TONs of copper fun: There is considerable interest in developing catalysts to harness the abundant natural supply of methane for various industrial applications. Two tricopper complexes capable of ...mediating efficient oxidation of methane to methanol under ambient conditions were tested: a biomimetic tricopper complex (see figure) and a tricopper‐peptide species derived from the particulate methane monooxygenase (pMMO) protein.
TRPA1 and TRPV1 are crucial pain mediators, but how their interaction contributes to persistent pain is unknown. Here, we identify Tmem100 as a potentiating modulator of TRPA1-V1 complexes. Tmem100 ...is coexpressed and forms a complex with TRPA1 and TRPV1 in DRG neurons. Tmem100-deficient mice show a reduction in inflammatory mechanical hyperalgesia and TRPA1- but not TRPV1-mediated pain. Single-channel recording in a heterologous system reveals that Tmem100 selectively potentiates TRPA1 activity in a TRPV1-dependent manner. Mechanistically, Tmem100 weakens the association of TRPA1 and TRPV1, thereby releasing the inhibition of TRPA1 by TRPV1. A Tmem100 mutant, Tmem100-3Q, exerts the opposite effect; i.e., it enhances the association of TRPA1 and TRPV1 and strongly inhibits TRPA1. Strikingly, a cell-permeable peptide (CPP) containing the C-terminal sequence of Tmem100-3Q mimics its effect and inhibits persistent pain. Our study unveils a context-dependent modulation of the TRPA1-V1 complex, and Tmem100-3Q CPP is a promising pain therapy.
•A unique context-dependent TRP channel regulation by disinhibitory mechanism•Tmem100 as a potentiating modulator of TRPA1 in the TRPA1-TRPV1 complex•Tmem100-mutant-derived cell-permeable peptide as novel pain therapeutics•The first mechanistic study of Tmem100, an important gene implicated in diseases
TRPA1 and TRPV1 are crucial pain mediators, but how their interaction contributes to persistent pain is unknown. Weng et al. identify Tmem100 as a potentiating modulator of TRPA1-V1 complexes. Targeting this modulation, they developed a strategy for blocking persistent pain.
Plasma membrane, proton-coupled Group II sucrose symporters (SUT) mediate apoplastic phloem loading and sucrose efflux from source leaves in Arabidopsis and agricultural crop species that have been ...studied to date. We now report that the most abundantly expressed SUT isoform in Populus tremula × alba, PtaSUT4, is a tonoplast (Group IV) symporter. PtaSUT4 transcripts were readily detected in conducting as well as mesophyll cells in stems and source leaves. In comparison, Group II orthologs PtaSUT1 and PtaSUT3 were very weakly expressed in leaves. Both Group II and Group IV SUT genes were expressed in secondary stem xylem of Populus. Transgenic poplars with RNAi-suppressed PtaSUT4 exhibited increased leaf-to-stem biomass ratios, elevated sucrose content in source leaves and stems, and altered phenylpropanoid metabolism. Transcript abundance of several carbohydrate-active enzymes and phenylalanine ammonia-lyases was also altered in transgenic source leaves. Nitrogen-limitation led to a down-regulation of vacuolar invertases in all plants, which resulted in an augmentation of sucrose pooling and hexose depletion in source leaves and secondary xylem of the transgenic plants. These results are consistent with a major role for PtaSUT4 in orchestrating the intracellular partitioning, and consequently, the efflux of sucrose from source leaves and the utilization of sucrose by lateral and terminal sinks. Our findings also support the idea that PtaSUT4 modulates sucrose efflux and utilization in concert with plant N-status.
The Telescope Array Experiment the largest extensive air-shower cosmic-ray detector in the northern hemisphere. TA combines three fluorescence detectors and a scintillation counter surface detector. ...The physics goals of TA are to measure the spectrum, composition, and arrival direction anisotropy of ultrahigh energy cosmic rays. We will present the latest results from Telescope Array.
This study examined the neural substrates underlying the implementation of phonological rule in lexical tone by the Tone 3 sandhi phenomenon in Mandarin Chinese. Tone 3 sandhi is traditionally ...described as the substitution of Tone 3 with Tone 2 when followed by another Tone 3 (33 →23) during speech production. Tone 3 sandhi enables the examination of tone processing in the phonological level with the least involvement of segments. Using the fMRI technique, we measured brain activations corresponding to the monosyllable and disyllable sequences of the four Chinese lexical tones, while manipulating the requirement on overt oral response. The application of Tone 3 sandhi to disyllable sequence of Tone 3 was confirmed by our behavioral results. Larger brain responses to overtly produced disyllable Tone 3 (33 > 11, 22, and 44) were found in right posterior IFG by both whole-brain and ROI analyses. We suggest that the right IFG was responsible for the processing of Tone 3 sandhi. Intense temporo-frontal interaction is needed in speech production for self-monitoring. The involvement of the right IFG in tone production might result from its interaction with the right auditory cortex, which is known to specialize in pitch. Future studies using tools with better temporal resolutions are needed to illuminate the dynamic interaction between the right inferior frontal regions and the left-lateralized language network in tone languages.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The response to lithium for the treatment of bipolar disease is variable. This genetic study showed a strong association between variants in
GADL1
and response to treatment in Han Chinese patients ...with bipolar I disease.
Bipolar disorder is a disabling mental illness that is characterized by episodes of both elevated or irritable mood and depression.
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,
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Currently, lithium is the first-line choice for maintenance treatment of bipolar disorder and reduces the risks of relapse and suicide.
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–
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Approximately 80% of patients with bipolar I disorder who are treated with lithium over the long term have at least a partial response,
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and 30% have an excellent response
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,
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with complete remission of symptoms observed in populations of patients of European descent.
Clinical predictors of a good response to lithium treatment have been reported, such as age . . .
The High Resolution Fly's Eye (HiRes) experiment has observed the Greisen-Zatsepin-Kuzmin suppression (called the GZK cutoff) with a statistical significance of five standard deviations. HiRes' ...measurement of the flux of ultrahigh energy cosmic rays shows a sharp suppression at an energy of 6 x 10(19) eV, consistent with the expected cutoff energy. We observe the ankle of the cosmic-ray energy spectrum as well, at an energy of 4 x 10(18) eV. We describe the experiment, data collection, and analysis and estimate the systematic uncertainties. The results are presented and the calculation of the statistical significance of our observation is described.
Paced breathing is a frequently performed technique for cardiovascular autonomic studies. The relative timing of inspiration and expiration during paced breathing, however, is not consistent. We, ...therefore, examined whether indexes of heart rate variability and spontaneous baroreflex sensitivity would be affected by the respiratory time ratio that is set. We studied 14 healthy young adults who controlled their breathing rates to either 0.1 or 0.25 Hz in the supine and sitting positions. Four different inspiratory-to-expiratory time ratios (I/E) (uncontrolled, 1:1, 1:2, and 1:3) were examined for each condition in a randomized order. The results showed spectral indexes of heart rate variability and spontaneous baroreflex sensitivity were not influenced by the I/E that was set during paced breathing under supine and sitting positions. Porta's and Guzik's indexes of heart rate asymmetry were also not different at various I/E during 0.1-Hz breathing, but had larger values at 1:1 during 0.25-Hz breathing, although significant change was found in the sitting position only. At the same time, Porta's and Guzik's indexes obtained during 0.1-Hz breathing were greater than during 0.25-Hz breathing in both positions. The authors suggest that setting the I/E during paced breathing is not necessary when measuring spectral indexes of heart rate variability and spontaneous baroreflex sensitivity under the conditions used in this study. The necessity of paced breathing for the measurement of heart rate asymmetry, however, requires further investigation.
We have searched for intermediate-scale anisotropy in the arrival directions of ultrahigh-energy cosmic rays with energies above 57 EeV in the northern sky using data collected over a 5 yr period by ...the surface detector of the Telescope Array experiment. We report on a cluster of events that we call the hotspot, found by oversampling using 20degrees radius circles. The hotspot has a Li-Ma statistical significance of 5.1sigma, and is centered at R.A. = 146degrees.7, decl. = 43degrees.2. The position of the hotspot is about 19degrees off of the supergalactic plane. The probability of a cluster of events of 5.1sigma significance, appearing by chance in an isotropic cosmic-ray sky, is estimated to be 3.7 x 10 super(-4) (3.4sigma).
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