60 research outputs found
Downregulation of pyrophosphate: d-fructose-6-phosphate 1-phosphotransferase activity in sugarcane culms enhances sucrose accumulation due to elevated hexose-phosphate levels
Analyses of transgenic sugarcane clones with 45–95% reduced cytosolic pyrophosphate: d-fructose-6-phosphate 1-phosphotransferase (PFP, EC 2.7.1.90) activity displayed no visual phenotypical change, but significant changes were evident in in vivo metabolite levels and fluxes during internode development. In three independent transgenic lines, sucrose concentrations increased between three- and sixfold in immature internodes, compared to the levels in the wildtype control. There was an eightfold increase in the hexose-phosphate:triose-phosphate ratio in immature internodes, a significant restriction in the triose phosphate to hexose phosphate cycle and significant increase in sucrose cycling as monitored by 13C nuclear magnetic resonance. This suggests that an increase in the hexose-phosphate concentrations resulting from a restriction in the conversion of hexose phosphates to triose phosphates drive sucrose synthesis in the young internodes. These effects became less pronounced as the tissue matured. Decreased expression of PFP also resulted in an increase of the ATP/ADP and UTP/UDP ratios, and an increase of the total uridine nucleotide and, at a later stage, the total adenine nucleotide pool, revealing strong interactions between PPi metabolism and general energy metabolism. Finally, decreased PFP leads to a reduction of PPi levels in older internodes indicating that in these developmental stages PFP acts in the gluconeogenic direction. The lowered PPi levels might also contribute to the absence of increases in sucrose contents in the more mature tissues of transgenic sugarcane with reduced PFP activity
The Network Structure of Childhood Psychopathology in International Adoptees
International adoptees are at an increased risk of emotional and behavioral problems, especially those who are adopted at an older age. We took a new approach in our study of the network structure and predictability of emotional and behavioral problems in internationally adopted children in Finland. Our sample was from the on-going adoption study and comprised 778 internationally adopted children (387 boys and 391 girls, mean age 10.5 (SD 3.4) years). Networks were estimated using Gaussian graphical models and lasso regularization for all the children, and separately for those who were adopted at different ages. The results showed that anxiety/depressive symptoms, social problems, and aggressiveness were the most central symptom domains. Somatic symptoms were the least central and had the weakest effect on the other domains. Similarly, aggressiveness, social problems, and attention problems were high in terms of predictability (73-65%), whereas internalizing problems were relatively low (28-56%). There were clear but local age-group differences in network structure, symptom centrality, and predictability. According to our findings, network models provide important additional information about the centrality and predictability of specific symptom domains, and thus may facilitate targeted interventions among international adoptees.Peer reviewe
Stochastic Resonance Modulates Neural Synchronization within and between Cortical Sources
Neural synchronization is a mechanism whereby functionally specific brain regions establish transient networks for perception, cognition, and action. Direct addition of weak noise (fast random fluctuations) to various neural systems enhances synchronization through the mechanism of stochastic resonance (SR). Moreover, SR also occurs in human perception, cognition, and action. Perception, cognition, and action are closely correlated with, and may depend upon, synchronized oscillations within specialized brain networks. We tested the hypothesis that SR-mediated neural synchronization occurs within and between functionally relevant brain areas and thus could be responsible for behavioral SR. We measured the 40-Hz transient response of the human auditory cortex to brief pure tones. This response arises when the ongoing, random-phase, 40-Hz activity of a group of tuned neurons in the auditory cortex becomes synchronized in response to the onset of an above-threshold sound at its “preferred” frequency. We presented a stream of near-threshold standard sounds in various levels of added broadband noise and measured subjects' 40-Hz response to the standards in a deviant-detection paradigm using high-density EEG. We used independent component analysis and dipole fitting to locate neural sources of the 40-Hz response in bilateral auditory cortex, left posterior cingulate cortex and left superior frontal gyrus. We found that added noise enhanced the 40-Hz response in all these areas. Moreover, added noise also increased the synchronization between these regions in alpha and gamma frequency bands both during and after the 40-Hz response. Our results demonstrate neural SR in several functionally specific brain regions, including areas not traditionally thought to contribute to the auditory 40-Hz transient response. In addition, we demonstrated SR in the synchronization between these brain regions. Thus, both intra- and inter-regional synchronization of neural activity are facilitated by the addition of moderate amounts of random noise. Because the noise levels in the brain fluctuate with arousal system activity, particularly across sleep-wake cycles, optimal neural noise levels, and thus SR, could be involved in optimizing the formation of task-relevant brain networks at several scales under normal conditions
Dynamical decoupling and noise spectroscopy with a superconducting flux qubit
The characterization and mitigation of decoherence in natural and artificial
two-level systems (qubits) is fundamental to quantum information science and
its applications. Decoherence of a quantum superposition state arises from the
interaction between the constituent system and the uncontrolled degrees of
freedom in its environment. Within the standard Bloch-Redfield picture of
two-level system dynamics, qubit decoherence is characterized by two rates: a
longitudinal relaxation rate Gamma1 due to the exchange of energy with the
environment, and a transverse relaxation rate Gamma2 = Gamma1/2 + Gamma_phi
which contains the pure dephasing rate Gamma_phi. Irreversible energy
relaxation can only be mitigated by reducing the amount of environmental noise,
reducing the qubit's internal sensitivity to that noise, or through multi-qubit
encoding and error correction protocols (which already presume ultra-low error
rates). In contrast, dephasing is in principle reversible and can be refocused
dynamically through the application of coherent control pulse methods. In this
work we demonstrate how dynamical-decoupling techniques can moderate the
dephasing effects of low-frequency noise on a superconducting qubit with
energy-relaxation time T1 = 1/Gamma1 = 12 us. Using the CPMG sequence with up
to 200 pi-pulses, we demonstrate a 50-fold improvement in the transverse
relaxation time T2 over its baseline value. We observe relaxation-limited times
T2(CPMG) = 23 us = 2 T1 resulting from CPMG-mediated Gaussian pure-dephasing
times in apparent excess of 100 us. We leverage the filtering property of this
sequence in conjunction with Rabi and energy relaxation measurements to
facilitate the spectroscopy and reconstruction of the environmental noise power
spectral density.Comment: 21 pages (incl. 11-page appendix); 4 (+7) figure
Anti-type II collagen antibodies, anti-CCP, IgA RF and IgM RF are associated with joint damage, assessed eight years after onset of juvenile idiopathic arthritis (JIA)
Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.
Transposição do enxerto vascularizado da fíbula pro fêmur diafisário sem microanastomoses
Molecularly Characterized Factors Governing the Growth of Murine Multipotent Stem Cells in Serum-Depleted Marrow Cultures
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