Escucha México, Estrategias Gráficas y Cultura Auditiva. Otoño 2022

Este reporte del PAP Escucha México, perteneciente al trabajo realizado durante el periodo de Otoño 2022, cuenta con información detallada sobre los resultados alcanzados en cada uno de los proyectos que integran esta organización en el período anteriormente establecido. Para este proceso en específico, se buscó enfocar la mayor cantidad de esfuerzos posibles a que el 4to Encuentro Internacional de Cultura Auditiva se desarrollara de la mejor forma posible, sin descuidar el trabajo que se siguió realizando en el resto de proyectos. Como resumen general, todos presentaron resultados positivos, pues se tuvo presencia importante en redes sociales, mejor que en periodos anteriores, además de que se combinaron esfuerzos para que el 4to Encuentro tuviera una difusión adecuada y alcanzara a la mayor cantidad de personas posibles, lo que a su vez resultó en eventos llenos de gente interesada en aprender sobre Cultura Auditiva y Discapacidad, ejes temáticos centrales de este PAP.ITESO, A.C

The Use of the Humanized Mouse Model in Gene Therapy and Immunotherapy for HIV and Cancer

HIV and cancer remain prevailing sources of morbidity and mortality worldwide. There are current efforts to discover novel therapeutic strategies for the treatment or cure of these diseases. Humanized mouse models provide the investigative tool to study the interaction between HIV or cancer and the human immune system in vivo. These humanized models consist of immunodeficient mice transplanted with human cells, tissues, or hematopoietic stem cells that result in reconstitution with a nearly full human immune system. In this review, we discuss preclinical studies evaluating therapeutic approaches in stem cell-based gene therapy and T cell-based immunotherapies for HIV and cancer using a humanized mouse model and some recent advances in using checkpoint inhibitors to improve antiviral or antitumor responses

Variation in the Susceptibility of Drosophila to Different Entomopathogenic Nematodes

Entomopathogenic nematodes (EPNs) in the genera Heterorhabditis and Steinernema are lethal parasites of insects that are of interest as models for understanding parasite-host interactions and as biocontrol agents for insect pests. EPNs harbor a bacterial endosymbiont in their gut that assists in insect killing. EPNs are capable of infecting and killing a wide range of insects, yet how the nematodes and their bacterial endosymbionts interact with the insect immune system is poorly understood. Here, we develop a versatile model system for understanding the insect immune response to parasitic nematode infection that consists of seven species of EPNs as model parasites and five species of Drosophila fruit flies as model hosts. We show that the EPN Steinernema carpocapsae, which is widely used for insect control, is capable of infecting and killing D. melanogaster larvae. S. carpocapsae is associated with the bacterium Xenorhabdus nematophila, and we show that X. nematophila induces expression of a subset of antimicrobial peptide genes and suppresses the melanization response to the nematode. We further show that EPNs vary in their virulence toward D. melanogaster and that Drosophila species vary in their susceptibilities to EPN infection. Differences in virulence among different EPN-host combinations result from differences in both rates of infection and rates of postinfection survival. Our results establish a powerful model system for understanding mechanisms of host-parasite interactions and the insect immune response to parasitic nematode infection

Chimeric antigen receptor engineered stem cells: a novel HIV therapy

Despite the success of combination antiretroviral therapy (cART) for suppressing HIV and improving patients' quality of life, HIV persists in cART-treated patients and remains an incurable disease. Financial burdens and health consequences of lifelong cART treatment call for novel HIV therapies that result in a permanent cure. Cellular immunity is central in controlling HIV replication. However, HIV adopts numerous strategies to evade immune surveillance. Engineered immunity via genetic manipulation could offer a functional cure by generating cells that have enhanced antiviral activity and are resistant to HIV infection. Recently, encouraging reports from several human clinical trials using an anti-CD19 chimeric antigen receptor (CAR) modified T-cell therapy for treating B-cell malignancies have provided valuable insights and generated remarkable enthusiasm in engineered T-cell therapy. In this review, we discuss the development of HIV-specific chimeric antigen receptors and the use of stem cell based therapies to generate lifelong anti-HIV immunity

A Single Set of Interneurons Drives Opposite Behaviors in C. elegans

Many chemosensory stimuli evoke innate behavioral responses that can be either appetitive or aversive, depending on an animal's age, prior experience, nutritional status, and environment [1-9]. However, the circuit mechanisms that enable these valence changes are poorly understood. Here, we show that Caenorhabditis elegans can alternate between attractive or aversive responses to carbon dioxide (CO2), depending on its recently experienced CO2 environment. Both responses are mediated by a single pathway of interneurons. The CO2-evoked activity of these interneurons is subject to extreme experience-dependent modulation, enabling them to drive opposite behavioral responses to CO2. Other interneurons in the circuit regulate behavioral sensitivity to CO2 independent of valence. A combinatorial code of neuropeptides acts on the circuit to regulate both valence and sensitivity. Chemosensory valence-encoding interneurons exist across phyla, and valence is typically determined by whether appetitive or aversive interneuron populations are activated. Our results reveal an alternative mechanism of valence determination in which the same interneurons contribute to both attractive and aversive responses through modulation of sensory neuron to interneuron synapses. This circuit design represents a previously unrecognized mechanism for generating rapid changes in innate chemosensory valence

Engineering CAR T Cells to Target the HIV Reservoir.

The HIV reservoir remains to be a difficult barrier to overcome in order to achieve a therapeutic cure for HIV. Several strategies have been developed to purge the reservoir, including the "kick and kill" approach, which is based on the notion that reactivating the latent reservoir will allow subsequent elimination by the host anti-HIV immune cells. However, clinical trials testing certain classes of latency reactivating agents (LRAs) have so far revealed the minimal impact on reducing the viral reservoir. A robust immune response to reactivated HIV expressing cells is critical for this strategy to work. A current focus to enhance anti-HIV immunity is through the use of chimeric antigen receptors (CARs). Currently, HIV-specific CARs are being applied to peripheral T cells, NK cells, and stem cells to boost recognition and killing of HIV infected cells. In this review, we summarize current developments in engineering HIV directed CAR-expressing cells to facilitate HIV elimination. We also summarize current LRAs that enhance the "kick" strategy and how new generation and combinations of LRAs with HIV specific CAR T cell therapies could provide an optimal strategy to target the viral reservoir and achieve HIV clearance from the body

Variation in the Susceptibility of Drosophila to Different Entomopathogenic Nematodes

Entomopathogenic nematodes (EPNs) in the genera Heterorhabditis and Steinernema are lethal parasites of insects that are of interest as models for understanding parasite-host interactions and as biocontrol agents for insect pests. EPNs harbor a bacterial endosymbiont in their gut that assists in insect killing. EPNs are capable of infecting and killing a wide range of insects, yet how the nematodes and their bacterial endosymbionts interact with the insect immune system is poorly understood. Here, we develop a versatile model system for understanding the insect immune response to parasitic nematode infection that consists of seven species of EPNs as model parasites and five species of Drosophila fruit flies as model hosts. We show that the EPN Steinernema carpocapsae, which is widely used for insect control, is capable of infecting and killing D. melanogaster larvae. S. carpocapsae is associated with the bacterium Xenorhabdus nematophila, and we show that X. nematophila induces expression of a subset of antimicrobial peptide genes and suppresses the melanization response to the nematode. We further show that EPNs vary in their virulence toward D. melanogaster and that Drosophila species vary in their susceptibilities to EPN infection. Differences in virulence among different EPN-host combinations result from differences in both rates of infection and rates of postinfection survival. Our results establish a powerful model system for understanding mechanisms of host-parasite interactions and the insect immune response to parasitic nematode infection