Biology subjects

Salinas, R.

Publications and source records attributed to Salinas, R..

3 recordsLinked to original sources

bioRxiv2024

Temporal multi-modal single-cell analyses reveal dynamic interactions of CAR-T cells with glioblastoma and targeting of antigen-negative neoplastic cells

CAR-T therapy is a promising new immunotherapy for cancers, but its efficacy for solid tumors requires improvement. A detailed understanding of the interplay between solid tumors and CAR-T cells is critical. Here we report temporal, multi-modal, single-cell profiling of patient-derived glioblastoma organoids with CAR-T treatment. We found that all tumor cell types responded to CAR-T cell activation and contributed to an initially anti-tumor, but subsequently pro-tumor and immune-inhibitory microenvironment, accompanied by CAR-T cell exhaustion. Unexpectedly, CAR-T treatment attenuated glioma stem-like states of both antigen-positive and antigen-negative neoplastic cells and reduced their proliferation via diffusible factors, including IFN{gamma}. Analysis of samples from additional patients, including those in clinical trials, supported these findings. Our study reveals the dynamic interplay among different tumor cells and T cells in adaptive responses to immunotherapy and identifies previously unappreciated benefits of CAR-T therapy directly on antigen-negative neoplastic cells that may be leveraged to enhance therapeutic efficacy.

cancer biology↗

bioRxiv2023

The stress history of soil bacteria under organic farming enhances the growth of wheat seedlings

The effects of stress factors associated with climate change and agricultural management practices on microorganisms are often studied separately, and it remains to be determined how these factors impact the soil microbiome and, subsequently, plant growth characteristics. The aim of this study was to understand how the historical climate and agriculture to which soil microbes have been exposed can influence the growth characteristics of wheat seedlings and their associated bacterial communities. We collected soil from organic and conventional fields with different histories of climate conditions to extract microbes to inoculate wheat seeds. The results showed a positive interaction between conventional farming practices and an ambient climate for faster and higher germination rates. We demonstrate that soil microbial extracts from organic farming with experience of the future climate significantly enhanced above-ground biomass along with bacterial diversity in the seedlings compared to the soil from conventional farming. Our data suggest that soil microbiomes selected by organic farming with a history of future climates can positively impact the aboveground biomass of wheat seedlings and their bacterial assemblages, emphasizing the potential benefits of organic farming practices under changing climate conditions.

ecology↗

bioRxiv2023

A leptin-responsive hypothalamic circuit inputs to the circadian feeding network

Salient cues, such as the rising sun or the availability of food, play a crucial role in entraining biological clocks, allowing for effective behavioral adaptation and ultimately, survival. While the light-dependent entrainment of the central circadian pacemaker (suprachiasmatic nucleus, SCN) is relatively well defined, the molecular and neural mechanisms underlying entrainment associated with food availability remains elusive. Using single nucleus RNA sequencing during scheduled feeding (SF), we identified a leptin receptor (LepR) expressing neuron population in the dorsomedial hypothalamus (DMH) that upregulates circadian entrainment genes and exhibits rhythmic calcium activity prior to an anticipated meal. We found that disrupting DMHLepR neuron activity had a profound impact on both molecular and behavioral food entrainment. Specifically, silencing DMHLepR neurons, mis-timed exogenous leptin administration, or mis-timed chemogenetic stimulation of these neurons all interfered with the development of food entrainment. In a state of energy abundance, repetitive activation of DMHLepR neurons led to the partitioning of a secondary bout of circadian locomotor activity that was in phase with the stimulation and dependent on an intact SCN. Lastly, we discovered that a subpopulation of DMHLepR neurons project to the SCN with the capacity to influence the phase of the circadian clock. This leptin regulated circuit serves as a point of integration between the metabolic and circadian systems, facilitating the anticipation of meal times.

neuroscience↗