Biology subjects

Romero, M. M.

Publications and source records attributed to Romero, M. M..

3 recordsLinked to original sources

bioRxiv2020

A decade of arbovirus emergence in the temperate southern cone of South America: dengue, Aedes aegypti and climate dynamics in Cordoba, Argentina

BackgroundArgentina is located at the southern temperate range of arboviral transmission by the mosquito Aedes aegypti and has experienced a rapid increase in disease transmission in recent years. Here we present findings from an entomological surveillance study that began in Cordoba, Argentina, following the emergence of dengue in 2009. MethodsFrom 2009 to 2017, larval surveys were conducted monthly, from November to May, in 600 randomly selected households distributed across the city. From 2009 to 2013, ovitraps (n=177) were sampled weekly to monitor the oviposition activity of Ae. aegypti. We explored seasonal and interannual dynamics of entomological variables and dengue transmission. Cross correlation analysis was used to identify significant lag periods. ResultsAedes aegypti were detected over the entire study period, and abundance peaked during the summer months (January to March). We identified a considerable increase in the proportion of homes with juvenile Ae. aegypti over the study period (from 5.7% of homes in 2009-10 to 15.4% of homes in 2016-17). Aedes aegypti eggs per ovitrap and larval abundance were positively associated with temperature in the same month. Autochthonous dengue transmission peaked in April, following a peak in imported dengue cases in March; autochthonous dengue was not positively associated with vector or climate variables. ConclusionsThis longitudinal study provides insights into the complex dynamics of arbovirus transmission and vector populations in a temperate region of arbovirus emergence. Our findings suggest that Cordoba is well suited for arbovirus disease transmission, given the stable and abundant vector populations. Further studies are needed to better understand the role of regional human movement. Author summaryThere is an increasing risk of arbovirus transmission in temperate regions. Argentina is located at the southern range of dengue virus transmission by the Aedes aegypti mosquito. In the last decade, epidemics of dengue fever have emerged for the first time in the city of Cordoba, Argentina. We present the study design and findings from an entomological surveillance study in Cordoba, which began following the emergence of dengue in 2009. We found that Ae. aegypti were most abundant from January to March, followed by a peak in local dengue transmission in April. Over the study period, we noted a considerable increase in the proportion of homes with Ae. aegypti. Vector indices were positively associated with warmer temperatures, which have been increasing in this region. However, the timing of local dengue transmission appears to be driven by the appearance of imported dengue cases associated with human movement. These results highlight the important role of long term surveillance studies in areas of disease emergence.

ecology↗

bioRxiv2019

Pharmacologic inhibition of lysine specific demethylase-1 (LSD1) as a therapeutic and immune-sensitization strategy in diffuse intrinsic pontine glioma (DIPG)

BackgroundDiffuse intrinsic pontine glioma (DIPG) is an incurable pediatric brain tumor. Mutations in the H3 histone tail (H3.1/3.3-K27M) are a feature of DIPG, potentially rendering them therapeutically sensitive to small-molecule inhibition of chromatin modifiers. Pharmacological inhibition of lysine specific demethylase-1 (LSD1) shows promise in pediatric cancers such as Ewings sarcoma, but has not been investigated in DIPG, which was the aim of our study.\n\nMethodsPatient-derived DIPG cell lines and pediatric high-grade glioma (pHGG) datasets were used to evaluate effects of several LSD1 inhibitors on selective cytotoxicity and immune gene expression. Immune cell cytotoxicity was assessed in DIPG cells treated with LSD1 inhibitors and informatics platforms were used to determine immune infiltration of pHGG and impact on survival.\n\nResultsSelective cytotoxicity and an immunogenic gene signature was established in DIPG lines using several clinically-relevant LSD1 inhibitors. Pediatric high-grade glioma patient sequencing data demonstrated survival benefit using this LSD1-dependent gene signature. On-target binding of catalytic LSD1 inhibitors was confirmed in DIPG and pre-treatment of DIPG with these inhibitors increased lysis by natural killer (NK) cells. CIBERSORT analysis of patient data confirmed NK infiltration is beneficial to patient survival while CD8 T-cells are negatively prognostic. Catalytic LSD1 inhibitors are non-perturbing to NK cells while scaffolding LSD1 inhibitors are toxic to NK cells and do not induce the gene signature in DIPG cells.\n\nConclusionsLSD1 inhibition using catalytic inhibitors are both selectively cytotoxic and promote an immune gene signature that is associated with NK cell killing, representing a therapeutic opportunity for pHGG.\n\nKey pointsO_LILSD1 inhibition using several clinically relevant compounds is selectively cytotoxic in DIPG.\nC_LIO_LIAn LSD1-controlled gene signature predicts survival in pediatric high-grade glioma patients.\nC_LIO_LILSD1 inhibition enhances NK cell cytotoxicity against DIPG with correlative genetic biomarkers.\nC_LI\n\nImportance of the studyThis is the first study to evaluate inhibition of LSD1 in a uniformly lethal type of pediatric brain tumor: DIPG. We demonstrate selective cytotoxicity of several clinically relevant compounds against patient derived DIPG cells, and identify an immune gene signature that is upregulated in DIPG cells by catalytic inhibitors of LSD1. This immune gene signature is predictive of prognosis in pHGG, consistent with the rationale of promoting this signature through LSD1 inhibition. NK cell killing of DIPG is enhanced by LSD1 inhibition, providing functional confirmation of this gene signature, and represents the first report of LSD1 inhibition promoting NK cell cytotoxicity of cancer cells. Given the poor prognosis of pHGGs and lack of effective treatments, our results suggest use of LSD1 inhibition as a single agent or in combination with NK cell therapy may be a safe and efficacious strategy.

cancer biology↗

bioRxiv2018

Zika Virus Outbreak, Barbados, 2015 - 2016

Barbados is a Caribbean island country of approximately 285,000 people, with a thriving tourism industry. In 2015, Zika spread rapidly throughout the Americas, and its proliferation through the Caribbean islands followed suit. Barbados reported its first confirmed autochthonous Zika transmission to the Pan American Health Organization (PAHO) in January 2016, a month before the global public health emergency was declared. Following detection of suspected Zika cases on Barbados in 2015, 926 individuals were described as suspected cases, and 147 lab confirmed cases were reported through December 2016, the end of the most recent epidemiological year. In this short report, we describe the epidemiological characteristics of 926 clinical case records which were originally suspected as cases of Zika, and which were subsequently sent for testing and confirmation; 147 were found positive for Zika, using RT-PCR methods, another 276 tested negative, and the remaining 503 were either pending results or still in the suspected category. Women were represented at about twice the rate of men in case records where sex was reported (71.9%), and confirmed cases (78.2%), and 19 of the confirmed positive cases were children under the age of 10.

epidemiology↗