The vast majority of currently licensed human vaccines work on the basis of long-term protective antibody responses. It is now conceivable that an antibody-dependent HIV vaccine might be possible, ...given the discovery of HIV broadly neutralizing antibodies (bnAbs) in some HIV-infected individuals. However, these antibodies are difficult to develop and have characteristics indicative of a high degree of affinity maturation in germinal centers (GCs). CD4+ T follicular helper (Tfh) cells are specialized for B cell help and necessary for GCs. Therefore, the development of HIV bnAbs might depend on Tfh cells. Here, we identified in normal individuals a subpopulation of circulating memory PD-1+CXCR5+CD4+ T cells that are resting memory cells most related to bona fide GC Tfh cells by gene expression profile, cytokine profile, and functional properties. Importantly, the frequency of these cells correlated with the development of bnAbs against HIV in a large cohort of HIV+ individuals.
•PD-1+CXCR5+CD4+ T cells are a population of circulating memory Tfh cells•Optimal Tfh-cell-like function is restricted to PD-1+CXCR3−CXCR5+CD4+ T cells•PD-1+CXCR3−CXCR5+CD4+ T cells correlate with HIV broadly neutralizing antibodies
Neuronal diversity is essential for mammalian brain function but poses a challenge to molecular profiling. To address the need for tools that facilitate cell-type-specific epigenomic studies, we ...developed the first affinity purification approach to isolate nuclei from genetically defined cell types in a mammal. We combine this technique with next-generation sequencing to show that three subtypes of neocortical neurons have highly distinctive epigenomic landscapes. Over 200,000 regions differ in chromatin accessibility and DNA methylation signatures characteristic of gene regulatory regions. By footprinting and motif analyses, these regions are predicted to bind distinct cohorts of neuron subtype-specific transcription factors. Neuronal epigenomes reflect both past and present gene expression, with DNA hyper-methylation at developmentally critical genes appearing as a novel epigenomic signature in mature neurons. Taken together, our findings link the functional and transcriptional complexity of neurons to their underlying epigenomic diversity.
•Affinity purification of nuclei in mice enables cell-type-specific epigenomics•3 neuron types adopt unique landscapes of DNA methylation and accessible chromatin•Distinct TF sets are predicted to bind neuron type-specific gene regulatory regions•A hyper-methylation signature in adult neurons captures developmental history
Mo et al. develop a broadly applicable tool to purify genetically labeled nuclei in mice and, using genome-wide maps of gene expression, DNA methylation, and chromatin accessibility, show how three neuronal subtypes adopt distinct epigenomic configurations associated with function and development.
A meta-analysis of 62 experimental and 10 non-experimental studies was conducted to evaluate the positive-mood-enhances-creativity generalization. While the results demonstrate that positive mood ...enhances creativity, the strength of that effect is contingent upon the comparative or referent mood state (i.e., neutral or negative mood) as well as the type of creative task. Further, the pattern of effect sizes supports a curvilinear relationship between affective intensity and creative performance. In general, a contextual perspective of mood–creativity relations is supported.
Recent studies have suggested a bacterial role in the development of autoimmune disorders including type 1 diabetes (T1D). Over 30 billion nucleotide bases of Illumina shotgun metagenomic data were ...analyzed from stool samples collected from four pairs of matched T1D case-control subjects collected at the time of the development of T1D associated autoimmunity (i.e., autoantibodies). From these, approximately one million open reading frames were predicted and compared to the SEED protein database. Of the 3,849 functions identified in these samples, 144 and 797 were statistically more prevalent in cases and controls, respectively. Genes involved in carbohydrate metabolism, adhesions, motility, phages, prophages, sulfur metabolism, and stress responses were more abundant in cases while genes with roles in DNA and protein metabolism, aerobic respiration, and amino acid synthesis were more common in controls. These data suggest that increased adhesion and flagella synthesis in autoimmune subjects may be involved in triggering a T1D associated autoimmune response. Extensive differences in metabolic potential indicate that autoimmune subjects have a functionally aberrant microbiome. Mining 16S rRNA data from these datasets showed a higher proportion of butyrate-producing and mucin-degrading bacteria in controls compared to cases, while those bacteria that produce short chain fatty acids other than butyrate were higher in cases. Thus, a key rate-limiting step in butyrate synthesis is more abundant in controls. These data suggest that a consortium of lactate- and butyrate-producing bacteria in a healthy gut induce a sufficient amount of mucin synthesis to maintain gut integrity. In contrast, non-butyrate-producing lactate-utilizing bacteria prevent optimal mucin synthesis, as identified in autoimmune subjects.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Giant vortex clusters in a two-dimensional quantum fluid Gauthier, Guillaume; Reeves, Matthew T; Yu, Xiaoquan ...
Science (American Association for the Advancement of Science),
06/2019, Letnik:
364, Številka:
6447
Journal Article
Recenzirano
Odprti dostop
Adding energy to a system through transient stirring usually leads to more disorder. In contrast, point-like vortices in a bounded two-dimensional fluid are predicted to reorder above a certain ...energy, forming persistent vortex clusters. In this study, we experimentally realize these vortex clusters in a planar superfluid: a
Rb Bose-Einstein condensate confined to an elliptical geometry. We demonstrate that the clusters persist for long time periods, maintaining the superfluid system in a high-energy state far from global equilibrium. Our experiments explore a regime of vortex matter at negative absolute temperatures and have relevance for the dynamics of topological defects, two-dimensional turbulence, and systems such as helium films, nonlinear optical materials, fermion superfluids, and quark-gluon plasmas.
Rheumatoid arthritis and cardiovascular disease Crowson, Cynthia S., MS; Liao, Katherine P., MD, MPH; Davis, John M., MD ...
The American heart journal,
10/2013, Letnik:
166, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Background Rheumatic disease and heart disease share common underpinnings involving inflammation. The high levels of inflammation that characterize rheumatic diseases provide a “natural experiment” ...to help elucidate the mechanisms by which inflammation accelerates heart disease. Rheumatoid arthritis (RA) is the most common of the rheumatic diseases and has the best studied relationships with heart disease. Methods A review of current literature on heart disease and RA was conducted. Results Patients with RA have an increased risk of developing heart disease that is not fully explained by traditional cardiovascular risk factors. Therapies used to treat RA may also affect the development of heart disease; by suppressing inflammation, they may also reduce the risk of heart disease. However, their other effects, as in the case of steroids, may increase heart disease risk. Conclusions Investigations of the innate and adaptive immune responses occurring in RA may delineate novel mechanisms in the pathogenesis of heart disease and help identify novel therapeutic targets for the prevention and treatment of heart disease.
Chabazite (CHA)-type zeolites are prepared from the hydrothermal conversion of faujasite (FAU)-type zeolites, dealuminated by high-temperature steam treatments (500–700 °C), and evaluated as ...catalysts for the methanol-to-olefins (MTO) reaction. The effects of temperature and partial pressure of water vapor during steaming are investigated. Powder X-ray diffraction (XRD) and Ar physisorption data show that the steam treatments cause partial structural collapse of the zeolite with the extent of degradation increasing with steaming temperature. 27Al MAS NMR spectra of the steamed materials reveal the presence of tetrahedral, pentacoordinate, and octahedral aluminum. NH3 and i-propylamine temperature-programmed desorption (TPD) demonstrate that steaming removes Brønsted acid sites, while simultaneously introducing larger pores into the CHA materials that make the remaining acid sites more accessible. Acid washing the steamed CHA-type zeolites removes a significant portion of the extra-framework aluminum, producing an increase in the bulk Si/Al ratio as well as the adsorption volume. The proton form of the as-synthesized CHA (Si/Al = 2.4) rapidly deactivates when tested for MTO at a reaction temperature of 400 °C and atmospheric pressure. CHA samples steamed at 600 °C performed the best among the samples tested, showing increased olefin selectivities as well as catalyst lifetime compared to the unsteamed CHA. Both lifetime and C2–C3 olefin selectivities are found to increase with increasing reaction temperature. At 450 °C, CHA steamed at 600 °C reached a combined C2–C3 olefin selectivity of 74.2% at 100% methanol conversion, with conversion remaining above 80% for more than 130 min of time-on-stream (TOS) before deactivating. More stable time-on-stream behavior is observed for 600 °C-steamed CHA that underwent acid washing: conversion above 90% for more than 200 min of TOS at 450 °C with a maximum total C2–C3 olefin selectivity of 71.4% at 100% conversion.
Natural Killer (NK) cells are innate immune cells that secrete lytic granules to directly kill virus-infected or transformed cells across an immune synapse. However, a major gap in understanding this ...process is in establishing how lytic granules pass through the mesh of cortical actin known to underlie the NK cell membrane. Research has been hampered by the resolution of conventional light microscopy, which is too low to resolve cortical actin during lytic granule secretion. Here we use two high-resolution imaging techniques to probe the synaptic organisation of NK cell receptors and filamentous (F)-actin. A combination of optical tweezers and live cell confocal microscopy reveals that microclusters of NKG2D assemble into a ring-shaped structure at the centre of intercellular synapses, where Vav1 and Grb2 also accumulate. Within this ring-shaped organisation of NK cell proteins, lytic granules accumulate for secretion. Using 3D-structured illumination microscopy (3D-SIM) to gain super-resolution of ~100 nm, cortical actin was detected in a central region of the NK cell synapse irrespective of whether activating or inhibitory signals dominate. Strikingly, the periodicity of the cortical actin mesh increased in specific domains at the synapse when the NK cell was activated. Two-colour super-resolution imaging revealed that lytic granules docked precisely in these domains which were also proximal to where the microtubule-organising centre (MTOC) polarised. Together, these data demonstrate that remodelling of the cortical actin mesh occurs at the central region of the cytolytic NK cell immune synapse. This is likely to occur for other types of cell secretion and also emphasises the importance of emerging super-resolution imaging technology for revealing new biology.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
SSZ-13 materials have been synthesized with varying amounts of Al to produce samples with different concentrations of Brønsted acid sites, and consequently, these SSZ-13 materials contain increasing ...numbers of paired Al heteroatoms with increasing Al content. These materials were then characterized and tested as catalysts for the methanol-to-olefins (MTO) reaction at 400 °C and 100% methanol conversion under atmospheric pressure. A SAPO-34 sample was also synthesized and tested for comparison. SSZ-13 materials exhibited significant differences in MTO reactivity as Si/Al ratios varied. Reduced Al content (higher Si/Al ratio) and, consequently, fewer paired Al sites led to more stable light olefin selectivities, with a reduced initial transient period, lower initial propane selectivities, and longer catalyst lifetime. To further support the importance of paired Al sites in the formation of propane during this initial transient period, a series of experiments was conducted wherein an H-SSZ-13 sample was exchanged with Cu2+, steamed, and then back-exchanged to the H form. The H-SSZ-13 sample exhibited high initial propane selectivity, while the steamed H-SSZ-13, the Cu2+-exchanged SSZ-13 sample, and the steamed Cu-SSZ-13 sample did not, as expected since steaming selectively removes paired Al sites and Cu2+ exchanges onto these sites. However, when it was back-exchanged to the proton form, the steamed Cu-SSZ-13 sample still exhibited the high initial alkane selectivity and transient period typical of the higher Al content materials. This is attributed to protection of paired Al sites during steaming via the Cu2+ cation. Post-reaction coke analyses reveal that the degree of methylation for each aromatic species increases with increasing Si/Al in SSZ-13. Further, SAPO-34 produces more polycyclic species than SSZ-13 samples. From these data, the paired Al site content appears to be correlated with both MTO reaction behavior and coke species formation in SSZ-13 samples.
PDF
