Studies of Paleozoic fungi. IV. Wall ultrastructure of fossil endogonaceous chlamydospores

Fossil endogonaceous chlamydospores are described from the aerial axes and roots of several Paleozoic plants preserved in calcilutite nodules and calcareous coal balls. Specimens come from six Paleozoic localities extending from the uppermost Lower Devonian through the Upper Pennsylvanian. Although fossil chlamydospores are markedly similar to the modern Endogonaceae in transmitted light, ultrastructural comparisons have not previously been made. The fine structure of the walls of these spores is consistent with past interpretations which relate them to the modern Endogonaceae, but thorough comparisons cannot be made due to the lack of comparable ultrastructural information from extant VA mycorrhizae. The evidence from mycorrhizal associations in the fossil record is evaluated

Impaired β-glucocerebrosidase activity and processing in frontotemporal dementia due to progranulin mutations.

Loss-of-function mutations in progranulin (GRN) are a major autosomal dominant cause of frontotemporal dementia. Most pathogenic GRN mutations result in progranulin haploinsufficiency, which is thought to cause frontotemporal dementia in GRN mutation carriers. Progranulin haploinsufficiency may drive frontotemporal dementia pathogenesis by disrupting lysosomal function, as patients with GRN mutations on both alleles develop the lysosomal storage disorder neuronal ceroid lipofuscinosis, and frontotemporal dementia patients with GRN mutations (FTD-GRN) also accumulate lipofuscin. The specific lysosomal deficits caused by progranulin insufficiency remain unclear, but emerging data indicate that progranulin insufficiency may impair lysosomal sphingolipid-metabolizing enzymes. We investigated the effects of progranulin insufficiency on sphingolipid-metabolizing enzymes in the inferior frontal gyrus of FTD-GRN patients using fluorogenic activity assays, biochemical profiling of enzyme levels and posttranslational modifications, and quantitative neuropathology. Of the enzymes studied, only β-glucocerebrosidase exhibited impairment in FTD-GRN patients. Brains from FTD-GRN patients had lower activity than controls, which was associated with lower levels of mature β-glucocerebrosidase protein and accumulation of insoluble, incompletely glycosylated β-glucocerebrosidase. Immunostaining revealed loss of neuronal β-glucocerebrosidase in FTD-GRN patients. To investigate the effects of progranulin insufficiency on β-glucocerebrosidase outside of the context of neurodegeneration, we investigated β-glucocerebrosidase activity in progranulin-insufficient mice. Brains from Grn-/- mice had lower β-glucocerebrosidase activity than wild-type littermates, which was corrected by AAV-progranulin gene therapy. These data show that progranulin insufficiency impairs β-glucocerebrosidase activity in the brain. This effect is strongest in neurons and may be caused by impaired β-glucocerebrosidase processing

T-cell derived acetylcholine aids host defenses during enteric bacterial infection with Citrobacter rodentium.

The regulation of mucosal immune function is critical to host protection from enteric pathogens but is incompletely understood. The nervous system and the neurotransmitter acetylcholine play an integral part in host defense against enteric bacterial pathogens. Here we report that acetylcholine producing-T-cells, as a non-neuronal source of ACh, were recruited to the colon during infection with the mouse pathogen Citrobacter rodentium. These ChAT+ T-cells did not exclusively belong to one Th subset and were able to produce IFNγ, IL-17A and IL-22. To interrogate the possible protective effect of acetylcholine released from these cells during enteric infection, T-cells were rendered deficient in their ability to produce acetylcholine through a conditional gene knockout approach. Significantly increased C. rodentium burden was observed in the colon from conditional KO (cKO) compared to WT mice at 10 days post-infection. This increased bacterial burden in cKO mice was associated with increased expression of the cytokines IL-1β, IL-6, and TNFα, but without significant changes in T-cell and ILC associated IL-17A, IL-22, and IFNγ, or epithelial expression of antimicrobial peptides, compared to WT mice. Despite the increased expression of pro-inflammatory cytokines during C. rodentium infection, inducible nitric oxide synthase (Nos2) expression was significantly reduced in intestinal epithelial cells of ChAT T-cell cKO mice 10 days post-infection. Additionally, a cholinergic agonist enhanced IFNγ-induced Nos2 expression in intestinal epithelial cell in vitro. These findings demonstrated that acetylcholine, produced by specialized T-cells that are recruited during C. rodentium infection, are a key mediator in host-microbe interactions and mucosal defenses

A Long, Hard Look at the Low-Hard State in Accreting Black Holes

We present the first results of coordinated multi-wavelength observations of the Galactic black hole GX 339-4 in a canonical low-hard state, obtained during its 2004 outburst. XMM-Newton observed the source for 2 revolutions, or approximately 280 ksec; RXTE monitored the source throughout this long stare. The resulting data offer the best view yet obtained of the inner accretion flow geometry in the low-hard state, which is thought to be analogous to the geometry in low-luminosity active galactic nuclei. The XMM-Newton spectra clearly reveal the presence of a cool accretion disk component, and a relativistic Fe K emission line. The results of fits made to both components strongly suggest that a standard thin disk remains at or near to the innermost stable circular orbit, at least in bright phases of the low-hard state. These findings indicate that potential links between the inner disk radius and the onset of a steady compact jet, and the paradigm of a radially-recessed disk in the low-hard state, do not hold universally. The results of our observations can best be explained if a standard thin accretion disk fuels a corona which is closely related to, or consistent with, the base of a compact jet. In a brief examination of archival data, we show that Cygnus X-1 supports this picture of the low/hard state. We discuss our results within the context of disk-jet connections and prevailing models for accretion onto black holes.Comment: 13 pages, 10 figures (6 in color), ApJ, in pres

In vivo magnetic resonance imaging of glucose - initial experience

A new noninvasive, nonradioactive approach for glucose imaging using spin hyperpolarization technology and stable isotope labeling is presented. A glucose analog labeled with 13C at all six positions increased the overall hyperpolarized imaging signal; deuteration at all seven directly bonded proton positions prolonged the spin-lattice relaxation time. High-bandwidth 13C imaging overcame the large glucose carbon chemical shift dispersion. Hyperpolarized glucose images in the live rat showed time-dependent organ distribution patterns. At 8s after the start of bolus injection, the inferior vena cava was demonstrated at angiographic quality. Distribution of hyperpolarized glucose in the kidneys, vasculature, and heart was demonstrated at 12 and 20s. The heart-to-vasculature intensity ratio at 20s suggests myocardial uptake. Cancer imaging, currently performed with 18F-deoxyglucose positron emission tomography (FDG-PET), warrants further investigation, and glucose imaging could be useful in a vast range of clinical conditions and research fields where the radiation associated with the FDG-PET examination limits its use. © 2012 John Wiley & Sons, Ltd

The Massive Progenitor of the Type II-Linear Supernova 2009kr

We present early-time photometric and spectroscopic observations of supernova (SN) 2009kr in NGC 1832. We find that its properties to date support its classification as Type II-linear (SN II-L), a relatively rare subclass of core-collapse supernovae (SNe). We have also identified a candidate for the SN progenitor star through comparison of pre-explosion, archival images taken with WFPC2 on board the Hubble Space Telescope with SN images obtained using adaptive optics plus NIRC2 on the 10 m Keck-II telescope. Although the host galaxy's substantial distance (similar to 26 Mpc) results in large uncertainties in the relative astrometry, we find that if this candidate is indeed the progenitor, it is a highly luminous (M(V)(0) = -7.8 mag) yellow supergiant with initial mass similar to 18-24 M(circle dot). This would be the first time that an SN II-L progenitor has been directly identified. Its mass may be a bridge between the upper initial mass limit for the more common Type II-plateau SNe and the inferred initial mass estimate for one Type II-narrow SN.Hungarian OTKA K76816NSF AST-0707769, AST-0908886Sylvia & Jim Katzman FoundationTABASGO FoundationNASA through STScI AR-11248, GO-10877Harvard UniversityUC BerkeleyUniversity of VirginiaNASA/Swift NNX09AQ66GDOEAstronom

The impact of surgeon volume and training status on implant alignment in total knee arthroplasty

BACKGROUND: Implant malalignment may predispose patients to prosthetic failure following total knee arthroplasty (TKA). A more thorough understanding of the surgeon-specific factors that contribute to implant malalignment following TKA may uncover actionable strategies for improving implant survival. The purpose of this study was to determine the impact of surgeon volume and training status on malalignment. METHODS: In this retrospective multicenter study, we performed a radiographic analysis of 1,570 primary TKAs performed at 4 private academic and state-funded centers in the U.S. and U.K. Surgeons were categorized as high-volume (≥50 TKAs/year) or low-volume (\u3c50 TKAs/year), and as a trainee (fellow/resident under the supervision of an attending surgeon) or a non-trainee (attending surgeon). On the basis of these designations, 3 groups were defined: high-volume non-trainee, low-volume non-trainee, and trainee. The postoperative medial distal femoral angle (DFA), medial proximal tibial angle (PTA), and posterior tibial slope angle (PSA) were radiographically measured. Outlier measurements were defined as follows: DFA, outside of 5° ± 3° of valgus; PTA, \u3e±3° deviation from the neutral axis; and PSA, \u3c0° or \u3e7° of flexion for cruciate-retaining or \u3c0° or \u3e5° of flexion for posterior-stabilized TKAs. Far outliers were defined as measurements falling \u3e± 2° outside of these ranges. The proportions of outliers were compared between the groups using univariate and multivariate analyses. RESULTS: When comparing the high and low-volume non-trainee groups using univariate analysis, the proportions of knees with outlier measurements for the PTA (5.3% versus 17.4%) and PSA (17.4% versus 28.3%) and the proportion of total outliers (11.8% versus 20.7%) were significantly lower in the high-volume group (all p \u3c 0.001). The proportions of DFA (1.9% versus 6.5%), PTA (1.8% versus 5.7%), PSA (5.5% versus 12.6%), and total far outliers (3.1% versus 8.3%) were also significantly lower in the high-volume non-trainee group (all p \u3c 0.001). Compared with the trainee group, the high-volume non-trainee group had significantly lower proportions of DFA (12.6% versus 21.6%), PTA (5.3% versus 12.0%), PSA (17.4% versus 33.3%), and total outliers (11.8% versus 22.3%) (all p \u3c 0.001) as well as DFA (1.9% versus 3.9%; p = 0.027), PSA (5.5% versus 12.6%; p \u3c 0.001), and total far outliers (3.1% versus 6.4%; p = 0.004). No significant differences were identified when comparing the low-volume non-trainee group and the trainee group, with the exception of PTA outliers (17.4% versus 12.0%; p = 0.041) and PTA far outliers (5.7% versus 2.6%; p = 0.033). Findings from multivariate analysis accounting for the effects of patient age, body mass index, and individual surgeon demonstrated similar results. CONCLUSIONS: Low surgical volume and trainee status were risk factors for outlier and far-outlier malalignment in primary TKA, even when accounting for differences in individual surgeon and patient characteristics. Trainee surgeons performed similarly, and certainly not inferiorly, to low-volume non-trainee surgeons. Even among high-volume non-trainees, the best-performing cohort in our study, the proportion of TKA alignment outliers was still high. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence