The timing of heading is largely affected by environmental conditions. In wheat, Vrn-1 and Ppd-1 have been identified as the major genes involved in vernalization requirement and photoperiod ...sensitivity, respectively. To compare the effects of Vrn-1 and Ppd-1 alleles on heading time under different environments, we genotyped Vrn-1 and Ppd-1 homoeologues and measured the heading time at Morioka, Tsukuba and Chikugo in Japan for two growing seasons. A total of 128 Japanese and six foreign varieties, classified into four populations based on the 519 genome-wide SNPs, were used for analysis. Varieties with the spring alleles (Vrn-D1a or Vrn-D1b) at the Vrn-D1 locus and insensitive allele (Hapl-I) at the Ppd-D1 locus were found in earlier heading varieties. The effects of Vrn-D1 and Ppd-D1 on heading time were stronger than those of the other Vrn-1 and Ppd-1 homoeologues. Analysis of variance revealed that heading time was significantly affected by the genotype-environment interactions. Some Vrn-1 and Ppd-1 alleles conferred earlier or later heading in specific environments, indicating that the effect of both alleles on the timing of heading depends on the environment. Information on Vrn-1 and Ppd-1 alleles, together with heading time in various environments, provide useful information for wheat breeding.
Highlights • Acute cardiac support with DOB improves hypoperfusion early after SAH. • The DOB effects can lead to lower incidence of DCI and better functional outcomes. • The DOB-mediated outcomes ...were attenuated by a HIF inhibitor 2ME2 pretreatment. • Neurocardiac protection with DOB can promote recovery from post-SAH EBI.
Pseudo-continuous arterial spin labeling (pCASL) is a completely non-invasive method of cerebral perfusion measurement. However, cerebral blood flow (CBF) quantification is hampered by arterial ...transit artifacts characterized by bright vascular signals surrounded by decreased signals in tissue regions, which commonly appear in patients with reduced cerebral perfusion pressure. The spatial coefficient of variation (CoV) of pCASL CBF images has been proposed as an alternative region-of-interest (ROI)-based hemodynamic measure to predict prolonged arterial transit time (ATT). This retrospective study investigates the utility of spatial CoV by comparison with 15O positron emission tomography (PET). For patients with cerebrovascular steno-occlusive disease (n = 17), spatial CoV was positively correlated with ATT independently measured by pulsed arterial spin labeling (r = 0.597, p < 0.001), confirming its role as an ATT-like hemodynamic measure. Comparisons with 15O PET demonstrated that spatial CoV was positively correlated with vascular mean transit time (r = 0.587, p < 0.001) and negatively correlated with both resting CBF (r = −0.541, p = 0.001) and CBF response to hypercapnia (r = −0.373, p = 0.030). ROI-based spatial CoV calculated from single time-point pCASL can potentially detect subtle perfusion abnormalities in clinical settings.
Regional cerebral blood flow (CBF) and oxygen metabolism can be measured by positron emission tomography (PET) with 15O-labeled compounds. Hemoglobin (Hb) concentration of blood, a primary ...determinant of arterial oxygen content (CaO2), influences cerebral circulation. We investigated interindividual variations of CBF, cerebral blood volume (CBV), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) in relation to Hb concentration in healthy human volunteers (n=17) and in patients with unilateral steno-occlusive disease (n=44). For the patients, data obtained only from the contralateral hemisphere (normal side) were analyzed. The CBF and OEF were inversely correlated with Hb concentration, but CMRO2 was independent of Hb concentration. Oxygen delivery defined as a product of CaO2 and CBF (CaO2 CBF) increased with a rise of Hb concentration. The analysis with a simple oxygen model showed that oxygen diffusion parameter (L) was constant over the range of Hb concentration, indicating that a homeostatic mechanism controlling CBF is necessary to maintain CMRO2. The current findings provide important knowledge to understand the control mechanism of cerebral circulation and to interpret the 15O PET data in clinical practice.
Adaptive thermogenesis is essential for survival, and therefore is tightly regulated by a central neural circuit. Here, we show that microRNA (miR)-33 in the brain is indispensable for adaptive ...thermogenesis. Cold stress increases miR-33 levels in the hypothalamus and miR-33
mice are unable to maintain body temperature in cold environments due to reduced sympathetic nerve activity and impaired brown adipose tissue (BAT) thermogenesis. Analysis of miR-33
dopamine-β-hydroxylase (DBH)-Cre mice indicates the importance of miR-33 in Dbh-positive cells. Mechanistically, miR-33 deficiency upregulates gamma-aminobutyric acid (GABA)
receptor subunit genes such as Gabrb2 and Gabra4. Knock-down of these genes in Dbh-positive neurons rescues the impaired cold-induced thermogenesis in miR-33
DBH-Cre mice. Conversely, increased gene dosage of miR-33 in mice enhances thermogenesis. Thus, miR-33 in the brain contributes to maintenance of BAT thermogenesis and whole-body metabolism via enhanced sympathetic nerve tone through suppressing GABAergic inhibitory neurotransmission. This miR-33-mediated neural mechanism may serve as a physiological adaptive defense mechanism for several stresses including cold stress.
Growing evidence has indicated that cellular reduction/oxidation (redox)
status regulates various aspects of cellular function. Oxidative stress can
elicit positive responses such as cellular ...proliferation or activation, as well
as negative responses such as growth inhibition or cell death. Cellular redox
status is maintained by intracellular redox-regulating molecules, including
thioredoxin (TRX). TRX is a small multifunctional protein that has a
redox-active disulfide/dithiol within the conserved active site sequence:
Cys-Gly-Pro-Cys. Adult T cell leukemia-derived factor (ADF), which we
originally defined as an IL-2 receptor α-chain/Tac inducer produced by
human T cell lymphotrophic virus-I (HTLV-I)-transformed T cells, has been
identified as human TRX. TRX/ADF is a stress-inducible protein secreted from
cells. TRX/ADF has both intracellular and extracellular functions as one of the
key regulators of signaling in the cellular responses against various stresses.
Extracellularly, TRX/ADF shows a cytoprotective activity against oxidative
stress-induced apoptosis and a growth-promoting effect as an autocrine
growth factor. Intracellularly, TRX/ADF is involved in the regulation of
protein-protein or protein-nucleic acid interactions through the
reduction/oxidation of protein cysteine residues. For example, TRX/ADF
translocates from the cytosol into the nucleus by a variety of cellular
stresses, to regulate the expression of various genes through the redox
factor-1 (Ref-1)/APEX. Further studies to clarify the regulatory roles of
TRX/ADF and its target molecules may elucidate the intracellular signaling
pathways in the responses against various stresses. The concept of "redox
regulation" is emerging as an understanding of the novel mechanisms in
the pathogenesis of several disorders, including viral infections,
immunodeficiency, malignant transformation, and degenerative disease.
Spinal cord injury (SCI) is a devastating mechanical trauma. Although locomotion of model animals that mimic contusion SCI was actively examined, locomotion after penetrating SCI caused by sharp ...objects was not extensively studied. Severity of walking difficulty after partial transection of the spinal cord including penetrating SCI likely depends on the regions affected. Therefore, we compared beam walking and overground walking between mice after penetrating SCI at inner spinal cord region and mice with the injury at the outer region. Mice with the both penetrating SCIs did not display changes in beam walking. When appearance and movements of hindlimbs during overground walking was rated using Basso Mouse Scale for locomotion (BMS), however, mice with inner penetrating SCI showed low score shortly after the SCI. However, the score became high at later time points, as seen in contusion SCI mice. By contrast, BMS score did not decrease shortly after the outer penetrating SCI. However, the score became low 3 weeks after the SCI. As quantitative values during overground walking, movement duration in an open field were shorter at 1 day after the two penetrating SCIs. However, slower moving speed and fewer number of movement at 1 day were specific to mice with inner and outer penetrating SCIs, respectively. Moreover, BMS score was correlated with walking distance in open field only in mice with inner penetrating SCI. Thus, inner and outer penetrating SCI cause difficulty in overground walking with different severity and progress.
•Procedure to produce penetrating spinal cord injury (SCI) was established.•Inner and outer penetrating spinal cord injuries lead to distinct progress of overground walking pattern.•Hindlimb movements were correlated to walking distance in open field only in mice with inner penetrating SCI.
•The aggregated polyglutamine induced neurite retraction of neuron-like cells.•The aggregated polyglutamine led to deficits in neuron-like differentiation.•FEL irradiation restored the retraction and ...the disturbed differentiation.
Proteins containing an expanded polyglutamine tract tend to aggregate, leading to the neuronal damage observed in polyglutamine diseases. We recently reported that free electron laser (FEL) irradiation markedly dissociates naked polyglutamine aggregates as well as the aggregate in the 293 T cells. In the present study, we investigated whether FEL irradiation of neuron-like cells with polyglutamine aggregates would restore the cellular damage and dysfunction. The aggregated polyglutamine peptides induced neurite retraction of differentiated SH-SY5Y cells. Upon FEL irradiation, the polyglutamine aggregates in the SH-SY5Y cells were dissociated, and the shorter length of individual neurite, fewer number of neurites per cell and shorter total length of neurite by polyglutamine were inhibited. Same results were essentially obtained in PC12 cells. Moreover, when FEL irradiation was applied to undifferentiated SH-SY5Y cells, the deficits in neuron-like differentiation seen in expanded polyglutamine peptide-containing cells were also rescued. Thus, FEL irradiation restored both the damage and differentiation caused by polyglutamine in neuron-like cells.
A quantitative description of glyco-alteration/differences in diseases can lead to the development of a diagnostic agent for use in vitro to monitor the degree of change in target glycoproteins. ...Analytical systems have been developed along with the progress of omics-oriented technologies. For clinical implementation, their full automation is required with an apparatus that is simple to operate. Here, we report an automatic analysis system for quantitative characterization of glyco-alteration/differences that depends on the unique strategy of “bead arrays in a single tip.” The alternative lectin array can obtain a minimum characterization of the glycan profile for nanogram quantities of an endogenous glycoprotein. A simple autopipetting robot produces the precise chemiluminescence detection of glycan–lectin interactions with a wide dynamic range that is superior to fluorescence-based lectin arrays. The tip-based array format enables automatic glycan profiling from sample pretreatment to detection with low variation and linear detection, which may facilitate the use of this lectin array in clinical practice.
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