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21.
Distinct neural activity associated with focused-attention meditation and loving-kindness meditation
This study examined the dissociable neural effects of ānāpānasati (focused-attention meditation, FAM) and mettā (loving-kindness meditation, LKM) on BOLD signals during cognitive (continuous performance test, CPT) and affective (emotion-processing task, EPT, in which participants viewed affective pictures) processing. Twenty-two male Chinese expert meditators (11 FAM experts, 11 LKM experts) and 22 male Chinese novice meditators (11 FAM novices, 11 LKM novices) had their brain activity monitored by a 3T MRI scanner while performing the cognitive and affective tasks in both meditation and baseline states. We examined the interaction between state (meditation vs. baseline) and expertise (expert vs. novice) separately during LKM and FAM, using a conjunction approach to reveal common regions sensitive to the expert meditative state. Additionally, exclusive masking techniques revealed distinct interactions between state and group during LKM and FAM. Specifically, we demonstrated that the practice of FAM was associated with expertise-related behavioral improvements and neural activation differences in attention task performance. However, the effect of state LKM meditation did not carry over to attention task performance. On the other hand, both FAM and LKM practice appeared to affect the neural responses to affective pictures. For viewing sad faces, the regions activated for FAM practitioners were consistent with attention-related processing; whereas responses of LKM experts to sad pictures were more in line with differentiating emotional contagion from compassion/emotional regulation processes. Our findings provide the first report of distinct neural activity associated with forms of meditation during sustained attention and emotion processing. 相似文献
22.
Ferree ED Dickinson JL Kleiber D Stern CA Haydock J Stanback MT Schmidt V Eisenberg L Stolzenburg C 《Molecular ecology resources》2008,8(6):1348-1350
Western and eastern bluebirds (Sialia mexicana and S. sialis) are socially monogamous passerines that engage in extra‐pair copulations. We obtained microsatellites from S. mexicana and optimized and characterized 15 microsatellite DNA loci in 60 individuals of this species. Primer pairs yielded an average of 13 alleles per locus in western bluebirds (range 3–35 alleles) with an average observed heterozygosity of 0.68 (range 0.27–0.88). All 15 loci also successfully amplified in S. sialis (n = 24), with an average of 11.5 alleles per locus (range 4–26) and an average observed heterozygosity of 0.59 (range 0.22–0.90). 相似文献
23.
Oncostatin M receptor-beta mutations underlie familial primary localized cutaneous amyloidosis 下载免费PDF全文
Arita K South AP Hans-Filho G Sakuma TH Lai-Cheong J Clements S Odashiro M Odashiro DN Hans-Neto G Hans NR Holder MV Bhogal BS Hartshorne ST Akiyama M Shimizu H McGrath JA 《American journal of human genetics》2008,82(1):73-80
Familial primary localized cutaneous amyloidosis (FPLCA) is an autosomal-dominant disorder associated with chronic skin itching and deposition of epidermal keratin filament-associated amyloid material in the dermis. FPLCA has been mapped to 5p13.1–q11.2, and by candidate gene analysis, we identified missense mutations in the OSMR gene, encoding oncostatin M-specific receptor β (OSMRβ), in three families. OSMRβ is a component of the oncostatin M (OSM) type II receptor and the interleukin (IL)-31 receptor, and cultured FPLCA keratinocytes showed reduced activation of Jak/STAT, MAPK, and PI3K/Akt pathways after OSM or IL-31 cytokine stimulation. The pathogenic amino acid substitutions are located within the extracellular fibronectin type III-like (FNIII) domains, regions critical for receptor dimerization and function. OSM and IL-31 signaling have been implicated in keratinocyte cell proliferation, differentiation, apoptosis, and inflammation, but our OSMR data in individuals with FPLCA represent the first human germline mutations in this cytokine receptor complex and provide new insight into mechanisms of skin itching. 相似文献
24.
25.
Joey Chua 《Arts Education Policy Review》2018,119(1):53-71
This article provides an overview of dance education in schools in Singapore with regard to physical education, co-curricular activity, initiatives by the National Arts Council's Arts Education unit, and pre-tertiary and tertiary dance programs. In an effort to gain a better understanding of how well the official discourse and the reality of schooling in dance interconnect, a meta-analysis of published articles, conference papers, committee reports, and curricula was conducted. Situated within the larger sociocultural, political, and historical contexts, Singapore presents a curious case for probing the merits and limitations of research, policy initiatives, and policy implementation. In the conclusion, the author argues that the development of a coherent dance education in Singapore requires “fixing” three dilemmas—meritocratic schooling in dance, the ill-defined and exhaustive use of the term “talent,” and the uneven research that has not kept pace with the policy initiatives. 相似文献
26.
The ability of Climacodon septentrionalis to immobilize and kill a mycophagous nematode (Aphelenchoides sp.) in vitro is described for the first time. Two isolates produced droplets (20–45 μm in diameter) that formed at the apices
of tall, stalked, and branching secretory cells (700–1,500 μm tall). On 2% modified malt extract agar, nematodes became enveloped
in the droplets, which restricted their ability to move and resulted in complete immobilization and death within several hours
of contact. The rate of decomposition of the nematodes varied considerably, with most individuals persisting for weeks whereas
others were degraded within several days and appeared to be colonized by dense hyphal growth. This study provides the first
documentation of a non-agaricoid fungus producing secretory cells that are able to immobilize nematodes. 相似文献
27.
Transcriptome analysis of the Brassica napus–Leptosphaeria maculans pathosystem identifies receptor,signaling and structural genes underlying plant resistance 下载免费PDF全文
28.
Sustained VEGF blockade results in microenvironmental sequestration of VEGF by tumors and persistent VEGF receptor-2 activation 总被引:3,自引:0,他引:3
Kadenhe-Chiweshe A Papa J McCrudden KW Frischer J Bae JO Huang J Fisher J Lefkowitch JH Feirt N Rudge J Holash J Yancopoulos GD Kandel JJ Yamashiro DJ 《Molecular cancer research : MCR》2008,6(1):1-9
Vascular endothelial growth factor (VEGF) blockade has been validated clinically as a treatment for human cancers, yet virtually all patients eventually develop progressive disease during therapy. In order to dissect this phenomenon, we examined the effect of sustained VEGF blockade in a model of advanced pediatric cancer. Treatment of late-stage hepatoblastoma xenografts resulted in the initial collapse of the vasculature and significant tumor regression. However, during sustained treatment, vessels recovered, concurrent with a striking increase in tumor expression of perlecan, a heparan sulfate proteoglycan. Whereas VEGF mRNA was expressed at the periphery of surviving clusters of tumor cells, both secreted VEGF and perlecan accumulated circumferential to central vessels. Vascular expression of heparanase, VEGF receptor-2 ligand binding, and receptor activation were concurrently maintained despite circulating unbound VEGF Trap. Endothelial survival signaling via Akt persisted. These findings provide a novel mechanism for vascular survival during sustained VEGF blockade and indicate a role for extracellular matrix molecules that sequester and release biologically active VEGF. 相似文献
29.
Joey Lai Oliver K. Bernhard Stuart G. Turville Andrew N. Harman John Wilkinson Anthony L. Cunningham 《The Journal of biological chemistry》2009,284(17):11027-11038
C-type lectin receptors expressed on the surface of dendritic cells and
macrophages are able to bind glycoproteins of microbial pathogens via mannose,
fucose, and N-acetylglucosamine. Langerin on Langerhans cells,
dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin
on dendritic cells, and mannose receptor (MR) on dendritic cells and
macrophages bind the human immunodeficiency virus (HIV) envelope protein gp120
principally via high mannose oligosaccharides. These C-type lectin receptors
can also oligomerize to facilitate enhanced ligand binding. This study
examined the effect of oligomerization of MR on its ability to bind to mannan,
monomeric gp120, native trimeric gp140, and HIV type 1 BaL. Mass spectrometry
analysis of cross-linked MR showed homodimerization on the surface of primary
monocyte-derived dendritic cells and macrophages. Both monomeric and dimeric
MR were precipitated by mannan, but only the dimeric form was
co-immunoprecipitated by gp120. These results were confirmed independently by
flow cytometry analysis of soluble monomeric and trimeric HIV envelope and a
cellular HIV virion capture assay. As expected, mannan bound to the
carbohydrate recognition domains of MR dimers mostly in a calcium-dependent
fashion. Unexpectedly, gp120-mediated binding of HIV to dimers on
MR-transfected Rat-6 cells and macrophages was not calcium-dependent, was only
partially blocked by mannan, and was also partially inhibited by
N-acetylgalactosamine 4-sulfate. Thus gp120-mediated HIV binding
occurs via the calcium-dependent, non-calcium-dependent carbohydrate
recognition domains and the cysteine-rich domain at the C terminus of MR
dimers, presenting a much broader target for potential inhibitors of gp120-MR
binding.The mannose receptor
(MR)2 is a C-type
lectin receptor that is expressed on the surface of a variety of cells,
including immature monocyte-derived dendritic cells (MDDC), dermal dendritic
cells, macrophages, and hepatic endothelial cells. It is a multifunctional
protein, involved in antigen recognition and internalization during the early
stages of the innate immune response
(1) as well as physiological
clearance of the endogenous pituitary hormones lutropin and thyrotropin
(2,
3). Recognition of foreign
antigens occurs via mannose, fucose, and GlcNAc residues
(4,
5), which are generally not
found as terminal residues on mammalian glycoproteins but are highly abundant
on surface proteins of pathogens such as the HIV-1 envelope gp120
(6,
7). Once bound, pathogens can
be internalized by endocytosis or phagocytosis, where they are targeted to
lysosomes for proteolytic degradation and presentation on major
histocompatibility complex class II
(8). In immature DCs, soluble
recombinant HIV envelope proteins are processed by this pathway, initially
binding to both dendritic cell-specific intracellular adhesion molecule 3
grabbing non-integrin (DC-SIGN) and MR and ultimately co-localizing with MR
but not DC-SIGN in lysosomes
(9). Furthermore, in immature
DCs and to a greater extent mature DCs, a proportion of intact HIV-1 enters a
unique vesicular compartment that co-localizes with tetraspanin proteins such
as CD81 (10,
11). Recently, this
compartment has been shown to be continuous with the plasma membrane
(11) and does not represent a
continuation of the endolysosomal network. Interestingly, this compartment can
translocate virus from DCs to CD4 T cells, upon the formation of a virological
synapse
(10–12).
Although viral uptake can occur in DCs independent of HIV env
(2), the efficiency of HIV
binding and uptake is greatly enhanced by the presence of C-type lectin-env
interactions. At least initial binding to DC-SIGN (and most likely also MR) is
required for T cell trans-infection
(13).Structurally, the extracellular domain of MR consists of an N-terminal
cysteine-rich domain (Cys-RD), followed by a fibronectin type II domain and
eight carbohydrate recognition domains (CRD) on a single polypeptide backbone
(1). Of the eight CRDs, CRD
4–8 have been shown to be required for high affinity binding of ligands
containing terminal mannose/fucose/GlcNAc residues, with CRD 4 having
demonstrable monosaccharide binding in isolation
(14). Binding and release of
ligand within the low pH environment of the endolysosomal compartment are also
Ca2+-dependent. Acid-induced removal of Ca2+ binding in
CRD 4 and 5 was shown to cause a conformational rearrangement of the domain,
resulting in a loss of carbohydrate binding activity
(15). In contrast, binding of
sulfated carbohydrates to the Cys-RD appears to be Ca2+-independent
as no Ca2+-binding sites were observed in its crystal structure
(2,
16).Oligomerization of CLRs such as DC-SIGN
(17), Langerin
(18), and mannose-binding
protein (19) has been reported
to be essential for binding of oligosaccharide-bearing ligands. Early studies
on MR suggested that it exists solely as a monomeric molecule and that
clustering of multiple CRDs within the single polypeptide backbone was
necessary for high affinity binding of oligosaccharide moieties
(20). However, more recent
studies have shown that dimerization is possible in the presence of
Ca2+ (21) and that
an equilibrium may exist between monomeric and dimeric forms on the cell
surface (22). It is currently
unclear what effect dimerization has on ligand binding to the CRDs; however,
there is evidence that dimerization of MR is required for high affinity
binding of ligands bearing terminal N-acetylgalactosamine 4-sulfate
(GalNAc-4-SO4) such as lutropin and thyrotropin
(22) to the Cys-RD.To date, studies on the oligomerization and ligand binding activity of MR
have used solubilized protein from cell lysates
(20) or purified recombinant
fragments (21). Because the
membrane microenvironment can influence protein associations, soluble forms of
MR may not necessarily be a true model of the quaternary structure and
function of the native protein. Here, we used a well established method of
cross-linking (23) on MDDCs,
monocyte-derived macrophages (MDMs), and MR-transfected Rat-6 cells to
preserve lateral protein-protein interactions between MR on the cell surface
prior to solubilization. Mass spectrometry analysis of affinity-purified
complexes showed they were homo-oligomers, and further resolution of the
complex on a low percentage polyacrylamide gel by SDS-PAGE strongly indicates
that they are dimers. Dimerization of MR was also found to be essential for
binding mannan, monomeric gp120, native trimeric gp140, and HIV-1 viral
particles. Persistence of monomeric gp120 and trimeric gp140 binding to
dimeric MR in the presence of EGTA and various CRD and other inhibitors,
however, suggested that gp120-mediated HIV-1 binding is not
Ca2+-dependent and that at least binding probably occurs to both
Ca2+-dependent and -independent CRDs and also the Cys-RD. 相似文献
30.
George EM Arany M Cockrell K Storm MV Stec DE Granger JP 《American journal of physiology. Regulatory, integrative and comparative physiology》2011,301(5):R1495-R1500
Preeclampsia (PE) is one of the leading causes of fetal and maternal morbidity, affecting 5-10% of all pregnancies, and lacks an effective treatment. The exact etiology of the disorder is unclear, but placental ischemia has been shown to be a central causative agent. In response to placental ischemia, the antiangiogenic protein fms-like tyrosine kinase-1 (sFlt-1), a VEGF antagonist, and reactive oxygen species are secreted, leading to the maternal syndrome. One promising therapeutic approach to treat PE is through manipulation of the heme oxygenase-1 (HO-1) protein. It has been previously reported that HO-1 and carbon monoxide downregulate sFlt-1 production in vitro, and we have recently shown that HO-1 induction significantly attenuates placental ischemia-induced hypertension, partially through normalization of the sFlt-1-to-VEGF ratio in the placenta. The purpose of this study was to determine whether HO-1 induction would have beneficial effects independently of sFlt-1 suppression. To that end, pregnant rats were continuously infused with recombinant sFlt-1 from gestational days 14-19, and circulating sFlt-1 increased approximately twofold, similar to rats with experimentally induced placental ischemia. In response, mean arterial pressure increased 17 mmHg, which was completely normalized by HO-1 induction. Unbound circulating VEGF was decreased ~17% in response to sFlt-1 infusion but was increased ~50% in response to HO-1 induction. Finally, endothelial function was improved as measured by reductions in vascular expression of preproendothelin mRNA. In conclusion, manipulation of HO-1 presents an intriguing therapeutic approach to the treatment of PE. 相似文献