Differences between organic and schizophrenic groups on the Halstead-Reitan battery: A reply to Watson.

Questions C. G. Watson's (see PA, Vol 52:Issue 3) attempt to explain apparent inconsistencies in findings between his and the present authors' studies in terms of sample differences. Despite Watson's reanalysis of his data by matched pairs, he fails adequately to control for differences in chronicity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An Adaptive Role for DNA Double-Strand Breaks in Hippocampus-Dependent Learning and Memory

DNA double-strand breaks (DSBs), classified as the most harmful type of DNA damage based on the complexity of repair, lead to apoptosis or tumorigenesis. In aging, DNA damage increases and DNA repair decreases. This is exacerbated in disease, as post-mortem tissue from patients diagnosed with mild cognitive impairment (MCI) or Alzheimer’s disease (AD) show increased DSBs. A novel role for DSBs in immediate early gene (IEG) expression, learning, and memory has been suggested. Inducing neuronal activity leads to increases in DSBs and upregulation of IEGs, while increasing DSBs and inhibiting DSB repair impairs long-term memory and alters IEG expression. Consistent with this pattern, mice carrying dominant AD mutations have increased baseline DSBs, and impaired DSB repair is observed. These data suggest an adaptive role for DSBs in the central nervous system and dysregulation of DSBs and/or repair might drive age-related cognitive decline (ACD), MCI, and AD. In this review, we discuss the adaptive role of DSBs in hippocampus-dependent learning, memory, and IEG expression. We summarize IEGs, the history of DSBs, and DSBs in synaptic plasticity, aging, and AD. DSBs likely have adaptive functions in the brain, and even subtle alterations in their formation and repair could alter IEGs, learning, and memory.     

Photorhabdus luminescens TccC3 Toxin Targets the Dynamic Population of F-Actin and Impairs Cell Cortex Integrity

Due to its essential role in cellular processes, actin is a common target for bacterial toxins. One such toxin, TccC3, is an effector domain of the ABC-toxin produced by entomopathogenic bacteria of Photorhabdus spp. Unlike other actin-targeting toxins, TccC3 uniquely ADP-ribosylates actin at Thr-148, resulting in the formation of actin aggregates and inhibition of phagocytosis. It has been shown that the fully modified F-actin is resistant to depolymerization by cofilin and gelsolin, but their effects on partially modified actin were not explored. We found that only F-actin unprotected by tropomyosin is the physiological TccC3 substrate. Yet, ADP-ribosylated G-actin can be produced upon cofilin-accelerated F-actin depolymerization, which was only mildly inhibited in partially modified actin. The affinity of TccC3-ADP-ribosylated G-actin for profilin and thymosin-β4 was weakened moderately but sufficiently to potentiate spontaneous polymerization in their presence. Interestingly, the Arp2/3-mediated nucleation was also potentiated by T148-ADP-ribosylation. Notably, even partially modified actin showed reduced bundling by plastins and α-actinin. In agreement with the role of these and other tandem calponin-homology domain actin organizers in the assembly of the cortical actin network, TccC3 induced intense membrane blebbing in cultured cells. Overall, our data suggest that TccC3 imposes a complex action on the cytoskeleton by affecting F-actin nucleation, recycling, and interaction with actin-binding proteins involved in the integration of actin filaments with each other and cellular elements.     

The Endothelium and COVID-19: An Increasingly Clear Link Brief Title: Endotheliopathy in COVID-19

The endothelium has a fundamental role in the cardiovascular complications of coronavirus disease 2019 (COVID-19). Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) particularly affects endothelial cells. The virus binds to the angiotensin-converting enzyme 2 (ACE-2) receptor (present on type 2 alveolar cells, bronchial epithelial cells, and endothelial cells), and induces a cytokine storm. The cytokines tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 have particular effects on endothelial cells—leading to endothelial dysfunction, endothelial cell death, changes in tight junctions, and vascular hyperpermeability. Under normal conditions, apoptotic endothelial cells are removed into the bloodstream. During COVID-19, however, endothelial cells are detached more rapidly, and do not regenerate as effectively as usual. The loss of the endothelium on the luminal surface abolishes all of the vascular responses mediated by the endothelium and nitric oxide production in particular, which results in greater contractility. Moreover, circulating endothelial cells infected with SARS-CoV-2 act as vectors for viral dissemination by forming clusters that migrate into the circulation and reach distant organs. The cell clusters and the endothelial dysfunction might contribute to the various thromboembolic pathologies observed in COVID-19 by inducing the formation of intravascular microthrombi, as well as by triggering disseminated intravascular coagulation. Here, we review the contributions of endotheliopathy and endothelial-cell-derived extracellular vesicles to the pathogenesis of COVID-19, and discuss therapeutic strategies that target the endothelium in patients with COVID-19.     

Adaptation of Oxidative Phosphorylation Machinery Compensates for Hepatic Lipotoxicity in Early Stages of MAFLD

Alterations in mitochondrial function are an important control variable in the progression of metabolic dysfunction-associated fatty liver disease (MAFLD), while also noted by increased de novo lipogenesis (DNL) and hepatic insulin resistance. We hypothesized that the organization and function of a mitochondrial electron transport chain (ETC) in this pathologic condition is a consequence of shifted substrate availability. We addressed this question using a transgenic mouse model with increased hepatic insulin resistance and DNL due to constitutively active human SREBP-1c. The abundance of ETC complex subunits and components of key metabolic pathways are regulated in the liver of these animals. Further omics approaches combined with functional assays in isolated liver mitochondria and primary hepatocytes revealed that the SREBP-1c-forced fatty liver induced a substrate limitation for oxidative phosphorylation, inducing enhanced complex II activity. The observed increased expression of mitochondrial genes may have indicated a counteraction. In conclusion, a shift of available substrates directed toward activated DNL results in increased electron flows, mainly through complex II, to compensate for the increased energy demand of the cell. The reorganization of key compounds in energy metabolism observed in the SREBP-1c animal model might explain the initial increase in mitochondrial function observed in the early stages of human MAFLD.     

Carbon Free and Noble Metal Free Ni2Mo6S8 Electrocatalyst for Selective Electrosynthesis of H2O2

Electrocatalytic two-electron reduction of oxygen is a promising method for producing sustainable H₂O₂ but lacks low-cost and selective electrocatalysts. Here, the Chevrel phase chalcogenide Ni₂Mo₆S₈ is presented as a novel active motif for reducing oxygen to H₂O₂ in an aqueous electrolyte. Although it has a low surface area, the Ni₂Mo₆S₈ catalyst exhibits exceptional activity for H₂O₂ synthesis with >90% H₂O₂ molar selectivity across a wide potential range. Chemical titration verified successful generation of H₂O₂ and confirmed rates as high as 90 mmol H₂O₂ g_cat⁻¹ h⁻¹. The outstanding activities are attributed to the ligand and ensemble effects of Ni that promote H₂O dissociation and proton-coupled reduction of O₂ to HOO*, and the spatial effect of the Chevrel phase structure that isolates Ni active sites to inhibit O O cleavage. The synergy of these effects delivers fast and selective production of H₂O₂ with high turn-over frequencies of ≈30 s⁻¹. In addition, the Ni₂Mo₆S₈ catalyst has a stable crystal structure that is resistive for oxidation and delivers good catalyst stability for continuous H₂O₂ production. The described Ni-Mo₆S₈ active motif can unlock new opportunities for designing Earth-abundant electrocatalysts to tune oxygen reduction for practical H₂O₂ production.     

Power consumption of analog circuits: a tutorial

A systematic approach to the power consumption of analog circuits is presented. The power consumption is related to basic circuit requirements, as dynamic range, bandwidth, noise figure and sampling speed and is considering basic device and device scaling behavior. Several kinds of circuits are treated, as samplers, amplifiers, filters and oscillators. The objective is to derive lower bounds to power consumption in analog circuits, to be used as design targets when designing power-constrained analog systems.     

Hide-n-Sense: Preserving Privacy Efficiently in Wireless mHealth

As healthcare in many countries faces an aging population and rising costs, mobile sensing technologies promise a new opportunity. Using mobile health (mHealth) sensing, which uses medical sensors to collect data about the patients, and mobile phones to act as a gateway between sensors and electronic health record systems, caregivers can continuously monitor the patients and deliver better care. Furthermore, individuals can become better engaged in monitoring and managing their own health. Although some work on mHealth sensing has addressed security, achieving strong privacy for low-power sensors remains a challenge. We make three contributions. First, we propose an mHealth sensing protocol that provides strong security and privacy properties at the link layer, with low energy overhead, suitable for low-power sensors. The protocol uses three novel techniques: adaptive security, to dynamically modify transmission overhead; MAC striping, to make forgery difficult even for small-sized Message Authentication Codes; and asymmetric resource requirements, in recognition of the limited resources in tiny mHealth sensors. Second, we demonstrate its feasibility by implementing a prototype on a Chronos wrist device, and evaluating it experimentally. Third, we provide a security, privacy, and energy analysis of our system.