CREB is a critical regulator of normal hematopoiesis and leukemogenesis

The cAMP-responsive element binding protein (CREB) is a 43-kDa nuclear transcription factor that regulates cell growth, memory, and glucose homeostasis. We showed previously that CREB is amplified in myeloid leukemia blasts and expressed at higher levels in leukemia stem cells from patients with myeloid leukemia. CREB transgenic mice develop myeloproliferative disease after 1 year, but not leukemia, suggesting that CREB contributes to but is not sufficient for leukemogenesis. Here, we show that CREB is most highly expressed in lineage negative hematopoietic stem cells (HSCs). To understand the role of CREB in hematopoietic progenitors and leukemia cells, we examined the effects of RNA interference (RNAi) to knock down CREB expression in vitro and in vivo. Transduction of primary HSCs or myeloid leukemia cells with lentiviral CREB shRNAs resulted in decreased proliferation of stem cells, cell- cycle abnormalities, and inhibition of CREB transcription. Mice that received transplants of bone marrow transduced with CREB shRNA had decreased committed progenitors compared with control mice. Mice injected with Ba/F3 cells expressing either Bcr-Abl wild-type or T315I mutation with CREB shRNA had delayed leukemic infiltration by bioluminescence imaging and prolonged median survival. Our results suggest that CREB is critical for normal myelopoiesis and leukemia cell proliferation

Episodic diamond growth beneath the Kaapvaal Craton at Jwaneng Mine, Botswana

Important implications for the interior workings of the Earth can be drawn by studying diamonds and their inclusions. To better understand the timing and number of diamond forming events beneath the NW margin of the Kaapvaal Craton, a comprehensive reassessment of Jwaneng’s diamond populations has been undertaken. We report new inclusion abundance data from the visual examination of ~130,000 diamonds that validate the predominance of an eclogitic diamond suite (up to 88%) with on average 5% inclusion-bearing diamonds (with inclusions >10 μm in size). From this population, polished plates from 79 diamonds of eclogitic and peridotitic paragenesis have been studied with cathodoluminescence (CL) imaging and infrared spectroscopy (FTIR) traverses. The majority (80%) record major changes in N concentration and aggregation states, as well as sharp boundaries in the CL images of individual plates that are interpreted to demarcate discrete diamond growth events. In addition, bulk FTIR data have been acquired for 373 unpolished diamonds. Silicate inclusions sampled from distinct growth zones define 2 compositional groups of omphacites and pyrope-almandines associated with different N contents in their diamond hosts. These findings reinforce previous observations that at Jwaneng at least seven individual diamond forming events can be identified – 3 peridotitic and 4 eclogitic. The results demonstrate that detailed examination of diamond plates by CL imaging and FTIR traverses is necessary to unveil the complex history recorded in diamonds

Allelic Exclusion and Peripheral Reconstitution by TCR Transgenic T Cells Arising From Transduced Human Hematopoietic Stem/Progenitor Cells

Transduction and transplantation of human hematopoietic stem/progenitor cells (HSPC) with the genes for a T-cell receptor (TCR) that recognizes a tumor-associated antigen may lead to sustained long-term production of T cells expressing the TCR and confer specific antitumor activity. We evaluated this using a lentiviral vector (CCLc-MND-F5) carrying cDNA for a human TCR specific for an HLA-A*0201-restricted peptide of Melanoma Antigen Recognized by T cells (MART-1). CD34+ HSPC were transduced with the F5 TCR lentiviral vector or mock transduced and transplanted into neonatal NSG mice or NSG mice transgenic for human HLA-A*0201 (NSG-A2). Human CD8+ and CD4+ T cells expressing the human F5 TCR were present in the thymus, spleen, and peripheral blood after 4–5 months. Expression of human HLA-A*0201 in NSG-A2 recipient mice led to significantly increased numbers of human CD8+ and CD4+ T cells expressing the F5 TCR, compared with control NSG recipients. Transduction of the human CD34+ HSPC by the F5 TCR transgene caused a high degree of allelic exclusion, potently suppressing rearrangement of endogenous human TCR-β genes during thymopoiesis. In summary, we demonstrated the feasibility of engineering human HSPC to express a tumor-specific TCR to serve as a long-term source of tumor-targeted mature T cells for immunotherapy of melanoma

Serodiagnosis of Echinococcus spp. Infection: Explorative Selection of Diagnostic Antigens by Peptide Microarray

Crude or purified, somatic or metabolic extracts of native antigens are routinely used for the serodiagnosis of human helminthic infections. These antigens are often cross-reactive, i.e., recognized by sera from patients infected with heterologous helminth species. To overcome limitations in antigen production, test sensitivity and specificity, chemically synthesized peptides offer a pure and standardized alternative, provided they yield acceptable operative characteristics. Ongoing genome and proteome work create new resources for the identification of antigens. Making use of the growing amount of genomic and proteomic data available in public databases, we tested a bioinformatic procedure for the selection of potentially antigenic peptides from a collection of protein sequences including conceptually translated nucleotide sequence data of Echinococcus multilocularis and E. granulosus (Plathyhelminthes, Cestoda). The in silico selection was combined with high-throughput screening of peptides on microarray and systematic validation of reactive candidates in enzyme-linked immunosorbent assay. Our study proved the applicability of this approach for selection of peptide antigens with good diagnostic characteristics. Our results suggested the pooling of several peptides to reach a high level of sensitivity required for reliable immunodiagnosis

Sustainable geohydrological model of San Luis Potosí aquifer, Mexico

Un estudio geofísico e hidrogeológico se llevó a cabo en el acuífero de San Luis Potosí, con la finalidad de realizar un modelo transitorio de flujo de agua subterránea que reproduzca el estado actual del acuífero, para posteriormente proponer escenarios alternativos de explotación del acuífero. Este estudio permitió hacer importantes revelaciones sobre el estado del acuífero: el balance de recarga–extracción de agua presentó un déficit de 100 Hm3 en el año 2005; los niveles potenciométricos de datos recuperados entre 1972 y 2005 muestran un cono de depresión de 80 m de profundidad y 70 km2 de área en la ciudad de San Luis Potosí; el modelo numérico realizado muestra que el acuífero es muy sensible a la localización de los pozos de extracción. También se realizaron modelos predictivos y algunas medidas de remediación fueron propuestas para obtener una recuperación del sistema acuífero. doi: https://doi.org/10.22201/igeof.00167169p.2011.50.4.15