Hydrogen peroxide (HO) is an oxidant produced endogenously by several enzymatic pathways. While it can cause molecular damage, HO also plays a role in regulating cell proliferation and survival through redox signaling pathways. In the vascular system, red blood cells (RBCs) are notably efficient at metabolizing HO.
View Article and Find Full Text PDFSchizophrenia results in part from a failure of prefrontal networks but we lack full understanding of how disruptions at a synaptic level cause failures at the network level. This is a crucial gap in our understanding because it prevents us from discovering how genetic mutations and environmental risks that alter synaptic function cause prefrontal network to fail in schizophrenia. To address that question, we developed a recurrent spiking network model of prefrontal local circuits that can explain the link between NMDAR synaptic and 0-lag spike synchrony deficits we recently observed in a pharmacological monkey model of prefrontal network failure in schizophrenia.
View Article and Find Full Text PDFWe have studied the reduction reactions of two cytosolic human peroxiredoxins (Prx) in their disulfide form by three thioredoxins (Trx; two human and one bacterial), with the aim of better understanding the rate and mechanism of those reactions, and their relevance in the context of the catalytic cycle of Prx. We have developed a new methodology based on stopped-flow and intrinsic fluorescence to study the bimolecular reactions, and found rate constants in the range of 10 -10 m s in all cases, showing that there is no marked kinetic preference for the expected Trx partner. By combining experimental findings and molecular dynamics studies, we found that the reactivity of the nucleophilic cysteine (C ) in the Trx is greatly affected by the formation of the Prx-Trx complex.
View Article and Find Full Text PDFAlthough the role of host movement in shaping infectious disease dynamics is widely acknowledged, methodological separation between animal movement and disease ecology has prevented researchers from leveraging empirical insights from movement data to advance landscape scale understanding of infectious disease risk. To address this knowledge gap, we examine how movement behaviour and resource utilization by white-tailed deer (Odocoileus virginianus) determines blacklegged tick (Ixodes scapularis) distribution, which depend on deer for dispersal in a highly fragmented New York City borough. Multi-scale hierarchical resource selection analysis and movement modelling provide insight into how deer's movements contribute to the risk landscape for human exposure to the Lyme disease vector-I.
View Article and Find Full Text PDFBackground: In Alzheimer's disease (AD) research, subjective reports of cognitive and functional decline from participant-study partner dyads is an efficient method of assessing cognitive impairment and clinical progression.
Methods: Demographics and subjective cognitive/functional decline (Everyday Cognition Scale [ECog]) scores from dyads enrolled in the Brain Health Registry (BHR) Study Partner Portal were analyzed. Associations between dyad characteristics and both ECog scores and study engagement were investigated.
Peroxiredoxins (Prx) are ubiquitous, highly conserved peroxidases whose activity depends on catalytic cysteine residues. The Prx1-class of the peroxiredoxin family, also called typical 2-Cys Prx, organize as head-to-tail homodimers containing two active sites. The peroxidatic cysteine C of one monomer reacts with the peroxide substrate to form sulfenic acid that reacts with the resolving cysteine (C) of the adjacent subunit to form an intermolecular disulfide, that is reduced back by the thioredoxin/thioredoxin reductase/NADPH system.
View Article and Find Full Text PDFPeroxiredoxins (Prx), thiol-dependent peroxidases, were first identified as HO detoxifiers, and more recently as HO sensors, intermediates in redox-signaling pathways, metabolism modulators, and chaperones. The multifaceted nature of Prx is not only dependent on their peroxidase activity but also strongly associated with specific protein-protein interactions that are being identified, and where the Prx oligomerization dynamics plays a role. Their oxidation by a peroxide substrate forms a sulfenic acid that opens a route to channel the redox signal to diverse protein targets.
View Article and Find Full Text PDFOrally delivered, host-targeted, systemic acaricide treatment has potential to be an effective areawide tick abatement strategy. Past efforts using ivermectin for livestock were reported effective at controlling both Amblyomma americanum (L.) and Ixodes scapularis Say on Odocoileus virginianus (Zimmermann).
View Article and Find Full Text PDFTo better understand how prefrontal networks mediate forms of cognitive control disrupted in schizophrenia, we translated a variant of the AX continuous performance task that measures specific deficits in the human disease to 2 male monkeys and recorded neurons in PFC and parietal cortex during task performance. In the task, contextual information instructed by cue stimuli determines the response required to a subsequent probe stimulus. We found parietal neurons encoding the behavioral context instructed by cues that exhibited nearly identical activity to their prefrontal counterparts (Blackman et al.
View Article and Find Full Text PDFProtein self-assembly is a common feature in biology and is often required for a myriad of fundamental processes, such as enzyme activity, signal transduction, and transport of solutes across membranes, among others. There are several techniques to find and assess homo-oligomer formation in proteins. Naturally, all these methods have their limitations, meaning that at least two or more different approaches are needed to characterize a case study.
View Article and Find Full Text PDFUnlabelled: White-tailed deer ( ) are highly susceptible to infection by SARS-CoV-2, with multiple reports of widespread spillover of virus from humans to free-living deer. While the recently emerged SARS-CoV-2 B.1.
View Article and Find Full Text PDFIn July 2021, I had the honor of becoming an elected member of the Council of the International Union for Pure and Applied Biophysics (IUPAB) and joined the Editorial Board of Biophysical Reviews. This is a short biographical sketch to introduce myself to the readers of the journal.
View Article and Find Full Text PDFHydrogen peroxide (HO) not only is an oxidant but also is an important signaling molecule in vascular biology, mediating several physiological functions. Red blood cells (RBCs) have been proposed to be the primary sink of HO in the vasculature because they are the main cellular component of blood with a robust antioxidant defense and a high membrane permeability. However, the exact permeability of human RBC to HO is neither known nor is it known if the mechanism of permeation involves the lipid fraction or protein channels.
View Article and Find Full Text PDFSchizophrenia results from hundreds of known causes, including genetic, environmental, and developmental insults that cooperatively increase risk of developing the disease. In spite of the diversity of causal factors, schizophrenia presents with a core set of symptoms and brain abnormalities (both structural and functional) that particularly impact the prefrontal cortex. This suggests that many different causal factors leading to schizophrenia may cause prefrontal neurons and circuits to fail in fundamentally similar ways.
View Article and Find Full Text PDFThe electrode-tissue interface surrounding a deep brain stimulation (DBS) lead is known to be highly dynamic following implantation, which may have implications on the interpretation of intraoperatively recorded local field potentials (LFPs). We characterized beta-band LFP dynamics following implantation of a directional DBS lead in the sensorimotor subthalamic nucleus (STN), which is a primary target for treating Parkinson's disease.Directional STN-DBS leads were implanted in four healthy, non-human primates.
View Article and Find Full Text PDFThe systematic investigation of oxidative modification of proteins by reactive oxygen species started in 1980. Later, it was shown that reactive nitrogen species could also modify proteins. Some protein oxidative modifications promote loss of protein function, cleavage or aggregation, and some result in proteo-toxicity and cellular homeostasis disruption.
View Article and Find Full Text PDFSirtuin 6, SIRT6, is critical for both glucose and lipid homeostasis and is involved in maintaining genomic stability under conditions of oxidative DNA damage such as those observed in age-related diseases. There is an intense search for modulators of SIRT6 activity, however, not many specific activators have been reported. Long acyl-chain fatty acids have been shown to increase the weak deacetylase activity of SIRT6 but this effect is modest at best.
View Article and Find Full Text PDFBackground: The causal biology underlying schizophrenia is not well understood, but it is likely to involve a malfunction in how neurons adjust synaptic connections in response to patterns of activity in networks. We examined statistical dependencies between neural signals at the cell, local circuit, and distributed network levels in prefrontal and parietal cortices of monkeys performing a variant of the AX continuous performance task paradigm. We then quantified changes in the pattern of neural interactions across levels of scale following NMDA receptor (NMDAR) blockade and related these changes to a pattern of cognitive control errors closely matching the performance of patients with schizophrenia.
View Article and Find Full Text PDFThe mediodorsal nucleus of the thalamus (MD) is reciprocally connected with the prefrontal cortex (PFC), and although the MD has been implicated in a range of PFC-dependent cognitive functions (Watanabe and Funahashi, 2012; Mitchell and Chakraborty, 2013; Parnaudeau et al., 2018), little is known about how MD neurons in the primate participate specifically in cognitive control, a capability that reflects the ability to use contextual information (such as a rule) to modify responses to environmental stimuli. To learn how the MD-PFC thalamocortical network is engaged to mediate forms of cognitive control that are selectively disrupted in schizophrenia, we trained male monkeys to perform a variant of the AX continuous performance task, which reliably measures cognitive control deficits in patients (Henderson et al.
View Article and Find Full Text PDFLife on Earth evolved in the presence of hydrogen peroxide, and other peroxides also emerged before and with the rise of aerobic metabolism. They were considered only as toxic byproducts for many years. Nowadays, peroxides are also regarded as metabolic products that play essential physiological cellular roles.
View Article and Find Full Text PDFThe free radical nitric oxide (NO) exerts biological effects through the direct and reversible interaction with specific targets ( soluble guanylate cyclase) or through the generation of secondary species, many of which can oxidize, nitrosate or nitrate biomolecules. The NO-derived reactive species are typically short-lived, and their preferential fates depend on kinetic and compartmentalization aspects. Their detection and quantification are technically challenging.
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