Key message
The multiple derivative lines (MDLs) characterized in this study offer a promising strategy for harnessing the diversity of wild emmer wheat for durum and bread wheat improvement.
Crop ...domestication has diminished genetic diversity and reduced phenotypic plasticity and adaptation. Exploring the adaptive capacity of wild progenitors offer promising opportunities to improve crops. We developed a population of 178 BC
1
F
6
durum wheat (
Triticum turgidum
ssp
. durum
) lines by crossing and backcrossing nine wild emmer wheat (
T. turgidum
ssp
. dicoccoides
) accessions with the common durum wheat cultivar ‘Miki 3’. Here, we describe the development of this population, which we named as multiple derivative lines (MDLs), and demonstrated its suitability for durum wheat breeding. We genotyped the MDL population, the parents, and 43 Sudanese durum wheat cultivars on a Diversity Array Technology sequencing platform. We evaluated days to heading and plant height in Dongola (Sudan) and in Tottori (Japan). The physical map length of the MDL population was 9 939 Mb with an average of 1.4 SNP/Mb. The MDL population had greater diversity than the Sudanese cultivars. We found high gene exchange between the nine wild emmer accessions and the MDL population, indicating that the MDL captured most of the diversity in the wild emmer accessions. Genome-wide association analysis identified three loci for days to heading on chromosomes 1A and 5A in Dongola and one on chromosome 3B in Tottori. For plant height, common genomic loci were found on chromosomes 4A and 4B in both locations, and one genomic locus on chromosome 7B was found only in Dongola. The results revealed that the MDLs are an effective strategy towards harnessing wild emmer wheat diversity for wheat genetic improvement.
Abstract
The presence of the apparently extended hard (2–10 keV) X-ray emission along the Galactic plane has been known since the early 1980s. With a deep X-ray exposure using the Chandra X-ray ...Observatory of a slightly off-plane region in the Galactic bulge, most of the extended emission was resolved into faint discrete X-ray sources in the Fe K band (Revnivtsev et al. 2009, Nature, 458, 1142). The major constituents of these sources have long been considered to be X-ray active stars and magnetic cataclysmic variables (CVs). However, recent works including our near-infrared (NIR) imaging and spectroscopic studies (Morihana et al. 2013, ApJ, 766, 14; Morihana et al. 2016, PASJ, 68, 57) argue that other populations should be more dominant. To investigate this further, we conducted a much deeper NIR imaging observation at the center of the Chandra’s exposure field. We have used the MOIRCS on the Subaru telescope, reaching the limiting magnitude of ∼18 mag in the J, H, and Ks bands in this crowded region, and identified ${\sim}50\%$ of the X-ray sources with NIR candidate counterparts. We classified the X-ray sources into three groups (A, B, and C) based on their positions in the X-ray color–color diagram and characterized them based on the X-ray and NIR features. We argue that the major populations of the Group A and C sources are, respectively, CVs (binaries containing magnetic or non-magnetic white dwarfs with high accretion rates) and X-ray active stars. The major population of the Group B sources is presumably white dwarf (WD) binaries with low mass accretion rates. The Fe K equivalent width in the composite X-ray spectrum of the Group B sources is the largest among the three and comparable to that of the Galactic bulge X-ray emission. This leads us to speculate that there are numerous WD binaries with low mass accretion rates which are not recognized as CVs but are the major contributor of the apparently extended X-ray emission.
During transduction of an apoptotic (death) signal into the cell, there is an alteration in the permeability of the membranes of the cell's mitochondria, which causes the translocation of the ...apoptogenic protein cytochrome c into the cytoplasm, which in turn activates death-driving proteolytic proteins known as caspases. The Bcl-2 family of proteins, whose members may be anti-apoptotic or pro-apoptotic, regulates cell death by controlling this mitochondrial membrane permeability during apoptosis, but how that is achieved is unclear. Here we create liposomes that carry the mitochondrial porin channel (also called the voltage-dependent anion channel, or VDAC) to show that the recombinant pro-apoptotic proteins Bax and Bak accelerate the opening of VDAC, whereas the anti-apoptotic protein Bcl-xL closes VDAC by binding to it directly. Bax and Bak allow cytochrome c to pass through VDAC out of liposomes, but passage is prevented by Bcl-xL. In agreement with this, VDAC1-deficient mitochondria from a mutant yeast did not exhibit a Bax/Bak-induced loss in membrane potential and cytochrome c release, both of which were inhibited by Bcl-xL. Our results indicate that the Bcl-2 family of proteins bind to the VDAC in order to regulate the mitochondrial membrane potential and the release of cytochrome c during apoptosis.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Humour‐based interventions are defined as any intervention that promotes health and wellness by stimulating a playful discovery, expression, or appreciation of the absurdity or incongruity ...of life's situations. Humour‐based interventions can be implemented in different settings, including hospitals, nursing homes and day care centres. They have been posed as an adjunct to usual care for people with schizophrenia, but a summary of the evidence is lacking.
Objectives
To examine the effects of humour‐based interventions as an add‐on intervention to standard care for people with schizophrenia.
Search methods
On 31 July 2019 and 10 February 2021 we searched the Cochrane Schizophrenia Group's study‐based register of trials, which is based on CENTRAL, CINAHL, ClinicalTrials.Gov, Embase, ISRCTN, MEDLINE, PsycINFO, PubMed, and WHO ICTRP.
Selection criteria
We included all randomised controlled trials comparing humour‐based interventions with active controls, other psychological interventions, or standard care for people with schizophrenia. We excluded studies fulfilling our prespecified selection criteria but without useable data from further quantitative synthesis.
Data collection and analysis
Two review authors independently inspected citations, selected studies, extracted data and appraised study quality, following the guidance from the Cochrane Handbook for Systematic Reviews of Interventions. For binary outcomes we calculated risk ratios (RRs) and their 95% confidence intervals (CIs). For continuous outcomes we calculated the mean differences (MDs) and their 95% CIs. We assessed risks of bias for included studies and created summary of findings tables using the GRADE approach.
Main results
We included three studies in this review for qualitative synthesis, although one study did not report any relevant outcomes. We therefore include two studies (n = 96) in our quantitative synthesis. No data were available on the following prespecified primary outcomes: clinically‐important change in general mental state, clinically‐important change in negative symptoms, clinically‐important change in overall quality of life, and adverse effects. As compared with active control, humour‐based interventions may not improve the average endpoint score of a general mental state scale (Positive and Negative Syndrome Scale (PANSS) total score: MD −1.70, 95% CI −17.01 to 13.61; 1 study, 30 participants; very low certainty of evidence); positive symptoms (PANSS positive symptom score: MD 0.00, 95% CI −2.58 to 2.58; 1 study, 30 participants; low certainty of evidence), negative symptoms (PANSS negative symptom score: MD −0.70, 95% CI −4.22 to 2.82; 1 study, 30 participants; very low certainty of evidence) and anxiety (State‐Trait Anxiety Inventory (STAI): MD −2.60, 95% CI −5.76 to 0.56; 1 study, 30 participants; low certainty of evidence). Due to the small sample size, we remain uncertain about the effect of humour‐based interventions on leaving the study early as compared with active control (no event, 1 study, 30 participants; very low certainty of evidence). On the other hand, humour‐based interventions may reduce depressive symptoms (Beck Depression Inventory (BDI): MD −6.20, 95% CI −12.08 to −0.32; 1 study, 30 participants; low certainty of evidence). Compared with standard care, humour‐based interventions may not improve depressive symptoms (BDI second edition: MD 0.80, 95% CI −2.64 to 4.24; 1 study, 59 participants; low certainty of evidence). We are uncertain about the effect of humour‐based interventions on leaving the study early for any reason compared with standard care (risk ratio 0.38, 95% CI 0.08 to 1.80; 1 study, 66 participants; very low certainty of evidence).
Authors' conclusions
We are currently uncertain whether the evidence supports the use of humour‐based interventions in people with schizophrenia. Future research with rigorous and transparent methodology investigating clinically important outcomes is warranted.
Microbubbles are tiny bubbles with a particle size of 1 - 100 μm. Microbubbles have been reported that the gas dissolving ability is excellent and hydroxyl radical generates when microbubbles ...collapse in water. On the other hand, ozone is a gas with high oxidation power and eventually decomposes into oxygen. So, ozone is environmentally friendly. Therefore, we thought that ozone microbubbles water, in which ozone is dissolved in microbubbles water, could be used to efficiently decompose persistent organic compounds while being environmentally friendly. In this study, we evaluated the decomposition of phenol, an object subject to wastewater regulation, by ozone water and ozone microbubbles water. At a constant dissolved ozone concentration, we could not confirm the effect of microbubbles in decomposing phenol. Also, under the same conditions, when the pH was changed, the effect of microbubbles could not be confirmed. However, under basic conditions, phenol was decomposed the most because of self-decomposition reaction of ozone. Therefore, the effect of microbubbles could not be confirmed in the phenol degradation by ozone microbubbles in this experiment.
The maintenance of energy homeostasis is essential for life, and its dysregulation leads to a variety of metabolic disorders. Under a fed condition, mammals use glucose as the main metabolic fuel, ...and short-chain fatty acids (SCFAs) produced by the colonic bacterial fermentation of dietary fiber also contribute a significant proportion of daily energy requirement. Under ketogenic conditions such as starvation and diabetes, ketone bodies produced in the liver from fatty acids are used as the main energy sources. To balance energy intake, dietary excess and starvation trigger an increase or a decrease in energy expenditure, respectively, by regulating the activity of the sympathetic nervous system (SNS). The regulation of metabolic homeostasis by glucose is well recognized; however, the roles of SCFAs and ketone bodies in maintaining energy balance remain unclear. Here, we show that SCFAs and ketone bodies directly regulate SNS activity via GPR41, a Gi/o protein-coupled receptor for SCFAs, at the level of the sympathetic ganglion. GPR41 was most abundantly expressed in sympathetic ganglia in mouse and humans. SCFA propionate promoted sympathetic outflow via GPR41. On the other hand, a ketone body, β-hydroxybutyrate, produced during starvation or diabetes, suppressed SNS activity by antagonizing GPR41. Pharmacological and siRNA experiments indicated that GPR41-mediated activation of sympathetic neurons involves Gβγ-PLCβ-MAPK signaling. Sympathetic regulation by SCFAs and ketone bodies correlated well with their respective effects on energy consumption. These findings establish that SCFAs and ketone bodies directly regulate GPR41-mediated SNS activity and thereby control body energy expenditure in maintaining metabolic homeostasis.
The Bcl-2 family of proteins that consists of anti-apoptotic and pro-apoptotic members determines life-or-death of a cell by controlling the release of mitochondrial apoptogenic factors, cytochrome
c ...and apoptosis-inducing factor (AIF), that activate downstream executional phases, including the activation of death proteases called caspases. Cytochrome
c release is, thus, central to apoptotic signal transduction in mammals, making study of the mechanism for cytochrome
c release a major issue. Several models for cytochrome
c release have been proposed, including rupture of mitochondrial outer membrane and involvement of a specific channel. Here, we provide an overview of recent findings on the role of Bcl-2 family members in the life-or-death decision of a cell.
We aimed to compare the effects of vitamin C, glucocorticoids, vitamin B1, combinations of these drugs, and placebo or usual care on longer-term mortality in adults with sepsis or septic shock. ...MEDLINE, Embase, CENTRAL, ClinicalTrials.gov and WHO-ICTRP were searched. The final search was carried out on September 3rd, 2021. Multiple reviewers independently selected randomized controlled trials (RCTs) comparing very-high-dose vitamin C (≥ 12 g/day), high-dose vitamin C (< 12, ≥ 6 g/day), vitamin C (< 6 g/day), glucocorticoid (< 400 mg/day of hydrocortisone), vitamin B1, combinations of these drugs, and placebo/usual care. We performed random-effects network meta-analysis and, where applicable, a random-effects component network meta-analysis. We used the Confidence in Network Meta-Analysis framework to assess the degree of treatment effect certainty. The primary outcome was longer-term mortality (90-days to 1-year). Secondary outcomes were severity of organ dysfunction over 72 h, time to cessation of vasopressor therapy, and length of stay in intensive care unit (ICU). Forty-three RCTs (10,257 patients) were eligible. There were no significant differences in longer-term mortality between treatments and placebo/usual care or between treatments (10 RCTs, 7,096 patients, moderate to very-low-certainty). We did not find any evidence that vitamin C or B1 affect organ dysfunction or ICU length of stay. Adding glucocorticoid to other treatments shortened duration of vasopressor therapy (incremental mean difference, − 29.8 h 95% CI − 44.1 to − 15.5) and ICU stay (incremental mean difference, − 1.3 days 95% CI − 2.2 to − 0.3). Metabolic resuscitation with vitamin C, glucocorticoids, vitamin B1, or combinations of these drugs was not significantly associated with a decrease in longer-term mortality.
Objective
This study aimed to use quantitative values, calculated from bone single photon emission computed tomography (SPECT) imaging, to estimate the reliability of progression evaluation for ...anti-resorptive agent-related osteonecrosis of the jaw (ARONJ).
Methods
The study population consisted of 21 patients (23 lesions), clinically diagnosed with mandibular ARONJ, who underwent SPECT/CT scanning. Diagnosis and staging of ARONJ were performed according to the American Association of Oral and Maxillofacial Surgeons (AAOMS) definition and the recommendations of the International Task Force on ONJ. Hybrid SPECT/CT imaging quantitative analyses were performed on a workstation. Each volume of interest (VOI) was semi-automatically placed over a lesion with areas of high tracer accumulation, using the GI-BONE
®
software default threshold method settings. Additionally, control VOI was manually set over an unaffected area. Measured parameters included standardized uptake values (SUV)—maximum (SUV
max
) and mean (SUV
mean
), metabolic bone volume (MBV)—the total volume above the threshold, and total bone uptake (TBU) as calculated by MBV × SUV
mean
. We also calculated the SUV ratio (rSUV) between the lesion and control area, factoring for differences in individual bone metabolism; the ratios were termed rSUV
max
and rSUV
mean
, accordingly. The product of multiplying the rSUV
mean
by MBV of a lesion was defined as the ratio of TBU (rTBU). Quantitative values were compared between clinical stages by the Kruskal–Wallis test and subsequent post hoc analysis.
Results
MBVs (cm
3
) were: median, IQR Stage 1, 8.28 5.62–9.49; Stage 2, 15.28 10.64–24.78; and Stage 3, 34.61 29.50–40.78. MBV tended to increase with stage increase. Furthermore, only MBV showed a significant difference between clinical stages (
p
< 0.01). Subsequent post hoc analysis showed no significant difference between stages 1 and 2 (
p
= 0.12) but a significant difference between stages 2 and 3 (
p
= 0.048). rSUVmax and rTBU tended to increase with stage increase, but the differences between the stages were not significant (
p
= 0.10 and
p
= 0.055, respectively).
Conclusion
MBV, which includes the concept of volume, showed significant differences between clinical stages and tended to increase with the stage increase. As an objective and reliable indicator, MBV might be an adjunct diagnostic method for staging ARONJ.
Propagation of genetic information is a fundamental property of living organisms. Escherichia coli has a 4.6 Mb circular chromosome with a replication origin, oriC. While the oriC replication has ...been reconstituted in vitro more than 30 years ago, continuous repetition of the replication cycle has not yet been achieved. Here, we reconstituted the entire replication cycle with 14 purified enzymes (25 polypeptides) that catalyze initiation at oriC, bidirectional fork progression, Okazaki-fragment maturation and decatenation of the replicated circular products. Because decatenation provides covalently closed supercoiled monomers that are competent for the next round of replication initiation, the replication cycle repeats autonomously and continuously in an isothermal condition. This replication-cycle reaction (RCR) propagates ∼10 kb circular DNA exponentially as intact covalently closed molecules, even from a single DNA molecule, with a doubling time of ∼8 min and extremely high fidelity. Very large DNA up to 0.2 Mb is successfully propagated within 3 h. We further demonstrate a cell-free cloning in which RCR selectively propagates circular molecules constructed by a multi-fragment assembly reaction. Our results define the minimum element necessary for the repetition of the chromosome-replication cycle, and also provide a powerful in vitro tool to generate large circular DNA molecules without relying on conventional biological cloning.