Obesity is characterized by an accumulation of macrophages in adipose, some of which form distinct crown-like structures (CLS) around fat cells. While multiple discrete adipose tissue macrophage ...(ATM) subsets are thought to exist, their respective effects on adipose tissue, and the transcriptional mechanisms that underlie the functional differences between ATM subsets, are not well understood. We report that obese fat tissue of mice and humans contain multiple distinct populations of ATMs with unique tissue distributions, transcriptomes, chromatin landscapes, and functions. Mouse Ly6c ATMs reside outside of CLS and are adipogenic, while CD9 ATMs reside within CLS, are lipid-laden, and are proinflammatory. Adoptive transfer of Ly6c ATMs into lean mice activates gene programs typical of normal adipocyte physiology. By contrast, adoptive transfer of CD9 ATMs drives gene expression that is characteristic of obesity. Importantly, human adipose tissue contains similar ATM populations, including lipid-laden CD9 ATMs that increase with body mass. These results provide a higher resolution of the cellular and functional heterogeneity within ATMs and provide a framework within which to develop new immune-directed therapies for the treatment of obesity and related sequela.
Non-neutralizing IgG to the V1V2 loop of HIV-1 gp120 correlates with a decreased risk of HIV-1 infection but the mechanism of protection remains unknown. This V1V2 IgG correlate was identified in ...RV144 Thai trial vaccine recipients, who were primed with a canarypox vector expressing membrane-bound gp120 (vCP1521) and boosted with vCP1521 plus a mixture gp120 proteins from clade B and clade CRF01_AE (B/E gp120). We sought to determine whether the mechanism of vaccine protection might involve antibody-dependent complement activation. Complement activation was measured as a function of complement component C3d deposition on V1V2-coated beads in the presence of RV144 sera. Variable levels of complement activation were detected two weeks post final boosting in RV144, which is when the V1V2 IgG correlate was identified. The magnitude of complement activation correlated with V1V2-specific serum IgG and was stronger and more common in RV144 than in HIV-1 infected individuals and two related HIV-1 vaccine trials, VAX003 and VAX004, where no protection was seen. After adjusting for gp120 IgA, V1V2 IgG, gender, and risk score, complement activation by case-control plasmas from RV144 correlated inversely with a reduced risk of HIV-1 infection, with odds ratio for positive versus negative response to TH023-V1V2 0.42 (95% CI 0.18 to 0.99, p = 0.048) and to A244-V1V2 0.49 (95% CI 0.21 to 1.10, p = 0.085). These results suggest that complement activity may have contributed in part to modest protection against the acquisition of HIV-1 infection seen in the RV144 trial.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Zika virus (ZIKV) is a flavivirus that is responsible for the current epidemic in Brazil and the Americas. ZIKV has been causally associated with fetal microcephaly, intrauterine growth restriction, ...and other birth defects in both humans and mice. The rapid development of a safe and effective ZIKV vaccine is a global health priority, but very little is currently known about ZIKV immunology and mechanisms of immune protection. Here we show that a single immunization with a plasmid DNA vaccine or a purified inactivated virus vaccine provides complete protection in susceptible mice against challenge with a strain of ZIKV involved in the outbreak in northeast Brazil. This ZIKV strain has recently been shown to cross the placenta and to induce fetal microcephaly and other congenital malformations in mice. We produced DNA vaccines expressing ZIKV pre-membrane and envelope (prM-Env), as well as a series of deletion mutants. The prM-Env DNA vaccine, but not the deletion mutants, afforded complete protection against ZIKV, as measured by absence of detectable viraemia following challenge, and protective efficacy correlated with Env-specific antibody titers. Adoptive transfer of purified IgG from vaccinated mice conferred passive protection, and depletion of CD4 and CD8 T lymphocytes in vaccinated mice did not abrogate this protection. These data demonstrate that protection against ZIKV challenge can be achieved by single-shot subunit and inactivated virus vaccines in mice and that Env-specific antibody titers represent key immunologic correlates of protection. Our findings suggest that the development of a ZIKV vaccine for humans is likely to be achievable.
In this randomized comparison of stenting and endarterectomy as treatment for carotid-artery stenosis, there was no significant difference in the rate of the composite primary end point of stroke, ...myocardial infarction, or death (7.2% and 6.8%, respectively; P=0.51). Stroke was more common with carotid-artery stenting than carotid endarterectomy; myocardial infarction was more common with carotid endarterectomy. The 4-year rate of stroke or death was 6.4% for carotid-artery stenting and 4.7% for carotid endarterectomy (P=0.03).
In this randomized comparison of stenting and endarterectomy as treatment for carotid-artery stenosis, there was no significant difference in the rate of the composite primary end point of stroke, myocardial infarction, or death (7.2% and 6.8%, respectively).
Carotid-artery atherosclerosis is an important cause of ischemic stroke.
1
Carotid endarterectomy has been established as effective treatment for both symptomatic patients and asymptomatic patients.
2
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4
Carotid-artery stenting is another option for treatment. The results of randomized trials comparing carotid-artery stenting and carotid endarterectomy for use in symptomatic patients are conflicting.
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7
The primary aim of the Carotid Revascularization Endarterectomy vs. Stenting Trial (CREST) was to compare the outcomes of carotid-artery stenting with those of carotid endarterectomy among patients with symptomatic or asymptomatic extracranial carotid stenosis.
Methods
Study Design
CREST is a randomized, controlled trial with blinded end-point adjudication. Ethics review . . .
Changes in motor development provide children with new learning opportunities to interact with objects, their environment, and with caregivers. Previous research finds that both gross and fine motor ...skills are predictive of later language outcomes across early infancy and childhood. However, gross and fine motor skills afford different types of interactions. Thus, gross and fine motor skills may potentially differ in the developmental trajectories through which cascading changes in language may occur. The aim of the present study was to investigate whether there are differences in the predictive capacities of gross and fine motor skills toward language outcomes across infancy and early childhood in typical development.
A systematic review of existing literature on motor-language cascades was conducted in across studies measuring gross and/or fine motor and language development in children from 0 to 5 years old. Searches were conducted in PsycINFO, PubMed, and MEDLINE. Keywords used were a combination of "gross motor," "fine motor," "motor performance," "motor development," or "psychomotor development" along with "language," "language development," or "communication skills." Two independent reviewers screened abstracts and full texts based on inclusion and exclusion criteria.
A total of 23 articles were retained. Of these, seven studies measured only gross motor skills, four studies measured only fine motor skills, and 12 studies measured both gross and fine motor skills in the same study. Studies used a variety of measures to assess gross motor skills, fine motor skills, and language development (e.g., parent report, in lab observations, standardized assessment), and findings varied based on analyses used. Results demonstrated that both gross and fine motor skills are related to language outcomes, but due to a smaller amount of studies testing fine motor skills, conclusions regarding whether one is more important for language outcomes cannot be drawn.
We conclude that both gross and fine motor skills help foster language development from infancy to early childhood. Limitations regarding current knowledge regarding the mechanisms that underlie motor-language cascades are discussed, as well as the need for more studies on fine motor skills.
The aggregation of molecules plays an important role in determining their function. Electron microscopy and other methods can only characterize the variation of microstructure, but are not capable of ...monitoring conformational changes. These techniques are also complicated, expensive and time-consuming. Here, we demonstrate a simple method to monitor in-situ and in real-time the conformational change of (R)-1,1'-binaphthyl-based polymers during the aggregation process using circular dichroism. Based on results from molecular dynamics simulations and experimental circular dichroism measurements, polymers with "open" binaphthyl rings are found to show stronger aggregation-annihilated circular dichroism effects, with more negative torsion angles between the two naphthalene rings. In contrast, the polymers with "locked" rings show a more restrained aggregation-annihilated circular dichroism effect, with only a slight change of torsion angle. This work provides an approach to monitor molecular aggregation in a simple, accurate, and efficient way.
The present study investigated the composition profiles and levels of polybrominated diphenyl ethers (PBDEs) and five PBDE alternatives in the blubber of two species of marine mammals, Indo-Pacific ...humpback dolphins (Sousa chinensis) and finless porpoises (Neophocaena phocaenoides) from the South China Sea. Despite the fact that PBDEs were the most predominant brominated flame retardants in the samples analyzed, decabromodiphenyl ethane (DBDPE), 1,2-bis (2,4,6-tribromophenoxy) ethane (BTBPE), bis- (2-ethylhexyl) -tetrabromophthalate (TBPH), 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (TBB) and Dechlorane Plus (DP) were all detected in both cetacean species. In addition, significantly increasing temporal shifting trends of Deca-BDE to DBDPE, Octa-BDE to BTBPE, and Deca-BDE to DP were observed in porpoise samples between 2003 and 2012 and dolphin samples between 2003 and 2011. These patterns may be attributed to the replacement of PBDEs by alternative halogenated flame retardants (HFRs) and the increasing usage of these alternatives following the restriction/voluntary withdrawal of the production and use of PBDE commercial mixtures. Our findings suggest that the study region may be a source of contamination by PBDE alternative flame retardants due to the high detection frequencies and levels of these compounds in marine mammals.
Display omitted
•Brominated and chlorinated HFRs were detected in marine mammals.•Temporal shifting trends of PBDEs to its alternatives are a novel finding.•BTBPE, DBDPE and DP were first detected in cetaceans from the Asia-Pacific region.•PBDEs, DP and DBDPE were the three predominant HFRs in the blubber.
Minimum Orbital Periods of H-rich Bodies Rappaport, S.; Vanderburg, A.; Schwab, J. ...
Astrophysical journal/The Astrophysical journal,
06/2021, Letnik:
913, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Abstract
In this work we derive the minimum allowed orbital periods of H-rich bodies ranging in mass from Saturn’s mass to 1
M
⊙
, emphasizing gas giants and brown dwarfs (BDs) over the range ...0.0003–0.074
M
⊙
. Analytic fitting formulae for
as a function of the mass of the body and as a function of the mean density are presented. We assume that the density of the host star is sufficiently high so as not to limit the minimum period. In many instances this implies that the host star is a white dwarf. This work is aimed, in part, toward distinguishing BDs from planets that are found transiting the host white dwarf without recourse to near-infrared or radial velocity measurements. In particular, orbital periods of ≲100 minutes are very likely to be BDs. The overall minimum period over this entire mass range is ≃37 minutes.
Studies have demonstrated cross-reactivity of anti-dengue virus (DENV) antibodies in human sera against Zika virus (ZIKV), promoting increased ZIKV infection in vitro. However, the correlation ...between in vitro and in vivo findings is not well characterized. Thus, we evaluated the impact of heterotypic flavivirus immunity on ZIKV titers in biofluids of rhesus macaques. Animals previously infected (≥420 days) with DENV2, DENV4, or yellow fever virus were compared to flavivirus-naïve animals following infection with a Brazilian ZIKV strain. Sera from DENV-immune macaques demonstrated cross-reactivity with ZIKV by antibody-binding and neutralization assays prior to ZIKV infection, and promoted increased ZIKV infection in cell culture assays. Despite these findings, no significant differences between flavivirus-naïve and immune animals were observed in viral titers, neutralizing antibody levels, or immune cell kinetics following ZIKV infection. These results indicate that prior infection with heterologous flaviviruses neither conferred protection nor increased observed ZIKV titers in this non-human primate ZIKV infection model.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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