Biology subjects

Lopez, C.

Publications and source records attributed to Lopez, C..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

A critical initialization for biological neural networks

Artificial neural networks learn faster if they are initialized well. Good initializations can generate high-dimensional macroscopic dynamics with long timescales. It is not known if biological neural networks have similar properties. Here we show that the eigenvalue spectrum and dynamical properties of large-scale neural recordings in mice (two-photon and electrophysiology) are similar to those produced by linear dynamics governed by a random symmetric matrix that is critically normalized. An exception was hippocampal area CA1: population activity in this area resembled an efficient, uncorrelated neural code, which may be optimized for information storage capacity. Global emergent activity modes persisted in simulations with sparse, clustered or spatial connectivity. We hypothesize that the spontaneous neural activity reflects a critical initialization of whole-brain neural circuits that is optimized for learning time-dependent tasks.

neuroscience↗

bioRxiv2024

OXA beta-lactamases from Acinetobacter spp. are membrane-bound and secreted into outer membrane vesicles

{beta}-lactamases from Gram-negative bacteria are generally regarded as soluble, periplasmic enzymes. NDMs have been exceptionally characterized as lipoproteins anchored to the outer membrane. A bioinformatics study on all sequenced {beta}-lactamases was performed that revealed a predominance of putative lipidated enzymes in the class D OXAs. Namely, 60% of the OXA class D enzymes contain a lipobox sequence in their signal peptide, that is expected to trigger lipidation and membrane anchoring. This contrasts with {beta}-lactamases from other classes, which are predicted to be mostly soluble proteins. Almost all (> 99%) putative lipidated OXAs are present in Acinetobacter spp. Importantly, we further demonstrate that OXA-23 and OXA-24/40 are lipidated, membrane-bound proteins in Acinetobacter baumannii. In contrast, OXA-48 (commonly produced by Enterobacterales) lacks a lipobox and is a soluble protein. Outer membrane vesicles (OMVs) from Acinetobacter baumannii cells expressing OXA-23 and OXA-24/40 contain these enzymes in their active form. Moreover, OXA-loaded OMVs were able to protect A. baumannii, Escherichia coli and Pseudomonas aeruginosa cells susceptible to piperacillin and imipenem. These results permit us to conclude that membrane binding is a bacterial host-specific phenomenon in OXA enzymes. These findings reveal that membrane-bound {beta}-lactamases are more common than expected and support the hypothesis that OMVs loaded with lipidated {beta}-lactamases are vehicles for antimicrobial resistance and its dissemination. This advantage could be crucial in polymicrobial infections, in which Acinetobacter spp. are usually involved, and underscore the relevance of identifying the cellular localization of lactamases to better understand their physiology and target them. IMPORTANCE{beta}-lactamases represent the main mechanism of antimicrobial resistance in Gram-negative pathogens. Their catalytic function (cleaving {beta}-lactam antibiotics) occurs in the bacterial periplasm, where they are commonly reported as soluble proteins. A bioinformatic analysis reveals a significant number of putative lipidated {beta}-lactamases, expected to be attached to the outer bacterial membrane. Notably, 60% of class D OXA {beta}-lactamases (all from Acinetobacter spp) are predicted as membrane-anchored proteins. We demonstrate that two clinically relevant carbapenemases, OXA-23 and OXA-24/40 are membrane-bound proteins in A. baumannii. This cellular localization favors secretion of these enzymes into outer membrane vesicles that transport them outside the boundaries of the cell. {beta}-lactamase-loaded vesicles can protect populations of antibiotic-susceptible bacteria, enabling them to thrive in the presence of {beta}-lactam antibiotics. The ubiquity of this phenomenon suggests that it may have influenced the dissemination of resistance mediated by Acinetobacter spp., particularly in polymicrobial infections, being a potent evolutionary advantage.

microbiology↗

bioRxiv2024

Translocations can drive expression changes of multiple genes in regulons covering entire chromosome arms

Translocations have largely been implicated in tumor development. However, beyond the consequences of aberrant gene expression near the breakpoint, their effects remain unexplored. In this work, we characterize the interplay between translocations, chromatin organization and gene expression using mantle cell lymphoma (MCL) as a model. We show that in vitro induced MCL-associated translocations can drive transcriptional changes at entire chromosome arms affecting multiple genes in a regulon-like fashion. Additionally, overexpressed genes in MCL patients are enriched in the exact same genomic regions, further underlining its potential relevance for lymphomagenesis. Moreover, we demonstrate a clear link between the translocation-induced transcriptional alterations and genome organization, with genes most susceptible to change expression residing in pre-existing long-range interacting loops spanning 50 megabases. The translocation places the strong immunoglobulin enhancer into this loop, allowing the spread of its regulatory potential over the entire affected chromosome arm. Finally, we show that translocation-induced effects mainly represent expression enhancement of genes already active prior to translocation formation, highlighting the importance of the epigenetic state of the cell in which this initial hit occurs. In summary, we show that translocations can induce ample, simultaneous gene expression changes affecting entire chromosome arms, representing an important new mechanism for tumorigenesis.

cancer biology↗

bioRxiv2024

Mouse parasubthalamic Crh neurons drive alcohol drinking escalation and behavioral disinhibition

Corticotropin-releasing factor (CRF, encoded by Crh) signaling is thought to play a critical role in the development of excessive alcohol drinking and the emotional and physical pain associated with alcohol withdrawal. Here, we investigated the parasubthalamic nucleus (PSTN) as a potential source of CRF relevant to the control of alcohol consumption, affect, and nociception in mice. We identified PSTN Crh neurons as a neuronal subpopulation that exerts a potent and unique influence on behavior by promoting not only alcohol but also saccharin drinking, while PSTN neurons are otherwise known to suppress consummatory behaviors. Furthermore, PSTN Crh neurons are causally implicated in the escalation of alcohol and saccharin intake produced by chronic intermittent ethanol (CIE) vapor inhalation, a mouse model of alcohol use disorder. In contrast to our predictions, the ability of PSTN Crh neurons to increase alcohol drinking is not mediated by CRF1 signaling. Moreover, the pattern of behavioral disinhibition and reduced nociception driven by their activation does not support a role of negative reinforcement as a motivational basis for the concomitant increase in alcohol drinking. Finally, silencing Crh expression in the PSTN slowed down the escalation of alcohol intake in mice exposed to CIE and accelerated their recovery from withdrawal-induced mechanical hyperalgesia. Altogether, our results suggest that PSTN Crh neurons may represent an important node in the brain circuitry linking alcohol use disorder with sweet liking and novelty seeking.

neuroscience↗

bioRxiv2024

A Rigorous Multi-Laboratory Study of Known PDAC Biomarkers Identifies Increased Sensitivity and Specificity Over CA19-9 Alone

A blood test that enables surveillance for early-stage pancreatic ductal adenocarcinoma (PDAC) is an urgent need. Independent laboratories have reported PDAC biomarkers that could improve biomarker performance over CA19-9 alone, but the performance of the previously reported biomarkers in combination is not known. Therefore, we conducted a coordinated case/control study across multiple laboratories using common sets of blinded training and validation samples (132 and 295 plasma samples, respectively) from PDAC patients and non-PDAC control subjects representing conditions under which surveillance occurs. We analyzed the training set to identify candidate biomarker combination panels using biomarkers across laboratories, and we applied the fixed panels to the validation set. The panels identified in the training set, CA19-9 with CA199.STRA, LRG1, TIMP-1, TGM2, THSP2, ANG, and MUC16.STRA, achieved consistent performance in the validation set. The panel of CA19-9 with the glycan biomarker CA199.STRA improved sensitivity from 0.44 with 0.98 specificity for CA19-9 alone to 0.71 with 0.98 specificity (p < 0.001, 1000-fold bootstrap). Similarly, CA19-9 combined with the protein biomarker LRG1 and CA199.STRA improved specificity from 0.16 with 0.94 sensitivity for CA19-9 to 0.65 with 0.89 sensitivity (p < 0.001, 1000-fold bootstrap). We further validated significantly improved performance using biomarker panels that did not include CA19-9. This study establishes the effectiveness of a coordinated study of previously discovered biomarkers and identified panels of those biomarkers that significantly increased the sensitivity and specificity of early-stage PDAC detection in a rigorous validation trial.

cancer biology↗

bioRxiv2024

Hetero-antagonism of avibactam and sulbactam with cefiderocol in carbapenem-resistant Acinetobacter spp.

The emergence of Gram-negative bacteria resistant to multiple antibiotics, particularly carbapenem-resistant (CR) Acinetobacter strains, poses a significant threat globally. Despite efforts to develop new antimicrobial therapies, limited progress has been made, with only two drugs--cefiderocol and sulbactam-durlobactam--showing promise for CR-Acinetobacter infections. Cefiderocol, a siderophore cephalosporin, demonstrates promising efficacy in the treatment of Gram-negative infections. However, resistance to cefiderocol has been reported in A. baumannii. Combination therapies, such as cefiderocol with avibactam or sulbactam, show reduced MICs against cefiderocol-non-susceptible strains with in vivo efficacy, although the outcomes can be complex and species-specific. In the present work, the molecular characterization of spontaneous cefiderocol-resistant variants, a CRAB strain displaying antagonism with sulbactam and an A. lwoffii strain showing antagonism with avibactam, were studied. The results reveal intriguing insights into the underlying mechanisms, including mutations affecting efflux pumps, transcriptional regulators, and iron homeostasis genes. Moreover, gene expression analysis reveals significant alterations in outer membrane proteins, iron homeostasis, and {beta}-lactamases, suggesting adaptive responses to selective pressure. Understanding these mechanisms is crucial for optimizing treatment strategies and preventing adverse clinical outcomes. This study highlights the importance of preemptively assessing drug synergies to navigate the challenges posed by antimicrobial resistance in CR-Acinetobacter infections.

microbiology↗

bioRxiv2023

Advancing Cell Therapies: Single-Cell Profiling, Generation, Expansion, and Gene Delivery in Rhesus Macaque Plasma B Cells

Engineered long lived plasma cells have the potential to be a new area of cell therapy. A key step in developing this cell therapy is testing in a model with an intact immune system similar to humans. To that end, we have developed methods to purify, expand, and differentiate non-human primate (NHP; rhesus macaque) B cells ex vivo. We consistently achieved 10-fold expansion of NHP B cells using a readily available commercial supplement. After only seven days in culture, large percentages of cells in NHP B cell cultures were differentiated. These cells expressed surface markers found in human antibody secreting cells (CD38 and CD138) and secreted immunoglobulin G. From single cell transcriptome analysis of NHP, we verified the presence of plasma cell markers commonly shared with humans, and have unearthed less recognized markers such as CD59 and CD79A. In addition, we identified unique NHP plasma cell markers that are absent in humans including the immune checkpoint molecule CD274 (PD-L1, Programmed Death-Ligand 1). Furthermore, we found that MHC class I molecules were upregulated in NHP plasma cells, in contrast to the pattern observed in humans. Lastly, we also identified the serotypes (AAVD-J) and established the conditions for efficient transduction of NHP B cells with AAV vectors, achieving an editing rate of approximately 60%. We envision that this work will accelerate proof-of-concept in vivo studies using engineered protein-secreting B cells in the NHP model.

bioengineering↗

bioRxiv2023

I feel your pain: Higher empathy is associated with higher posterior default mode network activity

Withdrawal StatementThe authors discovered an error in the primary analysis and have withdrawn the results from this version of the investigation.

neuroscience↗

bioRxiv2023

Genomic DNA extraction optimization and validation for genome sequencing using the marine gastropod Kellet's whelk

Next-generation sequencing technologies, such as Nanopore MinION, Illumina Hiseq and Novaseq, and PacBio Sequel II, hold immense potential for advancing genomic research on non-model organisms, including the vast majority of marine species. However, application of these technologies to marine invertebrate species is often impeded by challenges in extracting and purifying their genomic DNA due to high polysaccharide content and other secondary metabolites. In this study, we help resolve this issue by developing and testing DNA extraction protocols for Kellets whelk (Kelletia kelletii), a subtidal gastropod with ecological and commercial importance, by comparing four DNA extraction methods commonly used in marine invertebrate studies. We identified an optimized protocol that balances efficiency, cost, and DNA extraction quality; the Salting out protocol. We validated the protocol using an independent set of tissue samples, then applied it to extract high-molecular-weight (HMW) DNA from over three thousand Kellets whelk tissue samples. The protocol demonstrated scalability and, with added clean-up, suitability for RAD-seq, GT-seq, as well as whole genome sequencing using both long read (ONT MinION) and short read (Illumina Novaseq) sequencing platforms. Our findings offer a robust and versatile DNA extraction and clean-up protocol for supporting genomic research efforts on non-model marine organisms, to help mediate the under-representation of invertebrates in genomic studies.

genomics↗

bioRxiv2023

The parasubthalamic nucleus refeeding ensemble delays feeding initiation

The parasubthalamic nucleus (PSTN) is responsive to refeeding after food deprivation and PSTN subpopulations can suppress feeding. However, no study directly addressed the role of PSTN neurons activated upon food access resumption. Here we show that the ensemble of refeeding-activated PSTN neurons drastically increases the latency to initiate refeeding with both familiar and novel food but exerts limited control over the amount of food consumed by hungry mice. This ensemble also delays sucrose consumption but accelerates water consumption in thirsty mice. We next sought to identify which subpopulations of PSTN neurons might be driving these effects. We discovered that PSTN Tac1 neurons projecting to the CeA selectively suppress feeding initiation while PSTN Crh neurons surprisingly promote the consumption of novel, palatable substances. Our results demonstrate the key role of endogenous PSTN activity in the control of feeding initiation and identify PSTN subpopulations counteracting each others influence on consummatory behaviors.

neuroscience↗

bioRxiv2022

Climatic refugia in the coldest neotropical hotspot, the Andean paramo

AimThe Andean paramo is the most biodiverse high-mountain region on Earth and past glaciation dynamics during the Quaternary are greatly responsible for its plant diversification. Here, we aim at identifying potential climatic refugia since the Last Glacial Maximum (LGM) in the paramo, according to plant family, biogeographic origin, and life-form. LocationThe paramo region in the Northern Andes MethodsWe built species distribution models for 664 plant species to generate range maps under current and LGM conditions, using five General Circulation Models (GCMs). For each species and GCM, we identified potential (suitable) and potential active (likely still occupied) refugia where both current and LGM range maps overlap. We stacked and averaged the resulting refugia maps across species and GCMs to generate consensus maps for all species, plant families, biogeographic origins and life-forms. All maps were corrected for potential confounding effect due to species richness. ResultsWe found refugia to be chiefly located in the southern and central paramos of Ecuador and Peru, especially towards the paramo ecotone with lower-elevation forests. However, we found additional specific patterns according to plant family, biogeographic origin and life-form. For instance, endemics showed refugia concentrated in the northern paramos. Main conclusionsOur findings suggest that large and connected paramo areas, but also the transitional Amotape-Huancabamba zone with the Central Andes, are primordial areas for plant species refugia since the LGM. This study therefore enriches our understanding on paramo evolution and calls for future research on plant responses to future climate change.

ecology↗

bioRxiv2022

Observing the self and other in motion modulates the excitability of vestibulocollic reflexes

Vestibular inputs from the inner ear are at the basis of the vestibulo-spinal and vestibulocollic reflexes involved in balance control. Studies have focused on how attentional load and emotions influence balance, but low-level social cues, such as observing human bodies in motion, have been neglected. Yet, individuals observing another person in a challenging posture or in motion can experience imbalance, indicating that sensorimotor resonance between self and others is involved. The present study examines how the observation of videos depicting human bodies in motion modulates well-established neurophysiological signatures of vestibular information processing. The excitability of vestibulocollic reflexes was assessed by analyzing the waveform of vestibular-evoked myogenic potentials (VEMPs) over the sternocleidomastoid and trapezius muscles of 25 healthy participants (13 females, 12 males). Here we show that observing human bodies undergoing passive whole-body rotations reduced the VEMPs amplitude when compared to observing an object. Importantly, the modulation depended on the person depicted in the video as VEMPs were reduced when observing oneself, compared to someone else being moved. Direction-specific effects and electromyography recordings ruled out non-specific emotional and attentional effects. These results show that the vestibular system is sensitive to observing human bodies in motion, establishing new connections between social neuroscience and vestibular neurophysiology. Significance StatementVestibulocollic reflexes are thought to be consistent and of short latency. Yet, previous results show that observing conspecifics influences balance. We combined approaches from social neuroscience and vestibular electrophysiology to describe how the observation of self and other bodies in motion influences vestibular information processing. The results show that observing human bodies in motion reduces the amplitude of vestibulocollic reflexes involved in the stabilization of the head and balance. These results establish new relations between the sense of balance and social cognition and challenge classical views in vestibular neuroscience.

neuroscience↗

bioRxiv2022

Systematic functional screening of chromatin factors identifies strong lineage and disease dependencies in normal and malignant haematopoiesis

Interactions between transcription factors (TF) and chromatin factors (CF) regulate gene expression programmes to determine cellular fate. However, unlike for TF, the exact role of CF in this process is poorly understood. Using haematopoiesis as a model system and utilising novel functional CRISPR screens ex vivo and in vivo, coupled with Perturb-Seq, CF binding and genome-wide chromatin accessibility in primary murine cells, we assess the role of 550 chromatin factors in lineage choice in normal haematopoiesis and the maintenance of acute myeloid leukaemia (AML). These studies demonstrate marked specificity for a large number of CFs in lineage determination, highlighting functional diversity within specific families of chromatin regulators, including MLL-H3K4-methyltransferases and different BAF-complexes, that regulate disparate lineage decisions across haematopoiesis. Conversely, we demonstrate that unrelated Repressive complexes function similarly to restrain excessive myeloid differentiation and protect lineage diversity. We identify interactions between CF and TF that, at least in part, explain the regulatory function of CF and link Brd9-loss to a premalignant state. Utilising similar experiments in a relevant murine AML model, we demonstrate opposing effects for CF in normal haematopoiesis and AML, where MLL-H3K4-methyltransferases, c-BAF-remodelers and Repressive complexes prevent differentiation and maintain leukaemic fitness. We show that this alteration relates to differential utilisation of TF by CF complexes between normal and malignant haematopoiesis, highlighting corrupted TF-CF interactions as potential novel avenues for therapeutic intervention in AML. Together, this study provides novel insights on the functional diversity of chromatin factors in governing cell-fate.

genomics↗

bioRxiv2022

Predicting Dog Phenotypes from Genotypes

We analyze dog genotypes (i.e., positions of dog DNA sequences that often vary between different dogs) in order to predict the corresponding phenotypes (i.e., unique observed characteristics). More specifically, given chromosome data from a dog, we aim to predict the breed, height, and weight. We explore a variety of linear and non-linear classification and regression techniques to accomplish these three tasks. We also investigate the use of a neural network (both in linear and non-linear modes) for breed classification and compare the performance to traditional statistical methods. We show that linear methods generally outperform or match the performance of non-linear methods for breed classification. However, we show that the reverse is true for height and weight regression. Finally, we evaluate the results of all of these methods based on the number of input features used in the analysis. We conduct experiments using different fractions of the full genomic sequences, resulting in input sequences ranging from 20 SNPs to [~]200k SNPs. In doing so, we explore the impact of using a very limited number of SNPs for prediction. Our experiments demonstrate that these phenotypes in dogs can be predicted with as few as 0.5% of randomly selected SNPs (i.e., 992 SNPs) and that dog breeds can be classified with 50% balanced accuracy with as few as 0.02% SNPs (i.e., 40 SNPs).

genomics↗

bioRxiv2021

Fibroblast growth factor-9 expression in airway epithelial cells amplifies the type I interferon response and alters influenza A virus pathogenesis

Influenza A virus (IAV) preferentially infects conducting airway and alveolar epithelial cells in the lung. The outcome of these infections is impacted by the host response, including the production of various cytokines, chemokines, and growth factors. Fibroblast growth factor-9 (FGF9) is required for lung development, can display antiviral activity in vitro, and is upregulated in asymptomatic patients during early IAV infection. We therefore hypothesized that FGF9 would protect the lungs from respiratory virus infection and evaluated IAV pathogenesis in mice that overexpress FGF9 in club cells in the conducting airway epithelium (FGF9-OE mice). However, we found that FGF9-OE mice were highly susceptible to IAV and Sendai virus infection compared to control mice. FGF9-OE mice displayed elevated and persistent viral loads, increased expression of cytokines and chemokines, and increased numbers of infiltrating immune cells as early as 1 day post-infection (dpi). Gene expression analysis showed an elevated type I interferon (IFN) signature in the conducting airway epithelium and analysis of IAV tropism uncovered a dramatic shift in infection from the conducting airway epithelium to the alveolar epithelium in FGF9-OE lungs. These results demonstrate that FGF9 signaling primes the conducting airway epithelium to rapidly induce a localized, protective IFN and proinflammatory cytokine response during viral infection. Although this response protects the airway epithelial cells from IAV infection, it allows for early and enhanced infection of the alveolar epithelium, ultimately leading to increased morbidity and mortality. Our study illuminates a novel role for FGF9 in regulating respiratory virus infection and pathogenesis. Author SummaryInfluenza viruses are respiratory viruses that cause significant morbidity and mortality worldwide. In the lungs, influenza A virus primarily infects epithelial cells that line the conducting airways and alveoli. Fibroblast growth factor-9 (FGF9) is a growth factor that has been shown to have antiviral activity and is upregulated during early IAV infection in asymptomatic patients, leading us to hypothesize that FGF9 would protect the lung epithelium from IAV infection. However, mice that express and secrete FGF9 from club cells in the conducting airway had more severe respiratory virus infection and a hyperactive inflammatory immune response as early as 1 day post-infection. Analysis of the FGF9-expressing airway epithelial cells found an elevated antiviral and inflammatory interferon signature, which protected these cells from severe IAV infection. However, heightened infection of alveolar cells resulted in excessive inflammation in the alveoli, resulting in more severe disease and death. Our study identifies a novel antiviral and inflammatory role for FGFs in the lung airway epithelium and confirms that early and robust IAV infection of alveolar cells results in more severe disease.

immunology↗

bioRxiv2021

Spatial effects in parasite induced marine diseases of immobile hosts

Marine infectious diseases are more prevalent in recent times due to climate change and other anthropogenic pressures, posing a substantial threat to marine ecosystems and the conservation of their biodiversity. An important subset of marine organisms are sessile, for which the most common mechanism for disease transmission is direct contact with waterborne parasites. Only recently, some deterministic compartmental models have been proposed to describe this kind of epidemics, being these models based on non-spatial descriptions where space is homogenised and parasite mobility is not explicitly accounted for. However, in realistic situations, epidemic transmission is conditioned by the spatial distribution of hosts and the parasites mobility patterns. Thus, the interplay between these factors is expected to have a crucial effect in the evolution of the epidemic, so calling for a explicit description of space. In this work we develop a spatially-explicit individual-based model to study disease transmission by waterborne parasites in sessile marine populations. We investigate the impact of spatial disease transmission, performing extensive numerical simulations and analytical approximations. Specifically, the effects of parasite mobility into the epidemic threshold and the temporal evolution of the epidemic are assessed. We show that larger values of pathogen mobility have two main implications: more severe epidemics, as the number of infections increases, and shorter time-scales to extinction. Moreover, an analytical expression for the basic reproduction number of the spatial model, [Formula], is derived as function of the non-spatial counterpart, R0, which characterises a transition between a disease-free and a propagation phase, in which the disease propagates over a large fraction of the system. This allows to determine a phase diagram for the epidemic model as function of the parasite mobility and the basic reproduction number of the non-spatial model.

ecology↗

bioRxiv2021

Cytidine deaminase protects pancreatic cancer cells from replicative stress and drives resistance to DNA-targeting drugs

Chronic DNA replication stress and genome instability are two hallmarks of cancer that fuel oncogenesis and tumor diversity. Therapeutic approaches aimed to leverage tumor-specific replication stress to intolerable levels or to expose vulnerabilities for synthetic lethality purposes have recently gained momentum, especially for pancreatic cancer, a disease with no cure. However, the current knowledge regarding the molecular mechanisms involved in the replication stress response in pancreatic tumors is limited. Cytidine deaminase (CDA) is involved in the pyrimidine salvage pathway for DNA and RNA synthesis. Loss of CDA induces genomic instability in Bloom Syndrome, and CDA protects tumor cells from chemotherapy with pyrimidine analogs. Here, we show that CDA is overexpressed in genetically unstable pancreatic tumors, associates with a DNA replication signature, and is instrumental for experimental tumor growth. In cancer cells, CDA promotes DNA replication, increases replication fork speed, and controls replication stress and genomic stability levels. CDA expression is predictive of DNA-damaging drug efficacy and targeting CDA relieves resistance to chemotherapy in patients models, both in vitro and in vivo. Our findings shed new light on the mechanisms by which pancreatic cancer cells control replication stress, and highlight targeting of CDA as a potential therapeutic strategy to defeat tumor resistance to treatment.

cancer biology↗

bioRxiv2021

Efficient methods for generation and expansion of, and gene delivery to Rhesus Macaque plasma B cells

immunology↗