cDNA clones corresponding to the entire length of mRNA for the alpha subunit of human pyruvate dehydrogenase (EC 1.2.4.1), the E1 component of the pyruvate dehydrogenase complex, have been isolated ...from liver cDNA libraries. Two classes of cDNA clones were obtained and these correspond to two forms of pyruvate dehydrogenase E1 alpha mRNA. Both mRNA species have been demonstrated in a variety of human tissues and cultured fibroblasts. The cDNA sequence has been determined and, from it, the protein sequence of the human E1 alpha subunit was deduced. The protein is synthesized with a typical mitochondrial import leader sequence and the peptide bond at which this sequence is cleaved after transport into the mitochondrion has been determined by direct amino acid sequencing of the mature E1 alpha subunit. The human pyruvate dehydrogenase E1 alpha subunit contains identical phosphorylation sites to those found in the corresponding porcine protein. Preliminary studies of pyruvate dehydrogenase E1 alpha mRNA in cultured fibroblasts from patients with severe pyruvate dehydrogenase deficiency have revealed considerable heterogeneity as would be expected from protein studies.
The incidence and effect of tissue cyst rupture in the brains of mice chronically infected with Toxoplasma gondii was studied by immunocytochemistry and electron microscopy. Cyst rupture was ...extremely rare (2 of 750 tissue cysts) irrespective of the interval post-infection. The event was associated with a rapid cell-mediated immune response, giving rise to microglial or inflammatory nodules. Macrophages were observed to engulf and degrade the cystozoites and cyst debris. Initially, the nodules contained large amounts of immunologically reactive material, but this was degraded with the majority (94%) of lesions containing no recognizable parasites or Toxoplasma antigens. There was little evidence of parasite multiplication or new cyst formation associated with cyst rupture. This study shows that although intermittent cyst rupture occurs, in immunocompetent individuals the immune response limits the potential damage from the release of large numbers of infective organisms to small microglial/inflammatory nodules.
1 Department of Physiology, University of Toronto; 2 Toronto Western Research Institute; and 3 Division of Neurosurgery, Toronto Western Hospital, Toronto, Ontario, Canada
Submitted 31 July 2008;
...accepted in final form 7 November 2008
Rest tremor is one of the main symptoms in Parkinson's disease (PD), although in contrast to rigidity and akinesia, the severity of the tremor does not correlate well with the degree of dopamine deficiency or the progression of the disease. Studies suggest that akinesia in PD patients is related to abnormal increased beta (15–30 Hz) and decreased gamma (35–80 Hz) synchronous oscillatory activity in the basal ganglia. Here we investigated the dynamics of oscillatory activity in the subthalamic nucleus (STN) during tremor. We used two adjacent microelectrodes to simultaneously record neuronal firing and local field potential (LFP) activity in nine PD patients who exhibited resting tremor during functional neurosurgery. We found that neurons exhibiting oscillatory activity at tremor frequency are located in the dorsal region of STN, where neurons with beta oscillatory activity are observed, and that their activity is coherent with LFP oscillations in the beta frequency range. Interestingly, in 85% of the 58 sites examined, the LFP exhibited increased oscillatory activity in the low gamma frequency range (35–55 Hz) during periods with stronger tremor. Furthermore, in 17 of 26 cases where two LFPs were recorded simultaneously, their coherence in the gamma range increased with increased tremor. When averaged across subjects, the ratio of the beta to gamma coherence was significantly lower in periods with stronger tremor compared with periods of no or weak tremor. These results suggest that resting tremor in PD is associated with an altered balance between beta and gamma oscillations in the motor circuits of STN.
Address for reprint requests and other correspondence: J. O. Dostrovsky, Dept of Physiology, Med Sci Bldg 3302, 1 King's College Circle, University of Toronto, Toronto, ON M5S 1A8, Canada (E-mail: j.dostrovsky{at}utoronto.ca )
Drosophila suzukii Matsumura, often called spotted wing drosophila, is an exotic vinegar fly that is native to Southeast Asia and was first detected in the continental United States in 2008. Previous ...modeling studies have suggested that D. suzukii might not survive in portions of the northern United States or southern Canada due to the effects of cold. As a result, we measured two aspects of insect cold tolerance, the supercooling point and lower lethal temperature, for D. suzukii summer-morph pupae and adults and winter-morph adults. Supercooling points were compared to adults of Drosophila melanogaster Meigen. The lower lethal temperature of D. suzukii winter-morph adults was significantly colder than that for D. suzukii summer-morph adults, while supercooling points of D. suzukii winter-morph adults were actually warmer than that for D. suzukii summer-morph adults and pupae. D. suzukii summer-morph adult supercooling points were not significantly different than those for D. melanogaster adults. These measures indicate that D. suzukii is a chill intolerant insect, and winter-morph adults are the most cold-tolerant life stage. These results can be used to improve predictions of where D. suzukii might be able to establish overwintering populations and cause extensive damage to spring fruit crops.
Abstract
We present JWST/NIRSpec prism spectroscopy of seven galaxies selected from Cosmic Evolution Early Release Science (CEERS) survey NIRCam imaging with photometric redshifts
z
phot
> 8. We ...measure emission line redshifts of
z
= 7.65 and 8.64 for two galaxies. For two other sources without securely detected emission lines we measure
z
=
9.77
−
0.29
+
0.37
and
10.01
−
0.19
+
0.14
by fitting model spectral templates to the prism data, from which we detect continuum breaks consistent with Ly
α
opacity from a mostly neutral intergalactic medium. The presence of strong breaks and the absence of strong emission lines give high confidence that these two galaxies have redshifts
z
> 9.6, but the redshift values derived from the breaks alone have large uncertainties given the low spectral resolution and relatively low S/N of the CEERS NIRSpec prism data. The two
z
∼ 10 sources observed are relatively luminous (
M
UV
< −20), with blue continua (−2.3 ≲
β
≲ −1.9) and low dust attenuation (
A
V
≃
0.15
−
0.1
+
0.3
); and at least one of them has a high stellar mass for a galaxy at that redshift (
log
(
M
⋆
/
M
⊙
)
≃
9.3
−
0.3
+
0.2
). Considered together with spectroscopic observations of other CEERS NIRCam-selected high-
z
galaxy candidates in the literature, we find a high rate of redshift confirmation and low rate of confirmed interlopers (8%). Ten out of 35
z
> 8 candidates with CEERS NIRSpec spectroscopy do not have secure redshifts, but the absence of emission lines in their spectra is consistent with redshifts
z
> 9.6. We find that
z
> 8 photometric redshifts are generally in agreement (within their uncertainties) with the spectroscopic values, but also that the photometric redshifts tend to be slightly overestimated (〈Δ
z
〉 = 0.45 ± 0.11), suggesting that current templates do not fully describe the spectra of very-high-
z
sources. Overall, the spectroscopy solidifies photometric redshift evidence for a high spatial density of bright galaxies at
z
> 8 compared to theoretical model predictions, and further disfavors an accelerated decline in the integrated UV luminosity density at
z
> 8.
Abstract
We report on the discovery of two low-luminosity, broad-line active galactic nuclei (AGNs) at
z
> 5 identified using JWST NIRSpec spectroscopy from the Cosmic Evolution Early Release Science ...(CEERS) survey. We detect broad H
α
emission in the spectra of both sources, with FWHM of 2060 ± 290 km s
−1
and 1800 ± 200 km s
−1
, resulting in virial black hole (BH) masses that are 1–2 dex below those of existing samples of luminous quasars at
z
> 5. The first source, CEERS 2782 at
z
= 5.242, is 2–3 dex fainter than known quasars at similar redshifts and was previously identified as a candidate low-luminosity AGN based on its morphology and rest-frame optical spectral energy distribution (SED). We measure a BH mass of
M
BH
= (1.3 ± 0.4) × 10
7
M
⊙
, confirming that this AGN is powered by the least massive BH known in the Universe at the end of cosmic reionization. The second source, CEERS 746 at
z
= 5.624, is inferred to be a heavily obscured, broad-line AGN caught in a transition phase between a dust-obscured starburst and an unobscured quasar. We estimate its BH mass to be in the range of
M
BH
≃ (0.9–4.7) × 10
7
M
⊙
, depending on the level of dust obscuration assumed. We perform SED fitting to derive host stellar masses,
M
⋆
, allowing us to place constraints on the BH–galaxy mass relationship in the lowest mass range yet probed in the early Universe. The
M
BH
/
M
⋆
ratio for CEERS 2782, in particular, is consistent with or higher than the empirical relationship seen in massive galaxies at
z
= 0. We examine the narrow emission line ratios of both sources and find that their location on the BPT and OHNO diagrams is consistent with model predictions for moderately low metallicity AGNs with
Z
/
Z
⊙
≃ 0.2–0.4. The spectroscopic identification of low-luminosity, broad-line AGNs at
z
> 5 with
M
BH
≃ 10
7
M
⊙
demonstrates the capability of JWST to push BH masses closer to the range predicted for the BH seed population and provides a unique opportunity to study the early stages of BH–galaxy assembly.
Higher-order cognition emerges through the flexible interactions of large-scale brain networks, an aspect of temporal coordination that may be impaired in psychosis. Here, we map the dynamic ...functional architecture of the cerebral cortex in healthy young adults, leveraging this atlas of transient network configurations (states), to identify state- and network-specific disruptions in patients with schizophrenia and psychotic bipolar disorder. We demonstrate that dynamic connectivity profiles are reliable within participants, and can act as a fingerprint, identifying specific individuals within a larger group. Patients with psychotic illness exhibit intermittent disruptions within cortical networks previously associated with the disease, and the individual connectivity profiles within specific brain states predict the presence of active psychotic symptoms. Taken together, these results provide evidence for a reconfigurable dynamic architecture in the general population and suggest that prior reports of network disruptions in psychosis may reflect symptom-relevant transient abnormalities, rather than a time-invariant global deficit.
A new class of dialysis membrane, the mid cut-off (MCO) dialyzer, has been developed to improve the clearance of uremic toxins in hemodialysis (HD). The a tRial Evaluating Mid cut-Off Value membrane ...clearance of Albumin and Light chains in HemoDialysis patients (REMOVAL-HD) study aimed to determine if regular use of MCO dialyzer was safe and specifically did not result in a significant loss of albumin.
This investigator initiated, crossover, longitudinal, device study was conducted across 9 centers in Australia and New Zealand (n = 89). Participants had a 4-week wash-in with high-flux HD, followed by 24-week intervention with MCO HD and a subsequent 4-week wash-out with high-flux HD. The primary outcome was change in serum albumin between weeks 4 and 28. Secondary outcomes included trends in serum albumin, changes in kappa- and lambda-free light chains (FLC), 6-min walk test (6MWT), malnutrition inflammation score (MIS), restless legs score and quality of life.
Participants had a mean age of 66 ± 14 years, 62% were men, 45% were anuric, and 51% had -diabetes. There was no reduction in serum albumin following treatment with MCO HD (mean reduction -0.7 g/L, 95% CI -1.5 to 0.1). A sustained, unexplained reduction in serum albumin (>25%) was not observed in any participant. A reduction in FLC was observed 2 weeks into MCO HD (lambda-FLC: Δ -9.1 mg/L, 95% CI -14.4 to -3.7; kappa-FLC: Δ -5.7 mg/L, 95% CI -9.8 to -1.6) and was sustained for the rest of the study intervention. Both FLC increased after the cessation of MCO use. There was no improvement in restless legs symptoms, quality of life, 6MWT or MIS scores.
Regular HD using the MCO dialyzer did not result in a significant fall in serum albumin. There were no effects on quality of life, functional status or nutrition.
Australian New Zealand Clinical Trials Registry Number (ANZCTRN) 12616000804482.
Abstract
We report the discovery of an accreting supermassive black hole at
z
= 8.679. This galaxy, denoted here as CEERS_1019, was previously discovered as a Ly
α
-break galaxy by Hubble with a Ly
α
...redshift from Keck. As part of the Cosmic Evolution Early Release Science (CEERS) survey, we have observed this source with JWST/NIRSpec, MIRI, NIRCam, and NIRCam/WFSS and uncovered a plethora of emission lines. The H
β
line is best fit by a narrow plus a broad component, where the latter is measured at 2.5
σ
with an FWHM ∼1200 km s
−1
. We conclude this originates in the broadline region of an active galactic nucleus (AGN). This is supported by the presence of weak high-ionization lines (N V, N IV, and C III), as well as a spatial point-source component. The implied mass of the black hole (BH) is log (
M
BH
/
M
⊙
) = 6.95 ± 0.37, and we estimate that it is accreting at 1.2 ± 0.5 times the Eddington limit. The 1–8
μ
m photometric spectral energy distribution shows a continuum dominated by starlight and constrains the host galaxy to be massive (log M/M
⊙
∼9.5) and highly star-forming (star formation rate, or SFR ∼ 30 M
⊙
yr
−1
; log sSFR ∼ − 7.9 yr
−1
). The line ratios show that the gas is metal-poor (
Z
/
Z
⊙
∼ 0.1), dense (
n
e
∼ 10
3
cm
−3
), and highly ionized (log
U
∼ − 2.1). We use this present highest-redshift AGN discovery to place constraints on BH seeding models and find that a combination of either super-Eddington accretion from stellar seeds or Eddington accretion from very massive BH seeds is required to form this object.
Doped metal oxide nanocrystals that exhibit tunable localized surface plasmon resonances (LSPRs) represent an intriguing class of nanomaterials that show promise for a variety of applications from ...spectroscopy to sensing. LSPRs arise in these materials through the introduction of aliovalent dopants and lattice oxygen vacancies. Tuning the LSPR shape and energy is generally accomplished through controlling the concentration or identity of dopants in a nanocrystal, but the lack of finer synthetic control leaves several fundamental questions unanswered regarding the effects of radial dopant placement, size, and nanocrystalline architecture on the LSPR energy and damping. Here, we present a layer-by-layer synthetic method for core/shell nanocrystals that permits exquisite and independent control over radial dopant placement, absolute dopant concentration, and nanocrystal size. Using Sn-doped In2O3 (ITO) as a model LSPR system, we synthesized ITO/In2O3 core/shell as well as In2O3/ITO core/shell nanocrystals with varying shell thickness, and investigated the resulting optical properties. We observed profound influence of radial dopant placement on the energy and linewidth of the LSPR response, noting (among other findings) that core-localized dopants produce the highest values for LSPR energies per dopant concentration, and display the lowest damping in comparison to nanocrystals with shell-localized or homogeneously distributed dopants. Inactive Sn dopants present on ITO nanocrystal surfaces are activated upon the addition of a subnanometer thick undoped In2O3 shell. We show how LSPR energy can be tuned fully independent of dopant concentration, relying solely on core/shell architecture. Finally, the impacts of radial dopant placement on damping, independent of LSPR energy, are explored.
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