The hippocampus provides the brain's memory system with a subset of neurons holding a map-like representation of each environment experienced. We found in mice that optogenetic silencing those ...neurons active in an environment unmasked a subset of quiet neurons, enabling the emergence of an alternative map. When applied in a cocaine-paired environment, this intervention neutralized an otherwise long-lasting drug-place preference, showing that recoding a spatial memory engram can alleviate associated maladaptive behavior.
Interleukin-21 (IL-21) has been linked with the generation of virus-specific memory CD8+ T cells following acute infection with HIV-1 and reduced exhaustion of CD8+ T cells. IL-21 has also been ...implicated in the promotion of CD8+ T-cell effector functions during viral infection. Little is known about the expression of interleukin-21 receptor (IL-21R) during HIV-1 infection or its role in HIV-1-specific CD8+ T-cell maintenance and subsequent viral control.
We compared levels of IL-21R expression on total and memory subsets of CD8+ T cells from HIV-1-negative and HIV-1-positive donors. We also measured IL-21R on antigen-specific CD8+ T cells in volunteers who were positive for HIV-1 and had cytomegalovirus-responding T cells. Finally, we quantified plasma IL-21 in treatment-naive HIV-1-positive individuals and compared this with IL-21R expression.
IL-21R expression was significantly higher on CD8+ T cells (P = 0.0256), and on central memory (P = 0.0055) and effector memory (P = 0.0487) CD8+ T-cell subsets from HIV-1-positive individuals relative to HIV-1-negative individuals. For those infected with HIV-1, the levels of IL-21R expression on HIV-1-specific CD8+ T cells correlated significantly with visit viral load (r = 0.6667, P = 0.0152, n = 13) and inversely correlated with plasma IL-21 (r = -0.6273, P = 0.0440, n = 11). Lastly, CD8+ T cells from individuals with lower set point viral load who demonstrated better viral control had the lowest levels of IL-21R expression and highest levels of plasma IL-21.
Our data demonstrates significant associations between IL-21R expression on peripheral CD8+ T cells and viral load, as well as disease trajectory. This suggests that the IL-21 receptor could be a novel marker of CD8+ T-cell dysfunction during HIV-1 infection.
Despite the fact that much of the global microbial biosphere is believed to exist in high pressure environments, the effects of hydrostatic pressure on microbial physiology remain poorly understood. ...We use a genome-wide screening approach, combined with a novel high-throughput high-pressure cell culture method, to investigate the effects of hydrostatic pressure on microbial physiology in vivo. The Keio collection of single-gene deletion mutants in Escherichia coli K-12 was screened for growth at a range of pressures from 0.1 MPa to 60 MPa. This led to the identification of 6 genes, rodZ, holC, priA, dnaT, dedD and tatC, whose products were required for growth at 30 MPa and a further 3 genes, tolB, rffT and iscS, whose products were required for growth at 40 MPa. Our results support the view that the effects of pressure on cell physiology are pleiotropic, with DNA replication, cell division, the cytoskeleton and cell envelope physiology all being potential failure points for cell physiology during growth at elevated pressure.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
IFN-γ is a key cytokine of innate and adaptive immunity. It is important to understand temporal changes in IFN-γ production and how these changes relate to the role of IFN-γ in diverse models of ...infectious and autoimmune disease, making the ability to monitor and track IFN-γ production in vivo of a substantial benefit. IFN-γ ELISPOTs have been a central methodology to measure T cell immunity for many years. In this study, we add the capacity to analyze IFN-γ responses with high sensitivity and specificity, longitudinally, in vitro and in vivo. This allows the refinement of experimental protocols because immunity can be tracked in real-time through a longitudinal approach. We have generated a novel murine IFN-γ reporter transgenic model that allows IFN-γ production to be visualized and quantified in vitro and in vivo as bioluminescence using an imaging system. At baseline, in the absence of an inflammatory stimulus, IFN-γ signal from lymphoid tissue is detectable in vivo. Reporter transgenics are used in this study to track the IFN-γ response to
infection in the lung over time in vivo. The longitudinal development of the adaptive T cell immunity following immunization with Ag is identified from day 7 in vivo. Finally, we show that we are able to use this reporter transgenic to follow the onset of autoimmune T cell activation after regulatory T cell depletion in an established model of systemic autoimmunity. This IFN-γ reporter transgenic, termed "Gammaglow," offers a valuable new modality for tracking IFN-γ immunity, noninvasively and longitudinally over time.
Individual differences in dimensions of impulsivity personality including disinhibition and sensation seeking modulate approach responses to reinforcing stimuli, such as drugs and money. The current ...study examined the effects of monetary incentive on both behavioral performance and electrophysiological activity among individuals varying in disinhibition and sensation seeking. The monetary incentive delay (MID) task was completed under electroencephalogram (EEG) recording. Behavioral data showed that higher disinhibition and sensation-seeking were associated with lower performance accuracy. Event-related potential (ERP) data showed that high reinforcement cues elicited a larger late positive component (LPC) than other conditions among high disinhibition participants, indicating its strong emotional influence. Additionally, in the neutral incentive condition, the feedback-related negativity (FRN) elicited by correct outcomes was larger than that elicited by incorrect outcomes in the high disinhibition group only. This novel finding indicates that high disinhibition participants were less likely to expect correct outcomes compared to incorrect outcomes in the neutral incentive condition. Finally, the P3 component elicited by outcome presentation showed an interaction between two impulsivity dimensions; when disinhibition level was low, the P3 was larger among high than low sensation seeking participants.
•MID task accuracy decreased as a function of two dimensions of impulsivity.•Impulsivity biased brain responses to reinforcing stimuli at as early as 200ms.•Under no incentive, an atypical FRN was seen in people with high disinhibition.•The P3 was larger in high sensation seeking people when disinhibition was low.
Individuals infected with HIV display varying rates of viral control and disease progression, with a small percentage of individuals being able to spontaneously control infection in the absence of ...treatment. In attempting to define the correlates associated with natural protection against HIV, extreme heterogeneity in the datasets generated from systems methodologies can be further complicated by the inherent variability encountered at the population, individual, cellular and molecular levels. Furthermore, such studies have been limited by the paucity of well-characterised samples and linked epidemiological data, including duration of infection and clinical outcomes. To address this, we selected 10 volunteers who rapidly and persistently controlled HIV, and 10 volunteers each, from two control groups who failed to control (based on set point viral loads) from an acute and early HIV prospective cohort from East and Southern Africa. A propensity score matching approach was applied to control for the influence of five factors (age, risk group, virus subtype, gender, and country) known to influence disease progression on causal observations. Fifty-two plasma proteins were assessed at two timepoints in the 1st year of infection. We independently confirmed factors known to influence disease progression such as the B
57 HLA Class I allele, and infecting virus Subtype. We demonstrated associations between circulating levels of MIP-1α and IL-17C, and the ability to control infection. IL-17C has not been described previously within the context of HIV control, making it an interesting target for future studies to understand HIV infection and transmission. An in-depth systems analysis is now underway to fully characterise host, viral and immunological factors contributing to control.
To identify technical factors associated with nonunion after operative treatment with lateral locked plating.
Retrospective cohort study.
Ten Level I trauma centers.
Adult patients with supracondylar ...distal femur fractures (OTA/AO type 33A or C) treated with lateral locked plating from 2010 through 2019.
Surgery for nonunion stratified by risk for nonunion.
The cohort included 615 patients with supracondylar distal femur fractures. The median patient age was 61 years old (interquartile range: 46 -72years) and 375 (61%) were female. Observed were nonunion rates of 2% in a low risk of nonunion group (n = 129), 4% in a medium-risk group (n = 333), and 14% in a high-risk group (n = 153). Varus malreduction with an anatomic lateral distal femoral angle greater than 84 degrees, was associated with double the odds of nonunion compared to those without such varus odds ratio, 2.1; 95% confidence interval (CI), 1.1-4.2; P = 0.03. Malreduction by medial translation of the articular block increased the odds of nonunion, with 30% increased odds per 4 mm of medial translation (95% CI, 1.0-1.6; P = 0.03). Working length increased the odds of nonunion in the medium risk group, with an 18% increase in nonunion per 10-mm increase in working length (95% CI, 1.0-1.4; P = 0.01). Increased proximal screw density was protective against nonunion (odds ratio, 0.71; 95% CI, 0.53-0.92; P = 0.02) but yielded lower mRUST scores with each 0.1 increase in screw density associated with a 0.4-point lower mRUST (95% CI, -0.55 to -0.15; P < 0.001). Lateral plate length and type of plate material were not associated with nonunion. ( P > 0.05).
Malreduction is a surgeon-controlled variable associated with nonunion after lateral locked plating of supracondylar distal femur fractures. Longer working lengths were associated with nonunion, suggesting that bridge plating may be less likely to succeed for longer fractures.
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
We have developed a modular system for high-resolution microscopy at high hydrostatic pressure. The system consists of a pressurized cell of volume approximately 100 microl, a temperature controlled ...holder, a ram, and a piston. We have made each of these components in several versions which can be interchanged to allow a wide range of applications. Here, we report two pressure cells with pressure ranges 0.1-700 MPa and 0.1-100 MPa, which can be combined with hollow or solid rams and pistons. Our system is designed to work with fluorescent samples (using a confocal or epifluorescence microscope), but also allows for transmitted light microscopy via the hollow ram and piston. The system allows precise control of pressure and temperature (-20 to 70 degrees C), as well as rapid pressure quenching. We demonstrate its performance and versatility with two applications: time-resolved imaging of colloidal phase transitions caused by pressure changes between 0.1 and 100 MPa, and imaging the growth of Escherichia coli bacteria at 50 MPa. We also show that the isotropic-nematic phase transition of pentyl-cyanobiphenyl (5CB) liquid crystal provides a simple, convenient, and accurate method for calibrating pressure in the range 0.1-200 MPa.
To explore the individual dento-gingival manipulative procedures that together lead to the placement of a restoration and to estimate the associated intensity of bacteraemia.
Healthy children ...receiving dental treatment under general anaesthesia provided blood samples 30 seconds after one of four dento-gingival manipulative procedures: 1. Placement of rubber dam, 2. Use of the high speed drill, 3. Use of the slow speed drill, and 4. Placement of matrix band and wedge. Blood cultures were processed to give the percentage prevalence of bacteraemia, the intensity of organisms per millilitre of blood and the identity of the organisms cultured.
A total of 257 children were recruited to the study. The percentage positive prevalence of blood cultures was baseline--9.3%, rubber dam placement--31.4%, slow drill--12.2%, fast drill--4.3%, and matrix band and wedge--32.1%. The intensity of bacteraemia was baseline--1.2 cfu, rubber dam placement--1,962 cfu, slow drill--0.3 cfu, fast drill--1.9 cfu, matrix band and wedge--4.8 cfu.
These data indicate that dento-gingival manipulative procedures comprising a simple dental restoration can lead to a bacteraemia comparable to that from dental extractions. It is suggested that these data may indicate the need for antibiotic prophylaxis for some aspects of conservative dentistry.
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