The proliferative human monocyte subpopulation contains osteoclast precursors

Introduction  

Immediate precursors of bone-resorbing osteoclasts are cells of the monocyte/macrophage lineage. Particularly during clinical conditions showing bone loss, it would appear that osteoclast precursors are mobilized from bone marrow into the circulation prior to entering tissues undergoing such loss. The observed heterogeneity of peripheral blood monocytes has led to the notion that different monocyte subpopulations may have special or restricted functions, including as osteoclast precursors.     

Alpha-synuclein inhibits aromatic amino acid decarboxylase activity in dopaminergic cells

Alpha-synuclein is a presynaptic protein strongly implicated in Parkinson's disease (PD). Because dopamine neurons are invariably compromised during pathogenesis in PD, we have been exploring the functions of alpha-synuclein with particular relevance to dopaminergic neuronal cells. We previously discovered reduced tyrosine hydroxylase (TH) activity and minimal dopamine synthesis in stably-transfected MN9D cells overexpressing either wild-type or A53T mutant (alanine to threonine at amino acid 53) alpha-synuclein. TH, the rate-limiting enzyme in dopamine synthesis, converts tyrosine to l-dihydroxyphenylalanine (L-DOPA), which is then converted to dopamine by the enzyme, aromatic amino acid decarboxylase (AADC). We confirmed an interaction between alpha-synuclein and AADC in striatum. We then sought to determine whether wild-type or A53T mutant alpha-synuclein might have affected AADC activity in dopaminergic cells. Using HPLC with electrochemical detection, we measured dopamine and related catechols after L-DOPA treatments to bypass the TH step. We discovered that while alpha-synuclein did not reduce AADC protein levels, it significantly reduced AADC activity and phosphorylation in our cells. These novel findings further support a role for alpha-synuclein in dopamine homeostasis and may explain, at least in part, the selective vulnerability of dopamine neurons that occurs in PD.     

Gliclazide Microcrystals Prepared by Two Methods of <Emphasis Type="Italic">In Situ</Emphasis> Micronization: Pharmacokinetic Studies in Diabetic and Normal Rats

The low water-solubility of gliclazide (GL) leads to a low dissolution rate and variable bioavailability. The aim of this study was to investigate the effect of micronization on the absorption and pharmacokinetics of GL after oral administration in rats. GL microcrystals were prepared using solvent-change and pH-shift methods. Scanning electron microscopy showed considerable changes in the shape and size of crystals using both methods. In the optimized formulation of each method, the particle size of treated GL was reduced about 30 (from 290 to 9.9 μm) and 61 times (to 4.76 μm) by solvent-change and pH-shift methods, respectively. Recrystallized samples showed faster dissolution rate than untreated GL particles. Glucose-lowering effect, C _max, and area under the drug concentration-time profile (area under the curve (AUC)) were compared in diabetic and normal rats. AUC and C _max were increased by microcrystals in both groups of animals. Administration of 40 mg/kg of GL in the form of untreated drug and microcrystals obtained by solvent-change and pH-shift methods caused 12.49% and 21.04% enhancement in glucose-lowering effect of GL in diabetic rats, respectively.     

Maternal Exposure to Cadmium and Fetal Growth: a Systematic Review and Meta-Analysis

Biological Trace Element Research - This study aims to review the epidemiological studies on the association between cadmium (Cd) exposure during pregnancy and neonatal anthropometric measures....     

The potential impact of trigonelline loaded micelles on Nrf2 suppression to overcome oxaliplatin resistance in colon cancer cells

Molecular Biology Reports - Nuclear factor erythroid 2-related factor 2 (Nrf2) has a pivotal role in promoting chemoresistance by regulation of antioxidants and detoxification enzymes. Trigonelline...     

CO2 biofixation and fatty acid composition of two indigenous Dunaliella sp. isolates (ABRIINW-CH2 and ABRIINW-SH33) in response to extremely high CO2 levels

Bioprocess and Biosystems Engineering - Global warming, as a result of atmospheric CO2 increase, is regarded as an important universal concern. Microalgae are considered as appropriate...     

Intake of Dairy Products,Calcium, Magnesium,and Phosphorus in Childhood and Age at Menarche in the Tehran Lipid and Glucose Study

Purpose

Studies indicate that milk intake is associated with insulin-like growth factor 1 (IGF-1) concentrations and height in childhood, whether milk and other dairy products promote puberty remains unclear. This study aimed to investigate influences of pre-pubertal intakes of milk, yogurt and cheese on menarcheal age in Tehranian girls. The associations of total dietary calcium (Ca), magnesium (Mg), and phosphorus (P) with menarcheal age were also examined.

Methods

This prospective study was conducted on 134 pre-pubertal girls, aged 4-12 years at baseline, who participated in the Tehran Lipid and Glucose Study (TLGS), and were followed for a median of 6.5 years. Dietary intakes were determined at initiation of the study using two non-consecutive 24-h dietary recalls and the age of menarche was documented during the follow-up. Logistic regression was used to calculate the risk of reaching menarche ≤ 12 years according to pre-pubertal levels of dairy or mineral intakes.

Results

The risk of earlier menarche was higher in girls with higher intakes of milk [OR: 2.28 (95% CI: 1.03–5.05)], Ca [OR: 3.20 (95%CI: 1.39–7.42)], Mg [OR: 2.43 (95% CI: 1.12–5.27)] and P [OR: 3.37 (95 % CI: 1.44–7.87) after controlling for energy and protein intake, interval between the age at study initiation and the age of menarche, and maternal age at menarche (Model 1). Girls in the middle tertile of cheese intakes had a lower risk of reaching menarche ≤ 12 years than those in the lowest tertile after controlling for covariates in model 1. These associations remained significant after further adjustment of BMI Z-score at baseline. The relationship of Ca, Mg, and P with menarche remained after further adjustment for height Z-score at baseline, whereas the association between milk and cheese intakes became non-significant.

Conclusions

Pre-pubertal intake of milk, but not cheese and yogurt, may hasten age at menarche.     

Poor antibody validation is a challenge in biomedical research: a case study for detection of c-FLIP

Successful translation of findings derived from preclinical studies into effective therapies is critical in biomedical research. Lack of robustness and reproducibility of the preclinical data, due to insufficient number of repeats, inadequate cell-based and mouse models contribute to the poor success rate. Antibodies are widely used in preclinical research, notably to determine the expression of potential therapeutic targets in tissues of interest, including tumors, but also to identify disease and/or treatment response biomarkers. We sought to determine whether the current antibody characterization standards in preclinical research are sufficient to ensure reliability of the data found in peer-reviewed publications. To address this issue, we used detection of the protein c-FLIP, a major factor of resistance to apoptosis, as a proof of concept. Accurate detection of endogenous c-FLIP levels in the preclinical settings is imperative since it is considered as a potential theranostic biomarker. Several sources of c-FLIP antibodies validated by their manufacturer and recommended for western blotting were therefore rigorously tested. We found a wide divergence in immune recognition properties. While these antibodies have been used in many publications, our results show that several of them failed to detect endogenous c-FLIP protein by Western blotting. Our results suggest that antibody validation standards are inadequate, and that systematic use of genetic knockdowns and/or knockouts to establish proof of specificity is critical, even for antibodies previously used in the scientific literature. Because antibodies are fundamental tools in both preclinical and clinical research, ensuring their specificity is crucial.     

Cost–benefit analysis of pistachio twig borer,Kermania pistaciella Amsel (Lepidoptera: Oinophylidae) chemical control

Pistachio twig borer is a major pest of pistachio orchards in Iran. In order to reduce the pest damage, a conventional pesticide application is used annually. However, it is not known how much damage is caused by this pest. To determine the potential damage of Kermania pistaciella, and to qualify how efficient chemical control is in reduction of the pest damage, an experiment was conducted at two pistachio orchards in Kerman province (Kerman and Sirjan). A randomised complete block design, with two treatments – chemical control (a mixture of endosulfan EC 35 and volk, 2.5:5 l/ha) and check with five replications were performed. To estimate the pest damage, 25 randomly selected trees were chosen then the total fruit bunches of each tree were checked for infestation to the pest. The infestation percentage in Kerman was greater than that for Sirjan region (10.3% vs. 5.9%). When treatments were compared, the infestation rate of check plots were significantly more in comparison of treated plots in Kerman (10.3% vs. 3.6%); however, there was no significant difference between treatments in Sirjan (5.9% vs. 3.1%). The efficiency of chemical control was 60.7% and 48.7% in Kerman and Sirjan, respectively. There was not definite correlation between the number of capture and the infestation rate (r = 0.442). Cost–benefit ratio calculation was less than 1 (Kerman (?0.89) and Sirjan (?0.94)) and it means that chemical control at this damage percentage is not economic.     

Sublethal effects of Thymus vulgaris essential oil on life-table parameters of two-spotted spider mite,Tetranychus urticae Koch (Acari: Tetranychidae)

Sublethal effects of Thymus vulgaris were investigated on life-table parameters of Tetranychus urticae Koch (Acari: Tetranychidae) in the laboratory conditions at 25?±?1?°C, 70?±?10% RH and a 14:10?h (L:D) photoperiod. Bioassay was conducted to assess the effect of different concentrations of T. vulgaris essential oil on two-spotted spider mite. LC₅₀ and LC₂₀ of T. vulgaris on T. urticae were calculated as 18.86 and 6.24?μl/litre air for 24?h after treatment. In the sublethal effects, after 24?h exposure to LC₅₀ concentration, mortality, fecundity and longevity of the females that survived from treatment were determined. Results showed that T. vulgaris caused significant reductions in fecundity and longevity of adults. Life-table assay indicated that the intrinsic rate of increase (r _m), net reproductive rate (R ₀), finite rate of increase (λ), mean generation time (T), significantly reduced in treated females compared to control. These results suggest that T. vulgaris could be incorporated in integrated pest management programmes of T. urticae.