We report a measurement of the ionization efficiency of silicon nuclei recoiling with sub-keV kinetic energy in the bulk silicon of a charge-coupled device (CCD). Nuclear recoils are produced by ...low-energy neutrons (<24 keV) from a Sb124−Be9 photoneutron source, and their ionization signal is measured down to 60 eV electron equivalent. This energy range, previously unexplored, is relevant for the detection of low-mass dark matter particles. The measured efficiency is found to deviate from the extrapolation to low energies of the Lindhard model. This measurement also demonstrates the sensitivity to nuclear recoils of CCDs employed by DAMIC, a dark matter direct detection experiment located in the SNOLAB underground laboratory.
We report direct-detection constraints on light dark matter particles interacting with electrons. The results are based on a method that exploits the extremely low levels of leakage current of the ...DAMIC detector at SNOLAB of 2–6×10−22 A cm−2. We evaluate the charge distribution of pixels that collect <10e− for contributions beyond the leakage current that may be attributed to dark matter interactions. Constraints are placed on so-far unexplored parameter space for dark matter masses between 0.6 and 100 MeV c−2. We also present new constraints on hidden-photon dark matter with masses in the range 1.2–30 eV c−2.
In recent years, an increasing number of outbreaks of Dengue, Chikungunya and Zika viruses have been reported in Asia and the Americas. Monitoring virus genotype diversity is crucial to understand ...the emergence and spread of outbreaks, both aspects that are vital to develop effective prevention and treatment strategies. Hence, we developed an efficient method to classify virus sequences with respect to their species and sub-species (i.e. serotype and/or genotype). This tool provides an easy-to-use software implementation of this new method and was validated on a large dataset assessing the classification performance with respect to whole-genome sequences and partial-genome sequences. Available online: http://krisp.org.za/tools.php.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hepatocellular carcinoma incidence rates have increased worldwide, which encouraged the development of new chemotherapeutic drugs. l-Amino acid oxidases from snake venoms are cytotoxic towards human ...tumor cells in in vitro monoculture systems, which do not simulate the tumor microenvironment. We examined the antitumor potential of BjussuLAAO-II, an l-amino acid oxidase from Bothrops jararacussu venom, in hepatocarcinoma cells (HepG2) in monoculture and co-culture with human umbilical vein endothelial cells (HUVEC) in vitro. All the concentrations tested (0.25–5.00 μg/mL) were cytotoxic (MTT and clonogenic survival assays) towards HepG2 and HUVEC cells in monoculture, and increased oxidative stress by 2′,7′-dichlorofluorescin diacetate fluorescence assay. Only 1.00 and 5.00 μg/mL exerted these effects in HepG2 cells co-cultured with HUVEC cells, and were genotoxic (comet assay) to HUVEC cells in monoculture. BjussuLAAO-II at 5.00 μg/mL induced DNA, but not chromosomal damage (micronucleus assay) in HepG2 cells in mono- and co-culture. The cytotoxicity and genotoxicity was more pronounced in monoculture, indicating that the tumor microenvironment influences the cellular response. BjussuLAAO-II caused cell death and DNA damage in HepG2 cells in vitro by inducing oxidative stress. Therefore, BjussuLAAO-II is a promising molecule for the development of new antitumor drugs.
•BjussuLAAO-II toxin is cytotoxic towards HepG2 and HUVEC cells.•Oxidative stress mainly mediates the toxin-induced cell death and DNA damage.•Tumor microenvironment modulates the toxin action on HepG2 cell co-cultures.
Background Despite lipid-lowering and antiplatelet therapy, the pattern of residual lipoproteins seems relevant to long-term cardiovascular outcomes. This study aims to evaluate the effects of ...combined therapies, commonly used in subjects with acute myocardial infarction, in the quality of low-density lipoprotein (LDL) particles. Methods Prospective, open-label trial, included patients with acute myocardial infarction. Patients were randomized to antiplatelet treatment (ticagrelor or clopidogrel) and subsequently to lipid-lowering therapy (rosuvastatin or simvastatin/ezetimibe) and were followed up for six months. Nonlinear optical properties of LDL samples were examined by Gaussian laser beam (Z-scan) to verify the oxidative state of these lipoproteins, small angle X-ray scattering (SAXS) to analyze structural changes on these particles, dynamic light scattering (DLS) to estimate the particle size distribution, ultra violet (UV)-visible spectroscopy to evaluate the absorbance at wavelength 484 nm (typical from carotenoids), and polyacrylamide gel electrophoresis (Lipoprint) to analyze the LDL subfractions. Results Simvastatin/ezetimibe with either clopidogrel or ticagrelor was associated with less oxidized LDL, and simvastatin/ezetimibe with ticagrelor to lower cholesterol content in the atherogenic subfractions of LDL, while rosuvastatin with ticagrelor was the only combination associated with increase in LDL size. Conclusions The quality of LDL particles was influenced by the antiplatelet/lipid-lowering strategy, with ticagrelor being associated with the best performance with both lipid-lowering therapies. Trial registration: NCT02428374.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Patients with major depressive disorder (MDD) have clinically relevant, significant decreases in bone mineral density (BMD). We sought to determine if predictive markers of bone inflammation-the ...osteoprotegerin (OPG)-RANK-RANKL system or osteopontin (OPN)-play a role in the bone abnormalities associated with MDD and, if so, whether ketamine treatment corrected the abnormalities. The OPG-RANK-RANKL system plays the principal role in determining the balance between bone resorption and bone formation. RANKL is the osteoclast differentiating factor and diminishes BMD. OPG is a decoy receptor for RANKL, thereby increasing BMD. OPN is the bone glue that acts as a scaffold between bone tissues matrix composition to bind them together and is an important component of bone strength and fracture resistance. Twenty-eight medication-free inpatients with treatment-resistant MDD and 16 healthy controls (HCs) participated in the study. Peripheral bone marker levels and their responses to IV ketamine infusion in MDD patients and HCs were measured at four time points: at baseline, and post-infusion at 230 min, Day 1, and Day 3. Patients with MDD had significant decreases in baseline OPG/RANKL ratio and in plasma OPN levels. Ketamine significantly increased both the OPG/RANKL ratio and plasma OPN levels, and significantly decreased RANKL levels. Bone marker levels in HCs remained unaltered. We conclude that the OPG-RANK-RANKL system and the OPN system play important roles in the serious bone abnormalities associated with MDD. These data suggest that, in addition to its antidepressant effects, ketamine also has a salutary effect on a major medical complication of depressive illness.
•BjussuLAAO-II is a snake venom toxin with cytotoxic effects towards Caco-2 cells.•The toxin induces necrosis, apoptosis, oxidative stress, and DNA damage.•The toxin reduces cell viability by acting ...on multiple intracellular targets.•The toxin upregulates the inflammatory cytokine genes TNF and IL6 expression.•The toxin downregulates the apoptotic-related genes BAX, BCL2 and RELA expression.
Colorectal carcinoma is one of the most common cancers in adults. As chemotherapy, the first-choice treatment for colorectal carcinoma, is often infeasible due to acquired tumor resistance and several adverse effects, it is important to discover and explore new molecules with better therapeutic action. Snake venom toxins have shown promising results with high cytotoxicity against tumor cells, but their mechanisms of action remain unclear. Here we examined how BjussuLAAO-II, an L-amino acid oxidase isolated from Bothrops jararacussu snake venom, exerts cytotoxicity towards colorectal adenocarcinoma human cells (Caco-2) and human umbilical vein endothelial cell line (HUVEC). A 24-h treatment with BjussuLAAO-II at 0.25 − 5.00 μg/mL diminished cell viability by decreasing (i) mitochondrial activity, assessed by reduction of 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide and resazurin; (ii) the activity of acid phosphatases; and (iii) lysosomal function, assessed by neutral red uptake. BjussuLAAO-II also increased intracellular levels of reactive oxygen species and DNA damage, as assessed by fluorescence and the comet assay, respectively. BjussuLAAO-II altered the expression of cell proliferation-related genes, as determined by RT-qPCR: it elevated the expression of the inflammatory cytokine genes TNF and IL6, and lowered the expression of the apoptotic-related genes BAX, BCL2, and RELA. Therefore, BjussuLAAO-II induces Caco-2 cells death by acting on multiple intracellular targets, providing important data for further studies to assess whether these effects are seen in both tumor and normal cells, with the aim of selecting this drug for possible therapeutic purposes in the future.
NiO is a room-temperature antiferromagnetic (AF) insulator with important applications in AF spintronics. Although it is considered a prototypical AF material with a simple magnetic structure with ...two sublattice spins aligned in easy planes and having small in-plane magnetic anisotropy, its critical behavior has not been studied in detail. Here we present an experimental investigation of the critical magnetic field for the transition from the AF to the spin-flop (SF) phase obtained with magnetization and susceptibility measurements. The measured temperature dependence of the AF-SF critical field can be quite well explained by the instability of the low-lying magnon mode with energy renormalized by four-magnon interactions.
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 ± 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 (±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
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.
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