5 research outputs found
Study of the development and anatomy of the torus longitudinalis and marginal layer of the optic tectum in larval and juvenile zebrafish (Danio rerio)
El
toro
longitudinal
es
una
estructura
localizada
en
el
mesencéfalo
de
peces
teleósteos
y
estrechamente
asociada
con
el
techo
óptico.
Consiste
fundamentalmente
en
una
masa
de
células
grano
densamente
empaquetadas
y
encajadas
justo
por
debajo
de
la
comisura
intertectal.
Éstas
células
envían
axones
al
estrato
marginal,
la
capa
más
superficial
del
techo
óptico,
donde
se
orientan
en
paralelo
y
establecen
sinapsis
con
neuronas
piramidales
o
de
tipo
I.
Debido
a
sus
similitudes
con
los
circuitos
del
cerebelo,
el
toro
longitudinal-‐
estrato
marginal
se
considera
una
estructura
“cerebellum-‐like”.
Pese
a
que
el
pez
cebra
es
un
importante
sistema
modelo
para
estudios
funcionales
y
de
desarrollo,
se
desconoce
la
anatomía
y
función
del
toro
longitudinal
tanto
en
el
adulto
como
en
la
larva
de
esta
especie.
Por
tanto,
hemos
estudiado
la
organización
anatómica
del
toro
longitudinal
en
el
adulto
de
pez
cebra
mediante
una
tinción
general
de
tipo
Nissl.
Además,
hemos
utilizado
una
técnica
inmunofluorescente
frente
a
vesículas
sinápticas
(SV-‐2)
para
tratar
de
delimitar
el
estrato
marginal
del
techo
óptico.
Esta
misma
tinción
fue
utilizada
para
determinar
el
desarrollo
del
toro
longitudinal
en
la
larva
de
5
y
10
días
post-‐fertilización.
Como
resultado,
generamos
un
atlas
mostrando
la
anatomía
general
del
toro
longitudinal
en
el
adulto
de
pez
cebra,
pudiendo
diferenciar
dos
tipos
celulares:
células
pequeñas
(células
tipo
grano)
y
células
de
mayor
tamaño.
Estos
resultados
coinciden
con
estudios
anteriores
sobre
esta
estructura
en
otras
especies.
Observamos
también
que,
en
contraposición
a
lo
que
sugerían
estudios
preliminares,
el
toro
longitudinal
parece
estar
ya
presente
a
los
5
días
post-‐fertilización.
Por
tanto,
se
trata
de
una
estructura
de
desarrollo
temprano.
En
cuanto
al
estrato
marginal,
con
las
técnicas
aplicadas
no
pudimos
delimitarlo
claramente.Traballo fin de grao (UDC.CIE). Bioloxía. Curso 2013/201
Anatomy and Connectivity of the Torus Longitudinalis of the Adult Zebrafish
[Abstract] This study describes the cytoarchitecture of the torus longitudinalis (TL) in adult zebrafish by using light and electron microscopy, as well as its main connections as revealed by DiI tract tracing. In addition, by using high resolution confocal imaging followed by digital tracing, we describe the morphology of tectal pyramidal cells (type I cells) that are GFP positive in the transgenic line Tg(1.4dlx5a-dlx6a:GFP)ot1. The TL consists of numerous small and medium-sized neurons located in a longitudinal eminence attached to the medial optic tectum. A small proportion of these neurons are GABAergic. The neuropil shows three types of synaptic terminals and numerous dendrites. Tracing experiments revealed that the main efference of the TL is formed of parallel-like fibers that course within the marginal layer of the optic tectum. A toral projection to the thalamic nucleus rostrolateralis is also observed. Afferents to the TL come from visual and cerebellum-related nuclei in the pretectum, namely the central, intercalated and the paracommissural pretectal nuclei, as well as from the subvalvular nucleus in the isthmus. Additional afferents to the TL may come from the cerebellum but their origins could not be confirmed. The tectal afferent projection to the TL originates from cells similar to the type X cells described in other cyprinids. Tectal pyramidal neurons show round or piriform cell bodies, with spiny apical dendritic trees in the marginal layer. This anatomical study provides a basis for future functional and developmental studies focused on this cerebellum-like circuit in zebrafish.IB was supported by a Sir Henry Dale Fellowship from the Royal Society and Wellcome Trust (101195/Z/13/Z) and a UCL Excellence Fellowship. This project was also funded by University of A CoruñaReino Unido. Royal Society; 101195/Z/13/
Modeling ANXA2-overexpressing circulating tumor cells homing and high throughput screening for metastasis impairment in endometrial carcinomas
Cèl·lules tumorals circulants; Micrometàstasi; DaunorrubicinaCélulas tumorales circulantes; Micrometástasis; DaunorrubicinaCirculating tumor cells; Micrometastasis; DaunorubicinEndometrial cancer (EC) is the most common neoplasm of the female reproductive tract in the developed world. Patients usually are diagnosed in early stage having a good prognosis. However, up to 20–25% of patients are diagnosed in advanced stages and have a higher risk of recurrence, making the prognosis worse. Previously studies identified ANXA2 as a predictor of recurrent disease in EC even in low risk patients. Furthermore, Circulating Tumor Cells (CTC) released from the primary tumor into the bloodstream, are plasticity entities responsible of the process of metastasis, becoming into an attractive clinical target. In this work we validated ANXA2 expression in CTC from high-risk EC patients. After that, we modelled in vitro and in vivo the tumor cell attachment of ANXA2-expressing CTC to the endothelium and the homing for the generation of micrometastasis. ANXA2 overexpression does not provide an advantage in the adhesion process of CTC, but it could be playing an important role in more advanced steps, conferring a greater homing capacity. We also performed a high-throughput screening (HTS) for compounds specifically targeting ANXA2, and selected Daunorubicin as candidate hit. Finally, we validated Daunorubicin in a 3D transendothelial migration system and also in a in vivo model of advanced EC, demonstrating the ability of Daunorubicin to inhibit the proliferation of ANXA2-overexpressing tumor cells.This work was supported by grants from the Instituto de Salud Carlos III ( ISCIII ), grant PI17/01919 and PI20/00969 , co-financed by the European Regional Development Fund (FEDER); from Fundación Científica de la Asociación Española Contra el Cáncer (AECC), Grupos Clínicos Coordinados 2018; Xunta de Galicia ( ED431C 2018/21 ); Ministry of Economy and Competiveness (Innopharma Project) and from CIBERONC ( CB16/12/00328 ); Carolina Herrero is supported by a predoctoral i-PFIS fellowship from Instituto de Salud Carlos III ( IFI17/00047 )
Modeling ANXA2-overexpressing circulating tumor cells homing and high throughput screening for metastasis impairment in endometrial carcinomas
Endometrial cancer (EC) is the most common neoplasm of the female reproductive tract in the developed world. Patients usually are diagnosed in early stage having a good prognosis. However, up to 20–25% of patients are diagnosed in advanced stages and have a higher risk of recurrence, making the prognosis worse. Previously studies identified ANXA2 as a predictor of recurrent disease in EC even in low risk patients. Furthermore, Circulating Tumor Cells (CTC) released from the primary tumor into the bloodstream, are plasticity entities responsible of the process of metastasis, becoming into an attractive clinical target. In this work we validated ANXA2 expression in CTC from high-risk EC patients. After that, we modelled in vitro and in vivo the tumor cell attachment of ANXA2-expressing CTC to the endothelium and the homing for the generation of micrometastasis. ANXA2 overexpression does not provide an advantage in the adhesion process of CTC, but it could be playing an important role in more advanced steps, conferring a greater homing capacity. We also performed a high-throughput screening (HTS) for compounds specifically targeting ANXA2, and selected Daunorubicin as candidate hit. Finally, we validated Daunorubicin in a 3D transendothelial migration system and also in a in vivo model of advanced EC, demonstrating the ability of Daunorubicin to inhibit the proliferation of ANXA2-overexpressing tumor cells
Prevalence of reduced lung diffusing capacity and CT scan findings in smokers without airflow limitation: a population-based study
Background Population distribution of reduced diffusing capacity of the lungs for carbon monoxide (DLCO) in smokers and main consequences are not properly recognised. The objectives of this study were to describe the prevalence of reduced DLCO in a population-based sample of current and former smoker subjects without airflow limitation and to describe its morphological, functional and clinical implications.Methods A sample of 405 subjects aged 40 years or older with postbronchodilator forced expiratory volume in 1 s/forced vital capacity (FVC) >0.70 was obtained from a random population-based sample of 9092 subjects evaluated in the EPISCAN II study. Baseline evaluation included clinical questionnaires, exhaled carbon monoxide (CO) measurement, spirometry, DLCO determination, 6 min walk test, routine blood analysis and low-dose CT scan with evaluation of lung density and airway wall thickness.Results In never, former and current smokers, prevalence of reduced DLCO was 6.7%, 14.4% and 26.7%, respectively. Current and former smokers with reduced DLCO without airflow limitation were younger than the subjects with normal DLCO, and they had greater levels of dyspnoea and exhaled CO, greater pulmonary artery diameter and lower spirometric parameters, 6 min walk distance, daily physical activity and plasma albumin levels (all p<0.05), with no significant differences in other chronic respiratory symptoms or CT findings. FVC and exhaled CO were identified as independent risk factors for low DLCO.Conclusion Reduced DLCO is a frequent disorder among smokers without airflow limitation, associated with decreased exercise capacity and with CT findings suggesting that it may be a marker of smoking-induced early vascular damage.Trial registration number NCT03028207