The LUX-ZEPLIN experiment is a dark matter detector centered on a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility in Lead, South Dakota, USA. This ...Letter reports results from LUX-ZEPLIN's first search for weakly interacting massive particles (WIMPs) with an exposure of 60 live days using a fiducial mass of 5.5 t. A profile-likelihood ratio analysis shows the data to be consistent with a background-only hypothesis, setting new limits on spin-independent WIMP-nucleon, spin-dependent WIMP-neutron, and spin-dependent WIMP-proton cross sections for WIMP masses above 9 GeV/c^{2}. The most stringent limit is set for spin-independent scattering at 36 GeV/c^{2}, rejecting cross sections above 9.2×10^{-48} cm at the 90% confidence level.
Context
The monoclinic L-histidine crystal is critical for protein structure and function and is also found in the myelin of brain nerve cells. This study numerically examines its structural, ...electronic, and optical properties. Our findings indicate that the L-histidine crystal has an insulating band gap of approximately 4.38 eV. Additionally, electron and hole effective masses range between 3.92
m
0
–15.33
m
0
and 4.16
m
0
–7.53
m
0
, respectively. Furthermore, our investigation suggests that the L-histidine crystal is an excellent UV collector due to its strong optical absorption activity for photon energies exceeding 3.5 eV.
Methods
To investigate the structural, electronic, and optical properties of L-histidine crystals, we used the Biovia Materials Studio software to conduct Density Functional Theory (DFT) simulations as implemented in the CASTEP code. Our DFT calculations were performed using the generalized gradient approximation (GGA) as parameterized by the Perdew-Burke-Ernzerhof (PBE) exchange-correlation functional, with an additional dispersion energy correction (PBE
+
TS) based on the model proposed by Tkatchenko and Scheffler to describe van der Waals interactions. Additionally, we employed the norm-conserving pseudopotential to treat core electrons.
Amyotrophic lateral sclerosis (ALS) is the most frequent adult-onset motor neuron disorder. The disease is characterized by degeneration of upper and lower motor neurons, leading to death usually ...within five years after the onset of symptoms. While most cases are sporadic, 5%-10% of cases can be associated with familial inheritance, including ALS type 6, which is associated with mutations in the Fused in Sarcoma (FUS) gene. This work aimed to evaluate how the most frequent ALS-related mutations in FUS, R521C, R521H, and P525L affect the protein structure and function. We used prediction algorithms to analyze the effects of the non-synonymous single nucleotide polymorphisms and performed evolutionary conservation analysis, protein frustration analysis, and molecular dynamics simulations. Most of the prediction algorithms classified the three mutations as deleterious. All three mutations were predicted to reduce protein stability, especially the mutation R521C, which was also predicted to increase chaperone binding tendency. The protein frustration analysis showed an increase in frustration in the interactions involving the mutated residue 521C. Evolutionary conservation analysis showed that residues 521 and 525 of human FUS are highly conserved sites. The molecular dynamics results indicate that protein stability could be compromised in all three mutations. They also affected the exposed surface area and protein compactness. The analyzed mutations also displayed high flexibility in most residues in all variants, most notably in the interaction site with the nuclear import protein of FUS.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cross-talk between the gut microbiota and the host immune system regulates host metabolism, and its dysregulation can cause metabolic disease. Here, we show that the gut microbe Akkermansia ...muciniphila can mediate negative effects of IFNγ on glucose tolerance. In IFNγ-deficient mice, A. muciniphila is significantly increased and restoration of IFNγ levels reduces A. muciniphila abundance. We further show that IFNγ-knockout mice whose microbiota does not contain A. muciniphila do not show improvement in glucose tolerance and adding back A. muciniphila promoted enhanced glucose tolerance. We go on to identify Irgm1 as an IFNγ-regulated gene in the mouse ileum that controls gut A. muciniphila levels. A. muciniphila is also linked to IFNγ-regulated gene expression in the intestine and glucose parameters in humans, suggesting that this trialogue between IFNγ, A. muciniphila and glucose tolerance might be an evolutionally conserved mechanism regulating metabolic health in mice and humans.
Bidirectional air–surface exchange of ammonia (NH3) has been neglected in many air quality models. In this study, we implement the bidirectional exchange of NH3 in the GEOS-Chem global chemical ...transport model. We also introduce an updated diurnal variability scheme for NH3 livestock emissions and evaluate the recently developed MASAGE_NH3 bottom-up inventory. While updated diurnal variability improves comparison of modeled-to-hourly in situ measurements in the southeastern USA, NH3 concentrations decrease throughout the globe, up to 17 ppb in India and southeastern China, with corresponding decreases in aerosol nitrate by up to 7 μg m−3. The ammonium (NH4+) soil pool in the bidirectional exchange model largely extends the NH3 lifetime in the atmosphere. Including bidirectional exchange generally increases NH3 gross emissions (7.1 %) and surface concentrations (up to 3.9 ppb) throughout the globe in July, except in India and southeastern China. In April and October, it decreases NH3 gross emissions in the Northern Hemisphere (e.g., 43.6 % in April in China) and increases NH3 gross emissions in the Southern Hemisphere. Bidirectional exchange does not largely impact NH4+ wet deposition overall. While bidirectional exchange is fundamentally a better representation of NH3 emissions from fertilizers, emissions from primary sources are still underestimated and thus significant model biases remain when compared to in situ measurements in the USA. The adjoint of bidirectional exchange has also been developed for the GEOS-Chem model and is used to investigate the sensitivity of NH3 concentrations with respect to soil pH and fertilizer application rate. This study thus lays the groundwork for future inverse modeling studies to more directly constrain these physical processes rather than tuning bulk unidirectional NH3 emissions.
The number of substances nominally listed in the prohibited list of the World Anti‐Doping Agency increases each year. Moreover, many of these substances do not have a single analytical target and ...must be monitored through different metabolites, artifacts, degradation products, or biomarkers. A new analytical method was developed and validated for the simultaneous analysis of peptides and organic molecules using a single sample preparation and LC‐Q‐HRMS detection. The simultaneous analysis of 450 target molecules was performed after cleanup on a mixed‐mode solid‐phase extraction cartridge, combined with untreated urine. The cleanup solvent and reconstitution solvent were the most important parameters for achieving a comprehensive sample preparation approach. A fast chromatographic run based on a multistep gradient was optimized under different flows; the detection of all substances without isomeric coelution was achieved in 11 minutes, and the chromatographic resolution was considered a critical parameter, even in high‐resolution mass spectrometry detection. The mass spectrometer was set to operate by switching between positive and negative ionization mode for FULL‐MS, all‐ion fragmentation, and FULL‐MS/MS2. The suitable parameters for the curved linear trap (c‐trap) conditions were determined and found to be the most important factors for the development of the method. Only FULL‐MS/MS2 enables the detection of steroids and peptides at concentrations lower than the minimum required performance levels set by World Anti‐Doping Agency (1 ng mL−1). The combination of the maximum injection time of the ions into the c‐trap, multiplexing experiments, and loop count under optimized conditions enabled the method to be applied to over 10 000 samples in only 2 months during the 2016 Rio Summer Olympic and Paralympic Games. The procedure details all aspects, from sample preparation to mass spectrometry detection. FULL‐MS data acquisition is performed in positive and negative ion mode simultaneously and can be applied to untargeted approaches.
The objective of this study was to evaluate blood cells and metabolites, insulin-like growth factor-1 (IGF-1), digestibility, internal organs weight and histology, gene expression, and spleen cell ...proliferation of pre-weaned bull calves supplemented with a blend of essential oils in milk replacer (MR). Sixteen newborn Holstein × Gyr crossbred dairy bull calves, with body weight at birth of 33.3 ± 3.7 kg, were housed in individual sand bedded pens, blocked by genetic composition, and randomly assigned to 1 of 2 treatments in a randomized complete block design: Control (CON, n = 8) and blend of essential oils supplementation (BEO, n = 8, 1 g/day/calf, Apex Calf, Adisseo, China). The commercial blend was composed by plant extracts derived from anise, cinnamon, garlic, rosemary, and thyme. Animals were fed 5 L of MR/day reconstituted at 15% (dry matter basis), divided into two equal meals. Water and starter were provided ad libitum. ß-hydroxybutyrate, urea, and glucose were evaluated weekly, IGF-1 was evaluated biweekly, and total blood cell count was performed every four weeks until the end of the trial at eight weeks of age. Feed samples were collected three times a week and polled for weekly analysis. Apparent total nutrient digestibility was determined from d 56 to 60 of age. On d 60 ± 1, animals were euthanized for organ weight, histology, spleen cell proliferation, and intestinal gene expression analysis. Data were analyzed independently using linear mixed models using the REML method in the nlme package in R for continuous outcomes. A non-parametric test was used for ordered categorical outcomes using the Artools package in R. There were no differences between groups for blood evaluations, digestibility, gene expression, and a spleen cell proliferation assay. However, BEO calves presented a heavier pancreas, heavier intestines, bigger ileum villi, and higher cecum butyrate levels (P < 0.05), demonstrating that the EO supplementation helped intestinal development and symbiotic bacteria. It was also observed in CON animals' heavier respiratory tract and a higher eosinophil count (P < 0.05). Therefore, the organs where eosinophils are more active had a better response for BEO animals. No differences were found in the intestinal gene expression in the immune context. These results demonstrate that supplementing essential oils in MR could contribute to gut development and immune function. However, more research is needed to understand its impact on body development and define the best dosage and route of administration.
The effects of aging on ROS production and DNA damage were assessed in hematopoietic stem cells (HSCs) from apolipoprotein E–deficient (ApoE−/−) mice (2-, 12- and 24-month-old), a traditional ...experimental model of atherogenic dyslipidemia. HSCs from aged ApoE−/− mice were associated with increased ROS levels, leading to loss quiescence, DNA damage, apoptosis and telomere shortening. The concurrence of lack of ApoE and aging result in exhaustion and senescence of HSCs accompanied by increased oxidative stress and inflammation. Therefore, our data open avenues to a better understanding of age-related changes and genetic factors, which may synergistically compromise the efficacy of aged HSC recovery and/or transplantation.
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•Hematopoietic stem cells exhibit the ability of differentiation into mature cells.•Hypercholesterolemia increases reactive oxygen species leading to senescence.•In aging, high cellular recruitment leads dysfunction due to oxidative stress.
Plant extracts have been proposed as substitutes for chemical feed additives due to their potential as rumen fermentation modifiers and because of their antimicrobial and antioxidant activities, ...possibly reducing methane emissions. This study aimed to evaluate the use of oregano (OR), green tea extracts (GT), and their association as feed additives on the performance and methane emissions from dairy between 28 and 87 d of lactation. Thirty-two lactating dairy cows, blocked into 2 genetic groups: 16 Holstein cows and 16 crossbred Holstein-Gir, with 522.6 ± 58.3 kg of body weight, 57.2 ± 20.9 d in lactation, producing 27.5 ± 5.0 kg/cow of milk and with 3.1 ± 1.8 lactations were evaluated (means ± standard error of the means). Cows were allocated into 4 treatments: control (CON), without plant extracts in the diet; oregano extract (OR), with the addition of 0.056% of oregano extract in the dry matter (DM) of the diet; green tea (GT), with the addition of 0.028% of green tea extract in the DM of the diet; and mixture, with the addition of 0.056% oregano extract and 0.028% green tea extract in the DM of the diet. The forage-to-concentrate ratio was 60:40. Forage was composed of corn silage (94%) and Tifton hay (6%); concentrate was based on ground corn and soybean meal. Plant extracts were supplied as powder, which was previously added and homogenized into 1 kg of concentrate in natural matter, top-dressed onto the total mixed diet. No treatment by day interaction was observed for any of the evaluated variables, but some block by treatment interactions were significant. In Holstein cows, the mixture treatment decreased gross energy and tended to decrease the total-tract apparent digestibility coefficient for crude protein and total digestible nutrients when compared with OR. During the gas measurement period, GT and OR increased the digestible fraction of the ingested DM and decreased CH4 expressed in grams per kilogram of digestible DMI compared with CON. The use of extracts did not change rumen pH, total volatile fatty acid concentration, milk yield, or most milk traits. Compared with CON, oregano addition decreased fat concentration in milk. The use of plant extracts altered some milk fatty acids but did not change milk fatty acids grouped according to chain length (short or long), saturation (unsaturated or saturated), total conjugated linoleic acids, and n-3 and n-6 contents. Green tea and oregano fed separately reduced gas emission in cows during the first third of lactation and have potential to be used as feed additives for dairy cows.
The objective of this study was to evaluate whether pre-weaning heifer calves divergent for residual feed intake (RFI) or residual feed intake and body weight gain (RIG) exhibit differences in ...thermography, blood, and ruminal parameters. Thirty-two Gyr heifer calves were enrolled in a 63-d trial and classified into 2 feed efficiency (FE) groups based on RFI and RIG (mean #177; 0.5 SD). The groups were classified as high efficiency (HE) RFI (HE RFI, n = 9), HE RIG (HE RIG, n = 10), low efficiency (LE) RFI (LE RFI, n = 10), and LE RIG (LE RIG, n = 11). The amount of whole milk provided for each calf was calculated based on their metabolic weight at birth (42% x BW.sup.0.75). The liquid diet was divided into two meals at 0700 and 1400 h. The total solid diet (TSD) was composed of 92% concentrate and 8% of Tifton 85 hay chopped in 5-cm lengths, as fed. Intake was measured daily. Blood concentrations of insulin, beta hydroxybutyrate, urea, and glucose, and ruminal pH, N-NH.sub.3, and volatile fatty acids (VFA) were evaluated at 14, 28, 42, 56, and 70 days of age. Thermal images of the calves were taken with an infrared camera (FLIR T420, FLIR Systems Inc., Wilsonville, OR) on d 56 (#177;3) at 0600 h, before the morning feeding. Total VFA concentration and propionate as % of total VFA were 24.2% and 22.2% lower in HE RFI compared to LE RFI calves, respectively. On the other hand, acetate as % of total VFA was 10.6% greater in HE RFI than LE RFI calves. Blood urea concentration tended to be greater in LE RFI than HE RFI calves. High efficiency HE RIG tended to have 6.8% greater acetate and 15.4% lower propionate as % of total VFA than LE RIG. Blood insulin concentration was greater and blood glucose tended to be greater for LE RIG than HE RIG group. Low efficiency RIG group had greater left rib, left flank, and anus surface temperature measured by infrared thermography than the HE RIG group. Differences in ruminal fermentation do not seem to be associated with pre-weaning calves efficiency, while differences in protein metabolism seem to affect RFI during this phase. Infrared thermography appears to be correlated to RIG in pre-weaning heifer calves.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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