Hipótesis sobre la posición tectónica de la Sierra Arana (Granada)

La unidad de Sierra Arana, situada al NE de Granada, presenta caracteres estratigráficos bastante diferentes de las unidades más próximas (Sierra Elvira e Iznalloz). Por consideraciones paleogeográficas no es posible explicar satisfactoriatnctite el heteropismo entre la serie de Sierra Arana y las otras dos mencioriadas, como un simple cambio lateral de facies. De otro lado, es grande el parecido estratigráfico de Sierra Arana con unidades alóctonas del Subético Interno. En consecuencia se propone, como hipótesis verosímil, el carácter alóctono de la unidad de Sierra Arana

Datos estratigráficos sobre la serie mesozica del río de las Juntas (Montillana, Zona Subbética, Granada)

Se describe un corte de la serie mesozoica correspondiente al dominio Subbético medio. Una abundante fauna de Amonites precisa la edad Aalenense-Bajocense de una colada volcánica submarina interestratificada en la serie

Los Mantos apujárrides del tercio central de las Cordilleras Béticas. Ensayo de la correlación tectónica de los Alpujárrides

Los Mantos Alpujárrides se componen de una secuencia metapelítica constituída en general por tres formaciones esquistosas (Paleozoico-Triásico inferior), coronada por series carbonatadas triásicas; se detectan diferencias esiratigráficas de unos mantos a otros, sobre todo entre términos permetriásicos. Las superficies de corrimiento han cizallado la sucesión alpujárride y se hallan situadas a niveles diferentes según los mantos. El metamorfismo -y también varias fases de plegamiento- es anterior a la tectónica de corrimiento y ha afectado a los materiales con una intensidad variable, dependiente de las posiciones ocupadas por los mantos en el orógeno. Una vez discutido el valor de estas características como criterios para el agrupamiento de los Alpujárrides y considerando la posición de cada unidad en la pila de mantos, se ha realizado una subdivisión engrupos de mantos que poseen el carácter de subconjuntos con entidad tectónica significativa fundados esencialmente en datos y observaciones de los autores sobre el tercio central de las Cordilleras Béticas, se proponen los siguientes grupos: Lujar, Guadalfeo, Contraviesa y Almijara.Estos grupos tienen validez para el resto de la Zona Bética y se han usado en la correlación de elementos tectónicos de distintas áreas

Estudio geológico del sector de Puerto-López (Granada, zona subbética)

La geología del sector de Puerto-López, situado al NW de Granada, ofrece varios aspectos de interés. Hemos podido establecer la sucesión  estratigráfica, con términos comprendidos entre el Lías y el Senonense, con dataciones muchas veces precisas gracias a las faunas de Ammonites. La estructura es relativamente violenta y son de destacar los pliegues vergentes al S y las fallas inversas del mismo sentido. Por la naturaleza de la serie y por su posición en el Subbético medio, se ha llegado a la correlación de la serie establecida con otras series subbéticas, de la transversal de Granada

Sobre el Jurásico del Mencal y su relación con otras series sub-béticas de la transversal de Granada

Se describen nuevos términos pertenecientes a la serie jurásica del Mencal (Morrón de la Meseta), junto con otros de un corte próximo a Iznalloz (Granada). Ambas series se correlacionan entre si y con otras series que constituyen un umbral en la cuenca sedimentaria subbética

Converging circuits between pain and depression: the ventral tegmental area as a therapeutic hub

Chronic pain and depression are highly prevalent pathologies and cause a major socioeconomic burden to society. Chronic pain affects the emotional state of the individuals suffering from it, while depression worsens the prognosis of chronic pain patients and may diminish the effectiveness of pain treatments. There is a high comorbidity rate between both pathologies, which might share overlapping mechanisms. This review explores the evidence pinpointing a role for the ventral tegmental area (VTA) as a hub where both pain and emotional processing might converge. In addition, the feasibility of using the VTA as a possible therapeutic target is discussed. The role of the VTA, and the dopaminergic system in general, is highly studied in mood disorders, especially in deficits in reward-processing and motivation. Conversely, the VTA is less regarded where it concerns the study of central mechanisms of pain and its mood-associated consequences. Here, we first outline the brain circuits involving central processing of pain and mood disorders, focusing on the often-understudied role of the dopaminergic system and the VTA. Next, we highlight the state-of-the-art findings supporting the emergence of the VTA as a link where both pathways converge. Thus, we envision a promising part for the VTA as a putative target for innovative therapeutic approaches to treat chronic pain and its effects on mood. Finally, we emphasize the urge to develop and use animal models where both pain and depression-like symptoms are considered in conjunction

Leptin and Gestational Diabetes Mellitus

Emerging research has highlighted the importance of leptin in fetal growth and development, independent of its essential role in the regulation of feeding and energy metabolism. Leptin is now considered an important signaling molecule of the reproductive system, since it regulates the production of gonadotropins, the blastocyst formation and implantation, the normal placentation, as well as the feto-placental communication. Placental leptin is an important cytokine which regulates placental functions in an autocrine or paracrine manner. Leptin seems to play a crucial role during the first stages of pregnancy as it modulates critical processes like proliferation, protein synthesis, invasion, and apoptosis in placental cells. Furthermore, deregulation of leptin levels has been correlated with the pathogenesis of various disorders associated with reproduction and gestation, including gestational diabetes mellitus (GDM). Due to the relevant incidence of the GDM and the importance of leptin, we decided to review the latest information available about leptin action in normal and GDM pregnancies to support the idea of leptin as an important factor and/or predictor of diverse disorders associated with reproduction and pregnancy

Converging circuits between pain and depression: the ventral tegmental area as a therapeutic hub

Chronic pain and depression are highly prevalent pathologies and cause a major socioeconomic burden to society. Chronic pain affects the emotional state of the individuals suffering from it, while depression worsens the prognosis of chronic pain patients and may diminish the effectiveness of pain treatments. There is a high comorbidity rate between both pathologies, which might share overlapping mechanisms. This review explores the evidence pinpointing a role for the ventral tegmental area (VTA) as a hub where both pain and emotional processing might converge. In addition, the feasibility of using the VTA as a possible therapeutic target is discussed. The role of the VTA, and the dopaminergic system in general, is highly studied in mood disorders, especially in deficits in reward-processing and motivation. Conversely, the VTA is less regarded where it concerns the study of central mechanisms of pain and its mood-associated consequences. Here, we first outline the brain circuits involving central processing of pain and mood disorders, focusing on the often-understudied role of the dopaminergic system and the VTA. Next, we highlight the state-of-the-art findings supporting the emergence of the VTA as a link where both pathways converge. Thus, we envision a promising part for the VTA as a putative target for innovative therapeutic approaches to treat chronic pain and its effects on mood. Finally, we emphasize the urge to develop and use animal models where both pain and depression-like symptoms are considered in conjunction

Effect and safety of listening to music or audiobooks as a coadjuvant treatment for chronic pain patients under opioid treatment: a study protocol for an open-label, parallel-group, randomised, controlled, proof-of-concept clinical trial in a tertiary hospital in the Barcelona South Metropolitan area

BackgroundChronic non-cancer pain (CNCP) treatment's primary goal is to maintain physical and mental functioning while improving quality of life. Opioid use in CNCP patients has increased in recent years, and non-pharmacological interventions such as music listening have been proposed to counter it. Unlike other auditive stimuli, music can activate emotional-regulating and reward-regulating circuits, making it a potential tool to modulate attentional processes and regulate mood. This study's primary objective is to provide the first evidence on the distinct (separate) effects of music listening as a coadjuvant maintenance analgesic treatment in CNCP patients undergoing opioid analgesia.Methods and analysisThis will be a single-centre, phase II, open-label, parallel-group, proof-of-concept randomised clinical trial with CNCP patients under a minimum 4-week regular opioid treatment. We plan to include 70 consecutive patients, which will be randomised (1:1) to either the experimental group (active music listening) or the control group (active audiobooks listening). During 28 days, both groups will listen daily (for at least 30 min and up to 1 hour) to preset playlists tailored to individual preferences.Pain intensity scores at each visit, the changes (differences) from baseline and the proportions of responders according to various definitions based on pain intensity differences will be described and compared between study arms. We will apply longitudinal data assessment methods (mixed generalised linear models) taking the patient as a cluster to assess and compare the endpoints' evolution. We will also use the mediation analysis framework to adjust for the effects of additional therapeutic measures and obtain estimates of effect with a causal interpretation.Methods and analysisThis will be a single-centre, phase II, open-label, parallel-group, proof-of-concept randomised clinical trial with CNCP patients under a minimum 4-week regular opioid treatment. We plan to include 70 consecutive patients, which will be randomised (1:1) to either the experimental group (active music listening) or the control group (active audiobooks listening). During 28 days, both groups will listen daily (for at least 30 min and up to 1 hour) to preset playlists tailored to individual preferences.Pain intensity scores at each visit, the changes (differences) from baseline and the proportions of responders according to various definitions based on pain intensity differences will be described and compared between study arms. We will apply longitudinal data assessment methods (mixed generalised linear models) taking the patient as a cluster to assess and compare the endpoints' evolution. We will also use the mediation analysis framework to adjust for the effects of additional therapeutic measures and obtain estimates of effect with a causal interpretation.Ethics and disseminationThe study protocol has been reviewed, and ethics approval has been obtained from the Bellvitge University Hospital Institutional Review Board, L'Hospitalet de Llobregat, Barcelona, Spain. The results from this study will be actively disseminated through manuscript publications and conference presentations.Trial registration numberNCT05726266

Lineage-specific function of Engrailed-2 in the progression of chronic myelogenous leukemia to T-cell blast crisis

In hematopoietic malignancies, oncogenic alterations interfere with cellular differentiation and lead to tumoral development. Identification of the proteins regulating differentiation is essential to understand how they are altered in malignancies. Chronic myelogenous leukemia (CML) is a biphasic disease initiated by an alteration taking place in hematopoietic stem cells. CML progresses to a blast crisis (BC) due to a secondary differentiation block in any of the hematopoietic lineages. However, the molecular mechanisms of CML evolution to T-cell BC remain unclear. Here, we have profiled the changes in DNA methylation patterns in human samples from BC-CML, in order to identify genes whose expression is epigenetically silenced during progression to T-cell lineage-specific BC. We have found that the CpG-island of the ENGRAILED-2 (EN2) gene becomes methylated in this progression. Afterwards, we demonstrate that En2 is expressed during T-cell development in mice and humans. Finally, we further show that genetic deletion of En2 in a CML transgenic mouse model induces a T-cell lineage BC that recapitulates human disease. These results identify En2 as a new regulator of T-cell differentiation whose disruption induces a malignant T-cell fate in CML progression, and validate the strategy used to identify new developmental regulators of hematopoiesis.Research at C.C.’s lab was partially supported by FEDER, Fondo de Investigaciones Sanitarias, CSIC P.I.E., Junta de Castilla y León, and from an institutional grant from the Fundación Ramón Areces. Research in ISG group is partially supported by FEDER and by MICINN (SAF2012-32810), by MEC OncoBIO Consolider-Ingenio 2010 (Ref. CSD2007-0017), by NIH grant (R01 CA109335-04A1), the ARIMMORA project (FP7-ENV-2011, European Union Seventh Framework Program), by Junta de Castilla y León (BIO/SA06/13) and by “Proyecto en red de investigación en células madre tumorales” supported by Obra Social Kutxa y Consejería de Sanidad de la Junta de Castilla y Leon. C.V.D.’s research is supported by Junta de Castilla y León (proyecto de investigación en biomedicina SAN/39/2010). J.A.M.C.’s research is supported by the Instituto de Salud Carlos III (ISCIII), grants FIS-PI12/00202 and RTICC-RD12/0036/0063. All Spanish funding is co-sponsored by the European Union FEDER program. I.S.G. is an API lab of the EuroSyStem project and a partner of DECIDE European network. F.A.-J. and E.C.S. were supported by Spanish Ministry of Science and Innovation fellowships. E.C.-S. was a “Residencia de Estudiantes” Fellow. A.T.N. was the recipient of a “Beca de Postgrado de la Fundación Ramón Areces/UAM.”Peer Reviewe