
proceso
de
globalización
han
contribuido
al
logro
de
avances
significativos
en
la
ciencia
y
la
tecnología,
pero
también
han
propiciado
la
polarización
de
las
sociedades
lo
que
ha
impactado
de
manera
negativa
a
la
sociedad
en
su
conjunto,
pero
en
mayor
medida
a
los grupos
vulnerables. Dicha
polarización
ha
traído
consigo
un
desarrollo
desigual
del
mundo
que
se
expresa
de
diferentes
maneras
tanto
en
países
desarrollados
como
en
los
llamados
del
tercer
mundo,
en
donde
no
están
satisfechas
las
necesidades
humanas
elementales
de
todos
los
sectores
de
la
población,
siempre
falta
algo.
Si
a
esto
le
sumamos
los
conflictos
internacionales por
diferentes
motivos
que
enfrentan
algunas
naciones,
una
insuficiente
cobertura
educativa
y
de
salud,
desempleo
y
pobreza
extrema,
entre
otras
cosas;
estamos
frente
a
retos
de
gran
envergadura
para
los
gobiernos,
para
los
estudiosos
y
para
la
sociedad
civil
en
general. Uno
de
los
intentos
para
frenar
y prevenir
la
agudización
de
estas
problemáticas
es
la
cultura
de
paz,
cuyo
estudio
y propuestas
han
ido
avanzando
en
diferentes
sentidos
y
de
manera
favorable,
el
tema
está
presente
en
diferentes
Organismos
Internacionales
como
la
ONU,
la
UNESCO,
la
OCDE,
El
Banco
Mundial,
entre
otros.
Pero
falta
mucho
por
hacer.Universidad Autónoma del Estado de Méxic
una mirada desde las Ciencias de la Conducta
Este libro es el resultado de los trabajos presentados en el 1er Congreso Internacional "Convivencia y bienestar con sentido humanista para una cultura de paz"
Diseño para el desarrollo sustentable y la habitabilidad segura e incluyente
Este libro se divide en dos partes que permiten permear en el campo de la enseñanza del diseño; la primera se enfoca en temáticas que se desprenden del diseño en la educación para la sustentabilidad; en la segunda, se identifican las tendencias del diseño como un modo de verlo y sentirlo: va desde el diseño emocional hacia uno de conservación, reúso y reparación de objetos para reducir el consumo de recursos materiales
- …