We report here the first results of a multiwavelength campaign focussing on magnetospheric accretion processes of the classical TTauri star V2129Oph. In this paper, we present spectropolarimetric ...observations collected in 2009 July with ESPaDOnS at the Canada-France-Hawaii Telescope and contemporaneous photometry secured with the SMARTS facility. Circularly polarized Zeeman signatures are clearly detected, both in photospheric absorption and accretion-powered emission lines, from time-series of which we reconstruct new maps of the magnetic field, photospheric brightness and accretion-powered emission at the surface of V2129Oph using our newest tomographic imaging tool - to be compared with those derived from our old 2005 June data set, re-analysed in the exact same way. We find that in 2009 July, V2129Oph hosts octupolar and dipolar field components of about 2.1 and 0.9kG, respectively, both tilted by about 20° with respect to the rotation axis; we conclude that the large-scale magnetic topology changed significantly since 2005 June (when the octupole and dipole components were about 1.5 and three times weaker, respectively), demonstrating that the field of V2129Oph is generated by a non-stationary dynamo. We also show that V2129Oph features a dark photospheric spot and a localized area of accretion-powered emission, both close to the main surface magnetic region (hosting fields of up to about 4kG in 2009 July). We finally obtain that the surface shear of V2129Oph is about half as strong as solar. From the fluxes of accretion-powered emission lines, we estimate that the observed average logarithmic accretion rate (in Myr-1) at the surface of V2129Oph is -9.2 ± 0.3 at both epochs, peaking at -9.0 at magnetic maximum. It implies in particular that the radius at which the magnetic field of V2129Oph truncates the inner accretion disc is 0.93 and 0.50 times the corotation radius (where the Keplerian period equals the stellar rotation period) in 2009 July and 2005 June, respectively. PUBLICATION ABSTRACT
The 70S ribosome and its complement of factors required for initiation of translation in
E. coli were purified separately and reassembled in vitro with GDPNP, producing a stable initiation complex ...(IC) stalled after 70S assembly. We have obtained a cryo-EM reconstruction of the IC showing IF2•GDPNP at the intersubunit cleft of the 70S ribosome. IF2•GDPNP contacts the 30S and 50S subunits as well as fMet-tRNA
fMet. IF2 here adopts a conformation radically different from that seen in the recent crystal structure of IF2. The C-terminal domain of IF2 binds to the single-stranded portion of fMet-tRNA
fMet, thereby forcing the tRNA into a novel orientation at the P site. The GTP binding domain of IF2 binds to the GTPase-associated center of the 50S subunit in a manner similar to EF-G and EF-Tu. Additionally, we present evidence for the localization of IF1, IF3, one C-terminal domain of L7/L12, and the N-terminal domain of IF2 in the initiation complex.
Gene expression in skeletal muscle of older individuals may reflect compensatory adaptations in response to oxidative damage that preserve tissue integrity and maintain function. Identifying ...associations between oxidative stress response gene expression patterns and mitochondrial function, physical performance, and muscle mass in older individuals would further our knowledge of mechanisms related to managing molecular damage that may be targeted to preserve physical resilience. To characterize expression patterns of genes responsible for the oxidative stress response, RNA was extracted and sequenced from skeletal muscle biopsies collected from 575 participants (≥70 years old) from the Study of Muscle, Mobility, and Aging. Expression levels of 21 protein‐coding RNAs related to the oxidative stress response were analyzed in relation to six phenotypic measures, including maximal mitochondrial respiration from muscle biopsies (Max OXPHOS), physical performance (VO2 peak, 400‐m walking speed, and leg strength), and muscle size (thigh muscle volume and whole‐body D3Cr muscle mass). The mRNA level of the oxidative stress response genes most consistently associated across outcomes are preferentially expressed within the mitochondria. Higher expression of mRNAs that encode generally mitochondria located proteins SOD2, TRX2, PRX3, PRX5, and GRX2 were associated with higher levels of mitochondrial respiration and VO2 peak. In addition, greater SOD2, PRX3, and GRX2 expression was associated with higher physical performance and muscle size. Identifying specific mechanisms associated with high functioning across multiple performance and physical domains may lead to targeted antioxidant interventions with greater impacts on mobility and independence.
Identifying associations between oxidative stress response gene expression patterns and mitochondrial function, physical performance, and muscle mass in older individuals would further our knowledge of mechanisms related to functional decline. We performed gene expression in 575 skeletal muscle biopsies collected as part of the Study of Muscle, Mobility, and Aging, a large, longitudinal study of ≥70 year old people. Associations were identified between expression levels of 21 canonical mitochondrial and extramitochondrial antioxidant genes and muscle mitochondrial function (Max OXPHOS), physical performance (VO2 peak, 400‐m walking speed, and leg strength), and muscle size (thigh muscle volume and whole‐body D3Cr muscle mass). Higher expression of mRNAs that encode mitochondria located proteins were associated with higher levels of mitochondrial respiration, VO2 peak, walking speed, and muscle size.
A Neural Basis for Social Cooperation Rilling, James K.; Gutman, David A.; Zeh, Thorsten R. ...
Neuron (Cambridge, Mass.),
07/2002, Letnik:
35, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Cooperation based on reciprocal altruism has evolved in only a small number of species, yet it constitutes the core behavioral principle of human social life. The iterated Prisoner's Dilemma Game has ...been used to model this form of cooperation. We used fMRI to scan 36 women as they played an iterated Prisoner's Dilemma Game with another woman to investigate the neurobiological basis of cooperative social behavior. Mutual cooperation was associated with consistent activation in brain areas that have been linked with reward processing: nucleus accumbens, the caudate nucleus, ventromedial frontal/orbitofrontal cortex, and rostral anterior cingulate cortex. We propose that activation of this neural network positively reinforces reciprocal altruism, thereby motivating subjects to resist the temptation to selfishly accept but not reciprocate favors.
Review article: the pathogenesis of pouchitis Schieffer, K. M.; Williams, E. D.; Yochum, G. S. ...
Alimentary pharmacology & therapeutics,
October 2016, Letnik:
44, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Summary
Background
A total proctocolectomy followed by ileal pouch‐anal anastomosis is a potentially curative surgery for ulcerative colitis or familial adenomatous polyposis. About 5–35% of patients ...with ulcerative colitis and 0–11% of patients with familial adenomatous polyposis develop subsequent inflammation of the ileal pouch termed pouchitis.
Aim
To provide a comprehensive analysis of the research studying the possible pathogenesis of pouchitis. The goals were to identify promising areas of investigation, to help focus clinicians, researchers and patients on how to better understand and then potentially manage ileal pouchitis, and to provide avenues for future research investigations.
Methods
This review examined manuscripts from 1981 to 2015 that discussed and/or proposed hypotheses with supportive evidence for the potential underlying pathogenic mechanism for pouchitis.
Results
The pathogenesis of pouchitis is not definitively understood, but various hypotheses have been proposed, including (i) recurrence of ulcerative colitis, (ii) dysbiosis of the ileal pouch microbiota, (iii) deprivation of nutritional short‐chain fatty acids, (iv) mucosal ischaemia and oxygen‐free radical injury, (v) host genetic susceptibility and (vi) immune dysregulation. However, none of these alone are able to fully explain pouchitis pathogenesis.
Conclusions
Pouchitis, similar to inflammatory bowel disease, is a complex disorder that is not caused by any one single factor. More likely, pouchitis occurs through a combination of both dysregulated host inflammatory mechanisms and interaction with luminal microbiota.
Synthetic analogues of marine sponge guanidine alkaloids showed in vitro antiparasitic activity against Leishmania (L.) infantum and Trypanosoma cruzi. Guanidines 10 and 11 presented the highest ...selectivity index when tested against Leishmania. The antiparasitic activity of 10 and 11 was investigated in host cells and in parasites. Both compounds induced depolarization of mitochondrial membrane potential, upregulation of reactive oxygen species levels, and increased plasma membrane permeability in Leishmania parasites. Immunomodulatory assays suggested an NO-independent effect of guanidines 10 and 11 on macrophages. The same compounds also promoted anti-inflammatory activity in L. (L.) infantum-infected macrophages cocultived with splenocytes, reducing the production of cytokines MCP-1 and IFN-γ. Guanidines 10 and 11 affect the bioenergetic metabolism of Leishmania, with selective elimination of parasites via a host-independent mechanism.
The rise of molecular plasmonics and its application to ultrasensitive spectroscopic measurements has been enabled by the rational design and fabrication of a variety of metallic nanostructures. ...Advanced nano and microfabrication methods are key to the development of such structures, allowing one to tailor optical fields at the sub-wavelength scale, thereby optimizing excitation conditions for ultrasensitive detection. In this work, the control of both analyte and cell positioning on a plasmonic platform is enabled using nanofabrication methods involving patterning of fluorocarbon (FC) polymer (C
F
) thin films on a plasmonic platform fabricated by nanosphere lithography (NSL). This provides the possibility to probe biomolecules of interest in the vicinity of cells using plasmon-mediated surface enhanced spectroscopies. In this context, we demonstrate the surface enhanced biosensing of glycan expression in different cell lines by surface enhanced Raman spectroscopy (SERS) on these plasmonic platforms functionalized with 4-mercaptophenylboronic acid (4-MPBA) as the Raman reporter. These cell lines include human embryonic kidney (HEK 293), C2C12 mouse myoblasts, and HeLa (Henrietta Lacks) cervical cancer cells. A distinct glycan expression is observed for cancer cells compared to other cell lines by confocal SERS mapping. This suggests the potential application of these versatile SERS platforms for differentiating cancerous from non-cancerous cells.
Background. Gliotoxin is a epipolythiodioxopiperazine toxin that is made by the filamentous fungus Aspergillus fumigatus. Gliotoxin has a wide range of effects on metazoan cells in culture, including ...induction of apoptosis through inhibition of Nf-κB, and inhibition of superoxide production by phagocytes. These activities have led to the proposal that gliotoxin contributes to pathogenesis during invasive aspergillosis. We tested this hypothesis by creating isogenic strains of gliotoxin-producing and nonproducing strains. Methods. Wedeleted gliP, the gene that encodes the nonribosomal peptide synthetase GliP. gliP catalyzes the first biosynthetic step in the synthesis of gliotoxin. We then tested for gliotoxin production and virulence in different animal models. Results. Deletion of gliP resulted in strains that were wild type for growth, but they did not synthesize gliotoxin. Transformation of gliP deletion mutants with a full copy of gliP restored gliotoxin production. The gliP deletion strain had attenuated virulence in nonneutropenic mice immunosuppressed with corticosteroids, but had normal virulence in neutropenic mice. It also had reduced virulence in a Drosophila melanogaster model. Conclusions. Gliotoxin only contributes to the virulence of A. fumigatus in nonneutropenic mice and in fruit flies with functional phagocytes. These results suggest that the principal targets of gliotoxin are neutrophils or other phagocytes.
Autophagy is essential for proteostasis, energetic balance, and cell defense and is a key pathway in aging. Identifying associations between autophagy gene expression patterns in skeletal muscle and ...physical performance outcomes would further our knowledge of mechanisms related with proteostasis and healthy aging. Muscle biopsies were obtained from participants in the Study of Muscle, Mobility, and Aging (SOMMA). For 575 participants, RNA was sequenced and expression of 281 genes related to autophagy regulation, mitophagy, and mTOR/upstream pathways was determined. Associations between gene expression and outcomes including mitochondrial respiration in muscle fiber bundles (MAX OXPHOS), physical performance (VO2 peak, 400 m walking speed, and leg power), and thigh muscle volume, were determined using negative binomial regression models. For autophagy, key transcriptional regulators including TFE3 and NFKB‐related genes (RELA, RELB, and NFKB1) were negatively associated with outcomes. On the contrary, regulators of oxidative metabolism that also promote overall autophagy, mitophagy, and pexophagy (PPARGC1A, PPARA, and EPAS1) were positively associated with multiple outcomes. In line with this, several mitophagy, fusion, and fission‐related genes (NIPSNAP2, DNM1L, and OPA1) were also positively associated with outcomes. For mTOR pathway and related genes, expression of WDR59 and WDR24, both subunits of GATOR2 complex (an indirect inhibitor of mTORC1), and PRKAG3, which is a regulatory subunit of AMPK, were negatively correlated with multiple outcomes. Our study identifies autophagy and selective autophagy such as mitophagy gene expression patterns in human skeletal muscle related to physical performance, muscle volume, and mitochondrial function in older persons which may lead to target identification to preserve mobility and independence.
Our study identifies autophagy and selective autophagy (mitophagy) gene expression patterns in human skeletal muscle related to physical performance, muscle volume, and mitochondrial function in older persons.
Registry data on patients with type 1 diabetes mellitus who undergo pancreatic islet transplantation indicate that only 8 percent are free of the need for insulin therapy at one year.
Seven ...consecutive patients with type 1 diabetes and a history of severe hypoglycemia and metabolic instability underwent islet transplantation in conjunction with a glucocorticoid-free immunosuppressive regimen consisting of sirolimus, tacrolimus, and daclizumab. Islets were isolated by ductal perfusion with cold, purified collagenase, digested and purified in xenoprotein-free medium, and transplanted immediately by means of a percutaneous transhepatic portal embolization.
All seven patients quickly attained sustained insulin independence after transplantation of a mean (+/-SD) islet mass of 11,547+/-1604 islet equivalents per kilogram of body weight (median follow-up, 11.9 months; range, 4.4 to 14.9). All recipients required islets from two donor pancreases, and one required a third transplant from two donors to achieve sustained insulin independence. The mean glycosylated hemoglobin values were normal after transplantation in all recipients. The mean amplitude of glycemic excursions (a measure of fluctuations in blood glucose concentrations) was significantly decreased after the attainment of insulin independence (from 198+/-32 mg per deciliter 11.1+/-1.8 mmol per liter before transplantation to 119+/-37 mg per deciliter 6.7+/-2.1 mmol per liter after the first transplantation and 51+/-30 mg per deciliter 2.8+/-1.7 mmol per liter after the attainment of insulin independence; P<0.001). There were no further episodes of hypoglycemic coma. Complications were minor, and there were no significant increases in lipid concentrations during follow-up.
Our observations in patients with type 1 diabetes indicate that islet transplantation can result in insulin independence with excellent metabolic control when glucocorticoid-free immunosuppression is combined with the infusion of an adequate islet mass.
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