bioRxiv Science⌕ Search

Biology subjects

Campos, B.

Publications and source records attributed to Campos, B..

6 recordsLinked to original sources

Computational and Experimental Evaluation of a Flow-Conditioning Anastomotic Device for Arteriovenous Fistula Maturation

The arteriovenous fistula (AVF) is the preferred method of vascular access for hemodialysis; however, 30-50% of AVFs undergo primary failure and are unsuitable for clinical use. As disturbed hemodynamics initiate endothelial injury and intimal hyperplasia, we designed an endovascular flow-conditioning anastomotic device (FCAD) to directly improve AVF hemodynamics and protect the anastomotic region. Using computational fluid dynamics, we characterized the flow field and wall shear stress (WSS) profiles in idealized AVF models with and without the FCAD. Incorporation of the FCAD into a brachiocephalic AVF model reduced regions of oscillatory WSS and generated a symmetrical flow profile in the draining vein compared to a reference AVF. Parametric studies also identified an FCAD geometry with a tab angle, height, and aspect ratio of 30{degrees}, 0.1 diameters, and 1.0 restored time-averaged WSS along the inner venous wall, achieving a physiological level without inducing regions of oscillatory flow throughout the cardiac cycle. Similar findings were observed with an in vitro model using particle imaging velocimetry. This study demonstrates the feasibility of the FCAD to normalize venous flow and WSS while imposing minimal resistance to blood flow. Restoring physiological WSS levels on the venous wall is expected to preserve endothelial function and improve AVF maturation.

bioengineering↗

Dynamic recruitment of PV interneurons in the somatosensory cortex induced by experience dependent plasticity

Adaptive circuit plasticity plays crucial roles in the brain during development, learning, sensory experience, and after injury. During chronic whisker trimming, a well-studied paradigm for inducing experience dependent plasticity, whisker representations in the somatosensory barrel cortex (S1BF) undergo remapping, with expansion of maps for spared whiskers and contraction of maps for trimmed whiskers. At the cellular level, excitatory pyramidal cells in Layer 2/3 shift their whisker tuning, increasing selectivity to spared whiskers and away from deprived whiskers. While these changes are well documented, the circuit mechanisms regulating experience-dependent plasticity remain incompletely characterized. Parvalbumin (PV) interneurons play important roles in regulating the spatial and temporal dynamics of sensory evoked activity in Pyr cells and have been implicated in the regulation of experience dependent plasticity in other cortical regions. However, there is little evidence as to how the sensory evoked activity of PV cells change in S1BF during whisker trimming or how those changes might affect cortical remapping. To address these questions, we used longitudinal in vivo two-photon (2P) calcium imaging of PV cells in S1BF before, during, and after inducing experience-dependent plasticity by whisker trimming. At baseline, we found that PV cells have spatially distributed responses to whisker deflections, responding best to the principal whisker of a given barrel and less frequently to surround whiskers in a distance-dependent manner. After whisker trimming, there is a substantial recruitment of PV cells responsive to the spared whisker in deprived, but not spared, barrels. Upon whisker regrowth, this recruitment is reversed, but changes in individual PV cell whisker selectivity can persist for weeks. To probe the potential casual effects of increased PV activity during whisker trimming, we used chemogenetics to acutely manipulate the activity of PV cells and found that modulating PV cell activity strongly affects sensory evoked responses in local Pyr and PV cells, as well as Somatostatin (SST) interneurons. In particular, increased PV cell activity strongly suppressed activity in all three cell types. Together, our results reveal dynamic changes in the spatial distribution and tuning of PV cells during experience dependent plasticity and suggest that increased PV cell activity could constrain the extent of potential cortical remapping in the adult S1BF.

neuroscience↗

Building flexible and robust analysis frameworks for molecular subtyping of cancers

Molecular subtyping is essential to infer tumor aggressiveness and predict prognosis. In practice, tumor profiling requires in-depth knowledge of bioinformatics tools involved in the processing and analysis of the generated data. Additionally, data incompatibility (e.g., microarray vs. RNA sequencing data) and technical and uncharacterized biological variance between training and test data can pose challenges in classifying individual samples. In this article, we provide a roadmap for implementing bioinformatics frameworks for molecular profiling of human cancers in a clinical diagnostic setting. We describe a framework for integrating several methods for quality control, normalization, batch correction, classification, and reporting and a use case of the framework in breast cancer.

bioinformatics↗

High sensitivity intrinsic optical signal imaging through flexible, low-cost adaptations of an upright microscope

Intrinsic optical signal imaging (IOSI) is a staple technique in modern neuroscience. Pioneered over thirty years ago, IOSI allows macroscopic mapping of neuronal activity throughout the cortex. The technique has been used to study sensory processing and experience-dependent plasticity, and is often used as an adjunctive procedure to localize cortical areas for subsequent targeting by other imaging or physiology techniques. Despite the ubiquity of IOSI in neuroscience there are few commercially available IOSI systems. As a result, investigators have typically resorted to building their own imaging systems. Over the years, simplified systems built on existing microscope platforms have been proposed. Still, these often require additional, sometimes costly, custom-built hardware, which presents challenges for investigators without significant experience in optics or microscopy design. Here we present a straightforward set of adaptations that can be applied to any standard upright microscope, using readily available, inexpensive, commercial parts for illumination, optics, and signal detection, that enables high sensitivity IOSI. Using these adaptations, we are able to readily map sensory-evoked signals across the somatosensory and visual cortex, including single-whisker barrel cortical activity maps in mice. We show that these IOSI maps are highly reproducible across animals and can be used to study plasticity mechanisms in the somatosensory cortex. We also provide open-source applications to control illumination and analyze raw data to generate activity maps. We anticipate these resources will be particularly useful for neuroscience investigators from broad technical backgrounds looking to add IOSI capabilities to an existing microscope on a budget.

neuroscience↗

Default Mode Network patterns and its interactions with memory performance in patients with Temporal Lobe Epilepsy and controls

Objectiveto investigate abnormal functional connectivity in the resting-state default mode network (DMN) and its relation to memory impairments in patients with temporal lobe epilepsy with and without hippocampal sclerosis (HS)\n\nMethodwe enrolled 122 MTLE patients divided into right-HS (n=42), left-HS (n=49), MRI-negative MTLE (n=31) and controls (n=69). All underwent resting-state seed-based connectivity fMRI, with a seed placed at the posterior cingulate cortex, an essential node for the DMN. In addition, patients and 41 controls were tested for verbal and visual memory, estimated intelligence coefficient and delayed recall.\n\nResultsBoth right-HS and MRI-negative group presented the poorest visual memory scores, and right-HS and left-HS had a worse performance in verbal memory compared to controls and MRI-negative groups. As expected, hippocampus was less connected than controls in all groups of patients. Although EEGs indicated that 64.5% of MRI-negative patients were lateralized to the left, this group showed activations similar to the right-HS.\n\nConclusionOur data suggest that there is a disruption of the normal pattern of DMN in MTLE. Patients with left and right-HS presented similar, increased and decreased connectivity in the ipsilateral hemisphere; however, left-HS had abnormal decreased connectivity in the contralateral hemisphere. Per neuropsychological examination, the presence of HS in the left hemisphere had more impact on verbal memory, which was not found when the seizure focus is in the left hemisphere in the absence of HS. The absence of hippocampal atrophy seems to yield a less prominent disruption in both functional connectivity and neuropsychological performance.

neuroscience↗

Unbiased Strain-Typing of Arbovirus Directly from Mosquitoes Using Nanopore Sequencing: A Field-forward Biosurveillance Protocol

The future of infectious disease surveillance and outbreak response is trending towards smaller hand-held solutions for point-of-need pathogen detection.1-4 Although recent advances have paved the way for these technologies to include sequencing of pathogens directly from clinical samples, the ability to carry out unbiased sequencing for pathogen discovery and subtyping directly from environmental samples has yet to be demonstrated with hand-held platforms.5 Products such as the two3 qPCR system from Biomeme Inc., as well as the MinION from Oxford Nanopore Technologies, have generated renewed prospects for point-of-need diagnostics and near real-time environmental testing and characterization of viral and microbial pathogens. Here, samples of Culex cedecei mosquitoes collected in Southern Florida, USA were tested for Venezuelan Equine Encephalitis Virus (VEEV), a previously-weaponized arthropod-borne RNA-virus capable of causing acute and fatal encephalitis in animal and human hosts. A single 20-mosquito pool tested positive for VEEV by real-time reverse transcription quantitative PCR (RT-qPCR) on the Biomeme two3. The virus-positive sample was then subjected to unbiased metatranscriptome sequencing on the MinION and determined to contain Everglades Virus (EVEV), a strain of VEEV transmitted exclusively by Culex cedecei in South Florida. The result was confirmed on \"gold standard\" thermocyclers and sequencing machines, and comparison to nanopore results is discussed. Our results demonstrate, for the first time, the use of unbiased sequence-based detection and subtyping of a high-consequence biothreat pathogen directly from an environmental sample using field-forward hardware and protocols. The further development and validation of methods designed for field-based diagnostic metagenomics and pathogen discovery, such as those suitable for use in mobile \"pocket laboratories\", will address a growing demand for public health teams to carry out their mission where it is most urgent: at the point-of-need.6

genomics↗