Comparing Basal Area Diameter Distributions Estimated by Tree Species and for the Entire Stock in a Mixed Stand

Summary

Comparison of aminolevulinic acid and hexylester aminolevulinate induced protoporphyrin IX distribution in human bladder cancer.

PURPOSE: Successful photodynamic therapy of epithelial cancer requires a specific photosensitization of malignant tissue. We evaluate the intensity and localization of protoporphyrin IX (PpIX) in superficial transitional cell carcinoma and nonmalignant cells of the human bladder following topical administration of its precursor, either aminolevulinic acid (ALA) or hexylester aminolevulinate (HAL). MATERIALS AND METHODS: Solutions of ALA or HAL were instilled into the bladder of 18 patients presenting with recurrent transitional cell carcinoma. The distribution of PpIX through the bladder wall was studied on frozen biopsies using fluorescence microscopy and correlated with pathological findings. RESULTS: Topical bladder instillation with 180 mmol (3%) ALA administered for 6 hours or 8 mmol (0.2%) HAL administered for 4 hours gave similar results regarding intensity and tissue distribution of PpIX fluorescence, whereas 8 mmol HAL administered for 2 hours followed by 2 hours of resting time (2+2 hours concept) induced a PpIX fluorescence twice as high. The fluorescence remained limited to cancer cells. Only a trace of PpIX fluorescence was observed in suburothelial connective tissue, that is chorion, but none in the bladder smooth muscle regardless of experiment conditions. CONCLUSIONS: HAL is an excellent precursor for PpIX synthesis in bladder cancer. With the 2+2 hour topical administration condition it yielded the highest PpIX fluorescence intensity and fluorescence contrast between normal and malignant urothelial cells. This approach allows us to optimize PpIX tissue distribution for photodynamic therapy in superficial bladder cancer.

Molecular basis of leukocyte rolling on PSGL-1. Predominant role of core-2 O-glycans and of tyrosine sulfate residue 51.

Interactions between the leukocyte adhesion receptor L-selectin and P-selectin glycoprotein ligand-1 play an important role in regulating the inflammatory response by mediating leukocyte tethering and rolling on adherent leukocytes. In this study, we have examined the effect of post-translational modifications of PSGL-1 including Tyr sulfation and presentation of sialylated and fucosylated O-glycans for L-selectin binding. The functional importance of these modifications was determined by analyzing soluble L-selectin binding and leukocyte rolling on CHO cells expressing various glycoforms of PSGL-1 or mutant PSGL-1 targeted at N-terminal Thr or Tyr residues. Simultaneous expression of core-2 beta1,6-N-acetylglucosaminyltransferase and fucosyltransferase VII was required for optimal L-selectin binding to PSGL-1. Substitution of Thr-57 by Ala but not of Thr-44, strongly decreased L-selectin binding and leukocyte rolling on PSGL-1. Substitution of Tyr by Phe revealed that PSGL-1 Tyr-51 plays a predominant role in mediating L-selectin binding and leukocyte rolling whereas Tyr-48 has a minor role, an observation that contrasts with the pattern seen for the interactions between PSGL-1 and P-selectin where Tyr-48 plays a key role. Molecular modeling analysis of L-selectin and P-selectin interactions with PSGL-1 further supported these observations. Additional experiments showed that core-2 O-glycans attached to Thr-57 were also of critical importance in regulating the velocity and stability of leukocyte rolling. These observations pinpoint the structural characteristics of PSGL-1 that are required for optimal interactions with L-selectin and may be responsible for the specific kinetic and mechanical bond properties of the L-selectin-PSGL-1 adhesion receptor-counterreceptor pair.

La fi del censal: reducció de l'interès o vaga de pensions? (1750-1861)

La reducció de l'interès del 5 % al 3 % ha estat considerada el principi de la fi dels censals. Però aquest argument no té en compte que la de 1750 va ser només l'última d'una sèrie de reduccions del for de censal, que també es produïren a Anglaterra, França o Castella, i que els primers símptomes de retracció de l'oferta de préstecs censals no apareixerien fins a la darreria del segle XVIII o principi del segle XIX. L¿article proposa una explicació alternativa d¿aquelles reduccions, que ajustaven l'interès a l'alça coetània del valor patrimonial de la terra i la minva de la rendibilitat del seu esmerç, i de la fi del censal a partir de l'impagament de pensions que es desencadenà a les acaballes del segle XVIII, juntament amb la vaga de delmes i rendes de la terra, quan s'havien esgotat, en bona part, les possibilitats d'expansió agrària del segle XVIII.

Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study.

The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide single-nucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P= 3.6 × 10(-8)) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P= 4.7 × 10(-8)). The top IBC association for SBP was rs2012318 (P= 6.4 × 10(-6)) near SLC25A42 and for DBP was rs2523586 (P= 1.3 × 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P= 0.009; TBX3-TBX5, P= 0.03; and CSK-ULK3, P= 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity.

Bcl10 controls TCR- and FcgammaR-induced actin polymerization.

Bcl10 plays an essential role in the adaptive immune response, because Bcl10-deficient lymphocytes show impaired Ag receptor-induced NF-kappaB activation and cytokine production. Bcl10 is a phosphoprotein, but the physiological relevance of this posttranslational modification remains poorly defined. In this study, we report that Bcl10 is rapidly phosphorylated upon activation of human T cells by PMA/ionomycin- or anti-CD3 treatment, and identify Ser(138) as a key residue necessary for Bcl10 phosphorylation. We also show that a phosphorylation-deficient Ser(138)/Ala mutant specifically inhibits TCR-induced actin polymerization yet does not affect NF-kappaB activation. Moreover, silencing of Bcl10, but not of caspase recruitment domain-containing MAGUK protein-1 (Carma1) induces a clear defect in TCR-induced F-actin formation, cell spreading, and conjugate formation. Remarkably, Bcl10 silencing also impairs FcgammaR-induced actin polymerization and phagocytosis in human monocytes. These results point to a key role of Bcl10 in F-actin-dependent immune responses of T cells and monocytes/macrophages.

Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma.

Concentrations of liver enzymes in plasma are widely used as indicators of liver disease. We carried out a genome-wide association study in 61,089 individuals, identifying 42 loci associated with concentrations of liver enzymes in plasma, of which 32 are new associations (P = 10(-8) to P = 10(-190)). We used functional genomic approaches including metabonomic profiling and gene expression analyses to identify probable candidate genes at these regions. We identified 69 candidate genes, including genes involved in biliary transport (ATP8B1 and ABCB11), glucose, carbohydrate and lipid metabolism (FADS1, FADS2, GCKR, JMJD1C, HNF1A, MLXIPL, PNPLA3, PPP1R3B, SLC2A2 and TRIB1), glycoprotein biosynthesis and cell surface glycobiology (ABO, ASGR1, FUT2, GPLD1 and ST3GAL4), inflammation and immunity (CD276, CDH6, GCKR, HNF1A, HPR, ITGA1, RORA and STAT4) and glutathione metabolism (GSTT1, GSTT2 and GGT), as well as several genes of uncertain or unknown function (including ABHD12, EFHD1, EFNA1, EPHA2, MICAL3 and ZNF827). Our results provide new insight into genetic mechanisms and pathways influencing markers of liver function.

Sobre la violencia, Hannah Arendt, Àngela Lorena Fuster (trad.), Gerard Rosich (trad.), Fina Birulés (pròl.)

Motivada por el surgimiento de la reivindicación de la función de la violencia enla política, tanto en el terreno de la acción como en el discurso teórico, en Sobrela violència Arendt interroga la relación entre violencia y poder, entre política ydominación. Tal como señala Fina Birulés en el prólogo, sus reflexiones son elresultado del esfuerzo renovado por comprender las experiencias políticas a lasque Arendt se vio confrontada, en particular, la aparición en la escena pública deun discurso que reivindicaba la violencia como elemento central de la prácticarevolucionaria. Y como en otras ocasiones, la reflexión sobre el presente da lugara la crítica de la tradición de la filosofía política. En este sentido, y de modoejemplar, el libro se constituye como un “ejercicio de pensamiento político” que ala vez que interpreta los acontecimientos interroga las categorías con las que latradición ha pensado la política.

Mobbing: la voz de las enfermeras que han vivido esta experiencia

Este estudio es una investigación cualitativa que pretende conocer la experiencia demobbing entre el personal de enfermería, con la finalidad de aumentar el conocimientodel problema, difundir la existencia del mismo entre la profesión a partir de un grupo deestudio, y concienciar a las personas que dirigen las instituciones y a los demásprofesionales de la necesidad de intervenir.Objetivos: Conocer el significado que dan las enfermeras a la experiencia y sufrimientovividos, y conocer el significado de las reacciones del entorno frente a esta situaciónpersonal y laboral que viven o vivieron.Este estudio permitirá avanzar en el conocimiento de esta situación que afecta a lasalud física y psíquica de las víctimas de forma integral, y atenta contra el derechofundamental a la dignidad de trabajador.También servirá para aumentar entre los profesionales de enfermería laconcienciación sobre la necesidad de reconocer esta realidad y trabajar paradesarrollar estrategias para evitarla y prevenirla.Con ello estaremos no sólo atendiendo los derechos de las enfermeras y velando porsu salud, sino también incidiendo indirectamente en la mejora de la calidad de loscuidados que los pacientes reciben de ellas. En consecuencia, puede servir paraaumentar la calidad del sistema sanitario tanto interna como externamente.Además, mi propia experiencia personal como víctima de mobbing en una anterioretapa profesional, aumentan mi interés por profundizar en esta experiencia paraayudar con este estudio a otras personas en esta situación.

Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors.

The therapeutic efficacy of anticancer chemotherapies may depend on dendritic cells (DCs), which present antigens from dying cancer cells to prime tumor-specific interferon-gamma (IFN-gamma)-producing T lymphocytes. Here we show that dying tumor cells release ATP, which then acts on P2X(7) purinergic receptors from DCs and triggers the NOD-like receptor family, pyrin domain containing-3 protein (NLRP3)-dependent caspase-1 activation complex ('inflammasome'), allowing for the secretion of interleukin-1beta (IL-1beta). The priming of IFN-gamma-producing CD8+ T cells by dying tumor cells fails in the absence of a functional IL-1 receptor 1 and in Nlpr3-deficient (Nlrp3(-/-)) or caspase-1-deficient (Casp-1(-/-)) mice unless exogenous IL-1beta is provided. Accordingly, anticancer chemotherapy turned out to be inefficient against tumors established in purinergic receptor P2rx7(-/-) or Nlrp3(-/-) or Casp1(-/-) hosts. Anthracycline-treated individuals with breast cancer carrying a loss-of-function allele of P2RX7 developed metastatic disease more rapidly than individuals bearing the normal allele. These results indicate that the NLRP3 inflammasome links the innate and adaptive immune responses against dying tumor cells.