Effects of flow regulation in the life-cycles of a mediterranean cyprinid species, the Iberian chub (Squalius carolitertii Doadrio, 1987)

Streamflow is considered a driver of inter and intra‐specific life‐history differences among freshwater fish. Therefore, dams and related flow regulation, can have deleterious impacts on their life‐cycles. The main objective of this study is to assess the effects of flow regulation on the growth and reproduction of a non‐migratory fish species. During one year, samples were collected from two populations of Iberian chub, inhabiting rivers with non‐regulated and regulated flow regimes. Flow regulation for water derivation promoted changes in chub’s condition, duration of gonad maturation and spawning, fecundity and oocyte size. However, this non‐migratory species was less responsive to streamflow regulation than a migratory species analysed. Findings from this study are important to understand changes imposed by regulated rivers on fish and can be used as guidelines for flow requirements implementations; RESUMO: O caudal é um dos fatores responsáveis pelo funcionamento dos ciclos de vida das espécies piscícolas dulciaquícolas. As barragens, e a regularização de caudal associada, podem ter impactes nos ciclos de vida destas espécies. O objetivo deste estudo prende‐se com a avaliação dos efeitos da regularização de caudal no crescimento e reprodução de uma espécie piscícola não‐migradora. A análise de amostras recolhidas em populações de escalo do Norte provenientes de dois rios de caudal regularizado e não regularizado, identificaram impactes significativos a nível da condição corporal, da maturação das gónadas e desova, da fecundidade e da dimensão dos oócitos. Esta espécie não‐migradora parece ser menos responsiva à artificialização do caudal que uma espécie migradora previamente analisada. Estes resultados permitem compreender as alterações impostas pela regularização do caudal e podem ser usados em programas de reabilitação fluvial.

Identification and characterization of parasitism genes from the pinewood nematode Bursaphelenchus xylophilus reveals a multilayered detoxification strategy.

The migratory endoparasitic nematode Bursaphelenchus xylophilus, which is the causal agent of pine wilt disease, has phytophagous and mycetophagous phases during its life cycle. This highly unusual feature distinguishes it from other plantparasitic nematodes and requires profound changes in biology between modes. During the phytophagous stage, the nematode migrates within pine trees, feeding on the contents of parenchymal cells. Like other plant pathogens, B. xylophilus secretes effectors from pharyngeal gland cells into the host during infection.We provide the first description of changes in the morphology of these gland cells between juvenile and adult life stages. Using a comparative transcriptomics approach and an effector identification pipeline, we identify numerous novel parasitism genes which may be important for the mediation of interactions of B. xylophilus with its host. In-depth characterization of all parasitism genes using in situ hybridization reveals two major categories of detoxification proteins, those specifically expressed in either the pharyngeal gland cells or the digestive system. These data suggest that B. xylophilus incorporates effectors in a multilayer detoxification strategy in order to protect itself from host defence responses during phytophagy.

La población indígena de la Gran Talamanca: Tamaño y ubicación. Costa Rica, 1840-1927

ResumenEl artículo estudia el tamaño y ubicación de la población indígena de la zona denominada Gran Talamanca, que incluye todo el sur de Costa Rica, entre 1840 y 1927. En el período estudiado, la población indígena se mantuvo en cerca de tres mil personas. Su ubicación en general cambió poco, pero se vio afectada por corrientes migratorias, tanto de indígenas como de no indígenasAbstractThe article analyzes the extent and location between 1840 and 1927 of the indigenous population in the area known as Gran Talamanca, which comprises the entire southern region of Costa Rica. In the period under study, the indigenous population kept a steady figure of close to three thousand individuals. In general, their location experienced very slight changes, influenced by migratory flows, both of indigenous and non-indigenous people.

La migración internacional en Centroamérica y su evolución reciente

ResumenAnaliza las tendencias en los patrones migratorios de los centroamericanos a partir del decenio de 1980.AbstractThe author analyzes central american migratory patterns from the 1980´s onwards 

Café, mano de obra y poblamiento: invitación a un análisis comparado

ResumenEn este breve ensayo se plantean de modo general e introductorio ciertas relaciones históricas entre expansión cafetalera y procesos migratorios, concretamente referidos a la colonización agrícola y procesos migratorios, concretamente referidos a la colonización agrícola. Alude algunos casos caribeños y continentales, para luego sugerir posibles líneas de comparación y discusión comparada.AbstractThis brief essay provides a general introduction to certain historical relations between the expansion of coffee cultivation and migratory processes, specifically land settlement. Several Caribbean and mainland cases are mentioned, and possibilities of comparative research and discussion are suggested.

Urbanizarse o migrar: ¿Cuáles opciones ante la crisis? El devenir de las comunidades cafetaleras en el centro de Veracruz, México

ResumenLa baja de precios del café desde 1989 sorprendió a los pequeños productores en un momento en que tienen que adaptarse a las nuevas reglas de producción y comercialización impuestas por las políticas de modernización del gobierno de Salinas de Gortari (1988-1994). Las migraciones son una respuesta, entre otras, a la(s) crisis, a primera vista individual pero que afecta el devenir social, político y cultural de las comunidades. En este estudio se analizan los procesos migratorios nacientes en el centro de Veracruz, y se plantea  que si bien algunas comunidades pueden lograr una cierta “reconversión” gracias a la cercanía de centros urbanos que ofrecen alternativas de trabajo, en otras se inician procesos de migración lejana y colectiva que amenazan la reproducción misma de la comunidad rural en cuanto tal.AbstractThe sharp drop in the price of coffee since 1989 took small farmers by surprise at the time when they must adapt to the new rules of productions and marketing under the modernizing polices of the Salinas de Gortari government (1988-1994). Migrations are one response to the crisis (or crises). While seemingly an individual one, they affect the social, political and cultural future of those communities. This study discusses the emerging migratory processes in central Veracruz, and suggests that while some communities may attain a degree of “retrofitting” thanks to nearby urban centers offering job opportunities, others are undergoing long-distance, collective migratory processes which threaten the very reproduction of the rural community per se.

La política migratoria de los estados receptores de la migración centroamericana el caso de México y Estados Unidos

 El presente escrito aborda la situación de la migración humana por razones de trabajo hacia países cercanos o fronterizos, los cuales ofrecen un panorama económico y de oportunidades mejor que el del país de origen. Esto ha dado lugar a una serie de fenómenos sociales que comprenden aspectos no solo laborales sino incluyen también comerciales, legales, políticos y de derechos humanos en medio de los cuales son los trabajadores mismos los más afectados.  The present text addresses to show the situation of human migration due to labour reasons towards near or border countries, theses countries offer an economic and opportunity panorama better than the origin countries. This has allowed a series of social phenomena that include labour, commercial, legal, political and human rights aspects, in the middle of which the workers are the most affected.

La política del gobierno mexicano frente al fenómeno migratorio

El objetivo de la presente ponencia es evidenciar cómo la falta de una política migratoria ha afectado las relaciones de México con otros países, principalmente los centroamericanos, por los diferentes intereses que pretende resguardar: el respeto a los derechos humanos de los extranjeros y la prohibición de transitar para las personas indocumentadas. De esta manera, se demuestra la necesidad imperante de que el gobierno mexicano cuente con una política sólida la cual incida de manera positiva en cada uno de los flujos migratorios con los que se ve afectado México al ser un país de origen, tránsito y destino.This article aims to highlight that the lack of a migratory policy affects Mexican foreign affairs, especially with Central American countries, due to different interests in stake that it looks to safeguard such as foreigners human rights respect and the proscription of transit for undocumented people. It is obvious that Mexican Government needs to adopt a well grounded foreign policy with positive impact in each of the migratory flows currently affecting México, since it is a starting point, transit and destination country.

The impact of phosphoinositide metabolic enzymes in glioblastoma: a tale of phosphoinositide-specific phospholipase C PLCβ1 and 5-phosphatase SKIP

Background: Glioblastoma multiforme (GBM) is one of the deadliest and most aggressive form of primary brain tumor. Unfortunately, current GBM treatment therapies are not effective in treating GBM patients. They usually experience very poor prognosis with a median survival of approximately 12 months. Only 3-5% survive up to 3 years or more. A large-scale gene profile study revealed that several genes involved in essential cellular processes are altered in GBM, thus, explaining why existing therapies are not effective. The survival of GBM patients depends on understanding the molecular and key signaling events associated with these altered physiological processes in GBM. Phosphoinositides (PI) form just a tiny fraction of the total lipid content in humans, however they are implicated in almost all essential biological processes, such as acting as second messengers in spatio-temporal regulation of cell signaling, cytoskeletal reorganization, cell adhesion, migration, apoptosis, vesicular trafficking, differentiation, cell cycle and post-translational modifications. Interestingly, these essential processes are altered in GBM. More importantly, incoming reports have associated PI metabolism, which is mediated by several PI phosphatases such as SKIP, lipases such as PLCβ1, and other kinases, to regulate GBM associated cellular processes. Even as PLCβ1 and SKIP are involved in regulating aberrant cellular processes in several other cancers, very few studies, of which majority are in-silico-based, have focused on the impact of PLCβ1 and SKIP in GBM. Hence, it is important to employ clinical, in vitro, and in vivo GBM models to define the actual impact of PLCβ1 and SKIP in GBM. AIM: Since studies of PLCβ1 and SKIP in GBM are limited, this study aimed at determining the pathological impact of PI metabolic enzymes, PLCB1 and SKIP, in GBM patient samples, GBM cell line models, and xenograft models for SKIP. Results: For the first time, this study confirmed through qPCR that PLCβ1 gene expression is lower in human GBM patient samples. Moreover, PLCβ1 gene expression inversely correlates with pathological grades of glioma; it decreases as glioma grades increases or worsens. Silencing PLCβ1 in U87MG GBM cells produces a dual impact in GBM by participating in both pro-tumoral and anti-tumoral roles. PLCβ1 knockdown cells were observed to have more migratory abilities, increased cell to extracellular matrix (ECM) adhesion, transition from epithelial phenotype to mesenchymal phenotype through the upregulation of EMT transcription factors Twist1 and Slug, and mesenchymal marker, vimentin. On the other hand, p-Akt and p-mTOR protein expression were downregulated in PLCβ1 knockdown cells. Thus, the oncogenic pathway PI3K/Akt/mTOR pathway is inhibited during PLCβ1 knockdown. Consistently, cell viability in PLCβ1 knockdown cells were significantly decreased compared to controls. As for SKIP, this study demonstrated that about 48% of SKIP colocalizes with nuclear PtdIns(4,5)P2 to nuclear speckles and that SKIP knockdown alters nuclear PtdIns(4,5)P2 in a cell-type dependent manner. In addition, SKIP silencing increased tumor volume and weight in xenografts than controls by reducing apoptosis and increasing viability. All in all, these data confirm that PLCβ1 and SKIP are involved in GBM pathology and a complete understanding of their roles in GBM may be beneficial.

Studio degli effetti di citochine a basso dosaggio (LOW DOSE) su cellule di origine animale (3T3-L1) ed umana (hASC)

Nella sindrome metabolica l’insulino-resistenza e l’obesità rappresentano i fattori chiave nello sviluppo di tale patologia, ma il principale player risulta un’infiammazione cronica di basso grado (Chronic Low Grade Inflammation) a carico del tessuto adiposo. Lo scopo di questo progetto di ricerca è quindi stato quello di testare citochine a basso dosaggio come possibile trattamento dell’infiammazione cronica. Le citochine utilizzate (GUNA®-Interleukin 4 (IL-4), GUNA®-Interleukin 10 (IL-10), GUNA®-Melatonin, GUNA®-Melatonin+GUNA®-IL-4.) sono state fornite dall’azienda GUNA S.p.a. Poiché l’infiammazione cronica a basso grado inizia in seguito ad un aumento eccessivo del tessuto adiposo, inizialmente si è valutato l’effetto su una linea di preadipociti murini (3T3-L1). Questa prima parte dello studio ha messo in evidenza come le citochine a basso dosaggio non modificano la vitalità cellulare, anche se agiscono sull’espressione e la localizzazione di vimentina e E-caderina. Inoltre IL-4 e IL-10 sembrano avere una parziale attività inibitoria, non significativa, sull’adipogenesi ad eccezione dell’espressione dell’adiponectina che appare significativamente aumentata. In ultimo i trattamenti con IL-4 e IL-10 hanno mostrato una diminuzione del contenuto di ROS e una ridotta attività antiinfiammatoria dovuta alla diminuzione di IL-6 secreto. Un’altra popolazione cellulare principale nel tessuto adiposo è rappresentata dalle ASC (Adipose Stem Cell). Per tale motivo si è proseguito valutando l’effetto che le citochine low-dose su questo citotipo, evidenziando che il trattamento con le citochine non risulta essere tossico, anche se sembrerebbe rallentare la crescita cellulare, e determina un’inibizione del processo adipogenico. Inoltre il trattamento con IL-10 sembra stimolare le ASC a produrre fattori che inducono una maggiore vasculogenesi e le induce a produrre fattori chemiotattici che determinano una maggiore capacità di rigenerazione tissutale da parte di MSC da derma. Infine, il trattamento con IL-4 e IL-10 stimola probabilmente una minore produzione di citochine pro-infiammatorie che inducono in maniera significativa una minore mobilità di cellule MSC.

Dissecting the role of IGF2BP3 in the stress-adaptive response and in intercellular communication in Ewing Sarcoma.

Tumor microenvironment has emerged as key factor influencing tumor progression and metastatization. In this context, small vesicles produced by cancer cells can influence the fate of their surroundings via the horizontal transfer of specific molecular cargos. Ewing Sarcoma, the second most common bone tumor in young patients, presents early metastasis associated to worse prognosis. The RNA binding protein Insulin-like Growth Factor 2 mRNA Binding Protein 3 (IGF2BP3) exerts a pro-oncogenic role associated with metastasis formation and worse prognosis in Ewing Sarcoma. Our aim was to investigate the still unexplored role of IGF2BP3 in the stress-adaptive response to tumor microenvironment and in the interactions between Ewing Sarcoma cells. Hypoxia is a major feature of Ewing Sarcoma microenvironment and we demonstrated that IGF2BP3 can direct the CXCR4-mediated migratory response to CXCL12 in Ewing Sarcoma cells subjected to oxygen deprivation. We also discovered that the interaction between IGF2BP3 and CXCR4 is regulated through CD164 and which colocalize at plasma membrane level, upon CXCL12 exposure. Interestingly, high IGF2BP3 levels in Ewing Sarcoma metastatic lesions positively correlated with the expression of both CD164 and CXCR4, indicating the IGF2BP3/CD164/CXCR4 oncogenic axis as a critical modulator of Ewing Sarcoma metastatic progression. We demonstrated for the first time that IGF2BP3 is loaded into Ewing Sarcoma derived exosomes, accordingly to its cellular levels. We discovered that IGF2BP3+ exosomes carry high levels of IGF2BP3-client mRNAs involved in cellular migration, CD164 and IGF1R, and, by transferring this cargo, sustain the migratory abilities of receiving cells, induce a sharp up-regulation of CD164, CXCR4 and IGF1R and enhance the activation of AKT/mTOR and ERK down-stream signalling pathways. We demostrated that the pro-tumorigenic role of IGF2BP3 is not only exerted at cellular level, but that intercellular communication is crucial in the context of Ewing Sarcoma microenvironment.

Nuclear shape instability caused by lamin A deregulation promotes invasiveness in pediatric bone sarcomas: from nucleo-cytoskeleton dynamics to novel therapeutic opportunities

Osteosarcoma (OS) and Ewing sarcoma (EWS) are the two most frequent primary bone tumors, in which metastases remain the most relevant adverse prognostic factor. Lamin A is the main constituent of the nuclear lamina, with a fundamental role in maintaining the connection between nucleus and cytoskeleton (through LINC complex proteins interactions), and its alterations can be implicated in tumor progression. We investigated how nucleo-cytoskeleton dynamics is influenced by lamin A modulation in OS and EWS, demonstrating that both these cancer models had low levels of lamin A, which are linked to a significantly more marked nuclear misshaping. In our in vitro studies, reduced levels of lamin A promoted migratory abilities in these tumors. Moreover, these findings were corroborated by gene expression analyses on EWS patient samples, showing that LMNA levels were significantly lower in metastatic lesions compared to primary tumors and that patients with low LMNA had a significant worse overall survival. We also found that LMNA expression significantly impaired EWS metastases formation in vivo. We demonstrated that low lamin A expression was linked to a severe mislocalization of LINC complex proteins, thus disrupting nucleo-cytoskeleton interactions, with a corresponding gain in malignant properties, which resulted in increased invasiveness. Lamin A overexpression or its accumulation by a statin-based pharmacological treatment allowed us to reconstitute a functional nucleo-cytoskeleton interplay, which resulted in significant downmodulation of ROCK2 and YAP, two crucial drivers of EWS aggressiveness. Our study demonstrated that lamin A is a favorable mediator of nuclear shape stability in bone sarcomas, and its modulation rescues LINC complex protein localization and regulates mechano-signaling pathways, thus promoting a less aggressive cancer phenotype. We also identified statins, already employed in clinical practice, as a tool capable to increase lamin A levels, and to reconstitute functional nucleo-cytoskeletal dynamics, resulting in reduced cellular migration.

Le aporie del ritorno: la trasmissione intergenerazionale della memoria traumatica nel sud globale di lingua portoghese

Questa tesi propone un indagine sulla memoria del retorno a partire da una prospettiva critica che assume il “sud globale di lingua portoghese” come spazio storico e concettuale di riferimento. Si riflette sull'idea di specificità attribuita alla colonizzazione promossa dal Portogallo in Africa tenendo conto delle contraddizioni associate al movimento migratorio innescato dal processo violento di decolonizzazione dell’Africa portoghese.
 Le memorie trauamatiche sul retorno espongono la violenza come componente costitutiva della realtà coloniale ma ripropongono anche dinamiche che permettono l’occultamento del razzismo. L'esplorazione della “soffitta”, assunta come metafora della memoria familiare custodita nello spazio domestico, accompagna quella dell’archivio pubblico. L’analisi dell’archivio ufficiale e della memoria familiare riflette il tentativo di stabilire un dialogo tra storia e memoria superando la logica di antitesi che tradizionalmente le contrappone. Utilizzando il concetto criticamente problematico di “postmemoria” si riflette sulla riconfigurazione del rapporto con il passato in funzione di un’idea di “eredità come compito” assunto nel presente). La possibilità di “salvare” il passato dalla progressiva scomparsa dei testimoni comporta un pericolo di abuso ideologico connaturato al processo di trasmissione. La traduzione delle memorie coloniali sul retorno dallo spazio intimo allo spazio del dibattito pubblico mostra la relazione tra la costruzione della mitologia familiare e l’adozione del discorso lusotropicale. Il tentativo di definire la natura indecifrabile del retornado comporta la possibilità di sanzionare la violenza coloniale negando una responsabilità collettiva riferita al colonialismo. Si presenta il tentativo di configurare i termini di una questione post-coloniale portoghese dai contorni opachi. Questa tesi approda ad una conclusione aperta, articolata sul rischio sempre presente di appropriazione delle categorie critiche post-coloniali da parte dell’ideologia egemonica. Attraverso le (post)memorie (post)coloniali la denuncia del razzismo in quanto eredità permanente e la riconfigurazione dell’archivio coloniale costituiscono operazioni possibili, necessarie, ma non per questo scontate o prive di rischi.

The engagement of yugoslav technical cooperation experts in post-colonial Algeria (1962-1990). A global microhistory of east-south relations

The venture of socialist Eastern Europe in assisting the development efforts of the post-colonial countries opened up official migratory channels to the Global South for a specific labour group engaged under international technical cooperation programmes. By taking post-colonial Algeria as a space of East-South interactions and intense inter-socialist competition, the thesis studies labour mobility from socialist Yugoslavia of a heterogeneous group labelled “technical cooperation experts” in the period from 1962 to 1990. While CMEA members dispatched to the country personnel in great numbers, after 1965, Yugoslavia failed to do so. Tracing them beyond the institutional level, the thesis aims at detecting and exposing factors which inhibited the attempts to increase the presence of Yugoslav technical experts in Algeria. It argues that instead of building an alternative, solidarity-based aid model, Yugoslav technical cooperation with the developing countries was reduced to mediation in the employment of highly-skilled labour abroad. The cooperation scheme, which differed from one of its Eastern European counterparts, manifested in the employment and legal status as well as everyday life and work experiences of Yugoslav citizens. Relying on the methodological approach of global microhistory, which strongly favours the micro-historical analysis of primary sources in studying global processes, the thesis provides a more comprehensive and nuanced understanding of Yugoslav globalization endeavours. By shifting the focus to the experiences of ordinary people who were under the strong influence of globalization forces of the Cold War era, the thesis adds a “human” dimension to the history of East-South relations.

Aberrant c-MET activation impairs perinuclear actin cap organization with YAP1 cytosolic relocation

Growing evidence indicates that cell and nuclear deformability plays a crucial role in the determination of cancer cells tumorigenic and metastatic potential. The perinuclear actin cap, by wrapping the nucleus with a functional network of actomyosin cables, can modulate nuclear architecture and consequently cell/nuclear elasticity. The hepatocyte growth factor receptor (MET) stands out among other membrane receptors as crucial player of the actin filaments organization, but no data are available on a specific role for MET in the actin cap assembly and the overall nuclear architecture organization. In a cell system characterized by MET hyperactivation, we observed a strong rearrangement of the cellular actin caps, with a complete dismantling of apical stress fibers and a strikingly enhanced nuclear height. CRISPR/Cas9 silencing of MET completely reverted the aberrant phenotype, resulting in flattened cells with perfectly aligned perinuclear actomyosin bundles, as well as decreased MAPK and PI3K/AKT signaling, cell proliferation rate and aggressiveness. Interestingly, MET ablated cells acquired a remarkably directed and polarized migratory phenotype, contrarily to cells with MET sustained activation showing meandering random walk. A pathway enrichment analysis comparing MET-activated and MET-KO cells RNAseq data, unveiled the contribution of multiple pathways associated with cytoskeleton remodeling, regulation of cell shape and response to mechanical stimuli. In line, the co-transcriptional activator YAP1, playing a major role in cell mechanosensing and focal adhesions/actin stabilization, appeared the culprit of the genetic reassembling of KO cells. Indeed, MET silencing was shown to induce YAP1 nuclear shuttling and increased co-transcriptional activity. Finally, we were able to induce in a normal epithelial model a phenotype closer to MET activated cancer cells only by introducing a constitutive fusion protein of MET. Taken together, our results demonstrate a new mechanism of MET-mediated actin remodeling responsible for a tumor-initiating capacity and meandering random migration, which requires YAP1 inactivation.