Non-Optical, Label-free Electrical Capacitance Imaging of Microorganisms.

Unlabelled: Many fundamental insights into microbiology have come from imaging, which is typically synonymous with optical techniques. However, the sample preparation needed for many optical microscopy methods such as labeling, fixing, or genetic modification, limits the range of species and environments we can investigate. Here we demonstrate the use of electrical capacitance measurements as a non-optical method for imaging live microbial samples.

Electrical Capacitance Tomography of Cell Cultures on a CMOS Microelectrode Array.

Electrical capacitance tomography (ECT) can be used to predict information about the interior volume of an object based on measured capacitance at its boundaries. Here, we present a microscale capacitance tomography system with a spatial resolution of 10 microns using an active CMOS microelectrode array. We introduce a deep learning model for reconstructing 3-D volumes of cell cultures using the boundary capacitance measurements acquired from the sensor array, which is trained using a multi-objective loss function that combines a pixel-wise loss function, a distribution-based loss function, and a region-based loss function to improve model's reconstruction accuracy.

COVID-19 booster enhances IgG mediated viral neutralization by human milk .

Background: Facilitated by the inability to vaccinate, and an immature immune system, COVID-19 remains a leading cause of death among children. Vaccinated lactating mothers produce specific SARS-CoV-2 antibodies in their milk, capable of neutralizing the virus . Our objective for this study is to assess the effect of COVID-19 booster dose on SARS-CoV-2 antibody concentration and viral neutralization in milk, plasma, and infant stool.

Microscale 3-D Capacitance Tomography with a CMOS Sensor Array.

Electrical capacitance tomography (ECT) is a non-optical imaging technique in which a map of the interior permittivity of a volume is estimated by making capacitance measurements at its boundary and solving an inverse problem. While previous ECT demonstrations have often been at centimeter scales, ECT is not limited to macroscopic systems. In this paper, we demonstrate ECT imaging of polymer microspheres and bacterial biofilms using a CMOS microelectrode array, achieving spatial resolution of 10 microns.

SOCS1-KIR Peptide in PEGDA Hydrogels Reduces Pro-Inflammatory Macrophage Activation.

Macrophages modulate the wound healing cascade by adopting different phenotypes such as pro-inflammatory (M1) or pro-wound healing (M2). To reduce M1 activation, the JAK/STAT pathway can be targeted by using suppressors of cytokine signaling (SOCS1) proteins. Recently a peptide mimicking the kinase inhibitory region (KIR) of SOCS1 has been utilized to manipulate the adaptive immune response.

Programmable Electrochemical Stimulation on a Large-Scale CMOS Microelectrode Array.

In this paper we present spatio-temporally controlled electrochemical stimulation of aqueous samples using an integrated CMOS microelectrode array with 131,072 pixels. We demonstrate programmable gold electrodeposition in arbitrary spatial patterns, controllable electrolysis to produce microscale hydrogen bubbles, and spatially targeted electrochemical pH modulation. Dense spatially-addressable electrochemical stimulation is important for a wide range of bioelectronics applications.

Detection of SARS-CoV-2 IgA and IgG in human milk and breastfeeding infant stool 6 months after maternal COVID-19 vaccination.

Objective: Assess presence, durability, and neutralization capacity of SARS-CoV-2-specific antibodies in breastfeeding infants' stool, mother's plasma and milk following maternal vaccination.

Design: Thirty-seven mothers and 25 infants were enrolled between December 2020 and November 2021 for this prospective observational study. All mothers were vaccinated during lactation except three, which were vaccinated during pregnancy.

Detection of SARS-CoV-2 IgA and IgG in human milk and breastfeeding infant stool 6 months after maternal COVID-19 vaccination.

Assess the presence, durability, and neutralization capacity of SARS-CoV-2-specific antibodies in breastfeeding infants' stools, mother's plasma, and human milk following maternal vaccination. Thirty-seven mothers and 25 infants were enrolled between December 2020 and November 2021 for this prospective observational study. Human milk, maternal plasma, and infants' stools were collected pre-vaccination and at periods up to 6 months following COVID-19 vaccine series initiation/completion.

Localized electrical stimulation triggers cell-type-specific proliferation in biofilms.

Biological systems ranging from bacteria to mammals utilize electrochemical signaling. Although artificial electrochemical signals have been utilized to characterize neural tissue responses, the effects of such stimuli on non-neural systems remain unclear. To pursue this question, we developed an experimental platform that combines a microfluidic chip with a multielectrode array (MiCMA) to enable localized electrochemical stimulation of bacterial biofilms.

Open label safety and efficacy pilot to study mitigation of equine recurrent uveitis through topical suppressor of cytokine signaling-1 mimetic peptide.

Equine recurrent uveitis (ERU) is a painful and debilitating autoimmune disease and represents the only spontaneous model of human recurrent uveitis (RU). Despite the efficacy of existing treatments, RU remains a leading cause of visual handicap in horses and humans. Cytokines, which utilize Janus kinase 2 (Jak2) for signaling, drive the inflammatory processes in ERU that promote blindness.

CIFDock: A novel CHARMM-based flexible receptor-flexible ligand docking protocol.

Docking studies play a critical role in the current workflow of drug discovery. However, limitations may often arise through factors including inadequate ligand sampling, a lack of protein flexibility, scoring function inadequacies (e.g.

Toward Bacterial Bioelectric Signal Transduction.

Bacteria are electrically powered organisms; cells maintain an electrical potential across their plasma membrane as a source of free energy to drive essential processes. In recent years, however, bacterial membrane potential has been increasingly recognized as dynamic. Those dynamics have been implicated in diverse physiological functions and behaviors, including cell division and cell-to-cell signaling.

Detection of SARS-CoV-2-Specific IgA in the Human Milk of COVID-19 Vaccinated Lactating Health Care Workers.

In 2019, a deadly virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for coronavirus disease 2019 (COVID-19), emerged. In December 2020, two mRNA-based COVID-19 vaccines were approved for use in the United States, which provide immunity to those receiving the vaccine. Maternally derived antibodies are a key element of infants' immunity.

Suppressor of cytokine signaling-1 mimetic peptides attenuate lymphocyte activation in the MRL/lpr mouse autoimmune model.

Autoimmune diseases are driven largely by a pathogenic cytokine milieu produced by aberrantly activated lymphocytes. Many cytokines, including interferon gamma (IFN-γ), utilize the JAK/STAT pathway for signal propagation. Suppressor of Cytokine Signaling-1 (SOCS1) is an inducible, intracellular protein that regulates IFN-γ signaling by dampening JAK/STAT signaling.

Ameliorative Properties of Boronic Compounds in In Vitro and In Vivo Models of Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by amyloid (Aβ) aggregation, hyperphosphorylated tau, neuroinflammation, and severe memory deficits. Reports that certain boronic compounds can reduce amyloid accumulation and neuroinflammation prompted us to compare trans-2-phenyl-vinyl-boronic-acid-MIDA-ester (TPVA) and trans-beta-styryl-boronic-acid (TBSA) as treatments of deficits in in vitro and in vivo models of AD. We hypothesized that these compounds would reduce neuropathological deficits in cell-culture and animal models of AD.

Human Regulatory T Cells From Umbilical Cord Blood Display Increased Repertoire Diversity and Lineage Stability Relative to Adult Peripheral Blood.

The human T lymphocyte compartment is highly dynamic over the course of a lifetime. Of the many changes, perhaps most notable is the transition from a predominantly naïve T cell state at birth to the acquisition of antigen-experienced memory and effector subsets following environmental exposures. These phenotypic changes, including the induction of T cell exhaustion and senescence, have the potential to negatively impact efficacy of adoptive T cell therapies (ACT).

Encoding Membrane-Potential-Based Memory within a Microbial Community.

Cellular membrane potential plays a key role in the formation and retrieval of memories in the metazoan brain, but it remains unclear whether such memory can also be encoded in simpler organisms like bacteria. Here, we show that single-cell-level memory patterns can be imprinted in bacterial biofilms by light-induced changes in the membrane potential. We demonstrate that transient optical perturbations generate a persistent and robust potassium-channel-mediated change in the membrane potential of bacteria within the biofilm.

Spiral Wave Propagation in Communities with Spatially Correlated Heterogeneity.

Many multicellular communities propagate signals in a directed manner via excitable waves. Cell-to-cell heterogeneity is a ubiquitous feature of multicellular communities, but the effects of heterogeneity on wave propagation are still unclear. Here, we use a minimal FitzHugh-Nagumo-type model to investigate excitable wave propagation in a two-dimensional heterogeneous community.

Statistics of correlated percolation in a bacterial community.

Signal propagation over long distances is a ubiquitous feature of multicellular communities, but cell-to-cell variability can cause propagation to be highly heterogeneous. Simple models of signal propagation in heterogenous media, such as percolation theory, can potentially provide a quantitative understanding of these processes, but it is unclear whether these simple models properly capture the complexities of multicellular systems. We recently discovered that in biofilms of the bacterium Bacillus subtilis, the propagation of an electrical signal is statistically consistent with percolation theory, and yet it is reasonable to suspect that key features of this system go beyond the simple assumptions of basic percolation theory.

Therapeutic Implication of SOCS1 Modulation in the Treatment of Autoimmunity and Cancer.

The suppressor of cytokine signaling (SOCS) family of intracellular proteins has a vital role in the regulation of the immune system and resolution of inflammatory cascades. SOCS1, also called STAT-induced STAT inhibitor (SSI) or JAK-binding protein (JAB), is a member of the SOCS family with actions ranging from immune modulation to cell cycle regulation. Knockout of SOCS1 leads to perinatal lethality in mice and increased vulnerability to cancer, while several SNPs associated with the SOCS1 gene have been implicated in human inflammation-mediated diseases.

Modeling Boronic Acid Based Fluorescent Saccharide Sensors: Computational Investigation of d-Fructose Binding to Dimethylaminomethylphenylboronic Acid.

Designing organic saccharide sensors for use in aqueous solution is a nontrivial endeavor. Incorporation of hydrogen bonding groups on a sensor's receptor unit to target saccharides is an obvious strategy but not one that is likely to ensure analyte-receptor interactions over analyte-solvent or receptor-solvent interactions. Phenylboronic acids are known to reversibly and covalently bind saccharides (diols in general) with highly selective affinity in aqueous solution.

Signal Percolation within a Bacterial Community.

Signal transmission among cells enables long-range coordination in biological systems. However, the scarcity of quantitative measurements hinders the development of theories that relate signal propagation to cellular heterogeneity and spatial organization. We address this problem in a bacterial community that employs electrochemical cell-to-cell communication.

Monosubstituted Phenylboronic Acids, R-B(OH) (R = CH, CHCH, CHNH, CHOH, and CHF): A Computational Investigation.

Phenylboronic acids (PBAs) are an important class of compounds with diverse applications in synthetic, biological, medicinal, and materials chemistry. In this investigation we report structural and thermochemical parameters for several monosubstituted , , and PBAs, R-B(OH) (R = CH, CHCH, CHNH, CHOH, and CHF). Equilibrium geometries of all the PBAs discussed in this article were obtained using second-order Møller-Plesset perturbation theory (MP2) with the Dunning-Woon aug-cc-pVDZ basis set; heats of formation (HOF) were calculated at the Gaussian-3 (G3) level of theory.