We present a combined fit of a simple astrophysical model of UHECR sources to both the energy spectrum and mass composition data measured by the Pierre Auger Observatory. The fit has been performed ...for energies above $5 \cdot 10^{18}$ eV, i.e.~the region of the all-particle spectrum above the so-called "ankle" feature. The astrophysical model we adopted consists of identical sources uniformly distributed in a comoving volume, where nuclei are accelerated through a rigidity-dependent mechanism. The fit results suggest sources characterized by relatively low maximum injection energies, hard spectra and heavy chemical composition. We also show that uncertainties about physical quantities relevant to UHECR propagation and shower development have a non-negligible impact on the fit results.
The leaves of Syzygium cumini (L.) or Skeels (Myrtaceae) are widely used in Brazilian folk medicine to treat diabetes.
The present study evaluated the functional capacity, biochemical parameters, ...oxidative stress and DNA damage from eight weeks of intervention with a crude hydroalcoholic extract of S. cumini leaves (EBH) and continuous aerobic training (TAC) in diabetic (D) rats.
A hydroalcoholic (50%) extract was prepared by ultrasound and phytochemical parameters (total phenols, total tannins and myricetin content) were analyzed. Thirty-seven male Wistar rats were divided into five groups: normoglycemic controls (CONT), diabetic controls (D-CONT), diabetics treated with extract (D+EBH), trained diabetic (D+TAC) and diabetics treated with extract and trained (D+EBH+TAC). Functional capacity was assessed with a maximum exercise capacity test; biochemical parameters with enzymatic kits; oxidative stress by superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid reactive substances (TBARS) and oxidized dichlorofluorescein (DCF), and the DNA damage by the comet assay.
The D+TAC and D+EBH+TAC groups showed better functional capacity at the end of interventions. The D+EBH group showed glucose and triglyceride reduction, lowest DNA damage index in the blood, liver, kidney, heart, lung and gastrocnemius muscle, improved SOD levels in the liver, kidney and lung, improved CAT levels in the kidney and lower lipid peroxidation in all tissues studied, compared to the D-CONT group. The exercise (D+TAC) was effective in reducing triglycerides, improving SOD levels in the lung, reducing lipid peroxidation in all tissues studied and reducing the DCF oxidation in the kidney, in addition to protecting against DNA damage in the blood and heart. However, the additive effect of the intervention protocols when combined (EBH+TAC) was observed only in improving the gastrocnemius SOD levels. The phytochemical analyses showed a high content of phenols and the presence of myricetin glycosides.
The findings in this study suggest a crude hydroalcoholic extract of S. cumini leaves has potential hypoglycemic, hypolipidemic and protective properties acting against oxidative stress and against DNA damage, probably due to its phenols and myricetin glycoside content and the antioxidant properties of these constituents. Moreover, exercise was suggested to have beneficial effects on diabetes, improving functional capacity, ameliorating blood triglyceride control and decreasing lipid peroxidation, but with no effects on ameliorating blood glucose levels. The association of intervention protocols presented an additive effect on the antioxidant SOD activity in the muscle cells of diabetic rats.
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Tibial component malrotation is associated with pain, stiffness, and altered patellofemoral kinematics in total knee arthroplasty (TKA). However, measuring tibial component rotation following TKA is ...difficult. Proposed protocols utilizing computed tomography (CT) lack validity and can be time-consuming. This study aimed to (1) compare the reproducibility of the Berger (two-dimensional CT) and Mayo (three-dimensional CT) protocols and (2) validate a simple measurement technique using an anatomical distance on two-dimensional axial CT—the Center of the Tibial tray to the tip of the Tibial Tubercle (CTTT).
Rotational alignment of 70 TKA patients was evaluated by 3 independent observers using the Berger, Mayo, and CTTT protocols. The inter-rater and intra-rater interclass correlation coefficients, mean difference between measurements, and the mean measurement times were calculated.
The intra-rater reliability for all 3 protocols was rated as “very good” (Mayo 0.96, Berger 0.85, and CTTT 0.85). The inter-rater reliability for the Mayo and the Berger method was rated as “very good” (0.87 and 0.83, respectively), and the CTTT was rated as “good” (0.79). Comparing the CTTT to the Mayo method produced an r2 value of 0.73 with 92% of CTTT measurements ≤6 mm having <9° of tibial component internal rotation and 93% of patients with a CTTT ≥10 mm having ≥9° internal rotation.
Three-dimensional CT is the gold standard for measuring tibial component rotational alignment. The CTTT has the strongest correlation to the Mayo method and can be reliably used as a rapid screening tool.
We report a first measurement for ultrahigh energy cosmic rays of the correlation between the depth of shower maximum and the signal in the water Cherenkov stations of air-showers registered ...simultaneously by the fluorescence and the surface detectors of the Pierre Auger Observatory. Such a correlation measurement is a unique feature of a hybrid air-shower observatory with sensitivity to both the electromagnetic and muonic components. It allows an accurate determination of the spread of primary masses in the cosmic-ray flux. Up till now, constraints on the spread of primary masses have been dominated by systematic uncertainties. The present correlation measurement is not affected by systematics in the measurement of the depth of shower maximum or the signal in the water Cherenkov stations. The analysis relies on general characteristics of air showers and is thus robust also with respect to uncertainties in hadronic event generators. The observed correlation in the energy range around the ‘ankle’ at lg(E/eV)=18.5–19.0 differs significantly from expectations for pure primary cosmic-ray compositions. A light composition made up of proton and helium only is equally inconsistent with observations. The data are explained well by a mixed composition including nuclei with mass A>4. Scenarios such as the proton dip model, with almost pure compositions, are thus disfavored as the sole explanation of the ultrahigh-energy cosmic-ray flux at Earth.
Malrotation of tibial and femoral components is a potential source of pain following total knee arthroplasty (TKA). This study aimed to 1) compare component rotation in TKA patients with unexplained ...pain versus a control group with well-functioning TKAs and 2) investigate the relationship between TKA component rotation and pain.
Seventy one patients with unexplained pain after primary TKA were compared to a control cohort of 41 well functioning TKA patients. Both groups underwent post-operative computed tomography (CT) scans to assess component rotation. Findings were compared between the painful and control TKA groups.
We found no difference in femoral component rotation between the painful and control groups (mean 0.6° vs 1.0° external rotation (ER), p=0.4), and no difference in tibial component rotation (mean 11.2° vs 9.5° internal rotation (IR), p=0.3). Also, there was no difference in combined mal-rotation (tibial+femoral rotation) between the groups (mean 10.5° vs 8.5°IR, p=0.25). Fifty-nine percent of patients in the painful group had tibial component rotation >9°IR vs 49% in the control group.
In the largest study yet on component rotation after TKA, we found no difference in the incidence of tibial, femoral, or combined component mal-rotation in painful versus well-functioning TKAs. Tibial component IR relative to the junction of the medial to middle thirds of the tibial tubercle appears to be common in patients with well-functioning TKAs. The significance of slight tibial IR should be interpreted with caution when evaluating the painful TKA.
Level III retrospective case–control study.
•Nerolidol is a sesquiterpene present in the essential oil of Piper gaudichaudianum.•Essential oil and nerolidol led to cytotoxicity in XV185-14c and N123 strains.•BER defective strains showed ...pronounced sensitivity to essential oil and nerolidol.•Superoxide dismutase absence increases the sensitivity to the essential oil and nerolidol.•P. gaudichaudianum essential oil and nerolidol induce the ROS production.
Piper gaudichaudianum Kunth is used in popular medicine as anti-inflamatory and against liver disorders. One of the most studied components of the plant is the essential oil for which chemical analysis revealed (E)-nerolidol as major compound. Recently, we have shown that P. gaudichaudianum essential oil possesses strong cytotoxic effects in mammalian V79 cells. The aim of this study was to analyze the cytotoxicity and mutagenicity of P. gaudichaudianum essential oil and nerolidol using Saccharomyces cerevisiae as model study. Treatment of the XV185-14c and N123 strains with essential oil and nerolidol led to cytotoxicity but did not induce mutagenicity. Our results revealed an important role of base excision repair (BER) as the ntg1, ntg2, apn1 and apn2 mutants showed pronounced sensitivity to essential oil and nerolidol. In the absence of superoxide dismutase (in sod1Δ mutant strain) sensitivity to the essential oil and nerolidol increased indicating that this oil and nerolidol are generating reactive oxygen species (ROS). The ROS production was confirmed by DCF-DA probing assay in Sod-deficient strains. From this, we conclude that the observed cytotoxicity to P. gaudichaudianum essential oil and nerolidol is mainly related to ROS and DNA single strand breaks generated by the presence of oxidative lesions.
Twenty pharmacists and nurses handling anti-neoplastic drugs in a hospital were monitored during a working week, from Monday to Friday, in the morning (only on Monday) and afternoon (all days). ...Genotoxicity was analysed by the comet assay and the micronucleus (MN) test, while oxidative stress was analysed in serum by thiobarbituric acid reactive substances (TBARS) and by measurements of the antioxidant enzymes superoxide dismutase (Sod) and catalase (Cat). The exposed workers presented increased DNA damage levels by the comet assay as compared to the controls. The comet assay results have also shown significant positive correlation with the day of the week and with alcohol consumption. MN frequency was significantly higher in the exposed workers and presented noteworthy correlation with age and working time. In the oxidative stress parameters, only Cat presented a significant increase in the exposed group, considering all the samplings. However, TBARS data showed interesting results, considering the different sampling times; the exposed group presented a significant correlation with the working days and significantly higher results on Friday as compared to the controls and Monday morning. Monitoring occupational risk during a longer time, e.g. during a working week as done in this study, introduces additional aspects of risk behaviour, which can improve risk management. This study demonstrates the usefulness of evaluating oxidative stress also in genotoxic risk assessment since both events often result from the same factors.
Phosphoinositide (PtdInsP) lipids recruit effector proteins to membranes to mediate a variety of functions including signal transduction and membrane trafficking. Each PtdInsP binds to a specific set ...of effectors through characteristic protein domains such as the PH, FYVE and PX domains. Domains with high affinity for a single PtdInsP species are useful as probes to visualize the distribution and dynamics of that PtdInsP. The endolysosomal system is governed by two primary PtdInsPs: phosphatidylinositol 3-phosphate PtdIns(3)P and phosphatidylinositol 3,5-bisphosphate PtdIns(3,5)P2, which are thought to localize and control early endosomes and lysosomes/late endosomes, respectively. While PtdIns(3)P has been analysed with mammalian-derived PX and FYVE domains, PtdIns(3,5)P2 indicators remain controversial. Thus, complementary probes against these PtdInsPs are needed, including those originating from non-mammalian proteins. Here, we characterized in mammalian cells the dynamics of the PH domain from PH-containing protein-1 from the parasite Toxoplasma gondii (TgPH1), which was previously shown to bind PtdIns(3,5)P2 in vitro. However, we show that TgPH1 retains membrane-binding in PIKfyve-inhibited cells, suggesting that TgPH1 is not a viable PtdIns(3,5)P2 marker in mammalian cells. Instead, PtdIns(3)P depletion using pharmacological and enzyme-based assays dissociated TgPH1 from membranes. Indeed, TgPH1 co-localized with Rab5-positive early endosomes. In addition, TgPH1 co-localized and behaved similarly to the PX domain of p40phox and FYVE domain of EEA1, which are commonly used as PtdIns(3)P indicators. Collectively, TgPH1 offers a complementary reporter for PtdIns(3)P derived from a non-mammalian protein and that is distinct from commonly employed PX and FYVE domain-based probes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Two Schiff base derivatives synthesized from 2‑hydroxy-1-naphthaldehyde were synthesized.•DFT calculations show that 1 is more stable as an enol tautomer, while 2 is a keto.•The free radical ...scavenging potential of 1 and 2 was studied by DPPH and ABTS assay.•The SAR evaluation also included Schiff base derivatives of tert‑butylphenol.•The cytotoxicity in mammalian cells was investigated.
Naphthol-imine compounds containing N-phenylethylenediamine (1) and quinoline amine (2) moieties were synthesized and characterized. Density Functional Theory (DFT) calculations were performed aiming to obtain information on the chemical properties of these molecules. In silico ADME/Tox profile analyses were performed on molecules 1 and 2 using the web tools pkCSM-pharmacokinetics, Molinspiration, and Osiris Property Explorer. Drug-likeness levels of 1 and 2 were predicted according to the Lipinski rules. The radical scavenger activity of compounds 1 and 2 was determined by in vitro assays such as 1,1-diphenyl-2-picrylhydrazyl free radicals (DPPH.) and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radicals (ABTS.+). Molecules 1 and 2 were ineffective as radical scavengers in the DPPH radical capture assay at the test doses. However, 1 showed activity in eliminating ABTS+ radical with IC50 = 17.4 ± 0.9 µM. The neutral red assay determined the cytotoxicity of 1 and 2 against the V79 cell line. Molecule 1 was more cytotoxic than 2, with IC50 values of 36.67 µM and 51.26 µM, respectively. The alkaline comet assay was used to investigate the in vitro genotoxicity of 1 and 2. After 24 h of exposure to a dose of 20 μM, 1 did not cause significant DNA damage compared to non-exposed cells. The compounds were tested for toxicity using Artemia saline assay.
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