Biology subjects

Martinez, L. M.

Publications and source records attributed to Martinez, L. M..

9 recordsLinked to original sources

bioRxiv2026

Compression through internal and external information bottlenecks resolves information intractability across brains, bodies and worlds

Agents are constantly challenged to navigate uncertainty in a world that contains far more information that they can process, improving predictability by exploiting regularities from the environment. This frames the challenge of reducing information intractability as the main problem any artificial or biological agent needs to solve. We argue that this challenge is solved through the systematic use of information bottlenecks--a diverse suite of strategies functioning to compress and selectively filter environmental information so as to build tractable representations of the world. We show that such bottlenecks are adaptive and operate across multiple scales, from the evolution of neural circuits and sensory systems to the actions that organisms use in real-time to select and structure their own sensory inputs. A key aspect of our proposal is that information bottlenecks are not only internal and biological, but can also be externalized through actions in the world. By transforming their environments, agents construct external bottlenecks--material and cultural mechanisms that reduce the cost of inference and transmit regularities that are shared across individuals and even across generations. From this perspective, niche construction, material culture and even social and cultural norms, can be also understood as adaptive informational mechanisms, collective information bottlenecks that alter our worlds in ways that promote predictive success. Agents increasingly solve the intractability problem not only through evolutionary changes in their biology and internal neural mechanisms, but by systematically constructing and exploiting information bottlenecks in the world. Culture itself, we suggest, is just such a bottleneck-constructing mechanism.

neuroscience↗

bioRxiv2026

eIF4E and Ezrin cooperate in pseudopods to drive a localized migratory translation program in acute myeloid leukemia

Aggressive subtypes of acute myeloid leukemia (AML) are characterized by increased migratory behavior and poor prognosis prioritizing the need for uncovering relevant mechanisms. While attributed to transcriptional changes, these AMLs manifest dysregulated eIF4E implicating disrupted mRNA metabolism. Here, we observed in AML mouse models, patient specimens, and cell lines that eIF4E drives motility, colonization, engraftment and AML progression. AML cells migrate utilizing Ezrin-positive pseudopods. Unexpectedly, we discovered that eIF4E interacts with Ezrin, that these physically associated factors are required and cooperated to drive an on-demand translation program in pseudopods for motility. Indeed, pseudopods were sites of eIF4E- and Ezrin-dependent translation by implementing the first method to directly mark active ribosomes in situ (Visualizing Translation Activity using RiboLace, VISTA-R). Biochemically, Ezrin bound eIF4E, ribosomal components, and mRNAs consistent with our observed Ezrin-dependent modulation of protein production. This unprecedented physical coupling of motility and translation provisions migratory sites to sustain AML progression. Highlights- eIF4E reduction impairs AML cell motility and disease progression - eIF4E-dependent motility requires Ezrin - Ezrin binds eIF4E, transcripts encoding motility factors and active ribosomes - VISTA-R enabled visualization of active ribosomes and translationally active pseudopods (T-PODs) - T-PODs provide novel on-demand localized translation to sustain mobility at migratory sites Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=142 SRC="FIGDIR/small/707190v2_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@164f191org.highwire.dtl.DTLVardef@2f8928org.highwire.dtl.DTLVardef@d5ad7forg.highwire.dtl.DTLVardef@719a69_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2025

Tumor cell dissemination is facilitated through regulatory T cell-driven extracellular matrix remodeling

Regulatory T (Treg) cells function to enforce peripheral tolerance and are potent suppressors of tumor immunity. In breast cancer, we have shown that Treg cells promote tumor growth by favoring alternative activation of macrophages via suppression of IFN-{gamma}. The tumor-associated extracellular matrix (ECM) is a key regulator of metastatic dissemination and is emerging as a critical regulator of tumor immunity. However, the reciprocal effects of the immune system on the ECM remain elusive. Using a combination of murine in vivo, ex vivo and bioengineering models we describe Treg cell-dependent changes in the tumor ECM that facilitate tumor cell migration and metastatic dissemination. Importantly, Treg cell-dependent matrisome signatures correlate with delayed survival advantage in human breast cancer samples, and are upregulated in tumor-associated macrophages (TAMs). Further, both IFN-{gamma} and IFN-{gamma}-sensitivity in TAMs contribute to structural and functional changes of the ECM. This work underscores a previously unrecognized role of Treg cells on the ECM that facilitates metastasis and is consistent with tissue Treg cell emergent function as critical regulators of tissue repair and cancer.

cancer biology↗

bioRxiv2024

Sigma factors as potential targets to enhance recombinant protein expression

The transcriptional factors control the expression of many genes and represent an important layer of complexity in cell factories. However, the effect of individual sigma factor deletions from a biomanufacturing perspective has not been addressed. In this contribution, growth and oxygen consumption of E. coli BW25113 strains with individual inactivation of each sigma factor were characterized under various conditions. The deletion of rpoD has been reported to be lethal for E. coli. However, the evaluated rpoD mutant did not exhibit major growth defects in the mineral medium and is explained because the rpoD gene is duplicated in this strain. Recombinant protein was expressed at three different induction levels in a mineral and LB media. The fliA mutant was the best producer in the mineral medium, whereas the rpoD mutant overperformed the other strains in LB medium. This suggest that a lower rpoD gene dosage is positive for the performance of the cell factory in complex medium. In cultures at 20 {degrees}C, the rpoS mutant exhibited the greatest recombinant expression. To our knowledge, this is the first systematic study evaluating the potential of sigma factor deletion for improving recombinant protein production.

microbiology↗

bioRxiv2024

Automated adjustment of metabolic niches enables the control of natural and engineered microbial co-cultures

A lot of attention has been given to the understanding of microbial interactions leading to stable co-cultures, but the resulting technologies have been rarely challenged in dynamic cultivation conditions. In this work, substrate pulsing was performed to promote better control of the metabolic niches corresponding to each species, leading to the continuous co-cultivation of diverse microbial organisms. For this purpose, we used a cell-machine interface relying on automated flow cytometry, allowing to adjust the temporal profile of two metabolic niches according to a rhythm ensuring the successive growth of two species i.e., in our case a yeast and a bacterium. The resulting approach, called Automated Adjustment of Metabolic Niches (AAMN), was successfully employed for stabilizing both cooperative and competitive co-cultures. Additionally, AAMN can be considered as an enabling technology for the deployment of co-cultures in bioprocesses, demonstrated here based on the continuous bioproduction of p-coumaric acid. Taken altogether, the data accumulated suggest that AAMN could be used for a wider range of biological systems, but also to gain fundamental insights about microbial interaction mechanisms.

microbiology↗

bioRxiv2021

NMDAr BLOCKING BY MK801 ALTERS HIPPOCAMPAL AND PREFRONTAL CORTEX OSCILLATIONS AND IMPAIRS SPATIAL WORKING MEMORY IN MICE.

Abnormal NMDAr function has been linked to rhythmopathies, psychosis, and cognitive dysfunction in schizophrenia (SCZ). Here, we investigate the role of NMDAr hypofunction in pathological oscillations and behavior. We implanted mice with tetrodes in the dorsal hippocampus and medial prefrontal cortex (mPFC), administered the NMDAr antagonist MK801, and recorded oscillations during spontaneous exploration in an open field and in the y-maze spatial working memory test. Our results show that NMDAr blockade increased locomotor activity, impaired spatial working memory, and disrupted the correlation between oscillations and speed of movement, which is crucial for internal representations of distance. In the hippocampus, MK801 increased gamma oscillations and disrupted theta/gamma coupling. In the mPFC, MK801 increased the power of theta and gamma, generated high-frequency oscillations (HFO 155-185 Hz), and disrupted theta/gamma coupling. The performance of mice in the spatial working memory version of the y-maze was strongly correlated with CA1-PFC theta/ low gamma co-modulation. Thus, theta/gamma mediated by NMDAr function might be essential to explaining several of SCZs cognitive symptoms and might be crucial to explaining hippocampal-PFC interaction. Significance StatementNMDAr hypofunction might be the basis of cognitive symptoms and oscillopathies found in SCZ. In this work, we aimed to understand this link further. We found that NMDAr hypofunction altered theta/gamma co-modulation in the hippocampus and the PFC, explaining spatial working memory deficits.

neuroscience↗

bioRxiv2019

A single-cell transcriptional atlas identifies extensive heterogeneity in the cellular composition of tendons

Tendon is a connective tissue that transmits forces between muscles and bones. Cellular heterogeneity is increasingly recognized as an important factor in the biological basis of tissue homeostasis and disease, but little is known about the diversity of cells that populate tendon. Our objective was to explore the heterogeneity of cells in mouse Achilles tendons using single-cell RNA sequencing. We assembled a transcriptomic atlas and identified 11 distinct cell types in tendons, including 3 previously undescribed populations of fibroblasts. Using trajectory inference analysis, we provide additional support for the notion that pericytes are progenitor cells for the fibroblasts that compose adult tendons. We also modeled cell-interactions and identified ligand-receptor pairs involved in tendon homeostasis. Our findings highlight notable heterogeneity between and within tendon cell populations, which may contribute to our understanding of tendon extracellular matrix assembly and maintenance, and inform the design of therapies to treat tendinopathies.

cell biology↗

bioRxiv2019

Adaptive and Innate Immune Cell Responses in Tendons and Lymph Nodes After Tendon Injury and Repair

Tendon injuries are a common clinical condition with limited treatment options. The cellular components of the innate system, such as neutrophils and macrophages, have been well studied in tendon injuries. However the adaptive immune system, comprised of specialized lymphocytes, plays an important role in orchestrating the healing of numerous tissues but less is known about these cells in tendon healing. To gain a greater understanding of the biological processes that regulate tendon healing, we sought to determine how the cellular components of the adaptive and innate immune system respond to a tendon injury using two-month old male mice. We determined that the lymphatic vasculature is present in the epitenon and superficial regions of Achilles tendons. We then created an acute Achilles tenotomy followed by repair, and collected tendons and draining lymph nodes one, two, and four weeks after injury. Using flow cytometry and histology, after tendon injury we observed a robust adaptive immune cell response that followed an initial innate immune cell response. There was an accumulation of monocytes, neutrophils, and macrophages one week after injury that declined thereafter. Dendritic cells and CD4+ T cells peaked two weeks after injury, while B cells and CD8+ T cells progressively increased over time. In parallel, immune cells of the draining popliteal lymph node demonstrated a similarly coordinated response to the injury. These results suggest that there is an adaptive immune response to tendon injury and adaptive immune cells may play a role in regulating tendon healing.

physiology↗

bioRxiv2018

The Notch and EGFR signaling regulate caspase inhibitor Diap1 to match supply with intestinal demand

The regenerative activity of adult stem cells carries a high risk of cancer, particularly in highly renewable tissues. To guarantee that the correct organ size is attained and to cope with the continual risk of cancer, developing tissues often use programmed cell death (PCD) as an adaptive mechanism to cull excess and abnormal cells. Members of the family of Inhibitor of Apoptosis Proteins (IAPs) inhibit caspases and cell death and are often overexpressed in cancer. Here, we show that Diap1 is expressed in committed progenitor (enteroblast) cells in the adult Drosophila intestine. Blocking endogenous caspases uncovered that more than half of enteroblasts produced by intestinal stem cells (ISCs) are actively eliminated by apoptosis in the physiological intestine and also led to tumorigenesis. We find that antagonistic interplay between the Notch and EGFR signaling on Diap1 regulation governs the enteroblast cell death or survival decision via the conserved Klumpfuss/WT1-Lozenge/RUNX axis, which also regulates of differentiation plasticity of enteroblasts. These data provide new insights into how apoptosis drives adult tissue renewal and protection against tumors.

cell biology↗