Field-scale studies that examine the potential for adverse effects of Bt crop technology on non-target arthropods may supplement data from laboratory studies to support an environmental risk ...assessment. A three year field study was conducted in Brazil to evaluate potential for adverse effects of cultivating soybean event DAS-81419-2 that produces the Cry1Ac and Cry1F proteins. To do so, we examined the diversity and abundance of non-target arthropods (NTAs) in Bt soybean in comparison with its non-Bt near isoline, with and without conventional insecticide applications, in three Brazilian soybean producing regions. Non-target arthropod abundance was surveyed using Moericke traps (yellow pan) and pitfall trapping. Total abundance (N), richness (S), Shannon-Wiener (H'), Simpson's (D) and Pielou's evenness (J) values for arthropod samples were calculated for each treatment and sampling period (soybean growth stages). A faunistic analysis was used to select the most representative NTAs which were used to describe the NTA community structure associated with soybean, and to test for effects due to the treatments effects via application of the Principal Response Curve (PRC) method. Across all years and sites, a total of 254,054 individuals from 190 taxa were collected by Moericke traps, while 29,813 individuals from 100 taxa were collected using pitfall traps. Across sites and sampling dates, the abundance and diversity measurements of representative NTAs were not significantly affected by Bt soybean as compared with non-sprayed non-Bt soybean. Similarly, community analyses and repeated measures ANOVA, when applicable, indicated that neither Bt soybean nor insecticide sprays altered the structure of the NTA communities under study. These results support the conclusion that transgenic soybean event DAS-81419-2 producing Cry1Ac and Cry1F toxins does not adversely affect the NTA community associated with soybean.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The purpose of this study was to determine if in ovo feeding and rearing with glycosaminoglycans and vitamin C could influence bone and cartilage macroscopy, mineral composition, mineral density and ...surface area, bone breaking strength, and bone histology in broilers. Fertile eggs from breeders (Cobb) were either uninjected or injected with 4 μg of additive/100 μL water on day 4 of incubation. Every 100 g of in ovo additive contained 30 g of chondroitin sulfate, 30 g of glucosamine, and 5 g of vitamin C. After hatching, the chicks from both incubation treatments were submitted to additional treatments during the growth phase from 1 to 42 D of age (diet without and with 0.74 g of additive/kg of feed). Every 100 kg of feed contained 30 g of glucosamine sulfate, 24 g of chondroitin sulfate, and 20 g of vitamin C. A completely randomized factorial design (2 × 2) was applied. The data were submitted to variance analysis using the general linear model procedure of SAS (SAS Institute). In ovo feeding with 4 μg of additive plus dietary supplementation with 0.74 g of additive/kg of feed resulted in the highest cartilage weight of the femur proximal epiphysis in birds (P = 0.0098). The highest ash, phosphorus and calcium percentage, mineral density and mineral composition were identified for femur and tibia in the following treatments: in ovo feeding plus diet without additive during rearing, or uninjected eggs plus dietary supplementation during rearing. In ovo feeding with 4 μg of the additive reduced (P = 0.0008) the number of chondrocytes in the proximal epiphysis of the tibia cartilage and increased (P < 0.0001) the number of osteocytes in the tibia diaphysis of broilers. We conclude that in ovo feeding or dietary supplementation during broiler rearing with glycosaminoglycans (chondroitin sulfate and glucosamine sulfate) and vitamin C benefits the development of bird bones and cartilage, and may represent a solution to bone problems in broilers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This study seeks to provide a nuanced understanding of how residents’ views on tourism impacts and their awareness of the pandemic’s effects shape their attitudes and, consequently, influence their ...involvement and support for tourism by integrating emotional solidarity, the knowledge–attitude–practices theory, and social exchange theory. Furthermore, the study explores potential moderating factors such as gender and professional ties to tourism. Data were gathered from 545 residents of Manavgat, Turkey, following a cluster sampling scheme, confirming all ten hypotheses. The results reveal that residents’ knowledge and perceived positive impacts of tourism significantly forecast attitudes toward tourism and tourists, which explains their involvement and support. The results also demonstrate that residents with strong ties to tourism were more positive and involved than those with limited links to tourism. The complementary merger of theoretical frameworks enriches our understanding of residents’ support and involvement in tourism, shedding light on the intricacies of these relationships.
•A synthetic analogue (p-BTX-I) of a snake venom peptide mimics NGF in PC12 cells.•p-BTX-I increases neuritogenesis and viability of PC12 cells exposed to MPP+.•Like NGF, p-BTX-I activates trkA, ...PI3K/AKT and MAPK-ERK pathways.•Like NGF, p-BTX-I increases the expression of GAP-43 and synapsin I.•The neurotrophic action of p-BTX-I in PC12 cells is not dependent on NGF.
Venom small peptides that target neurotrophin receptors might be beneficial in neurodegeneration, including Parkinsońs disease (PD). Their small size, ease of synthesis, structural stability and target selectivity make them important tools to overcome the limitations of endogenous neurotrophins as therapeutic agents. Additionally, they might be optimized to improve resistance to enzymatic degradation, bioavailability, potency and, mainly, lipophilicity, important to cross the blood brain barrier (BBB). Here, we evaluated the neuroprotective effects and mechanisms of the synthetic snake-venom-based peptide p-BTX-I (Glu-Val-Trp) in PC12 cells treated with MPP+ (1-methyl-4-phenylpyridinium), a dopaminergic neurotoxin that induces Parkinsonism in vivo. The peptide p-BTX-I induced neuritogenesis, which was reduced by (i) k252a, antagonist of the NGF-selective receptor, trkA (tropomyosin receptor kinase A); (ii) LY294002, inhibitor of the PI3 K/AKT pathway and (iii) U0126, inhibitor of the MAPK-ERK pathway. Besides that, p-BTX-I also increased the expression of GAP-43 and synapsin, which are molecular markers of axonal growth and synaptic communication. In addition, the peptide increased the viability and differentiation of cells exposed to MPP+, known to inhibit neuritogenesis. Altogether, our findings suggest that the synthetic peptide p-BTX-I protects PC12 cells from MPP+ toxicity by a mechanism that mimics the neurotrophic action of NGF. Therefore, the molecular structure of p-BTX-I might be relevant in the development of drugs aimed at restoring the axonal connectivity in neurodegenerative processes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
This manuscript describes the preparation of a new Ru(
ii
) nitrosylsulphito complex,
trans
-Ru(NH
3
)
4
(isn)(N(O)SO
3
)
+
(complex
1
), its spectroscopic and structural characterization, ...photochemistry, and thermal reactivity. Complex
1
was obtained by the reaction of sulfite ions (SO
3
2−
) with the nitrosyl complex
trans
-Ru(NH
3
)
4
(isn)(NO)
3+
(complex
2
) in aqueous solution resulting in the formation of the N-bonded nitrosylsulphito (N(O)SO
3
) ligand. To the best of our knowledge, only four nitrosylsulphito metal complexes have been described so far (
J. Chem. Soc., Dalton Trans., 1983, 2465-2472
), and there is no information about the photochemistry of such complexes. Complex
1
was characterized by spectroscopic means (UV-Vis, EPR, FT-IR,
1
H- and
15
N-NMR), elemental analysis and single-crystal X-ray diffraction. The X-ray structure of the precursor complex
2
is also discussed in the manuscript and is used as a reference for comparisons with the structure of
1
. Complex
1
is water-soluble and kinetically stable at pH 7.4, with a first-order rate constant of 3.1 × 10
−5
s
−1
for isn labilization at 298 K (
t
1/2
∼ 373 min). Under acidic conditions (1.0 M trifluoroacetic acid),
1
is stoichiometrically converted into the precursor complex
2
. The reaction of hydroxide ions (OH
−
) with
1
and with
2
yields the Ru(
ii
) nitro complex
trans
-Ru(NH
3
)
4
(isn)(NO
2
)
+
with second-order rate constants of 2.1 and 10.5 M
−1
s
−1
(at 288 K), respectively, showing the nucleophilic attack of OH
−
at the nitrosyl in
2
(Ru-NO) and at the nitrosylsulphito in
1
(Ru-N(O)SO
3
). The p
K
a
value of the -SO
3
moiety of the N(O)SO
3
ligand in
1
was determined to be 5.08 ± 0.06 (at 298 K). The unprecedented photochemistry of a nitrosylsulphito complex is investigated in detail with
1
. The proposed mechanism is based on experimental (UV-Vis, EPR, NMR and Transient Absorption Laser Flash Photolysis) and theoretical data (DFT) and involves photorelease of the N(O)SO
3
−
ligand followed by formation of nitric oxide (NO&z.rad;) and sulfite radicals (SO
3
&z.rad;
−
, sulfur trioxide anion radical).
This manuscript describes the preparation of a new Ru(
ii
) nitrosylsulphito complex,
trans
-Ru(NH
3
)
4
(isn)(N(O)SO
3
)
+
(complex
1
), its spectroscopic and structural characterization, photochemistry, and thermal reactivity.
Lung cancer is one of the most frequent neoplasms in the world. Because it is a complex disease, its formation occurs in several stages, stemming from interactions between environmental risk factors, ...such as smoking, and individual genetic susceptibility. Our objective was to investigate associations between a
gene polymorphism (rs8175347) and lung cancer risk in an Amazonian population. This is a pilot study, case-controlled study, which included 276 individuals with cancer and without cancer. The samples were analyzed for polymorphisms of the
gene (rs8175347) and genotyped in PCR, followed by fragment analysis in which we applied a previously developed set of informative ancestral markers. We used logistic regression to identify differences in allelic and genotypic frequencies between individuals. Individuals with the TA7 allele have an increased chance of developing lung adenocarcinoma (
= 0.035; OR: 2.57), as well as those with related genotypes of reduced or low enzymatic activity: TA6/7, TA5/7, and TA7/7 (
= 0.048; OR: 8.41). Individuals with homozygous TA7/7 have an increased chance of developing squamous cell carcinoma of the lung (
= 0.015; OR: 4.08). Polymorphism in the
gene (rs8175347) may contribute as a risk factor for adenocarcinoma and lung squamous cell carcinoma in the population of the Amazon region.
To examine whether combined testosterone replacement and exercise training (ET) therapies would potentiate the beneficial effects of isolated therapies on neurovascular control and muscle wasting in ...patients with heart failure (HF) with testosterone deficiency.
From January 10, 2010, through July 25, 2013, 39 male patients with HF, New York Heart Association functional class III, total testosterone level less than 249 ng/dL (to convert to nmol/L, multiply by .03467), and free testosterone level less than 131 pmol/L were randomized to training (4-month cycloergometer training), testosterone (intramuscular injection of testosterone undecylate for 4 months), and training + testosterone groups. Muscle sympathetic nerve activity was measured using microneurography, forearm blood flow using plethysmography, body composition using dual X-ray absorptiometry, and functional capacity using cardiopulmonary test. Skeletal muscle biopsy was performed in the vastus lateralis.
Muscle sympathetic nerve activity decreased in ET groups (training, P<.01; training + testosterone, P<.01), whereas no changes were observed in the testosterone group (P=.89). Forearm blood flow was similar in all groups. Lean mass increased in ET groups (training, P<.01; training + testosterone, P<.01), whereas lean mass decreased in the testosterone group (P<.01). The response of cross-sectional area of type I (P<.01) and type II (P<.05) fibers increased in the training + testosterone group as compared with the isolated testosterone group.
Our findings provide evidence for a superior effect of combined ET and testosterone replacement therapies on muscle sympathetic nerve activity, muscle wasting, and functional capacity in patients with HF with testosterone deficiency.
The use of transcranial Electrical Stimulation (tES) in the modulation of cognitive brain functions to improve neuropsychiatric conditions has extensively increased over the decades. tES techniques ...have also raised new challenges associated with study design, stimulation protocol, functional specificity, and dose-response relationship. In this paper, we addressed challenges through the emerging methodology to investigate the dose-response relationship of High Definition-transcranial Direct Current Stimulation (HD tDCS), identifying the role of negative valence in tinnitus perception. In light of the neurofunctional testable framework and tES application, hypotheses were formulated to measure clinical and surrogate endpoints. We posited that conscious pairing adequately pleasant stimuli with tinnitus perception results in correction of the loudness misperception and would be reinforced by concurrent active HD-tDCS on the left Dorsolateral Prefrontal Cortex (dlPFC). The dose-response relationship between HD-tDCS specificity and the loudness perception is also modeled. We conducted a double-blind, randomized crossover pilot study with six recruited tinnitus patients. Accrued data was utilized to design a well-controlled adaptive seamless Bayesian dose-response study. The sample size (
= 47, for 90% power and 95% confidence) and optimum interims were anticipated for adaptive decision-making about efficacy, safety, and single session dose parameters. Furthermore, preliminary pilot study results were sufficient to show a significant difference (90% power, 99% confidence) within the longitudinally detected self-report tinnitus loudness between before and under positive emotion induction. This study demonstrated a research methodology used to improve emotion regulation in tinnitus patients. In the projected method, positive emotion induction is essential for promoting functional targeting under HD-tDCS anatomical specificity to indicate the efficacy and facilitate the dose-finding process. The continuous updating of prior knowledge about efficacy and dose during the exploratory stage adapts the anticipated dose-response model. Consequently, the effective dose range to make superiority neuromodulation in correcting loudness misperception of tinnitus will be redefined. Highly effective dose adapts the study to a standard randomized trial and transforms it into the confirmatory stage in which active HD-tDCS protocol is compared with a sham trial (placebo-like). Establishing the HD-tDCS intervention protocols relying on this novel method provides reliable evidence for regulatory agencies to approve or reject the efficacy and safety. Furthermore, this paper supports a technical report for designing multimodality data-driven complementary investigations in emotion regulation, including EEG-driven neuro markers, Stroop-driven attention biases, and neuroimaging-driven brain network dynamics.
Twelve to 66% of patients with clinically non-functioning pituitary adenoma (NFPA) experience tumor recurrence 1–5 years after the first surgery. Nevertheless, there is still no recurrence prediction ...factor concisely established and reproduced in the literature for NFPA management. The present study evaluates the prognostic value of MRI Radiomics features combined with machine learning models to assess recurrence after the first surgery in patients with clinically non-functioning pituitary adenomas (NFPA). We carried out a retrospective study on 27 patients with NFPA, 10 patients having experienced tumor recurrence after the first surgery and 17 who did not. Preoperative 3D T1 contrast-enhanced MR images of patients were used to extract up to 255 Radiomics features from two and three-dimensional segmented regions. Additionally, gender, age at first surgery, and the presence of remnant tumor tissue were investigated to find the correlation with NFPA recurrence. Conventional statistics tests were used to evaluate whether the outcome patient groups (stable and recurrent) were different considering each feature individually. Additionally, five well-known machine-learning algorithms were used in combination with Radiomic features to classify recurrent and stable lesions. We found statistical evidence (p < 0.02) for 6 two-dimensional and 13 three-dimensional radiomic features. We achieved accuracies of up to 96.3% for 3D-feature based models and up to 92.6% accuracies for 2D-feature based models. 3D-feature based models achieved better performances using considerably fewer features when compared to 2D-feature based models. We concluded that Radiomics have the potential of NFPA recurrence prediction after the first surgery. Three-dimensional Radiomics have superior discrimination power to predict NFPA recurrence than two-dimensional radiomic features. Finally, the combination of Radiomics with machine-learning algorithms can offer computational models capable of non-invasive, unbiased, and quick assessment that might improve the prediction of NFPA recurrence.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Cannabidiol prevented cocaine-induced seizures in mice.•CB1 and CB2 antagonists failed to prevent cannabidiol effects.•Cocaine increases, whereas cannabidiol reduced glutamate release.•mTOR ...inhibition prevents cannabidiol effects.
Cannabidiol (CBD), a major non-psychotomimetic constituent of Cannabis sativa, has therapeutic potential for certain psychiatric and neurological disorders. Studies in laboratory animals and limited human trials indicate that CBD has anticonvulsant and neuroprotective properties. Its effects against cocaine neurotoxicity, however, have remained unclear. Thus, the present study tested the hypothesis that CBD protects against cocaine-induced seizures and investigated the underlying mechanisms. CBD (30mg/kg) pre-treatment increased the latency and reduced the duration of cocaine (75mg/kg)-induced seizures in mice. The CB1 receptor antagonist, AM251 (1 and 3mg/kg), and the CB2 receptor antagonist, AM630 (2 and 4mg/kg), failed to reverse this protective effect, suggesting that alternative mechanisms are involved. Synaptosome studies with the hippocampus of drug-treated animals revealed that cocaine increases glutamate release, whereas CBD induces the opposite effect. Finally, the protective effect of this cannabinoid against cocaine-induced seizure was reversed by rapamycin (1 and 5mg/kg), an inhibitor of the mammalian target of rapamycin (mTOR) intracellular pathway. In conclusion, CBD protects against seizures in a model of cocaine intoxication. These effects possibly occur through activation of mTOR with subsequent reduction in glutamate release. CBD should be further investigated as a strategy for alleviating psychostimulant toxicity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK