Antibody-deficiency and Acute Nephritic Syndrome in a Patient with Homozygous Disruption of the CD81 Gene

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Intercambios de masa y energía entre la vegetación y la capa límite atmosférica en dos ecosistemas de Argentina

Dentro del contexto del Cambio Global ha surgido el interés en conocer y entender la dinámica de los ecosistemas. La técnica Eddy Covariance (EC) es utilizada a nivel global para el registro continuo de los intercambios turbulentos de masa y energía en una diversidad de ecosistemas, con sensores montados en torres micrometeorológicas y en plataformas móviles. Así mismo, el empleo de modelos atmosféricos de mesoescala suma un aporte a la compresión de los procesos de intercambio suelo-atmósfera dentro de la Capa Límite Atmosférica. Lo enunciado anteriormente motivó la elaboración de la presente tesis en la cual se planteó caracterizar los intercambios turbulentos, estudiando su variabilidad sobre un bosque seco nativo y uno implantado en Argentina y evaluar el desempeño del modelo BRAMS-4.2 en alta resolución en reproducir estos intercambios. A partir de los valores observados, se encontró que la concentración media diaria y los flujos de CO2 presentaron un marcado ciclo diurno. El valor medio de las concentraciones en el bosque implantado fue igual a 736.2 más o menos 42.4 mg/m3 y en el bosque nativo igual a 641.9 más o menos 22.4 mg/m3. Los flujos de CO2 presentaron una amplitud media mayor en verano igual a 1.42 mg/m2s (0.27 mg/m2s) en el bosque implantado (bosque nativo). Los flujos de calor latente registrados en el bosque implantado fueron mayores a los registrados en el bosque nativo. La implementación del sistema de sensores instalados a bordo del avión Sky Arrow 650 ERA permitió realizar mediciones en los primeros metros de la atmósfera. El modelo BRAMS-4.2 supo reproducir razonablemente bien distintas variables meteorológicas así como también los flujos de masa y energía. Los resultados obtenidos en esta tesis son un aporte para ampliar el conocimiento sobre los intercambios turbulentos entre la vegetación y las capas bajas de la atmósfera en distintos ecosistemas de Argentina.

Intercambios de masa y energía entre la vegetación y la capa límite atmosférica en dos ecosistemas de Argentina

Dentro del contexto del Cambio Global ha surgido el interés en conocer y entender la dinámica de los ecosistemas. La técnica Eddy Covariance (EC)es utilizada a nivel global para el registro continuo de los intercambios turbulentos de masa y energía en una diversidad de ecosistemas, con sensores montados en torres micrometeorológicas y en plataformas móviles. Así mismo, el empleo de modelos atmosféricos de mesoescala suma un aporte a la compresión de los procesos de intercambio suelo-atmósfera dentro de la Capa Límite Atmosférica. Lo enunciado anteriormente motivó la elaboración de la presente tesis en la cual se planteó caracterizar los intercambios turbulentos, estudiando su variabilidad sobre un bosque seco nativo y uno implantado en Argentina y evaluar el desempeño del modelo BRAMS-4.2 en alta resolución en reproducir estos intercambios. A partir de los valores observados, se encontró que la concentración media diaria y los flujos de CO2 presentaron un marcado ciclo diurno. El valor medio de las concentraciones en el bosque implantado fue igual a 736.2 ± 42.4 mg/m3 y en el bosque nativo igual a 641.9 ± 22.4 mg/m3. Los flujos de CO2 presentaron una amplitud media mayor en verano igual a 1.42 mg/m2s (0.27 mg/m2s)en el bosque implantado (bosque nativo). Los flujos de calor latente registrados en el bosque implantado fueron mayores a los registrados en el bosque nativo. La implementación del sistema de sensores instalados a bordo del avión Sky Arrow 650 ERA permitió realizar mediciones en los primeros metros de la atmósfera. El modelo BRAMS-4.2 supo reproducir razonablemente bien distintas variables meteorológicas así como también los flujos de masa y energía. Los resultados obtenidos en esta tesis son un aporte para ampliar el conocimiento sobre los intercambios turbulentos entre la vegetación y las capas bajas de la atmósfera en distintos ecosistemas de Argentina.

Hepatocyte growth factor (HGF) protects c-met-expressing Burkitt''s lymphoma cell lines from apoptotic death induced by DNA damaging agents

The relative sensitivity of neoplastic cells to DNA damaging agents is a key factor in cancer therapy. In this paper, we show that pretreatment of Burkitt's lymphoma cell lines expressing the c-met protooncogene with hepatocyte growth factor (HGF) protects them from death induced by DNA damaging agents commonly used in tumour therapy. This protection was observed in assays based on morphological assessment of apoptotic cells and DNA fragmentation assays. The protection was dose- and time-dependent — maximal protection requiring pre-incubation with 100 ng/ml HGF for 48 h. Western blotting analysis and flow cytometric studies revealed that HGF inhibited doxorubicin- and etoposide-induced decreases in the levels of the anti-apoptotic proteins Bcl-XL, and to a lesser extent Bcl-2, without inducing changes in the pro-apoptotic Bax protein. Overall, these studies suggest that the accumulation of HGF within the microenvironment of neoplastic cells may contribute to the development of a chemoresistant phenotype.

Correlation of TACC3, FGFR3, MMSET and p21 expression with the t(4;14)(p16.3;q32) in multiple myeloma

The t(4;14)(p16;q32) translocation seen in c. 18% of newly diagnosed multiple myeloma (MM) cases, results in FGFR3 activation and creation of an IGH/MMSET fusion transcript. We have recently shown that FGFR3 is activated in only 75% of t(4;14)(+) cases, suggesting that alternative genes near the breakpoint may be involved in the transforming event. The gene, TACC3, located just 50 kb telomeric of FGFR3, with transforming capacity, therefore represented a candidate gene. Using a real-time quantitative polymerase chain reaction-based approach on a cohort of 54 patients, we found a statistically significant, twofold increase in TACC3 expression in t(4;14)(+) cases. TACC3, MMSET and p21 values were positively correlated in all cases and, of particular interest, six patient samples [three t(4;14)(-), three t(4;14)(+)] samples showed a joint up-regulation of TACC3, MMSET and p21. Although a poor prognosis is linked with elevated MMSET expression, an extended follow-up period will be required to evaluate the significance of elevated TACC3 and p21 expression in this subgroup of MM.

Increased cancellous bone and connectivity in coxarthrosis

Patients with coxarthrosis (cOA) have a reduced incidence of intracapsular femoral neck fracture, suggesting that cOA offers protection. The distribution of bone in the femoral neck was compared in cases of coxarthrosis and postmortem controls to assess the possibility that disease-associated changes might contribute to reduced fragility. Whole cross-section femoral neck biopsies were obtained from 17 patients with cOA and 22 age- and sex-matched cadaveric controls. Densitometry was performed using peripheral quantitated computed tomography (pQCT) and histomorphometry on 10-µm plastic-embedded sections. Cortical bone mass was not different between cases and controls (P > 0.23), but cancellous bone mass was increased by 75% in cOA (P = 0.014) and histomorphometric cancellous bone area by 71% (P <0.0001). This was principally the result of an increase of apparent density (mass/vol) of cancellous bone (+45%, P = 0.001). Whereas cortical porosity was increased in the cases (P <0.0001), trabecular width was also increased overall in the cases by 52% (P <0.001), as was cancellous connectivity measured by strut analysis (P <0.01). Where osteophytic bone was present (n = 9) there was a positive relationship between the amount of osteophyte and the percentage of cancellous area (P <0.05). Since cancellous bone buttresses and stiffens the cortex so reducing the risk of buckling, the increased cancellous bone mass and connectivity seen in cases of cOA probably explain, at least in part, the ability of patients with cOA to resist intracapsular fracture of the femoral neck during a fall.

CD33 reponses are blocked by SOCS3 through accelerated proteasomal-mediated turnover

CD33 is a member of the sialic acid–binding immunoglobulin-like lectin (Siglec) family of inhibitory receptors and a therapeutic target for acute myeloid leukemia (AML). CD33 contains a cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM), which can recruit SHP-1 and SHP-2. How CD33 expression is regulated is unclear. Suppressor of cytokine signaling 3 (SOCS3) is expressed in response to cytokines, LPS, and other PAMPs, and competes with SHP-1/2 binding to ITIMs of cytokine receptors, thereby inhibiting signaling. In this study, using peptide pull-down experiments, we found that SOCS3 can specifically bind to the phosphorylated ITIM of CD33. Additionally, following cross-linking SOCS3 can recruit the ECS E3 ligase resulting in accelerated proteasomal degradation of both CD33 and SOCS3. Our data suggest that the tyrosine motifs in CD33 are not important for internalization, while they are required for degradation. Moreover, SOCS3 inhibited the CD33-induced block on cytokine-induced proliferation. This is the first receptor shown to be degraded by SOCS3 and where SOCS3 and its target protein are degraded concomitantly. Our findings clearly suggest that during an inflammatory response, the inhibitory receptor CD33 is lost by this mechanism. Moreover, this has important clinical implications as tumors expressing SOCS3 may be refractory to -CD33 therapy.

Three-dimensional cultures of normal human osteoblasts: proliferation and differentiation potential in vitro and upon ectopic implantation in nude mice.

This paper is novel andreports on the in vitro establishment of 3-D cultures of human osteoblasts. These were evaluated for protein markers of bone cells. Sequentially alkaline phosphatase, calcium incorporation for matrix mineralisation and then finally osteocalcin expression were detected in cultures. The extracellular matrix was composed of type 1 collagen and as it mineralised, needle shaped crystals were often associated with matrix vesicles initiating mineralisation. In vivo implantation in nude mice showed progression of mineralisation from the inner region outward with peripheral cells in a non-mineralised matrix. Host vessels invaded the implanted cell area. The research has relevance to musculoskeletal tissue engineering.