Cronología radiocarbónica en paleoambientes del Pleistoceno tardío y Holoceno de la Pampa Deprimida, provincia de Buenos Aires

En la Pampa Deprimida de la provincia de Buenos Aires, se pueden diferenciar dos regiones: la continental y la planicie marina costera. En ambas se observan rasgos geomorfológicos y secuencias sedimentarias que conservan evidencias de las condiciones climáticas bajo las cuales se han generado. En momentos de morfogénesis –en la llanura de inundación del río Salado- se depositaron unidades litoestratigráficas en forma de sedimentos fluvio-lacustres con edades radiocarbónicas entre 14 ka y 0,5 ka del Pleistoceno tardío y Holoceno. En la planicie marina costera se encuentran depósitos ingresivolitorales del pico máximo de la ingresión marina del MIS 1, del orden de los 6 ka, con un posterior y paulatino retiro del mar. En momentos de estabilidad ambiental se formaron suelos, de los cuales se han podido individualizar y datar los geosuelos Puesto Callejón Viejo y Puesto Berrondo en sus sitios tipo, con edades que los sitúan en el Holoceno tardío. Las edades en años C14 AP se determinaron sobre megamamíferos extinguidos, invertebrados marinos y dulceacuícolas y materia orgánica, provenientes de las unidades litoestratigráficas y pedoestratigráficas estudiadas. El clima durante el Pleistoceno tardío fue árido-semiárido. En el Holoceno con alternancias a cálido-húmedo. Este estudio aporta información referente a la factibilidad de ámbitos para los asentamientos humanos y para estudios que necesiten aportes de índole crono/litoestratigráfico.In the Depressed Pampa of Buenos Aires Province, two regions can be differentiated: the continental and the coastal marine plain environments. Geomorphological characteristics and sedimentary sequences of both sectors preserve evidences of the climatic conditions under which they were generated. In morphogenesis periods -in the foodplain of the Salado river- lithostratigraphic units were deposited in the form of fluvio-lacustrine sediments with radiocarbon ages between 14 ka and 0,5 ka in the Late Pleistocene and Holocene. In the coastal marine plain there are deposits of the MIS 1 marine ingression of circa 6 ka, with a later and gradual retreat of the sea. In periods of environmental stability soils were formed. Among them the geosoils Puesto Callejón Viejo and Puesto Berrondo have been individualized and dated on their type sites with radiocarbon ages corresponding to the Late Holocene. The 14C ages in years BP were determined using bones of extinct megamammals, shells of marine and fresh water invertebrates and organic matter from the lithostratigraphic and pedostratigraphic units. The climate during the Late Pleistocene was arid-semiarid. In the Holocene there were alternations to warm-humid. This study provides information on the feasibility of areas for human settlements and for studies requiring contributions of a chrono/lithoestratigraphic nature.Facultad de Ciencias Naturales y Muse

Morfogénesis y estabilidad ambiental en el Holoceno del centro norte y centro este de la pcia de Buenos Aires

Desde el punto de vista fisiográfico, en el centro-norte y centro-este de la provincia de Buenos Aires, podemos diferenciar por sus aspectos evolutivos en tres sectores muy contrastantes: la Pampa Ondulada (PO), la Pampa Deprimida (PD) y la Llanura Marina Costera (LMC). Las dos primeras están separadas por la divisoria que con dirección NO-SE limita las cuencas con drenaje hacia los ríos Paraná y de la Plata (Areco, Luján, Arrecifes, Matanza, Reconquista, entre las más importantes), de aquellas con drenaje hacia la bahía Samborombón (Samborombón y Salado). La Llanura Marina Costera se extiende como una franja paralela a la costa actual del Río de la Plata y hasta la cota de + 5m. En las dos primeras unidades fisiográficas (PO y PD) los rasgos geomorfológicos más comunes están constituidos por divisorias, valles y bajos y en LMC, las llanuras de marea, los cordones conchiles y marismas, son las mas representativas. En éste trabajo nos referiremos a la Pampa Ondulada y a la Llanura Marina Costera.Facultad de Ciencias Naturales y Museo (FCNM)Facultad de Ciencias Agrarias y Forestales (FCAF

Morfogénesis y estabilidad ambiental en el Holoceno del centro norte y centro este de la pcia de Buenos Aires

Desde el punto de vista fisiográfico, en el centro-norte y centro-este de la provincia de Buenos Aires, podemos diferenciar por sus aspectos evolutivos en tres sectores muy contrastantes: la Pampa Ondulada (PO), la Pampa Deprimida (PD) y la Llanura Marina Costera (LMC). Las dos primeras están separadas por la divisoria que con dirección NO-SE limita las cuencas con drenaje hacia los ríos Paraná y de la Plata (Areco, Luján, Arrecifes, Matanza, Reconquista, entre las más importantes), de aquellas con drenaje hacia la bahía Samborombón (Samborombón y Salado). La Llanura Marina Costera se extiende como una franja paralela a la costa actual del Río de la Plata y hasta la cota de + 5m. En las dos primeras unidades fisiográficas (PO y PD) los rasgos geomorfológicos más comunes están constituidos por divisorias, valles y bajos y en LMC, las llanuras de marea, los cordones conchiles y marismas, son las mas representativas. En éste trabajo nos referiremos a la Pampa Ondulada y a la Llanura Marina Costera.Facultad de Ciencias Naturales y Museo (FCNM)Facultad de Ciencias Agrarias y Forestales (FCAF

Characterization of an immunologically conserved epitope from hepatitis C virus E2 glycoprotein recognized by HLA-A2 restricted cytotoxic T lymphocytes

BACKGROUND/AIMS: Identification of epitopes recognized by cytotoxic T lymphocytes (CTL) in hepatitis C virus (HCV) proteins is of importance because they can be used for vaccination, treatment of infection or monitoring of immune responses. Our purpose was to characterize new CTL epitopes in HCV structural proteins. METHODS: Peptides were synthesized and tested in HLA-A2 binding assays. Binder peptides were used to stimulate peripheral blood mononuclear cells from HCV+ patients and controls, and activity measured in chromium release and ELISPOT assays. RESULTS: Twenty binder peptides were found, and stimulation of HCV+ patient cells with nine peptides showing high binding ability led to the growth of CD8+ CTL recognizing peptide E2(614-622) in association with HLA-A2. Peptide E2(614-622) was recognized by 30% of HLA-A2+ patients with chronic HCV infection, but no responses were observed in control groups. Five peptides derived from region E2(614-622) from 26 different viral isolates bound to HLA-A2 molecules, and all of them but one, containing Phe at position 622, were recognized by E2(614-622) specific CTL. CONCLUSIONS: These results show that peptide E2(614-622) belongs to a highly conserved region of HCV E2, and might be a good candidate to induce anti-HCV CTL responses in HLA-A2+ subjects

Specific and general HLA-DR binding motifs: comparison of algorithms

Using panels of peptides well characterized for their ability to bind to HLA DR1, DRB1*1101, or DRB1*0401 molecules, algorithms were deduced to predict binding to these molecules. These algorithms consist of blocks of 8 amino acids containing an amino acid anchor (Tyr, Phe, Trp, Leu, Ile, or Val) at position i and different amino acid combinations at positions i+2 to i+7 depending on the class II molecule. The sensitivity (% of correctly predicted binder peptides) and specificity (% of correctly predicted non-binder peptides) of these algorithms, were tested against different independent panels of peptides and compared to other algorithms reported in the literature. Similarly, using a panel of 232 peptides able to bind to one or more HLA molecules as well as 43 non-binder peptides, we deduced a general motif for the prediction of binding to HLA-DR molecules. The sensitivity and specificity of this general motif was dependent on the threshold score used for the predictions. For a score of 0.1, the sensitivity and specificity were 84.7% and 69.8%, respectively. This motif was validated against several panels of binder and non-binder peptides reported in the literature, as well as against 35, 15-mer peptides from hepatitis C virus core protein, that were synthesized and tested in a binding assay against a panel of 19 HLA-DR molecules. The sensitivities and specificities against these panels of peptides were similar to those attained against the panels used to deduce the algorithm. These results show that comparison of binder and non-binder peptides, as well as correcting for the relative abundance of amino acids in proteins, is a useful approach to deduce performing algorithms to predict binding to HLA molecules

Identification of an antigenic epitope for helper T lymphocytes from carcinoembryonic antigen

PURPOSE: The product of the carcinoembryonic antigen (CEA) gene is an attractive candidate for T-cell-based immunotherapy because it is frequently expressed in epithelial solid carcinomas. Although many CEA peptide epitopes capable of stimulating CTLs have been identified, no MHC class II-restricted T helper epitope has yet been reported. Experimental Design: The amino acid sequence of CEA was examined for the presence of potential T helper epitopes, and candidate peptides were used to stimulate in vitro T-cell responses. RESULTS: We describe here that using an algorithm to identify promiscuous helper T-cell epitopes, a peptide of CEA occupying residue positions 653 to 667 (CEA(653-667)), was effective in inducing in vitro T helper responses in the context of the HLA-DR4, HLA-DR7, and HLA-DR 9 alleles. Most significantly, some of the peptide-reactive helper T lymphocytes were also capable of recognizing naturally processed antigen in the form of recombinant CEA protein or cell lysates from tumors that express CEA. Interestingly, the newly identified helper T-cell epitope was found to overlap with a previously described HLA-A24-restricted CTL epitope, CEA(652-660), which could facilitate the development of a therapeutic vaccine capable of eliciting both CTL and T helper responses in patients suffering from epithelial carcinomas. CONCLUSION: These results indicate that T helper lymphocytes are capable of recognizing CEA as a tumor antigen and that epitope CEA(653-667) could be used for immunotherapy against tumors expressing CEA

Evolución geológica-geomorfológica de la cuenca del río Areco, NE de la provincia de Buenos Aires

La cuenca del río Areco integra la red de drenaje de la Pampa Ondulada, NE de la provincia de Buenos Aires. Los procesos geomórficos marinos, fluvio-lacustres y eólicos actuaron sobre los sedimentos loéssicos y loessoides de la Formación Pampeano (Pleistoceno) dejando, con diferentes grados de desarrollo, el registro sedimentario del Pleistoceno tardío y Holoceno a lo largo de toda la cuenca. En estos depósitos se han reconocido, al menos, dos episodios pedogenéticos. Edades14C sobre MO de estos paleosuelos arrojaron valores de 7.000 ± 240 y 1.940 ± 80 años AP en San Antonio de Areco y 2.320 ± 90 y 2.000 ± 90 años AP en Puente Castex, para dos importantes estabilizaciones del paisaje, separadas en esta última localidad por un breve episodio de sedimentación. La cuenca inferior en la cañada Honda, fue ocupada por la ingresión durante MIS 1 (Formación Campana), dejando un amplio paleoestuario limitado por acantilados. El retroceso de la línea de costa y la continentalización del ambiente permitió la formación de un suelo datado en 3.070 ± 90 años14C AP cubierto por sedimentos aluviales. Los sedimentos litorales son en general de baja energía, asociados a tres litofacies diferentes, cuyas edades fluctúan entre los 4.270 ± 70 años14C AP en esta cuenca y 6.000 ± 8014C años AP, 6.370 ± 90 años14C AP, 3.640 ± 70 años14C AP, 5.630 ± 100 años14C AP y 5.420 ± 110 años14C AP, en cuencas aledañas. La ingresión durante MIS 5e también entró por el río Areco evidenciando ya la existencia de esta depresión. El límite externo de esta cuenca lo constituye el delta del Paraná cuya progradación ha dejado expuesto morfologías y depósitos de ambientes fluviales, observándose que el contacto entre ambas unidades morfológicas (delta y paleoestuario) está determinado por los cursos de agua, que con cambio bruscos de dirección, acompañan el sentido de avance del complejo deltaico.The Areco River Basin is part of the drainage system of Pampa Ondulada region, NE Buenos Aires Province. Geomorphic processes that it formed, acted on the loessoid sediments of the Pampeano Formation (Pleistocene) building a morphology contrasting with those of the surrounding environment. In the upper and middle basin there are fluvial successions (Late Pleistocene-Holocene) with different development of pedogenesis.14C on OM of these paleosoils yielded 7,000 ± 240 and 1,940 ± 80 years BP in San Antonio de Areco, and 2,320 ± 90 and 2,000 ± 90 years14C BP in Castex Bridge, for two important landscape stabilizations, separated in the latter place for a brief episode of sedimentation. The lower basin, together with Cañada Honda locality, was occupied during MIS 1 ingression (Campana Formation) leaving a wide paleoestuary, limited by fossil cliffs. These sediments were generally deposited in low energy environments, associated with three different lithofacies;14C ages range between 4,270 ± 70 years BP in this basin and 6,000 ± 80, 6,370 ± 90, 3,640 ±70, 5,630 ± 100, and 5,420 ±,110 years BP in near basins. Based on this information, the late Pleistocene ingression MIS 5e also entered by Areco River putting in evidence, already, the existence of this depression. The external limit of this unit is the Paraná Delta River whose progradation exposed specific morphologies and deposits. In the contact between both morphological units (delta and paleoestuary) is determined by the water streams that, with abrupt direction changes according to deltaic complex development.Facultad de Ciencias Naturales y Muse

The immunotherapy potential of agonistic anti-CD137 (4-1BB) monoclonal antibodies for malignancies and chronic viral diseases

Pharmacological intervention on the immune system to achieve more intense lymphocyte responses has potential application in tumour immunology and in the treatment of chronic viral diseases. Immunostimulating monoclonal antibodies are defined as a new family of drugs that augment cellular immune responses. They interact as artificial ligands with functional proteins of the immune system, either activating or inhibiting their functions. There are humanized monoclonal antibodies directed to the inhibitory receptor CD152 (CTLA-4) that are being tested in clinical trials with evidence of antitumoural activity. As a drawback, anti-CTLA-4 monoclonal antibodies induce severe autoimmunity reactions in a fraction of the patients. Anti-CD137 monoclonal antibodies have the ability to induce potent immune responses mainly mediated by cytotoxic lymphocytes with the result of frequent complete tumour eradications in mice. Comparative studies in experimental models indicate that the antitumour activity of anti-CD137 monoclonal antibodies is superior to that of anti-CD152. CD137 (4-1BB) is a leukocyte differentiation antigen selectively expressed on the surface of activated T and NK lymphocytes, as well as on dendritic cells. Monoclonal antibodies acting as artificial stimulatory ligands of this receptor (anti-CD137 agonist antibodies) enhance cellular antitumoural and antiviral immunity in a variety of mouse models. Paradoxically, anti-CD137 monoclonal antibodies are therapeutic or preventive in the course of model autoimmune diseases in mice. In light of these experimental results, a number of research groups have humanized antibodies against human CD137 and early clinical trials are about to start

Dendritic cells delivered inside human carcinomas are sequestered by interleukin-8

In the course of a clinical trial consisting of intratumoral injections of dendritic cells (DCs) transfected to produce interleukin-12, the use of (111)In-labeled tracing doses of DCs showed that most DCs remained inside tumor tissue, instead of migrating out. In search for factors that could explain this retention, it was found that tumors from patients suffering hepatocellular carcinoma, colorectal or pancreatic cancer were producing IL-8 and that this chemokine attracted monocyte-derived dendritic cells that uniformly express both IL-8 receptors CXCR1 and CXCR2. Accordingly, neutralizing antihuman IL-8 monoclonal antibodies blocked the chemotactic attraction of DCs by recombinant IL-8, as well as by the serum of the patients or culture supernatants of human colorectal carcinomas. In addition, tissue culture supernatants of colon carcinoma cells inhibited DC migration induced by MIP-3beta in an IL-8-dependent fashion. IL-8 production in malignant tissue and the responsiveness of DCs to IL-8 are a likely explanation of the clinical images, which suggest retention of DCs inside human malignant lesions. Impairment of DC migration toward lymphoid tissue could be involved in cancer immune evasion

Low surface expression of B7-1 (CD80) is an immunoescape mechanism of colon carcinoma

Artificially enforced expression of CD80 (B7-1) and CD86 (B7-2) on tumor cells renders them more immunogenic by triggering the CD28 receptor on T cells. The enigma is that such B7s interact with much higher affinity with CTLA-4 (CD152), an inhibitory receptor expressed by activated T cells. We show that unmutated CD80 is spontaneously expressed at low levels by mouse colon carcinoma cell lines and other transplantable tumor cell lines of various tissue origins. Silencing of CD80 by interfering RNA led to loss of tumorigenicity of CT26 colon carcinoma in immunocompetent mice, but not in immunodeficient Rag-/- mice. CT26 tumor cells bind CTLA-4Ig, but much more faintly with a similar CD28Ig chimeric protein, thus providing an explanation for the dominant inhibitory effects on tumor immunity displayed by CD80 at that expression level. Interestingly, CD80-negative tumor cell lines such as MC38 colon carcinoma and B16 melanoma express CD80 at dim levels during in vivo growth in syngeneic mice. Therefore, low CD80 surface expression seems to give an advantage to cancer cells against the immune system. Our findings are similar with the inhibitory role described for the dim CD80 expression on immature dendritic cells, providing an explanation for the low levels of CD80 expression described in various human malignancies