Noves aportacions sobre agricultura i alimentació durant la primera edat del ferro a Catalunya: dades de l'assentament de Sant Jaume/Mas d'en Serrà (Alcanar, Montsià)

Els resultats de l'estudi arqueobotànic realitzat sobre diferents àmbits de l'assentament de Sant Jaume aporta noves dades al coneixement de la gestió dels recursos vegetals de la protohistòria del nordest peninsular. El registre arqueològic constata una certa homogeneïtzació en la funcionalitat dels àmbits, que s'interpreten com a magatzems en el pis superior i espais d'estabulació a l'inferior. L'àmbit millor representat és l'A4, que conserva com a fet singular un elevat nombre de restes de llavors i fruits amb molt bon estat de conservació. Els tàxons conreats més importants són la pisana (Triticum dicoccum) i les guixes i guixols (Lathyrus sativus i Lathyrus cicera), seguits d¿una menor proporció d'ordi vestit (Hordeum vulgare), blat nu (comú/dur) (Triticum aestivum/durum), pèsol (Pisum sativum), llentia (Lens culinaris) i erb (Vicia ervilia). D'altra banda, el registre arqueobotànic del pis inferior de l'àmbit A4 sembla posar en evidència la presència de l¿associació de pisana i guixa, destinada a l'alim.

Genetic variants influencing circulating lipid levels and risk of coronary artery disease.

OBJECTIVE: Genetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic determinants of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. METHODS AND RESULTS: We combined genome-wide association data from 8 studies, comprising up to 17 723 participants with information on circulating lipid concentrations. We did independent replication studies in up to 37 774 participants from 8 populations and also in a population of Indian Asian descent. We also assessed the association between single-nucleotide polymorphisms (SNPs) at lipid loci and risk of CAD in up to 9 633 cases and 38 684 controls. We identified 4 novel genetic loci that showed reproducible associations with lipids (probability values, 1.6×10(-8) to 3.1×10(-10)). These include a potentially functional SNP in the SLC39A8 gene for HDL-C, an SNP near the MYLIP/GMPR and PPP1R3B genes for LDL-C, and at the AFF1 gene for triglycerides. SNPs showing strong statistical association with 1 or more lipid traits at the CELSR2, APOB, APOE-C1-C4-C2 cluster, LPL, ZNF259-APOA5-A4-C3-A1 cluster and TRIB1 loci were also associated with CAD risk (probability values, 1.1×10(-3) to 1.2×10(-9)). CONCLUSIONS: We have identified 4 novel loci associated with circulating lipids. We also show that in addition to those that are largely associated with LDL-C, genetic loci mainly associated with circulating triglycerides and HDL-C are also associated with risk of CAD. These findings potentially provide new insights into the biological mechanisms underlying lipid metabolism and CAD risk.

An investigation of the resolution of inflammation (catabasis) in COPD.

Background: Chronic Obstructive Pulmonary Disease (COPD) is characterized by an enhanced inflammatory response to smoking that persists despite quitting. The resolution of inflammation (catabasis) is a complex and highly regulated process where tissue resident macrophages play a key role since they phagocytose apoptotic cells (efferocytosis), preventing their secondary necrosis and the spill-over of their pro-inflammatory cytoplasmic content, and release pro-resolution and tissue repair molecules, such as TGFβ, VEGF and HGF. Because inflammation does not resolve in COPD, we hypothesized that catabasis may be abnormal in these patients. Methods: To explore this hypothesis, we studied lung tissue samples obtained at surgery from 21 COPD patients,22 smokers with normal spirometry and 13 non-smokers controls. In these samples we used: (1)immunohistochemistry to assess the expression of CD44, CD36, VEGF and TGFβ in lung macrophages; (2) real time PCR to determine HGF, PPARγ, TGFβ, VEGF and MMP-9 gene expression; and, (3) ELISA to quantify lipoxin A4, a lipid mediator of catabasis. Results: We found that current and former smokers with COPD showed: (1) more inflammation (higher MMP-9 expression); (2) reduced macrophage surface expression of CD44, a key efferocytosis receptor; and, (3) similar levels of TGFβ, VEGF, HGF, PPARγ, and lipoxin A4 than smokers with normal spirometry, despite the presence of inflammation and disease. Conclusions: These results identify several potential abnormalities of catabasis in patients with COPD.

Immunotherapies for uro-genital cancers

Les cancers du col utérin et de la vessie prennent tous deux leur origine dans les sites muqueux et peuvent évoluer lentement de lésions superficielles (lésions squameuses intra-épithéliales de bas à haut grade (HSIL) et carcinomes in situ du col utérin (CIS); ou tumeurs non musculo-invasives de la vessie (NMIBC)) à des cancers invasifs plus avancés. L'éthiologie de ces deux cancers est néanmoins très différente. Le cancer du col utérin est, à l'échelle mondiale, le deuxième cancer le plus mortel chez la femme. Ce cancer résulte de l'infection des cellules basales de l'épithélium stratifié du col utérin par le papillomavirus humain à haut risque (HPV). Les vaccins prophylactiques récemment développés contre le HPV (Gardasil® et Cervarix®) sont des moyens de prévention efficaces lorsqu'ils sont administrés chez les jeunes filles qui ne sont pas encore sexuellement actives; cependant ces vaccins ne permettent pas la régression des lésions déjà existantes. Malgré un développement actif, les vaccins thérapeutiques ciblant les oncogènes viraux E6/E7 n'ont montré qu'une faible efficacité clinique jusqu'à présent. Nous avons récemment démontré qu'une immunisation sous-cutanée (s.c.) était capable de faire régresser les petites tumeurs génitales chez 90% des souris, mais chez seulement 20% des souris présentant de plus grandes tumeurs. Dans cette étude, nous avons développé une nouvelle stratégie où la vaccination est associée à une application locale (intra-vaginale (IVAG)) d'agonistes de TLR. Celle-ci induit une augmentation des cellules T CD8 totales ainsi que T CD8 spécifiques au vaccin, mais pas des cellules T CD4. L'attraction sélective des cellules T CD8 est permise par leur expression des récepteurs de chemokines CCR5 et CXCR3 ainsi que par les ligants E-selectin. La vaccination, suivie de l'application IVAG de CpG, a conduit, chez 75% des souris, à la régression de grandes tumeurs établies. Le cancer de la vessie est le deuxième cancer urologique le plus fréquente. La plupart des tumeurs sont diagnostiquées comme NMIBC et sont restreintes à la muqueuse de la vessie, avec une forte propension à la récurrence et/ou progression après une résection locale. Afin de développer des vaccins contre les antigènes associés à la tumeur (TAA), il est nécessaire de trouver un moyen d'induire une réponse immunitaire CD8 spécifique dans la vessie. Pour ce faire, nous avons comparé différentes voies d'immunisation, en utilisant un vaccin composé d'adjuvants et de l'oncogène de HPV (E7) comme modèle. Les vaccinations s.c. et IVAG ont toutes deux induit un nombre similaire de cellules T CD8 spécifiques du vaccin dans la vessie, alors que l'immunisation intra-nasale fut inefficace. Les voies s.c. et IVAG ont induit des cellules T CD8 spécifiques du vaccin exprimant principalement aL-, a4- et le ligand d'E-selectin, suggérant que ces intégrines/sélectines sont responsables de la relocalisation des cellules T dans la vessie. Une unique immunisation avec E7 a permis une protection tumorale complète lors d'une étude prophylactique, indépendemment de la voie d'immunisation. Dans une étude thérapeutique, seules les vaccinations s.c. et IVAG ont efficacement conduit, chez environ 50% des souris, à la régression de tumeurs de la vessie établies, alors que l'immunisation intra-nasale n'a eu aucun effet. La régression de la tumeur est correlée avec l'infiltration dans la tumeur des cellules T CD8 spécifiques au vaccin et la diminution des cellules T régulatrices (Tregs). Afin d'augmenter l'efficacité de l'immunisation avec le TAA, nous avons testé une vaccination suivie de l'instillation d'agonistes de TLR3 et TLR9, ou d'un vaccin Salmonella Typhi (Ty21a). Cette stratégie a entraîné une augmentation des cellules T CD8 effectrices spécifiques du vaccin dans la vessie, bien qu'à différentes échelles. Ty21a étant l'immunostimulant le plus efficace, il mérite d'être étudié de manière plus approfondie dans le contexte du NMIBC. - Both cervical and bladder cancer originates in mucosal sites and can slowly progress from superficial lesions (low to high-grade squamous intra-epithelial lesions (HSIL) and carcinoma in situ (CIS) in the cervix; or non-muscle invasive tumors in the bladder (NMIBC)), to more advanced invasive cancers. The etiology of these two cancers is however very different. Cervical cancer is the second most common cause of cancer death in women worldwide. This cancer results from the infection of the basal cells of the stratified epithelium of the cervix by high-risk human papillomavirus (HPV). The recent availability of prophylactic vaccines (Gardasil® and Cervarix®) against HPV is an effective strategy to prevent this cancer when administered to young girls before sexual activity; however, these vaccines do not induce regression of established lesions. Despite active development, therapeutic vaccines targeting viral oncogenes E6/E7 had limited clinical efficacy to date. We recently reported that subcutaneous (s.c.) immunization was able to regress small genital tumors in 90% of the mice, but only 20% of mice had regression of larger tumors. Here, we developed a new strategy where vaccination is combined with the local (intravaginal (IVAG)) application of TLR agonists. This new strategy induced an increase of both total and vaccine-specific CD8 T cells in cervix-vagina, but not CD4 T cells. The selective attraction of CD8 T cells is mediated by the expression of CCR5 and CXCR3 chemokine receptors and E-selectin ligands in these cells. Vaccination followed by IVAG application of CpG resulted in tumor regression of large established tumors in 75% of the mice. Bladder cancer is the second most common urological malignancy. Most tumors are diagnosed as NMIBC, and are restricted to the mucosal bladder with a high propensity to recur and/or progress after local resection. Aiming to develop vaccines against tumor associated antigens (TAA) it is necessary to investigate how to target vaccine-specific T-cell immune responses to the bladder. Here we thus compared using an adjuvanted HPV oncogene (E7) vaccine, as a model, different routes of immunization. Both s.c. and IVAG vaccination induced similar number of vaccine-specific CD8 T-cells in the bladder, whereas intranasal (i.n.) immunization was ineffective. S.c. and IVAG routes induced predominantly aL-, a4- and E-selectin ligand-expressing vaccine-specific CD8 T-cells suggesting that these integrin/selectin are responsible for T-cell homing to the bladder. A single E7 immunization conferred full tumor protection in a prophylactic setting, irrespective of the immunization route. In a therapeutic setting, only ivag and s.c. vaccination efficiently regressed established bladder-tumors in ca. 50 % of mice, whereas i.n. immunization had no effect. Tumor regression correlated with vaccine- specific CD8 T cell tumor-infiltration and decrease of regulatory T cells (Tregs). To increase efficacy of TAA immunization, we tested vaccination followed by the local instillation of TLR3 or TLR9 agonist or of a Salmonella Typhi vaccine (Ty21a). This strategy resulted in an increase of vaccine-specific effector CD8 T cells in the bladder, although at different magnitudes. Ty21a being the most efficient, it deserves further investigation in the context of NMIBC. We further tested another strategy to improve therapies of NMIBC. In the murine MB49 bladder tumor model, we replaced the intravesical (ives) BCG therapy by another vaccine strain the Salmonella Ty21a. Ives Ty21a induced bladder tumor regression at least as efficiently as BCG. Ty21a bacteria did not infect nor survive neither in healthy nor in tumor-bearing bladders, suggesting its safety. Moreover, Ty21a induced a transient inflammatory response in healthy bladders, mainly through infiltration of neutrophils and macrophages that rapidly returned to basal levels, confirming its potential safety. The tumor regression was associated to a robust infiltration of immune cells, and secretion of cytokines in urines. Infection of murine tumor cell lines by Ty21a resulted in cell apoptosis. The infection of both murine and human urothelial cell lines induced secretion of in vitro inflammatory cytokines. Ty21a may be an attractive alternative for the ives treatment of NMIBC after transurethral resection and thus deserves more investigation.

Traumakuvantamisen asetteluopas : oppimateriaali opiskelijoille

Opinnäytetyömme on oppimateriaali, joka käsittelee ensivaiheen traumakuvantamisen asettelua. Tuotos on A4-kokoinen, 22-sivuinen opas, joka on myös tulostettavissa Metropolian Moodle-työtilasta. Opas sisältää esipuheen, sanasto-osuuden ja muistilistan traumakuvantamisessa huomioitavista asioista. Näitä seuraa kolme potilastapausta, jotka simuloivat autenttisia kokemuksia työelämässä. Jokaisen tapauksen ensimmäisellä sivulla on lähetetiedot ja pohdittavaa kuvauksen suorittamisesta. Ensimmäinen tapaus käsittelee olkapäätä ja kyynärpäätä, toinen lantiota ja polvea. Kolmas tapaus käsittelee kaularankapotilasta. Idea opinnäytetyön aiheesta tuli meiltä itseltämme käytyämme traumakuvantamisen vapaasti valittavan kurssin. Opas on tarkoitettu yhteistoiminnalliseen oppimiseen. Oppaan materiaalia voidaan käyttää koulussa kontaktitunneilla tapahtuvaan ryhmätyöskentelyyn ja se soveltuu myös itseopiskeluun. Opas on tarkoitettu yhteistoiminnalliseen oppimiseen. Röntgenhoitajat tarvitsevat päivittäisessä työskentelyssään ryhmätyötaitoja. Yksilö pystyy ryhmässä työskennellessään ulkoistamaan ajatteluaan ja näin kehittämään omia ideoitaan ja käsityksiään. Työn kirjallisessa osuudessa käsitellään lyhyesti oppimista ilmiönä, oppimisprosessia ja opettamista. Työssä analysoidaan traumakuvantamiseen liityviä käsitteitä. Teoriaosuuden loppuosassa käymme läpi oppimateriaalin suunnittelua, sisältöä ja ulkoasua. Lähdemateriaalia oppimismenetelmistä löytyi runsaasti. Valitsimme teoreettiseksi viitekehykseksi ongelmaperustaisen oppimisen. Se on yleistyvä oppimismenetelmä, joka tukee toiminnallista oppimista ja lisää opiskelijan valmiuksia aktiiviseen tiedonhakuun. Ongelmaperustaisen oppimisen mukaan opittavalle sisällölle saavutetaan parempi käyttöarvo, mikäli oppiminen tapahtuu aitoja tosielämän ongelmia ratkomalla aiheen pelkän teoreettisen käsittelyn sijaan. Opinnäytetyömme tuotos syventää opiskelijoiden teoreettista osaamista ja antaa valmiudet kirjasessa esiintyvien projektioiden hallitsemiseen harjoittelun ja ongelmaperustaisen oppimisen avulla.

Rendimento de grãos de soja em função de sistemas de plantio e irrigação por superfície em Planossolos

Resumo: O objetivo deste trabalho foi avaliar o efeito de sistemas de plantio e irrigação suplementar em faixas sobre o rendimento de grãos de soja, em áreas com presença de camada compactada próxima à superfície do solo. Dois experimentos foram realizados em blocos ao acaso, em faixas, com quatro repetições, no Estado do Rio Grande do Sul. O experimento 1 foi realizado em Santa Maria, correspondente às safras de 2013/2014 e 2014/2015; e o experimento 2, em Formigueiro, na safra 2013/2014. Os tratamentos consistiram dos fatores A e D. O fator A considerou os seguintes sistemas de plantio: A1, semeadura com discos duplos desencontrados; A2, semeadura com disco ondulado de 12 ondas; A3, semeadura com haste sulcadora; A4, semeadura com haste sulcadora e um mecanismo de acomodação do solo; A5, semeadura em microcamalhão; e A6, escarificação do solo e semeadura com disco duplo desencontrado. O fator D consistiu de tratamentos com ou sem irrigação. Na safra 2014/2015, alterou-se o fator A4 por haste desencontrada a 5 cm da linha de semeadura. O experimento 2 constituiu-se apenas do fator A do experimento 1, sem o tratamento microcamalhão. Os sistemas com escarificação do solo e haste sulcadora são os que proporcionam maior rendimento de grãos. A irrigação realizada em condições de umidade do solo abaixo de 60% da capacidade de campo aumenta o rendimento de grãos.

Lipoxin A₄ prevents the progression of de novo and established endometriosis in a mouse model by attenuating prostaglandin E₂ production and estrogen signaling.

Endometriosis, a leading cause of pelvic pain and infertility, is characterized by ectopic growth of endometrial-like tissue and affects approximately 176 million women worldwide. The pathophysiology involves inflammatory and angiogenic mediators as well as estrogen-mediated signaling and novel, improved therapeutics targeting these pathways are necessary. The aim of this study was to investigate mechanisms leading to the establishment and progression of endometriosis as well as the effect of local treatment with Lipoxin A4 (LXA₄), an anti-inflammatory and pro-resolving lipid mediator that we have recently characterized as an estrogen receptor agonist. LXA₄ treatment significantly reduced endometriotic lesion size and downregulated the pro-inflammatory cytokines IL-1β and IL-6, as well as the angiogenic factor VEGF. LXA₄ also inhibited COX-2 expression in both endometriotic lesions and peritoneal fluid cells, resulting in attenuated peritoneal fluid Prostaglandin E₂ (PGE₂) levels. Besides its anti-inflammatory effects, LXA₄ differentially regulated the expression and activity of the matrix remodeling enzyme matrix metalloproteinase (MMP)-9 as well as modulating transforming growth factor (TGF)-β isoform expression within endometriotic lesions and in peritoneal fluid cells. We also report for first time that LXA₄ attenuated aromatase expression, estrogen signaling and estrogen-regulated genes implicated in cellular proliferation in a mouse model of disease. These effects were observed both when LXA₄ was administered prior to disease induction and during established disease. Collectively, our findings highlight potential targets for the treatment of endometriosis and suggest a pleotropic effect of LXA₄ on disease progression, by attenuating pro-inflammatory and angiogenic mediators, matrix remodeling enzymes, estrogen metabolism and signaling, as well as downstream proliferative pathways.

Le Théâtre-italien : journal spécial au théâtre

1884/12 (A4).

Le Théâtre-italien : journal spécial au théâtre

1884/11 (A4).

Revue Mabillon : archives de la France monastique

1908/05 (A4,N13)-1909/02 (A4,N16).

L'Alerte : Bulletin de liaison de la région lyonnaise

1937/03 (A4,N39).

L'Alerte : Bulletin de liaison de la région lyonnaise

1937/11 (A4,N46).

L'Alerte : Bulletin de liaison de la région lyonnaise

1937/04 (A4,N40).