Fundación Instituto Leloir

About: Fundación Instituto Leloir is a facility organization based out in Buenos Aires, Argentina. It is known for research contribution in the topics: Dentate gyrus & Neurogenesis. The organization has 702 authors who have published 1052 publications receiving 39299 citations.

A large deletion within the clock gene LNK2 contributed to the spread of tomato cultivation from Central America to Europe

Abstract: Plant domestication is regarded as one of the most pivotal events in human history, as it allowed the growth and development of human civilization by providing the surplus of food needed for its expansion. Occurring independently and almost simultaneously in several parts of the world, plant domestication involved only a few species. Humans selected genetic variants of these species with favorable traits, such as increased fruit size (1). In turn, the expansion of human settlements promoted the spread of the newly domesticated crop species across the continents. This expansion was much quicker in Eurasia than in other regions, which likely contributed to the domination of the world by the cultures originating in this region. The faster spread of domesticated crops throughout Eurasia was most likely due to its predominant east–west axis: distant locations in Eurasia share similar latitudes, day lengths, and climates, and therefore, crops did not require additional genetic changes to adapt to new places (1). By contrast, large changes in latitude, day length, and climate are associated with the spread of plants in the Americas or Africa, where north–south axes predominate. Therefore, adaptation to new locations in these continents did require additional genetic changes that adjusted the growth and development of the plants to the different daily and seasonal environmental cycles that result in contrasting climates. In PNAS, Muller et al. (2) report that the expansion of the area of tomato ( Solanum lycopersicum ) cultivation from Central America to Europe and North America involved the selection of genetic variants associated with a large deletion within the clock gene LNK2 , which synchronizes internal rhythms with the external light/dark cycle and, therefore, adjusts the timing of multiple biological processes in response to the long-day characteristics of high latitudinal regions. Most organisms possess endogenous timing devices, known as circadian clocks, which … [↵][1]1To whom correspondence should be addressed. Email: mjyanovsky{at}gmail.com. [1]: #xref-corresp-1-1

Cerebrospinal fluid (CSF) boosts metabolism and virulence expression factors in Acinetobacter baumannii

Abstract: In a recent report by the Centers for Disease Control and Prevention (CDC), multidrug resistant (MDR) Acinetobacter baumannii is a pathogen described as an "urgent threat". Infection with this bacterium manifests as different diseases such as community and nosocomial pneumonia, bloodstream infections, endocarditis, urinary tract, wound infections, burn infections, skin and soft tissue infections, and meningitis. In particular, nosocomial meningitis, a common complication of neurosurgery caused by extensively-drug resistant (XDR) A. baumannii, is extremely challenging to manage. Therefore, it is necessary to identify signals, such as exposure to cerebrospinal fluid (CSF), that trigger expression of virulence factors that are associated with the successful establishment and progress of this infection. While a hypervirulent A. baumannii strain did not show changes in its transcriptome when incubated in the presence of CSF, a low-virulence isolate showed significant differences in gene expression and phenotypic traits. Exposure to 4% CSF caused increased expression of virulence factors such as fimbriae, pilins, and iron chelators, and virulence as determined in various model systems. Furthermore, although CSF9s presence did not enhance bacterial growth, it was associated with an increase of expression of genes encoding transcription, translation, and the ATP synthesis machinery. Experiments to identify the active CSF component pointed to human serum albumin (HSA).

Promoter inducible by reactive oxygen species and vector comprising the same

Abstract: The invention provides promoters inducible by reactive oxygen species (ROS), capable of driving the expression of a gene of interest, particularly in a tumor cell. More particularly, it refers to promoters inducible by reactive oxygen species, that may be used to drive the expression of a gene of interest, such as a therapeutic gene, or a reporter gene for use in image diagnosis. The promoters comprise at least a fragment of a promoter sequence responsive to said reactive oxygen species, and corresponding to a gene highly expressed in cancer cells, wherein the fragment of the promoter sequence responsive to reactive oxygen species (ROS) is selected from the group of: the VE element of the VEGF promoter, the E6 element of the promoter of the EGR-1 gene, the MMP-1 element and a chimeric promoter containing an E6 element and a VE element. It also provides vectors carrying a human therapeutic or non therapeutic gene of interest, operably linked to said promoter sequence and compositions comprising the same.

Abstract A37: Immunization of cutaneous melanoma patients with the allogeneic cell vaccine CSF-470 enhances immune infiltration of metastatic lesions and would favor subsequent response to Vemurafenib

Abstract: Therapeutic cancer vaccines are aimed at promoting tumor-specific immunity with long-term memory. We have developed the CSF-470 therapeutic vaccine, a mini-allograft of four irradiated allogeneic cutaneous melanoma cell lines, combined with BCG and rhGM-CSF as adjuvants; that is currently being assayed in adjuvancy against medium-dose IFN-alfa2b in the CASVAC-0401 phase II/III clinical trial (ClinicalTrials.gov identifier: NCT01729663). An update to September 2014 reveals that after inclusion of 31 patients, a significant benefit in the distant metastasis-free survival for the CSF-470 arm is obtained (p=0.034). Of the 20 patients assigned to the CSF-470 arm, with a mean follow-up of 26 months, six patients developed distant metastases, of whom two died, and fourteen patients are distant metastases-free (70%). Five patients of the vaccine arm were treated with Vemurafenib after progression; two of them achieved complete remission and two of them partial remission (>50%); only one developed severe dermatitis. Before Vemurafenib treatment, metastases biopsies from only three patients could be obtained; two of them later achieved complete responses. In this work, we present the analysis of the peripheral blood and in situ immune populations during CSF-470 immunization in the two patients that achieved complete responses with Vemurafenib treatment. To attain this task, histopathological characterization of tumor biopsies, along with immune populations determined by immunohistochemistry, was performed by microscopy and image analysis. Peripheral blood mononucleated cells were obtained from patients at different times during CSF-470 immunization and immune populations were assessed by flow cytometry. Patient #006 entered the CASVAC-0401 study after a primary and lymph node tumor resection. By the end of CSF-470 immunization, she developed simultaneously subcutaneous and lung metastases. Following a 3-month cycle of Vemurafenib 960mg bid, patient #006 achieved complete remission of lung tumor nodules. Analysis of immune response evolution during protocol revealed a marked increase in in situ immune infiltration at the cutaneous metastasis relative to the primary tumor, especially in CD8+, CD4+ and CD20+ cells. Several dying tumor cells could be distinguished in the cutaneous metastasis, with attached and surrounding CD8+, CD4+ and CD45Ro+ T lymphocytes and CD68+ cells; and with Granzyme B vesicles and DNA strand breaks. Patient #005 developed sequential in transit metastases; CD8+, CD4+ and CD20+ lymphocyte infiltration increased in situ in biopsies following CSF-470 immunization. Vemurafenib treatment allowed achieving a complete response characterized by brisk infiltration of CD68+ macrophages, CD11c+ dendritic cells, CD8+ and CD4+ lymphocytes. In both patients, analysis of peripheral immune populations revealed an increment of NK cells detected after 6-months treatment, followed by an increase in CD4+ and CD8+ cells by the end of the protocol (2 years). Also, serum reactivity to CSF-470 cutaneous melanoma cells increased during vaccination. We suggest that previous immunization of melanoma patients with CSF-470 vaccine increases tumor immune infiltration and subsequent response to Vemurafenib. These encouraging results may open new options for combined therapies in cutaneous melanoma. Citation Format: Mariana Aris, Maria Betina Pampena, Estrella M. Levy, Alicia I. Bravo, Florencia P. Madorsky-Rowdo, Ana Mordoh, Julio Kaplan, Antonela Baron, Mariela Urrutia, Paula A. Blanco, Maria Marcela Barrio, Jose Mordoh. Immunization of cutaneous melanoma patients with the allogeneic cell vaccine CSF-470 enhances immune infiltration of metastatic lesions and would favor subsequent response to Vemurafenib. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr A37.