Biology subjects

Monge, M.

Publications and source records attributed to Monge, M..

5 recordsLinked to original sources

bioRxiv2025

Highly replicated experiments studying complex genotypes using nested DNA barcodes.

Many biological experiments involve studying the differences caused by genetic modifications, including genotypes composed of modifications at more than one locus. However, as the number and complexity of the genotypes increases, independently generating and tracking the necessary number of biological replicate samples becomes a major challenge. We developed a barcode-based method to track large numbers of independent replicates of combinatorial genotypes in a pooled format, enabling robust detection of subtle phenotypic differences. To construct a plasmid library of combinatorial genotypes, we utilized a nested serial cloning process to combine gene variants of interest that have associated DNA barcodes. The final plasmids each contain variants of multiple genes of interest, and a combined barcode that specifies the genotype of all the genes while also encoding a random sequence for tracking individual replicates. Sequencing of the pool of barcodes by next-generation sequencing allows the whole population to be studied in a single flask, enabling a high degree of replication even for complex genotypes. Using this approach, we tested the functionality of combinations of yeast, human, and null orthologs of the nucleotide excision repair factor I (NEF-1) complex and found that cells expressing all three yeast NEF-1 subunits had superior growth in DNA-damaging conditions. We also assessed the sensitivity of our method by simulating downsampling of barcodes across different degrees of phenotypic differentiation. Our results demonstrate the utility of NICR barcodes for high-throughput combinatorial genetic screens and provide a scalable framework for exploring complex genotype-phenotype relationships.

genetics↗

bioRxiv2022

Modifying the trajectory of epicardial leads can substantially reduce MRI-induced RF heating in pediatric patients with a cardiac implantable electronic device

PurposeInfants and children with congenital heart defects, inherited arrhythmia syndromes, and congenital cardiac conduction disorders often receive epicardial implantable electronic devices. Unfortunately, once an epicardial device is implanted, the patient is no longer eligible to receive MRI exams due to an elevated risk of RF heating. Here we show that a simple modification in the trajectory of epicardial leads can substantially and reliably reduce RF heating during MRI at 1.5 T, with benefits extending to abandoned leads. MethodsElectromagnetic simulations were performed to assess RF heating of two common epicardial lead trajectories exhibiting different degrees of coupling with MRI incident electric fields. Experiments in anthropomorphic phantoms implanted with commercial cardiac implantable electronic devices (CIEDs) confirmed the findings. ResultsSimulations of an epicardial lead with a trajectory where the excess length of the lead was looped and placed on the anterior surface of the heart showed a 9-fold reduction in 0.1g-averaged SAR compared to the lead with excess length looped on the inferior surface of the heart. Repeated experiments with a commercial epicardial device confirmed the results, showing a 16-fold reduction in the average temperature rise for fully implanted systems with leads following low-SAR trajectories, and a 20-fold reduction in RF heating on an abandoned lead. ConclusionSurgical modification of epicardial lead trajectory can substantially reduce RF heating at 1.5 T, with benefits extending to abandoned leads.

biophysics↗

bioRxiv2022

The Layer 7 Cortical Interface: A Scalable and Minimally Invasive Brain-Computer Interface Platform

Progress toward the development of brain-computer interfaces has signaled the potential to restore, replace, and augment lost or impaired neurological function in a variety of disease states. Existing approaches to developing high-bandwidth brain-computer interfaces rely on invasive surgical procedures or brain-penetrating electrodes, which limit addressable applications of the technology and the number of eligible patients. Here we describe a novel approach to constructing a neural interface, comprising conformable thin-film electrode arrays and a minimally invasive surgical delivery system that together facilitate bidirectional communication with large portions of the cortical surface (enabling both recording and stimulation). We demonstrate the feasibility and safety of delivering reversible implants containing over 2,000 microelectrodes to multiple functional regions in both hemispheres of the brain simultaneously, without requiring a craniotomy or damaging the cortical surface, at an effective insertion rate faster than 40 ms per channel. We further evaluate the performance of this system immediately following implantation for high-density neural recording and visualizing cortical surface activity at spatial and temporal resolutions and extents not previously possible in multiple preclinical large animal studies as well as in a five-patient pilot clinical study involving both anesthetized and awake neurosurgical patients. We characterize the spatial scales at which sensorimotor activity and speech are represented at the cortical surface, demonstrate accurate neural decoding of somatosensory, visual, and volitional walking activity, and achieve precise neuromodulation through cortical stimulation at sub-millimeter scales. The resulting system generates 90 Gb/h of electrophysiologic data, and demonstrates the highly scalable nature of micro-electrocorticography and its utility for next-generation brain-computer interfaces that may expand the patient population that could benefit from neural interface technology.

neuroscience↗

bioRxiv2020

Regulatory roles of 5' UTR and ORF-internal RNAs detected by 3' end mapping

Many bacterial genes are regulated by RNA elements in their 5' untranslated regions (UTRs). However, the full complement of these elements is not known even in the model bacterium Escherichia coli. Using complementary RNA-sequencing approaches, we detected large numbers of 3' ends in 5' UTRs and open reading frames (ORFs), suggesting extensive regulation by premature transcription termination. We documented regulation for multiple transcripts, including spermidine induction involving Rho and translation of an upstream ORF for an mRNA encoding a spermidine efflux pump. In addition to discovering novel sites of regulation, we detected short, stable RNA fragments derived from 5' UTRs and sequences internal to ORFs. Characterization of three of these transcripts, including an RNA internal to an essential cell division gene, revealed that they have independent functions as sRNA sponges. Thus, these data uncover an abundance of cis- and trans-acting RNA regulators in bacterial 5' UTRs and internal to ORFs.

microbiology↗

bioRxiv2019

Influence of selective treatment on Haematobia irritans infestation of untreated cattle

To reduce the use of insecticide treatments against Haematobia irritans we evaluated the impact of treating 15% of the bovines, with the greatest number of flies including bulls, with 40% diazinon ear tags, on the infestation of untreated cows. Horn fly susceptibility to diazinon was measured before and after treatment, and peaks of infestation were recorded. Three groups of Bradford bovines were evaluated: Group 1 (control untreated), Group 2 (15% treated) and Group 3 (control 100% treated). Weekly counts of horn flies were performed on the same animals for 78 days. Two peaks of infestation were recorded, and a higher number of horn flies occurred in the untreated control group than in the untreated cows of the selectively treated group throughout the entire period of the study, except for a single week. The horn fly field population was significantly more susceptible to diazinon than the reference susceptible strain both before and after insecticide treatment. In conclusion, treatment of 15% of the most infested animals from a herd, with 40% diazinon ear tags, quickly reduced horn fly infestations of the entire herd and may be a practical approach for horn fly control, reducing costs and chemical use.

ecology↗