Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
3,180
result(s) for
"Jackson, Kenneth"
Sort by:
T cell recognition of Mycobacterium tuberculosis peptides presented by HLA-E derived from infected human cells
HLA-E is a non-conventional MHC Class I molecule that has been recently demonstrated to present pathogen-derived ligands, resulting in the TCR-dependent activation of αβ CD8+ T cells. The goal of this study was to characterize the ligandome displayed by HLA-E following infection with Mycobacterium tuberculosis (Mtb) using an in-depth mass spectrometry approach. Here we identified 28 Mtb ligands derived from 13 different source proteins, including the Esx family of proteins. When tested for activity with CD8+ T cells isolated from sixteen donors, nine of the ligands elicited an IFN-γ response from at least one donor, with fourteen of 16 donors responding to the Rv0634A19-29 peptide. Further evaluation of this immunodominant peptide response confirmed HLA-E restriction and the presence of Rv0634A19-29-reactive CD8+ T cells in the peripheral blood of human donors. The identification of an Mtb HLA-E ligand that is commonly recognized may provide a target for a non-traditional vaccine strategy.
Journal Article
Social approach and social vigilance are differentially regulated by oxytocin receptors in the nucleus accumbens
Oxytocin is currently being considered as a novel therapeutic for anxiety disorders due to its ability to promote affiliative behaviors. In the nucleus accumbens (NAc) activation of oxytocin receptors (OTR) promotes social approach (time spent near an unfamiliar individual). Here, we show that stressful social experiences reduce the expression of NAc OTR mRNA, coinciding with decreases in social approach. Social stressors also increase social vigilance, characterized as orienting to an unfamiliar individual without approaching. Vigilance is a key component of behavioral inhibition, a personality trait that is a risk factor for anxiety disorders. To understand whether NAc OTR can modulate both social approach and vigilance, we use pharmacological approaches to assess the impact of activation or inhibition of NAc OTR downstream pathways on these behaviors. First, we show that in unstressed male and female California mice, inhibition of OTR by an unbiased antagonist (L-368,899) reduces social approach but does not induce social vigilance. Next, we show that infusion of Atosiban, an OTR-Gq antagonist/OTR-Gi agonist, has the same effect in unstressed females. Finally, we show that Carbetocin, a biased OTR-Gq agonist, increases social approach in stressed females while simultaneously inhibiting social vigilance. Taken together these data suggest that OTR in the NAc differentially modulate social approach and social vigilance, primarily through an OTR-Gq mechanism. Importantly, pharmacological inhibition of OTR alone is insufficient to induce vigilance in unstressed mice, suggesting that mechanisms modulating social approach may be distinct from mechanisms modulating social vigilance.
Journal Article
Extrahypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance
Oxytocin increases the salience of both positive and negative social contexts and it is thought that these diverse actions on behavior are mediated in part through circuit-specific action. This hypothesis is based primarily on manipulations of oxytocin receptor function, leaving open the question of whether different populations of oxytocin neurons mediate different effects on behavior. Here we inhibited oxytocin synthesis in a stress-sensitive population of oxytocin neurons specifically within the medioventral bed nucleus of the stria terminalis (BNSTmv). Oxytocin knockdown prevented social stress-induced increases in social vigilance and decreases in social approach. Viral tracing of BNSTmv oxytocin neurons revealed fibers in regions controlling defensive behaviors, including lateral hypothalamus, anterior hypothalamus, and anteromedial BNST (BNSTam). Oxytocin infusion into BNSTam in stress naïve mice increased social vigilance and reduced social approach. These results show that a population of extrahypothalamic oxytocin neurons plays a key role in controlling stress-induced social anxiety behaviors.
Journal Article
Oxidative Stress and Inflammation in Renal Patients and Healthy Subjects
The first goal of this study was to measure the oxidative stress (OS) and relate it to lipoprotein variables in 35 renal patients before dialysis (CKD), 37 on hemodialysis (HD) and 63 healthy subjects. The method for OS was based on the ratio of cholesteryl esters (CE) containing C18/C16 fatty acids (R2) measured by gas chromatography (GC) which is a simple, direct, rapid and reliable procedure. The second goal was to investigate and identify a triacylglycerol peak on GC, referred to as TG48 (48 represents the sum of the three fatty acids carbon chain lengths) which was markedly increased in renal patients compared to healthy controls. We measured TG48 in patients and controls. Mass spectrometry (MS) and MS twice in tandem were used to analyze the fatty acid composition of TG48. MS showed that TG48 was abundant in saturated fatty acids (SFAs) that were known for their pro-inflammatory property. TG48 was significantly and inversely correlated with OS. Renal patients were characterized by higher OS and inflammation than healthy subjects. Inflammation correlated strongly with TG, VLDL-cholesterol, apolipoprotein (apo) C-III and apoC-III bound to apoB-containing lipoproteins, but not with either total cholesterol or LDL-cholesterol.In conclusion, we have discovered a new inflammatory factor, TG48. It is characterized with TG rich in saturated fatty acids. Renal patients have increased TG48 than healthy controls.
Journal Article
Influence of insurance type on rate and type of initial concussion-related medical visits among youth
Background
A growing number of studies report increased concussion-related health care utilization in recent years, but factors impacting care-seeking behaviors among youth following a concussion are not well described. This study aimed to evaluate the influence of insurance type on the rate and type of initial concussion visits and the time from injury to the initial visit in youth.
Methods
We extracted and analyzed initial concussion-related medical visits for youth ages 10 to 17 from electronic health records. Patients must have visited Nationwide Children’s Hospital’s (NCH) concussion clinic at least once between 7/1/2012 and 12/31/2017. We evaluated the trends and patterns of initial concussion visits across the study period using regression analyses.
Results
Of 4955 unique concussion visits included, 60.1% were males, 80.5% were white, and 69.5% were paid by private insurance. Patients’ average age was 13.9 years (SD = 3.7). The rate of the initial concussion visits per 10,000 NCH visits was consistently higher in privately insured than publicly insured youth throughout the study period (
P
< .0001). Privately insured youth had greater odds of initial concussion visits to sports medicine clinics (AOR = 1.45, 95% CI = 1.20, 1.76) but lower odds of initial concussion visits to the ED/urgent care (AOR = 0.74, 95% CI = 0.60, 0.90) than publicly insured youth. Days from injury to initial concussion visit significantly decreased among both insurance types throughout the study (
P
< .0001), with a greater decrease observed in publicly insured than privately insured youth (
P
= .011).
Conclusions
Results on the differences in the rate, type, and time of initial concussion-related visits may help inform more efficient care of concussion among youth with different types of insurance.
Journal Article
Intraamniotic Zika virus inoculation of pregnant rhesus macaques produces fetal neurologic disease
Zika virus (ZIKV) infection of pregnant women can cause fetal microcephaly and other neurologic defects. We describe the development of a non-human primate model to better understand fetal pathogenesis. To reliably induce fetal infection at defined times, four pregnant rhesus macaques are inoculated intravenously and intraamniotically with ZIKV at gestational day (GD) 41, 50, 64, or 90, corresponding to first and second trimester of gestation. The GD41-inoculated animal, experiencing fetal death 7 days later, has high virus levels in fetal and placental tissues, implicating ZIKV as cause of death. The other three fetuses are carried to near term and euthanized; while none display gross microcephaly, all show ZIKV RNA in many tissues, especially in the brain, which exhibits calcifications and reduced neural precursor cells. Given that this model consistently recapitulates neurologic defects of human congenital Zika syndrome, it is highly relevant to unravel determinants of fetal neuropathogenesis and to explore interventions.
Zika virus infection of pregnant women can cause congenital brain defects. Here, Coffey et al. establish a pregnant rhesus macaque model, using intravenous and intraamniotic route of infection, that reliably reproduces fetal neurologic defects of congenital Zika syndrome in humans.
Journal Article
Emergent s -Wave Interactions between Identical Fermions in Quasi-One-Dimensional Geometries
Orbital degrees of freedom play an essential role in metals, semiconductors, and strongly confined electronic systems. Experiments with ultracold atoms have used highly anisotropic confinement to explore low-dimensional physics, but they typically eliminate orbital degrees of freedom by preparing atoms in the motional ground states of the strongly confined directions. Here, we prepare multiband systems of spin-polarized fermionic potassium (K40) in the quasi-one-dimensional (q1D) regime and quantify the strength of atom-atom correlations using radio-frequency spectroscopy. The activation of orbital degrees of freedom leads to a new phenomenon: a low-energy scattering channel that has even particle-exchange parity along the q1D axis, as if the underlying interactions weres-wave. This emergent exchange symmetry is enabled by orbital singlet wave functions in the strongly confined directions, which also confer high-momentum components to low-energy q1D collisions. We measure both the q1D odd-wave and even-wave “contact” parameters for the first time and compare them to theoretical predictions of one-dimensional many-body models. The strength and spatial symmetry of interactions are tuned by ap-wave Feshbach resonance and by transverse confinement strength. Near resonance, the even-wave contact approaches its theoretical unitary value, whereas the maximum observed odd-wave contact remains several orders of magnitude below its unitary limit. Low-energy scattering channels of multi-orbital systems, such as those found here, may provide new routes for the exploration of universal many-body phenomena.
Journal Article