Biology subjects

Hernandez, L. F.

Publications and source records attributed to Hernandez, L. F..

3 recordsLinked to original sources

bioRxiv2022

UGDH promotes tumor-initiating cells and a fibroinflammatory tumor microenvironment in ovarian cancer.

Epithelial ovarian cancer (EOC) is a global health burden, with the poorest five-year survival rate of the gynecological malignancies due to diagnosis at advanced stage and high recurrence rate. Recurrence in EOC is driven by the survival of chemoresistant, stem-like tumor-initiating cells (TICs) that are supported by a complex extracellular matrix (ECM) and immunosuppressive microenvironment. To target TICs to prevent recurrence, we identified genes critical for TIC viability from a whole genome siRNA screen. A top hit was the cancer-associated, proteoglycan subunit synthesis enzyme UDP-glucose dehydrogenase (UGDH). Immunohistochemistry was used to delineate UGDH expression in histological and molecular subtypes of EOC. High UGDH expression was observed in the majority of high-grade serous ovarian cancers with variable expression in clear cell, mucinous and endometrioid histotypes. A distinctive prognostic difference was revealed when serous cancers were stratified by molecular subtype, where high UGDH was associated with poor prognosis in the C1/Mesenchymal subtype and low UGDH was associated with poor prognosis in the C4/Differentiated subtype. Ovarian cancer cell lines were subtyped according to the molecular subtypes, and we examined the effect of modulating UGDH expression in cell lines representing the C1/Mesenchymal subtype and C4/Differentiated subtypes. Knockdown of UGDH in the C1/Mesenchymal subtype reduced spheroid viability, sphere-formation and the CD133+/ALDH high TIC population. Conversely, overexpression of UGDH in the differentiated subtype enhanced spheroid formation but reduced the TIC population. Inflammatory cytokine expression was altered by UGDH expression. In co-culture models, altering UGDH expression in spheroids affected the gene expression of mesothelial cells causing changes to matrix remodeling proteins. The effect of UGDH knockdown or overexpression in the C1/Mesenchymal and C4/Differentiated subtypes, respectively, was tested on mouse intrabursal xenografts and showed dynamic changes to the tumor stroma. Knockdown of UGDH reduced tumor burden in C1/Mesenchymal xenografts compared to controls. These data show that modulation of UGDH expression in tumors influences cells in the microenvironment and reveals distinct roles for UGDH in the mesenchymal and differentiated molecular subtypes of EOC. UGDH is a potential therapeutic target in TICs, for the treatment of metastatic and recurrent EOC, particularly in patients with the mesenchymal molecular subtype.

cancer biology↗

bioRxiv2021

Transient dopamine neuron activity precedes and encodes the vigor of contralateral movements

Dopamine neurons (DANs) in the substantia nigra pars compacta (SNc) have been related to movement vigor, and loss of these neurons leads to bradykinesia in Parkinsons disease. However, it remains unclear whether DANs encode a general motivation signal or modulate movement kinematics. We imaged activity of SNc DANs in mice trained in a novel operant task which relies on individual forelimb sequences. We uncovered that a similar proportion of SNc DANs increased their activity before ipsi- vs. contralateral sequences. However, the magnitude of this activity was higher for contralateral actions, and was related to contralateral but not ipsilateral sequence length. In contrast, the activity of reward-related DANs, largely distinct from those modulated by movement, was not lateralized. Finally, unilateral dopamine depletion impaired contralateral, but not ipsilateral, sequence length. These results indicate that movement-initiation DANs encode more than a general motivation signal, and invigorate kinematic aspects of contralateral movements. TeaserTransient activity in substantia nigra compacta dopamine neurons encodes contralateral, but not ipsilateral action vigor.

neuroscience↗

bioRxiv2018

Using Google Trends to Examine the Spatio-Temporal Incidence and Behavioral Patterns of Dengue Disease: A Case Study in Metropolitan Manila, Philippines

Dengue is a major public health concern and an economic burden in the Philippines. Despite the countrys improved dengue surveillance, it still suffers from various setbacks and therefore needs to be complemented with alternative approaches. Previous studies have demonstrated the potential of internet-based surveillance such as Google Dengue Trends (GDT) in supplementing current epidemiological methods for predicting future dengue outbreaks and patterns. With this, our study aims to assess the temporal relationship of GDT and dengue incidence in Metropolitan Manila from previous years and examine web search behavior of the population towards the disease. The study collated and organized the population statistics and reported dengue cases in Metropolitan Manila from respective government agencies to calculate the spatial and temporal dengue incidence. The relative search volume of the term dengue and top dengue-related search queries in Metropolitan Manila were obtained and organized from the Google trends platform. Data processing of GDT and dengue incidence was performed by conducting an adjustment procedure and subsequently used for correlation and cross-correlation analyses. Moreover, a thematic analysis was employed on the top dengue-related search queries. Results revealed a high temporal relationship between GDT and dengue incidence when either one of the variables is adjusted. Cross-correlation showed that there is delayed effect (1-2 weeks) of GDT to dengue incidence, demonstrating its potential in predicting future dengue outbreaks and patterns in Metropolitan Manila. Thematic analysis of dengue-related search queries indicated 5 categories namely; (a) dengue, (b) sign and symptoms of dengue, (c) treatment and prevention, (d) mosquito and (e) other diseases where the majority of the search queries was signs and symptoms which indicate the health-seeking behavior of the population towards the disease.

epidemiology↗