Correction: A PDK-1 allosteric agonist neutralizes insulin signaling derangements and beta-amyloid toxicity in neuronal cells and in vitro.

[This corrects the article DOI: 10.1371/journal.pone.

Soft-tissue volume augmentation using a connective tissue graft and a volume-stable collagen matrix with polydeoxyribonucleotide for immediate implant placement: a pilot study in a dog model.

Purpose: The aims of this study were 1) to investigate the effects of a subepithelial connective tissue graft (SCTG) and a volume-stable collagen matrix (VCMX) on soft-tissue volume gain in the immediate implant placement protocol, and 2) to determine whether polydeoxyribonucleotide (PDRN) can enhance the effects of a VCMX.

Methods: Dental implants were placed in 4 mongrel dogs immediately after extracting the distal roots of their third and fourth mandibular premolars. The gap between the implant and the buccal bone plate was filled with synthetic bone substitute particles.

Differential peripheral immune signatures elicited by vegan versus ketogenic diets in humans.

Nutrition has broad impacts on all physiological processes. However, how nutrition affects human immunity remains largely unknown. Here we explored the impact of a dietary intervention on both immunity and the microbiota by performing a post hoc analysis of a clinical trial in which each of the 20 participants sequentially consumed vegan or ketogenic diets for 2 weeks ( NCT03878108 ).

Effect of polydeoxyribonucleotide with xenogeneic collagen matrix on gingival phenotype modification: a pilot preclinical study.

Purpose: To investigate the effect of xenogeneic collagen matrix (XCM) with polydeoxyribonucleotide (PDRN) for gingival phenotype modification compared to autogenous connective tissue graft.

Methods: Five mongrel dogs were used in this study. Box-type gingival defects were surgically created bilaterally on the maxillary canines 8 weeks before gingival augmentation.

Developmental expression of the Sturge-Weber syndrome-associated genetic mutation in Gnaq: a formal test of Happle's paradominant inheritance hypothesis.

Sturge-Weber Syndrome (SWS) is a sporadic (non-inherited) syndrome characterized by capillary vascular malformations in the facial skin, leptomeninges, or the choroid. A hallmark feature is the mosaic nature of the phenotype. SWS is caused by a somatic mosaic mutation in the GNAQ gene (p.

Sex and prior exposure jointly shape innate immune responses to a live herpesvirus vaccine.

Background: Both sex and prior exposure to pathogens are known to influence responses to immune challenges, but their combined effects are not well established in humans, particularly in early innate responses critical for shaping subsequent outcomes.

Methods: We employed systems immunology approaches to study responses to a replication-defective, herpes simplex virus (HSV) 2 vaccine in men and women either naive or previously exposed to HSV.

Results: Blood transcriptomic and cell population profiling showed substantial changes on day 1 after vaccination, but the responses depended on sex and whether the vaccinee was naive or previously exposed to HSV.

Influenza vaccination reveals sex dimorphic imprints of prior mild COVID-19.

Acute viral infections can have durable functional impacts on the immune system long after recovery, but how they affect homeostatic immune states and responses to future perturbations remain poorly understood. Here we use systems immunology approaches, including longitudinal multimodal single-cell analysis (surface proteins, transcriptome and V(D)J sequences) to comparatively assess baseline immune statuses and responses to influenza vaccination in 33 healthy individuals after recovery from mild, non-hospitalized COVID-19 (mean, 151 days after diagnosis) and 40 age- and sex-matched control individuals who had never had COVID-19. At the baseline and independent of time after COVID-19, recoverees had elevated T cell activation signatures and lower expression of innate immune genes including Toll-like receptors in monocytes.

A PDK-1 allosteric agonist improves spatial learning and memory in a βAPP/PS-1 transgenic mouse-high fat diet intervention model of Alzheimer's disease.

Diabetes mellitus (DM), peripheral insulin resistance (IR) and obesity are clear risk factors for Alzheimer's disease. Several anti-diabetic drugs and insulin have been tested in rodents and humans with MCI or AD, yielding promising but inconclusive results. The PDK-1/Akt axis, essential to the action of insulin, has not however been pharmacologically interrogated to a similar degree.

Cardiac Troponin I-Interacting Kinase Affects Cardiomyocyte S-Phase Activity but Not Cardiomyocyte Proliferation.

Background: Identifying genetic variants that affect the level of cell cycle reentry and establishing the degree of cell cycle progression in those variants could help guide development of therapeutic interventions aimed at effecting cardiac regeneration. We observed that C57Bl6/NCR (B6N) mice have a marked increase in cardiomyocyte S-phase activity after permanent coronary artery ligation compared with infarcted DBA/2J (D2J) mice.

Methods: Cardiomyocyte cell cycle activity after infarction was monitored in D2J, (D2J×B6N)-F1, and (D2J×B6N)-F1×D2J backcross mice by means of bromodeoxyuridine or 5-ethynyl-2'-deoxyuridine incorporation using a nuclear-localized transgenic reporter to identify cardiomyocyte nuclei.

A cross-species approach using an in vivo evaluation platform in mice demonstrates that sequence variation in human RABEP2 modulates ischemic stroke outcomes.

Ischemic stroke, caused by vessel blockage, results in cerebral infarction, the death of brain tissue. Previously, quantitative trait locus (QTL) mapping of cerebral infarct volume and collateral vessel number identified a single, strong genetic locus regulating both phenotypes. Additional studies identified RAB GTPase-binding effector protein 2 (Rabep2) as the casual gene.

Peroxisome proliferator activated receptor-γ agonist pioglitazone improves vascular and metabolic dysfunction in systemic lupus erythematosus.

Objectives: Premature cardiovascular events in systemic lupus erythematosus (SLE) contribute to morbidity and mortality, with no effective preventive strategies described to date. Immune dysregulation and metabolic disturbances appear to play prominent roles in the induction of vascular disease in SLE. The peroxisome proliferator activated receptor-gamma agonist pioglitazone (PGZ suppresses vascular damage and immune dysregulation in murine lupus and improves endothelial dysfunction in other inflammatory diseases.

Influenza vaccination and single cell multiomics reveal sex dimorphic immune imprints of prior mild COVID-19.

Viral infections can have profound and durable functional impacts on the immune system. There is an urgent need to characterize the long-term immune effects of SARS-CoV-2 infection given the persistence of symptoms in some individuals and the continued threat of novel variants. Here we use systems immunology, including longitudinal multimodal single cell analysis (surface proteins, transcriptome, and V(D)J sequences) from 33 previously healthy individuals after recovery from mild, non-hospitalized COVID-19 and 40 age- and sex-matched healthy controls with no history of COVID-19 to comparatively assess the post-infection immune status (mean: 151 days after diagnosis) and subsequent innate and adaptive responses to seasonal influenza vaccination.

A PDK-1 allosteric agonist neutralizes insulin signaling derangements and beta-amyloid toxicity in neuronal cells and in vitro.

The Alzheimer's brain is affected by multiple pathophysiological processes, which include a unique, organ-specific form of insulin resistance that begins early in its course. An additional complexity arises from the four-fold risk of Alzheimer's Disease (AD) in type 2 diabetics, however there is no definitive proof of causation. Several strategies to improve brain insulin signaling have been proposed and some have been clinically tested.

The Role of Prostaglandin E1 as a Pain Mediator through Facilitation of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 via the EP2 Receptor in Trigeminal Ganglion Neurons of Mice.

Cyclooxygenase metabolizes dihomo-γ-linolenic acid and arachidonic acid to form prostaglandin (PG) E, including PGE1 and PGE2, respectively. Although PGE2 is well known to play an important role in the development and maintenance of hyperalgesia and allodynia, the role of PGE1 in pain is unknown. We confirm whether PGE1 induced pain using orofacial pain behavioral test in mice and determine the target molecule of PGE1 in TG neurons with whole-cell patch-clamp and immunohistochemistry.

A Neuroprotective Locus Modulates Ischemic Stroke Infarction Independent of Collateral Vessel Anatomy.

Although studies with inbred strains of mice have shown that infarct size is largely determined by the extent of collateral vessel connections between arteries in the brain that enable reperfusion of the ischemic territory, we have identified strain pairs that do not vary in this vascular phenotype, but which nonetheless exhibit large differences in infarct size. In this study we performed quantitative trait locus (QTL) mapping in mice from an intercross between two such strains, WSB/EiJ (WSB) and C57BL/6J (B6). This QTL mapping revealed only one neuroprotective locus on Chromosome 8 (Chr 8) that co-localizes with a neuroprotective locus we mapped previously from F2 progeny between C3H/HeJ (C3H) and B6.

Riboflavin Inhibits Histamine-Dependent Itch by Modulating Transient Receptor Potential Vanilloid 1 (TRPV1).

Riboflavin, also known as vitamin B, isfound in foods and is used as a dietary supplement. Its deficiency (also called ariboflavinosis) results in some skin lesions and inflammations, such as stomatitis, cheilosis, oily scaly skin rashes, and itchy, watery eyes. Various therapeutic effects of riboflavin, such as anticancer, antioxidant, anti-inflammatory, and anti-nociceptive effects, are well known.

Mammalian/mechanistic target of rapamycin (mTOR) complexes in neurodegeneration.

Novel targets to arrest neurodegeneration in several dementing conditions involving misfolded protein accumulations may be found in the diverse signaling pathways of the Mammalian/mechanistic target of rapamycin (mTOR). As a nutrient sensor, mTOR has important homeostatic functions to regulate energy metabolism and support neuronal growth and plasticity. However, in Alzheimer's disease (AD), mTOR alternately plays important pathogenic roles by inhibiting both insulin signaling and autophagic removal of β-amyloid (Aβ) and phospho-tau (ptau) aggregates.

GPR171 Activation Modulates Nociceptor Functions, Alleviating Pathologic Pain.

Modulation of the function of somatosensory neurons is an important analgesic strategy, requiring the proposal of novel molecular targets. Many G-protein-coupled receptors (GPRs) have been deorphanized, but the receptor locations, outcomes due to their activations, and their signal transductions remain to be elucidated, regarding the somatosensory nociceptor function. Here we report that GPR171, expressed in a nociceptor subpopulation, attenuated pain signals via Gi/o-coupled modulation of the activities of nociceptive ion channels when activated by its newly found ligands.

A machine learning approach for early warning of cyanobacterial bloom outbreaks in a freshwater reservoir.

Understanding the dynamics of harmful algal blooms is important to protect the aquatic ecosystem in regulated rivers and secure human health. In this study, artificial neural network (ANN) and support vector machine (SVM) models were used to predict algae alert levels for the early warning of blooms in a freshwater reservoir. Intensive water-quality, hydrodynamic, and meteorological data were used to train and validate both ANN and SVM models.

Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19.

COVID-19 exhibits extensive patient-to-patient heterogeneity. To link immune response variation to disease severity and outcome over time, we longitudinally assessed circulating proteins as well as 188 surface protein markers, transcriptome, and T cell receptor sequence simultaneously in single peripheral immune cells from COVID-19 patients. Conditional-independence network analysis revealed primary correlates of disease severity, including gene expression signatures of apoptosis in plasmacytoid dendritic cells and attenuated inflammation but increased fatty acid metabolism in CD56CD16 NK cells linked positively to circulating interleukin (IL)-15.

Immunity of nanoscale magnetic tunnel junctions with perpendicular magnetic anisotropy to ionizing radiation.

Spin transfer torque magnetic random access memory (STT-MRAM) is a promising candidate for next generation memory as it is non-volatile, fast, and has unlimited endurance. Another important aspect of STT-MRAM is that its core component, the nanoscale magnetic tunneling junction (MTJ), is thought to be radiation hard, making it attractive for space and nuclear technology applications. However, studies on the effects of ionizing radiation on the STT-MRAM writing process are lacking for MTJs with perpendicular magnetic anisotropy (pMTJs) required for scalable applications.

Multimodal immune phenotyping of maternal peripheral blood in normal human pregnancy.

Changes in maternal immunity during pregnancy can result in an altered immune state, and as a natural perturbation, this provides an opportunity to understand functional interactions of the immune system in vivo. We report characterization of maternal peripheral immune phenotypes for 33 longitudinally sampled normal pregnancies, using clinical measurements of complete blood counts and major immune cell populations, as well as high parameter flow cytometry for 30 leukocyte antigens characterizing 79 cell populations, and monitoring of 1305 serum proteins using the SomaLogic platform. Cellular analyses characterized transient changes in T cell polarization and more persistent alterations in T and B cell subset frequencies and activation.

Novel Neuroprotective Loci Modulating Ischemic Stroke Volume in Wild-Derived Inbred Mouse Strains.

To identify genes involved in cerebral infarction, we have employed a forward genetic approach in inbred mouse strains, using quantitative trait loci (QTL) mapping for cerebral infarct volume after middle cerebral artery occlusion. We had previously observed that infarct volume is inversely correlated with cerebral collateral vessel density in most strains. In this study, we expanded the pool of allelic variation among classical inbred mouse strains by utilizing the eight founder strains of the Collaborative Cross and found a wild-derived strain, WSB/EiJ, that breaks this general rule that collateral vessel density inversely correlates with infarct volume.