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Follows ten teens who are left alone in the wilderness amid a three-day survival test.

Recent research on changing fears has examined targeting reconsolidation. During reconsolidation, stored information is rendered labile after being retrieved. Pharmacological manipulations at this stage result in an inability to retrieve the memories at later times, suggesting that they are erased or persistently inhibited. Unfortunately, the use of these pharmacological manipulations in humans can be problematic. Here we introduce a non-invasive technique to target the reconsolidation of fear memories in humans. We provide evidence that old fear memories can be updated with non-fearful information provided during the reconsolidation window. As a consequence, fear responses are no longer expressed, an effect that lasted at least a year and was selective only to reactivated memories without affecting others. These findings demonstrate the adaptive role of reconsolidation as a window of opportunity to rewrite emotional memories, and suggest a non-invasive technique that can be used safely in humans to prevent the return of fear. An appointment with fear Reconsolidation is a natural mechanism in human memory: the reconsolidation phase allows new information available at the time of retrieval to be incorporated into an old memory. Although pharmacological blockade of reconsolidation has been used to prevent the return of fear in animal models, many of these manipulations involve compounds that are toxic to humans. Elizabeth Phelps and co-workers now report a non-invasive technique of rewriting fear memories that avoids the use of drugs. The procedure is based on an established technique in which memories of traumatic events are 'extinguished' by repeated exposure to traumatic reminders in a safe environment. This works up to a point, but memories are masked rather than eliminated and can return, for example with the passage of time or due to stress. The new advance lies in timing: if the 'safe' information is introduced during the reconsolidation window of old fear memories, the fear does not return. This work suggests that post-traumatic stress disorder and other anxiety conditions might be responsive to new types of non-invasive therapy. During reconsolidation of memories, stored information is rendered labile after being retrieved and can be manipulated. Previous studies have used pharmacological intervention to disrupt retrieved memories; here, however, a non-invasive, behavioural technique is used to target the reconsolidation of fear memories in humans. Non-fearful information provided during the reconsolidation window appears to update old fear memories, causing a lack of expression of fear responses.

Cross-species studies enable rapid translational discovery and produce the broadest impact when both mechanism and phenotype are consistent across organisms. We developed a knock-in mouse that biologically recapitulates a common human mutation in the gene for fatty acid amide hydrolase (FAAH) (C385A; rs324420), the primary catabolic enzyme for the endocannabinoid anandamide. This common polymorphism impacts the expression and activity of FAAH, thereby increasing anandamide levels. Here, we show that the genetic knock-in mouse and human variant allele carriers exhibit parallel alterations in biochemisty, neurocircuitry and behaviour. Specifically, there is reduced FAAH expression associated with the variant allele that selectively enhances fronto-amygdala connectivity and fear extinction learning, and decreases anxiety-like behaviours. These results suggest a gain of function in fear regulation and may indicate for whom and for what anxiety symptoms FAAH inhibitors or exposure-based therapies will be most efficacious, bridging an important translational gap between the mouse and human. Fatty acid amide hydrolase (FAAH) is a key regulator of endocannabinoid signalling. Here, the authors develop a knock-in mouse that recapitulates a common human mutation in the FAAH gene and demonstrate parallel neural and behavioural alterations across species, suggesting a gain-of-function in fear regulation.

The rational design of improved electrode–electrolyte interfaces (EEI) for energy storage is critically dependent on a molecular-level understanding of ionic interactions and nanoscale phenomena. The presence of non-redox active species at EEI has been shown to strongly influence Faradaic efficiency and long-term operational stability during energy storage processes. Herein, we achieve substantially higher performance and long-term stability of EEI prepared with highly dispersed discrete redox-active cluster anions (50 ng of pure ∼0.75 nm size molybdenum polyoxometalate (POM) anions on 25 μg (∼0.2 wt%) carbon nanotube (CNT) electrodes) by complete elimination of strongly coordinating non-redox species through ion soft landing (SL). Electron microscopy provides atomically resolved images of a uniform distribution of individual POM species soft landed directly on complex technologically relevant CNT electrodes. In this context, SL is established as a versatile approach for the controlled design of novel surfaces for both fundamental and applied research in energy storage. The design and understanding of electrode–electrolyte interfaces is important for the development of improved energy storage devices. Here, the authors study the controlled deposition of molybdenum polyoxometalate anions onto carbon nanotube electrodes, and show this can result in increased specific capacitance.

The only evidence-based behavioral treatment for anxiety and stress-related disorders involves desensitization techniques that rely on principles of extinction learning. However, 40% of patients do not respond to this treatment. Efforts have focused on individual differences in treatment response, but have not examined when, during development, such treatments may be most effective. We examined fear-extinction learning across development in mice and humans. Parallel behavioral studies revealed attenuated extinction learning during adolescence. Probing neural circuitry in mice revealed altered synaptic plasticity of prefrontal cortical regions implicated in suppression of fear responses across development. The results suggest a lack of synaptic plasticity in the prefrontal regions, during adolescence, is associated with blunted regulation of fear extinction. These findings provide insight into optimizing treatment outcomes for when, during development, exposure therapies may be most effective.

Herpesvirus capsids are assembled in the nucleus and undergo a two-step process to cross the nuclear envelope. Capsids bud into the inner nuclear membrane (INM) aided by the nuclear egress complex (NEC) proteins UL31/34. At that stage of egress, enveloped virions are found for a short time in the perinuclear space. In the second step of nuclear egress, perinuclear enveloped virions (PEVs) fuse with the outer nuclear membrane (ONM) delivering capsids into the cytoplasm. Once in the cytoplasm, capsids undergo re-envelopment in the Golgi/trans-Golgi apparatus producing mature virions. This second step of nuclear egress is known as de-envelopment and is the focus of this review. Compared with herpesvirus envelopment at the INM, much less is known about de-envelopment. We propose a model in which de-envelopment involves two phases: (i) fusion of the PEV membrane with the ONM and (ii) expansion of the fusion pore leading to release of the viral capsid into the cytoplasm. The first phase of de-envelopment, membrane fusion, involves four herpes simplex virus (HSV) proteins: gB, gH/gL, gK and UL20. gB is the viral fusion protein and appears to act to perturb membranes and promote fusion. gH/gL may also have similar properties and appears to be able to act in de-envelopment without gB. gK and UL20 negatively regulate these fusion proteins. In the second phase of de-envelopment (pore expansion and capsid release), an alpha-herpesvirus protein kinase, US3, acts to phosphorylate NEC proteins, which normally produce membrane curvature during envelopment. Phosphorylation of NEC proteins reverses tight membrane curvature, causing expansion of the membrane fusion pore and promoting release of capsids into the cytoplasm.

BackgroundA 4-year field study, on the adoption of a Biologically-Enhanced Agricultural Management (BEAM) protocol, in a cotton/cover-crop rotation in Turkey, was designed to observe “change-over-time” of soil organic carbon (SOC%) and total soil nitrogen (TSN%) at three soil profile depths (0–15 cm, 15–30 cm and 30–45 cm) while tracking farm productivity and profitability.MethodsBEAM systems employ regenerative practices: (a) no-till, (b) no, or reduced synthetic nutrient amendments, (c) continuous roots in the ground (commodity/cover), accompanied with an injection (in-furrow at planting) of an extract of beneficial microbes, from a Johnson-Su bioreactor. Three field nitrogen treatments: (1) BEAM+100% N (203 kg N ha−1); (2) BEAM+15% N (30.53 kg N ha−1); and (3) BEAM-0% N (No N applied), were implemented, on a 5.22-hectare plot, to assess the influence of BEAM protocols and nitrogen amendments, on SOC%, TSN%, cotton production, and profitability.ResultsThe SOC%, in the 0–15 cm soil profile demonstrated a significant increase from 0.39% SOC to 1.83% SOC, for a total increase of 1.44%, over the 4-year study period, (y = 0.3136x + 0.1206; r2 = 0.96; F(1,2) = 45.1616, p = 0.02143); The 15–30 cm soil profile demonstrated a non-significant loss of −0.23% SOC (y = −0.3161x + 0.156; r2 = 0.3183; F(1,2) = 0.9339, p = 0.4358), and the 30–45 cm soil profile exhibited a significant increase of 0.28% SOC; (y = 0.0477x + 0.4743; r2 = 0.9363; F(1,2) = 29.4005, p = 0.03237). Annual SOC cumulative increases of ~6.59 metric tons (t) carbon (C) ha−1yr−1, were observed, from 2019 to 2023, in the top 45 cm of the soil profile along with annual TSN increases of ~0.68 t N ha−1yr−1 in all three treatments. Cover-crop aboveground biomass increased annually in 2021, 2022 and 2023 from ~400 g, to ~692 g, to ~925 g dry biomass m−2yr−1 providing annual agroecosystem surface carbon accumulation of ~1.78 t C, ~3.08 t C and ~4.11 t C ha−1. Earthworm populations increased from zero earthworms m−2 in 2019 to ~100 earthworms m−2 in 2023. BEAM protocols also promoted: (a) farm input reductions of: 100% for herbicide, 56% for insecticide, 61% for diesel fuel, 85% for synthetic nitrogen fertilizer, and 100% for phosphorus fertilizer applications, reducing farm input costs ~$470 ha−1yr−1. Adoption of a BEAM regenerative agricultural management system, increased: (a) SOC (~6.59 t C ha−1yr−1); (b) C in the annual growth of cover-crop biomass (~4.12 t of C ha−1yr−1); (c) carbon in residual surface cover-crop plant residues from previous annual cover crops (~0.82 t C ha−1yr−1); and (d) C exported in cotton lint (~0.77 t C ha−1yr−1). Total C avoidance included: (a) reductions in fertilizer, pesticides and diesel inputs (~0.33 t C ha−1yr−1); and (b) reduction of C respiration from adoption of zero-till (~0.64 t C ha−1yr−1). Adoption of BEAM management, in this cotton/cover-crop agroecosystem, provided productive utilization, or avoidance of ~13.27 t of atmospheric C ha−1yr−1.

Human cytomegalovirus (HCMV) replicates in many diverse cell types in vivo , and entry into different cells involves distinct entry mechanisms and different envelope glycoproteins. HCMV glycoprotein gB is thought to act as the virus fusogen, apparently after being triggered by different gH/gL proteins that bind distinct cellular receptors or entry mediators. A trimer of gH/gL/gO is required for entry into all cell types, and entry into fibroblasts involves trimer binding to platelet-derived growth factor receptor alpha (PDGFRα). HCMV entry into biologically relevant epithelial and endothelial cells and monocyte-macrophages also requires a pentamer, gH/gL complexed with UL128, UL130, and UL131, and there is evidence that the pentamer binds unidentified receptors. We screened an epithelial cell cDNA library and identified the cell surface protein CD147, which increased entry of pentamer-expressing HCMV into HeLa cells but not entry of HCMV that lacked the pentamer. A panel of CD147-specific monoclonal antibodies inhibited HCMV entry into epithelial and endothelial cells, but not entry into fibroblasts. shRNA silencing of CD147 in endothelial cells inhibited HCMV entry but not entry into fibroblasts. CD147 colocalized with HCMV particles on cell surfaces and in endosomes. CD147 also promoted cell-cell fusion induced by expression of pentamer and gB in epithelial cells. However, soluble CD147 did not block HCMV entry and trimer and pentamer did not bind directly to CD147, supporting the hypothesis that CD147 acts indirectly through other proteins. CD147 represents the first HCMV entry mediator that specifically functions to promote entry of pentamer-expressing HCMV into epithelial and endothelial cells. IMPORTANCE Human cytomegalovirus infects nearly 80% of the world’s population and causes significant morbidity and mortality. The current method of treatment involves the use of antiviral agents that are prone to resistance and can be highly toxic to patients; currently, there is no vaccine against HCMV available. HCMV infections involve virus dissemination throughout the body, infecting a wide variety of tissues; however, the mechanism of spread is not well understood, particularly with regard to which cellular proteins are utilized by HCMV to establish infection. This report describes the characterization of a newly identified cellular molecule that affects HCMV entry into epithelial and endothelial cells. These results will lead to a better understanding of HCMV pathogenesis and have implications for the development of future therapeutics. Human cytomegalovirus infects nearly 80% of the world’s population and causes significant morbidity and mortality. The current method of treatment involves the use of antiviral agents that are prone to resistance and can be highly toxic to patients; currently, there is no vaccine against HCMV available. HCMV infections involve virus dissemination throughout the body, infecting a wide variety of tissues; however, the mechanism of spread is not well understood, particularly with regard to which cellular proteins are utilized by HCMV to establish infection. This report describes the characterization of a newly identified cellular molecule that affects HCMV entry into epithelial and endothelial cells. These results will lead to a better understanding of HCMV pathogenesis and have implications for the development of future therapeutics.

Human cytomegalovirus (HCMV) is a ubiquitous virus that is a major pathogen in newborns and immunocompromised or immunosuppressed patients. HCMV infects a wide variety of cell types using distinct entry pathways that involve different forms of the gH/gL glycoprotein: gH/gL/gO and gH/gL/UL128-131 as well as the viral fusion glycoprotein, gB. However, the minimal or core fusion machinery (sufficient for cell-cell fusion) is just gH/gL and gB. Here, we demonstrate that HCMV gB and gH/gL form a stable complex early after their synthesis and in the absence of other viral proteins. gH/gL can interact with gB mutants that are unable to mediate cell-cell fusion. gB-gH/gL complexes included as much as 16-50% of the total gH/gL in HCMV virus particles. In contrast, only small amounts of gH/gL/gO and gH/gL/UL128-131 complexes were found associated with gB. All herpesviruses express gB and gH/gL molecules and most models describing herpesvirus entry suggest that gH/gL interacts with gB to mediate membrane fusion, although there is no direct evidence for this. For herpes simplex virus (HSV-1) it has been suggested that after receptor binding gH/gL binds to gB either just before, or coincident with membrane fusion. Therefore, our results have major implications for these models, demonstrating that HCMV gB and gH/gL forms stable gB-gH/gL complexes that are incorporated virions without receptor binding or membrane fusion. Moreover, our data is the best support to date for the proposal that gH/gL interacts with gB.

Human cytomegalovirus (HCMV) forms two different membrane protein complexes, gH/gL/gO and gH/gL/UL128/UL130/UL131, that function in different cell types. gH/gL/gO appears to be important for HCMV entry into or spread between fibroblasts, processes that occur at neutral pH. We demonstrated that HCMV entry into epithelial and endothelial cells requires gH/gL/UL128-131 and involves endocytosis and low pH. A complex of all five HCMV proteins, gH, gL, UL128, UL130, and UL131, is the functionally important mediator of this entry pathway into epithelial/endothelial cells. Here, we report that expression of gH/gL/UL128-131 in ARPE-19 epithelial cells causes the cells to be resistant to HCMV infection. Another HCMV glycoprotein, gB, did not interfere, and expression of all five gH/gL/UL128-131 proteins was required for this interference. gH/gL/UL128-131 interference was at the stage of virus entry into cells rather than the initial adsorption onto cell surfaces or after-entry defects. By contrast, expression of gH/gL/UL128-131 in primary human fibroblasts did not block HCMV infection. Previously, interference by retrovirus and herpes-simplex-virus entry mediators resulted from sequestration or obstruction of receptors. We concluded that epithelial cells express gH/gL/UL128-131 receptors that mediate HCMV entry. Fibroblasts either lack the gH/gL/UL128-131 receptors, the receptors are more numerous, or fibroblasts express other functional receptors.