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The present study aimed to investigate whether dietary choline can regulate lipid metabolism and suppress NFκB activation and, consequently, attenuate inflammation induced by a high-fat diet in black sea bream (Acanthopagrus schlegelii). An 8-week feeding trial was conducted on fish with an initial weight of 8·16 ± 0·01 g. Five diets were formulated: control, low-fat diet (11 %); HFD, high-fat diet (17 %); and HFD supplemented with graded levels of choline (3, 6 or 12 g/kg) termed HFD + C1, HFD + C2 and HFD + C3, respectively. Dietary choline decreased lipid content in whole body and tissues. Highest TAG and cholesterol concentrations in serum and liver were recorded in fish fed the HFD. Similarly, compared with fish fed the HFD, dietary choline reduced vacuolar fat drops and ameliorated HFD-induced pathological changes in liver. Expression of genes of lipolysis pathways were up-regulated, and genes of lipogenesis down-regulated, by dietary choline compared with fish fed the HFD. Expression of nfκb and pro-inflammatory cytokines in liver and intestine was suppressed by choline supplementation, whereas expression of anti-inflammatory cytokines was promoted in fish fed choline-supplemented diets. In fish that received lipopolysaccharide to stimulate inflammatory responses, the expression of nfκb and pro-inflammatory cytokines in liver, intestine and kidney were all down-regulated by dietary choline compared with the HFD. Overall, the present study indicated that dietary choline had a lipid-lowering effect, which could protect the liver by regulating intrahepatic lipid metabolism, reducing lipid droplet accumulation and suppressing NFκB activation, consequently attenuating HFD-induced inflammation in A. schlegelii.
Low methane (CH4) emissions from sheep fed forage rape (Brassica napus) might be related to low ruminal pH value. In this study, sodium carbonate (Na2CO3: SC) was supplemented to the diet to alter ruminal pH for evaluation of its role in CH4 emissions from sheep fed forage rape. Fourteen intact and eight fistulated Romney sheep were adapted to forage rape over 32 days and then randomly allocated to one of two groups: diets supplemented with SC or not (control). Methane emissions were measured from intact sheep in seven experimental periods. In parallel, ruminal pH and fermentation characteristics were assessed using the fistulated sheep. In the first (P01) and the second (P02) periods, none of the sheep received SC to examine the baseline CH4 emissions. The P01 period was used as a covariate for analysis of gas emission measurements in subsequent measurement periods. Sodium carbonate was offered at 5% of the forage DM in P03 and P04, increased to 8% in P05 and P06 to assess the effect of pH increase on CH4 emissions and stopped in P07 to assess if the CH4 emissions reverted to values similar to those measured before the supplementation started. Methane yield (g/kg forage DM intake) was similar for the sheep in both groups during P02 and P03, but sheep supplemented with SC in the diet emitted 36%, 49% and 30% more CH4 per unit of forage DM intake than those in the control group during P04, P05 and P06, respectively. Emissions returned to similar levels when SC supplementation was ceased in P07. Ruminal pH was 0.412 to 0.565 units higher in SC supplemented sheep than for the control group during the SC treatment periods. Based on the lack of an immediate response in CH4 emissions to the supplementation of SC in P03, the positive responses in P04 to P06 and the rapid disappearance of the response after supplementation with SC stopped in P07, we propose a new hypothesis that ruminal pH effects on CH4 emissions are possibly through medium-term changes in microbial and methanogenic communities in the rumen, rather than a direct, short-term impact on methanogens per se. In conclusion, SC supplemented to the forage rape diet of sheep increased rumen pH, leading to an increase in CH4 emissions. Low ruminal pH in sheep fed forage rape explains, at least partially, the reported low CH4 emissions from sheep fed with this forage crop.
The regulation of lipogenesis and lipolysis mechanisms related to consumption of lipid has not been studied in swimming crab. The aims of present study were to evaluate the effects of dietary lipid levels on growth, enzymes activities, and expression of genes of lipid metabolism in hepatopancreas of juvenile swimming crab. Three isonitrogenous diets were formulated to contain crude lipid levels at 5.8 %, 9.9 % and 15.1 %, respectively. Crabs fed the diet containing 15.1 % lipid had significantly lower weight gain, specific growth rate and survival, and higher feed conversion ratio than those fed the 5.8 % and 9.9 % lipid diets. Crabs fed 5.8 % lipid had lower malondialdehyde concentrations in the hemolymph and hepatopancreas than those fed the other diets. Highest glutathione peroxidase in hemolymph and superoxide dismutase in hepatopancreas were observed in crabs fed 5.8 % lipid. The lowest fatty acid synthase and glucose 6-phosphate dehydrogenase activities in hepatopancreas were observed in crabs fed 15.1 % lipid, whereas crabs fed 5.8 % lipid had lower carnitine palmitoyltransferase-1 activity than those fed the other diets. Crabs fed 15.1 % lipid showed lower hepatopancreas expression of genes involved in LC-PUFA biosynthesis, lipoprotein clearance, fatty acid uptake, fatty acid oxidation, lipid anabolism and lipid catabolism than those fed the other diets, whereas expression of some genes of lipoprotein assembly and fatty acid oxidation were up-regulated compared with crabs fed 5.8 % lipid. Overall, high dietary lipid level can inhibit growth, reduce feed utilization and reduce antioxidant enzyme activities. Moreover, dietary lipid influenced enzyme activities and gene expression involved in lipid metabolism of juvenile swimming crab.
A right aortic arch with an isolated left innominate artery is a rare form of aortic arch anomaly. We present a case of neonatal diagnosis of this anomaly with concerning findings of global cerebral white matter atrophy at 13 months of age.
Frailty is associated with cognitive decline in older adults. However, the mechanisms explaining this relationship are poorly understood. We hypothesized that sleep quality may mediate the relationship between frailty and cognition.
154 participants aged between 50-90 years (mean = 69.1 years, SD = 9.2 years) from the McKnight Brain Registry were included.
Participants underwent a full neuropsychological evaluation, frailty and subjective sleep quality assessments. Direct relationships between frailty and cognitive function were assessed using linear regression models. Statistical mediation of these relationships by sleep quality was assessed using nonparametric bootstrapping procedures.
Frailty severity predicted weaker executive function (B = −2.77, β = −0.30, 95% CI = −4.05 – −1.29) and processing speed (B = −1.57, β = −0.17, 95% CI = −3.10 – −0.16). Poor sleep quality predicted poorer executive function (B = −0.47, β = −0.21, 95% CI = −0.79 – −0.08), processing speed (B = −0.64, β = −0.28, 95% CI = −0.98 – −0.31), learning (B = −0.42, β = −0.19, 95% CI = −0.76 – −0.05) and delayed recall (B = −0.41, β = −0.16, 95% CI = −0.80 – −0.31). Poor sleep quality mediated the relationships between frailty severity and executive function (B = −0.66, β = −0.07, 95% CI = −1.48 – −0.39), learning (B = −0.85, β = −0.07, 95% CI = −1.85 – −0.12), delayed recall (B = −0.47, β = −0.08, 95% CI = −2.12 – −0.39) and processing speed (B = −0.90, β = −0.09, 95% CI = −1.85 – −0.20).
Relationships between frailty severity and several cognitive outcomes were significantly mediated by poor sleep quality. Interventions to improve sleep quality may be promising avenues to prevent cognitive decline in frail older adults.
Advances in material science and semiconductor technology have enabled a variety of inventions to be implemented in electronic systems and devices used in the medical, telecommunications, and consumer electronics sectors. In this paper, a wireless charging system is described as a wearable body heater that uses a chair as a transmitter (Tx). This system incorporates the widely accepted Qi wireless charging standard. Alignment conditions of a linear three-element coil arrangement and a 3 × 3 coil matrix array are investigated using voltage induced in a coil as a performance indicator. The efficiency obtained is demonstrated to be up to 80% for a voltage of over 6.5 Volts and a power transfer of over 5 Watts. Our results and proposed approach can be useful for many applications. This is because the wireless charging system described herein can help design seating areas for the elderly and disabled, commercial systems, consumer electronics, medical devices, electronic textiles (e-textiles), and other electronic systems and devices.
Firefighters are routinely exposed to various traumatic events and often experience a range of trauma-related symptoms. Although these repeated traumatic exposures rarely progress to the development of post-traumatic stress disorder, firefighters are still considered to be a vulnerable population with regard to trauma.
To investigate how the human brain responds to or compensates for the repeated experience of traumatic stress.
We included 98 healthy firefighters with repeated traumatic experiences but without any diagnosis of mental illness and 98 non-firefighter healthy individuals without any history of trauma. Functional connectivity within the fear circuitry, which consists of the dorsal anterior cingulate cortex, insula, amygdala, hippocampus and ventromedial prefrontal cortex (vmPFC), was examined using resting-state functional magnetic resonance imaging. Trauma-related symptoms were evaluated using the Impact of Event Scale – Revised.
The firefighter group had greater functional connectivity between the insula and several regions of the fear circuitry including the bilateral amygdalae, bilateral hippocampi and vmPFC as compared with healthy individuals. In the firefighter group, stronger insula–amygdala connectivity was associated with greater severity of trauma-related symptoms (β = 0.36, P = 0.005), whereas higher insula–vmPFC connectivity was related to milder symptoms in response to repeated trauma (β = −0.28, P = 0.01).
The current findings suggest an active involvement of insular functional connectivity in response to repeated traumatic stress. Functional connectivity of the insula in relation to the amygdala and vmPFC may be potential pathways that underlie the risk for and resilience to repeated traumatic stress, respectively.
Strong strain-mediated magnetoelectric (ME) coupling in magnetic/ferroelectric heterostructures has great potential for different high-frequency multiferroic devices. In this article, we present the most recent progress in integrated multiferroic devices. Integrated magnetic tunable inductors with a wide operation frequency range, integrated nonreciprocal bandpass filters with dual magnetic and electric-field tunability based on magnetostatics surface waves, and novel radio-frequency nanomechanical ME resonators with pico-Tesla sensitivity for direct current magnetic fields are presented. Finally, a new antenna miniaturization mechanism, acoustically actuated nanomechanical ME antennas, which can successfully miniaturize the size by 1–2 orders, is introduced. With the advantages of high magnetic field sensitivity, highest antenna gain among all nanoscale antennas at similar frequency, integrated capability with complementary metal oxide semiconductor technology, and ground-plane immunity from metallic surfaces and the human body, ME antennas have a bright future for biomedical applications, wearable antennas, and the Internet of Things due to their unique and particular properties.
Hydrogen is an important intermediate that is produced during carbohydrate fermentation to volatile fatty acid and utilized by methanogens to produce methane in the rumen. Ruminal volatile fatty acid and dissolved methane concentrations are more than 500 times greater than dissolved hydrogen concentration. Therefore, we hypothesized that dissolved hydrogen might have a higher sensitivity in response to dietary changes compared with volatile fatty acid and dissolved methane. Using goats, we investigated the effects of increasing dietary starch content (maize replaced with wheat bran) and supplementing with rhubarb rhizomes and roots on the relationships among dissolved hydrogen, dissolved methane and other fermentation end products. The study was conducted in a replicated 4×4 Latin square with a 2×2 factorial arrangement of four treatments: two starch levels (220 v. 320 g/kg dry matter (DM)), without and with rhubarb supplement (0% v. 2.8% of total mixed ration). Increased dietary starch and rhubarb supplementation did not alter volatile fatty acid concentrations or methane emissions in terms of g/day, g/g DM intake and g/g organic matter digested. However, goats fed the high-starch diet had greater dissolved hydrogen (P=0.005) and relative abundance of Selenomonas ruminantium (P<0.01), and lower (P=0.02) copy number of protozoa than those fed the low-starch diet. Rhubarb increased ruminal dissolved H2 (P=0.03) and total volatile fatty acid concentration (P<0.001), but decreased copies of bacteria (P=0.002). In conclusion, dissolved hydrogen appears to be more sensitive to dietary changes with starch content and rhubarb supplementation, when compared with volatile fatty acid concentrations and methane production.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Ternary sulfides and selenides in the distorted-perovskite structure (“chalcogenide perovskites”) are predicted by theory to be semiconductors with band gap in the visible-to-infrared and may be useful for optical, electronic, and energy conversion technologies. Density functional theory can be used in combination with computational thermodynamics to predict the pressure-temperature phase diagrams for chalcogenide perovskites. We report results using the Strongly Constrained and Appropriately Normed (SCAN) and the rVV10 density functionals, and compare to previously-published results using the PBEsol functional. We highlight the windows of thermodynamic equilibrium between solid chalcogenide perovskites and the vapor phase at high temperature and very low pressure. These phase diagrams can guide adsorption-limited growth of ternary chalcogenides by molecular beam epitaxy (MBE).
Group-3 medulloblastoma (MBL) is highly resistant to radiation (IR) and chemotherapy and has the worst prognosis. Hence, there is an urgent need to elucidate targets that sensitize these tumors to chemotherapy and IR. Employing standard assays for viability and sensitization to IR, we identified PRDX1 as a therapeutic target in Group-3 MBL. Specifically, targeting PRDX1 by RNAi or inhibition by Adenanthin led to specific killing and sensitization to IR of Group-3 MBL cells. We rescued sensitization of Daoy and UW228 cells by hypermorphic expression of PRDX1. PRDX1 knockdown caused oxidative DNA damage and induced apoptosis. We correlated PRDX1 expression to patient outcomes in a validated MBL tumor-microarray. Whole genome sequencing identified pathways/genes that were dysregulated with PRDX1 inhibition or silencing. Our in vivo studies in mice employing flank/orthotopic tumors from patient derived xenografts/Group-3 MBL cells confirmed in vitro observations. Animals with tumors in which PRDX1 was targeted by RNAi or Adenanthin (using mini osmotic pumps) showed decreased tumor burden and increased survival when compared to controls. Since, Adenanthin does not cross the blood brain barrier (BBB) we used HAV6 peptide to transiently disrupt the BBB and deliver Adenanthin to the tumor. Immunohistochemistry confirmed that targeting PRDX1 resulted in increased oxidative DNA damage, apoptosis and decreased proliferation. In summary, we have validated PRDX1 as a therapeutic target in group-3 MBL, identified Adenanthin as a potent chemical inhibitor of PRDX1 and confirmed the role of HAV peptide (in the transient modulation of BBB permeability) in an orthotopic model of group-3 MBL.
Background: EMBRACE (NCT02462759) Part 1 is a randomized, double-blind, sham-procedure controlled study assessing safety/tolerability of intrathecal nusinersen (12-mg equivalent dose) in symptomatic infants/children with SMA who were not eligible to participate in ENDEAR or CHERISH. Methods: Eligible participants had onset of SMA symptoms at ≤6 months with 3 SMN2 copies; onset at ≤6 months, age >7 months and 2 copies; or onset at >6 months, age ≤18 months, and 2/3 copies. Safety/tolerability was the primary endpoint. Exploratory endpoints included Hammersmith Infant Neurological Examination Section 2 (HINE-2) motor milestone attainment, change in ventilator use, and growth. Results: EMBRACE Part 1 was terminated early based on positive results from ENDEAR. Safety/tolerability was similar to previous trials. More nusinersen-treated (11/14;79%) vs. sham–treated individuals (2/7;29%) were HINE-2 motor milestone responders. Between Day 183 and 302, mean (SD) hours of ventilator use changed by +1.236 (3.712) hours in nusinersen-treated (n=12) and +2.123 (3.023) hours in sham–treated individuals (n=7). Similar increases in weight and body length were observed in nusinersen-treated and sham–treated individuals by Day 183. Conclusions: In EMBRACE Part 1, nusinersen demonstrated a favorable benefit-risk profile. These results add to the aggregated efficacy, safety/tolerability data of nusinersen in SMA.
Ternary sulfides and selenides in the distorted-perovskite structure (“chalcogenide perovskites”) are predicted by theory to be semiconductors with a band gap in the visible-to-infrared and may be useful for optical, electronic, and energy conversion technologies. Here we use computational thermodynamics to predict the pressure–temperature phase diagrams for select chalcogenide perovskites. Our calculations incorporate formation energies calculated by density functional theory, and empirical estimates of heat capacities. We highlight the windows of thermodynamic equilibrium between solid chalcogenide perovskites and the vapor phase at high temperature and very low pressure. These results can guide the adsorption-limited growth of ternary chalcogenides by molecular beam epitaxy.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
Athetis lepigone (Möschler) (Lepidoptera: Noctuidae) is a new outbreak pest in China. Consequently, it is unclear whether the emergence and spread of the outbreak of this pest are triggered by rapid in situ population size increases in each outbreak area, or by immigrants from a potential source area in China. In order to explore the outbreak process of this pest through a population genetics approach, we developed ten novel polymorphic expressed sequence tags (EST)-derived microsatellites. These new microsatellites had moderately high levels of polymorphism in the tested population. The number of alleles per locus ranged from 3 to 19, with an average of 8.6, and the expected heterozygosity ranged from 0.269 to 0.783. A preliminary population genetic analysis using these new microsatellites revealed a lack of population genetic structure in natural populations of A. lepigone. The estimates of recent migration rate revealed strong gene flow among populations. In conclusion, our study developed the first set of EST-microsatellite markers and shed a new light on the population genetic structure of this pest in China.
We present techniques developed to calibrate and correct Murchison Widefield Array low-frequency (72–300 MHz) radio observations for polarimetry. The extremely wide field-of-view, excellent instantaneous (u, v)-coverage and sensitivity to degree-scale structure that the Murchison Widefield Array provides enable instrumental calibration, removal of instrumental artefacts, and correction for ionospheric Faraday rotation through imaging techniques. With the demonstrated polarimetric capabilities of the Murchison Widefield Array, we discuss future directions for polarimetric science at low frequencies to answer outstanding questions relating to polarised source counts, source depolarisation, pulsar science, low-mass stars, exoplanets, the nature of the interstellar and intergalactic media, and the solar environment.