We have previously shown that an HIV vaccine regimen including three HIV-DNA immunizations and a single HIV-modified vaccinia virus Ankara (MVA) boost was safe and highly immunogenic in Swedish ...volunteers. A median 38 months after the first HIV-MVA vaccination, 24 volunteers received 10(8) plaque-forming units of HIV-MVA. The vaccine was well tolerated. Two weeks after this HIV-MVA vaccination, 18 (82%) of 22 evaluable vaccinees were interferon (IFN)-γ enzyme-linked immunospot (ELISpot) reactive: 18 to Gag and 10 (45%) to Env. A median minimal epitope count of 4 to Gag or Env was found in a subset of 10 vaccinees. Intracellular cytokine staining revealed CD4(+) and/or CD8(+) T cell responses in 23 (95%) of 24 vaccinees, 19 to Gag and 19 to Env. The frequency of HIV-specific CD4(+) and CD8(+) T cell responses was equally high (75%). A high proportion of CD4(+) and CD8(+) T cell responses to Gag was polyfunctional with production of three or more cytokines (40% and 60%, respectively). Of the Env-specific CD4(+) T cells 40% were polyfunctional. Strong lymphoproliferative responses to Aldrithiol-2 (AT-2)-treated subtype A, B, C, and A_E virus were demonstrable in 21 (95%) of 22 vaccinees. All vaccinees developed binding antibodies to Env and Gag. Neutralizing antibodies were detected in a peripheral blood mononuclear cell (PBMC)-based assay against subtype B and CRF01_AE viruses. The neutralizing antibody response rates were influenced by the vaccine dose and/or mode of delivery used at the previous HIV-MVA vaccination. Thus, a second late HIV-MVA boost induced strong and broad cellular immune responses and improved antibody responses. The data support further exploration of this vaccine concept.
Control of incipient invaders—established invasive species in the early stages of spreading—can be inhibited by incomplete knowledge of the species' habitat use. By identifying consistent habitat ...associations for incipient invaders early, control efforts can be more effective. Yet, because habitat associations are the result of multiscale processes, approaches are needed for integrating data collected across scales to identify them.
We employed a hierarchical, multiscale approach to identify oviposition habitat associations in the spotted lanternfly (Lycorma delicatula), an incipient invasive species of high concern in the United States. We targeted four oviposition habitat spatial scales most likely to be used by lanternflies and the spatial scales of explanatory habitat variables most easily used by managers to locate egg masses to control.
Spotted lanternflies exhibited oviposition habitat associations at the landscape, site, and tree scales. Overall, lanternflies oviposited more frequently at sites and on trees with low canopy cover in the surrounding landscape indicating higher use of human‐impacted habitat. Additionally, they oviposited more frequently on trees from the Acer genus and in the crowns of larger trees beyond the reach of managers without special equipment. The duration a site had been invaded had opposing effects on oviposition at the site and tree scales.
Despite high variation in the number of eggs per egg mass, no habitat variables explained this variation, suggesting more work is needed to understand spotted lanternfly reproductive output.
Synthesis and applications: Our results indicate that a multiscale approach is needed for spotted lanternfly control with unique strategies for locating egg masses at sites and on trees that vary in invasion duration. Specifically, at younger sites at the invasion edge, managers should expect patchy colonization of sites, yet when a site is colonized, many trees will have egg masses. Comparatively, older sites at the invasion core are more likely to have egg masses present, yet often at a lower density, which may make them difficult to find on individual trees. Based on our results, we assert that multiscale investigations of habitat associations would likely inform the control of other incipient invasive species as well.
Our results indicate that a multiscale approach is needed for spotted lanternfly control with unique strategies for locating egg masses at sites and on trees that vary in invasion duration. Specifically, at younger sites at the invasion edge, managers should expect patchy colonization of sites, yet when a site is colonized, many trees will have egg masses. Comparatively, older sites at the invasion core are more likely to have egg masses present, yet often at a lower density, which may make them difficult to find on individual trees. Based on our results, we assert that multiscale investigations of habitat associations would likely inform the control of other incipient invasive species as well.
Having valid and reliable resting energy expenditure (REE) estimations is crucial to establish reachable goals for dietary and exercise interventions. However, most of the REE predictive equations ...were developed some time ago and, as the body composition of the current population has changed, it is highly relevant to assess the validity of REE predictive equations in contemporary young adults. In addition, little is known about the role of sex and weight status on the validity of these predictive equations. Therefore, this study aimed to investigate the role of sex and weight status in congruent validity of REE predictive equations in young adults. A total of 132 young healthy adults (67.4% women, 18⁻26 years old) participated in the study. We measured REE by indirect calorimetry strictly following the standard procedures, and we compared it to 45 predictive equations. The most accurate equations were the following: (i) the Schofield and the "Food and Agriculture Organization of the United Nations/World Health Organization/United Nations" (FAO/WHO/UNU) equations in normal weight men; (ii) the Mifflin and FAO/WHO/UNU equations in normal weight women; (iii) the Livingston and Korth equations in overweight men; (iv) the Johnstone and Frankenfield equations in overweight women; (v) the Owen and Bernstein equations in obese men; and (vi) the Owen equation in obese women. In conclusion, the results of this study show that the best equation to estimate REE depends on sex and weight status in young healthy adults.
Atherosclerosis is driven by synergistic interactions between pathological, biomechanical, inflammatory, and lipid metabolic factors. Our previous studies demonstrated that absence of caveolin-1 ...(Cav1)/caveolae in hyperlipidemic mice strongly inhibits atherosclerosis, which was attributed to activation of endothelial nitric oxide (NO) synthase (eNOS) and increased production of NO and reduced inflammation and low-density lipoprotein trafficking. However, the contribution of eNOS activation and NO production in the athero-protection of Cav1 and the exact mechanisms by which Cav1/caveolae control the pathogenesis of diet-induced atherosclerosis are still not clear.
Triple-knockout mouse lacking expression of eNOS, Cav1, and Ldlr were generated to explore the role of NO production in Cav1-dependent athero-protective function. The effects of Cav1 on lipid trafficking, extracellular matrix remodeling, and vascular inflammation were studied both in vitro and in vivo with a mouse model of diet-induced atherosclerosis. The expression of Cav1 and distribution of caveolae regulated by flow were analyzed by immunofluorescence staining and transmission electron microscopy.
We found that absence of Cav1 significantly suppressed atherogenesis in Ldlr
eNOS
mice, demonstrating that athero-suppression is independent of increased NO production. Instead, we find that the absence of Cav1/caveolae inhibited low-density lipoprotein transport across the endothelium and proatherogenic fibronectin deposition and disturbed flow-mediated endothelial cell inflammation. Consistent with the idea that Cav1/caveolae may play a role in early flow-dependent inflammatory priming, distinct patterns of Cav1 expression and caveolae distribution were observed in athero-prone and athero-resistant areas of the aortic arch even in wild-type mice.
These findings support a role for Cav1/caveolae as a central regulator of atherosclerosis that links biomechanical, metabolic, and inflammatory pathways independently of endothelial eNOS activation and NO production.
Abstract
Exercise modulates both brown adipose tissue (BAT) metabolism and white adipose tissue (WAT) browning in murine models. Whether this is true in humans, however, has remained unknown. An ...unblinded randomized controlled trial (ClinicalTrials.gov ID: NCT02365129) was therefore conducted to study the effects of a 24-week supervised exercise intervention, combining endurance and resistance training, on BAT volume and activity (primary outcome). The study was carried out in the Sport and Health University Research Institute and the Virgen de las Nieves University Hospital of the University of Granada (Spain). One hundred and forty-five young sedentary adults were assigned to either (i) a control group (no exercise,
n
= 54), (ii) a moderate intensity exercise group (MOD-EX, n = 48), or (iii) a vigorous intensity exercise group (VIG-EX
n
= 43) by unrestricted randomization. No relevant adverse events were recorded. 97 participants (34 men, 63 women) were included in the final analysis (Control;
n
= 35, MOD-EX;
n
= 31, and VIG-EX;
n
= 31). We observed no changes in BAT volume (Δ Control: −22.2 ± 52.6 ml; Δ MOD-EX: −15.5 ± 62.1 ml, Δ VIG-EX: −6.8 ± 66.4 ml; P = 0.771) or
18
F-fluorodeoxyglucose uptake (SUVpeak Δ Control: −2.6 ± 3.1 ml; Δ MOD-EX: −1.2 ± 4.8, Δ VIG-EX: −2.2 ± 5.1;
p
= 0.476) in either the control or the exercise groups. Thus, we did not find any evidence of an exercise-induced change on BAT volume or activity in young sedentary adults.
Although magnesium has been shown to prevent vascular calcification in vitro, controlled in vivo studies in uremic animal models are limited. To determine whether dietary magnesium supplementation ...protects against the development of vascular calcification, 5/6 nephrectomized Wistar rats were fed diets with different magnesium content increasing from 0.1 to 1.1%. In one study we analyzed bone specimens from rats fed 0.1%, 0.3%, and 0.6% magnesium diets, and in another study we evaluated the effect of intraperitoneal magnesium on vascular calcification in 5/6 nephrectomized rats. The effects of magnesium on established vascular calcification were also evaluated in uremic rats fed on diets with either normal (0.1%) or moderately increased magnesium (0.6%) content. The increase in dietary magnesium resulted in a marked reduction in vascular calcification, together with improved mineral metabolism and renal function. Moderately elevated dietary magnesium (0.3%), but not high dietary magnesium (0.6%), improved bone homeostasis as compared to basal dietary magnesium (0.1%). Results of our study also suggested that the protective effect of magnesium on vascular calcification was not limited to its action as an intestinal phosphate binder since magnesium administered intraperitoneally also decreased vascular calcification. Oral magnesium supplementation also reduced blood pressure in uremic rats, and in vitro medium magnesium decreased BMP-2 and p65–NF-κB in TNF-α–treated human umbilical vein endothelial cells. Finally, in uremic rats with established vascular calcification, increasing dietary magnesium from 0.1% magnesium to 0.6% reduced the mortality rate from 52% to 28%, which was associated with reduced vascular calcification. Thus, increasing dietary magnesium reduced both vascular calcification and mortality in uremic rats.
Introduction The intersection between perinatal mental health and the coronavirus disease 2019 (COVID‐19) pandemic remains of significant public health importance. The current study examined the ...emotional and financial well‐being and predictors of elevated depressive symptoms among pregnant women during the COVID‐19 pandemic. Methods This online survey was conducted with 2118 women ≥18 years old who were pregnant at the time of the survey and living in the United States or Puerto Rico. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale, with scores ≥10 indicative of elevated depressive symptoms. The final logistic regression model included housing insecurity, financial distress, COVID‐19 diagnosis, exposure to COVID‐19, and demographic covariates. Results More than half the sample (53.8%) had elevated depressive symptoms. In logistic regression analyses, the odds of having elevated depressive symptoms were significantly higher for participants reporting housing insecurity (adjusted odds ratio aOR, 1.56; 95% CI, 1.22‐2.01), financial distress (aOR, 1.57; 95% CI, 1.17‐2.12), COVID‐19 diagnosis (aOR, 2.53; 95% CI, 1.53‐4.17), and COVID‐19 exposure (aOR, 1.41; 95% CI, 1.07‐1.86), after adjusting for covariates. The association of elevated depressive symptoms with housing insecurity was especially strong among those who experienced COVID‐19 (aOR, 6.04; 95% CI, 2.15‐17.0). Discussion Our findings are consistent with previous literature revealing that diagnosis, exposure, concerns about family, and effects on financial stability were related to depressive symptoms during the pandemic. The relationships between financial and housing concerns with elevated depressive symptoms, independent of concerns about infection in family members, suggest that there may be direct and indirect effects of the pandemic on mental health.
Autoantibodies against leucine-rich glioma inactivated 1 (LGI1) are found in patients with limbic encephalitis and focal seizures. Here, we generate patient-derived monoclonal antibodies (mAbs) ...against LGI1. We explore their sequences and binding characteristics, plus their pathogenic potential using transfected HEK293T cells, rodent neuronal preparations, and behavioural and electrophysiological assessments in vivo after mAb injections into the rodent hippocampus. In live cell-based assays, LGI1 epitope recognition was examined with patient sera (n = 31), CSFs (n = 11), longitudinal serum samples (n = 15), and using mAbs (n = 14) generated from peripheral B cells of two patients. All sera and 9/11 CSFs bound both the leucine-rich repeat (LRR) and the epitempin repeat (EPTP) domains of LGI1, with stable ratios of LRR:EPTP antibody levels over time. By contrast, the mAbs derived from both patients recognized either the LRR or EPTP domain. mAbs against both domain specificities showed varied binding strengths, and marked genetic heterogeneity, with high mutation frequencies. LRR-specific mAbs recognized LGI1 docked to its interaction partners, ADAM22 and ADAM23, bound to rodent brain sections, and induced internalization of the LGI1-ADAM22/23 complex in both HEK293T cells and live hippocampal neurons. By contrast, few EPTP-specific mAbs bound to rodent brain sections or ADAM22/23-docked LGI1, but all inhibited the docking of LGI1 to ADAM22/23. After intrahippocampal injection, and by contrast to the LRR-directed mAbs, the EPTP-directed mAbs showed far less avid binding to brain tissue and were consistently detected in the serum. Post-injection, both domain-specific mAbs abrogated long-term potentiation induction, and LRR-directed antibodies with higher binding strengths induced memory impairment. Taken together, two largely dichotomous populations of LGI1 mAbs with distinct domain binding characteristics exist in the affinity matured peripheral autoantigen-specific memory pools of individuals, both of which have pathogenic potential. In human autoantibody-mediated diseases, the detailed characterization of patient mAbs provides a valuable method to dissect the molecular mechanisms within polyclonal populations.
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