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.     

Muscle specific kinase: organiser of synaptic membrane domains

Muscle Specific Kinase (MuSK) is a transmembrane tyrosine kinase vital for forming and maintaining the mammalian neuromuscular junction (NMJ: the synapse between motor nerve and skeletal muscle). MuSK expression switches on during skeletal muscle differentiation. MuSK then becomes restricted to the postsynaptic membrane of the NMJ, where it functions to cluster acetylcholine receptors (AChRs). The expression, activation and turnover of MuSK are each regulated by signals from the motor nerve terminal. MuSK forms the core of an emerging signalling complex that can be acutely activated by neural agrin (N-agrin), a heparin sulfate proteoglycan secreted from the nerve terminal. MuSK activation initiates complex intracellular signalling events that coordinate the local synthesis and assembly of synaptic proteins. The importance of MuSK as a synapse organiser is highlighted by cases of autoimmune myasthenia gravis in which MuSK autoantibodies can deplete MuSK from the postsynaptic membrane, leading to complete disassembly of the adult NMJ.     

Do arbuscular mycorrhizas or heterotrophic soil microbes contribute toward plant acquisition of a pulse of mineral phosphate?

Aims

We investigated the role of arbuscular mycorrhizal fungi (AMF) and heterotrophic soil microbes in the uptake of phosphorus (P) by Trifolium subterraneum from a pulse.

Methods

Plants were grown in sterilised pasture field soil with a realistic level of available P. There were five treatments, two of which involved AMF: 1) unsterilised field soil containing a community of AMF and heterotrophic organisms; 2) Scutellospora calospora inoculum (AMF); 3) microbes added as filtrate from the field soil; 4) microbes added as filtrate from the S. calospora inoculum; 5) no additions, i.e. sterilised field soil. After 11 weeks, plants were harvested: 1 day before (day 0), 1 day after (day 2) and 7 days after (day 8) the pulse of P (10 mg kg^?1).

Results

There was no difference among treatments in shoot and root dry weight, which increased from day 0 to day 8. At day 0, shoots and roots of plants in the colonised treatments had higher P and lower Mn concentrations. After the pulse, the rate of increase in P concentration in the shoots was slower for the colonised plants, and the root Mn concentration declined by up to 50 % by day 2.

Conclusions

Plants colonised by AMF had a lower rate of increase in shoot P concentration after a pulse, perhaps because intraradical hyphae accumulated P and thus reduced its transport to the shoots.     

Modulation of the cell growth regulator mTOR by Epstein-Barr virus-encoded LMP2A

Control of translation initiation is one means by which cells regulate growth and proliferation, with components of the protein-synthesizing machinery having oncogenic potential. Expression of latency protein LMP2A by the human tumor virus Epstein-Barr virus (EBV) activates phosphatidylinositol 3-kinase/Akt located upstream of an essential mediator of growth signals, mTOR (mammalian target of rapamycin). We show that mTOR is activated by expression of LMP2A in carcinoma cells, leading to wortmannin- and rapamycin-sensitive inhibition of the negative regulator of translation, eukaryotic initiation factor 4E-binding protein 1, and increased c-Myc protein translation. Intervention by this DNA tumor virus in cellular translational controls is likely to be an integral component of EBV tumorigenesis.     

Computational model of excitatory/inhibitory ratio imbalance role in attention deficit disorders

Impairments in attentional behaviors, including over-selectivity, under-selectivity, distractibility and difficulty in shift of attention, are widely reported in several developmental disorders, including autism. Uncharacteristic inhibitory to excitatory neuronal number ratio (IER) and abnormal synaptic strength levels in the brain are two broadly accepted neurobiological disorders observed in autistic individuals. These neurobiological findings are contrasting and their relation to the atypical attentional behaviors is not clear yet. In this paper, we take a computational approach to investigate the relation of imbalanced IER and abnormal synaptic strength to some well-documented spectrum of attentional impairments. The computational model is based on a modified version of a biologically plausible neural model of two competing minicolumns in IT cortex augmented with a simple model of top-down attention. Top-down attention is assumed to amplify (attenuates) attended (unattended) stimulus. The inhibitory synaptic strength parameter in the model is set such that typical attentional behavior is emerged. Then, according to related findings, the parameter is changed and the model's attentional behavior is considered. The simulation results show that, without any change in top-down attention, the abnormal inhibitory synaptic strength values - and IER imbalance- result in over-selectivity, under-selectivity, distractibility and difficulty in shift of attention in the model. It suggests that the modeled neurobiological abnormalities can be accounted for the attentional deficits. In addition, the atypical attentional behaviors do not necessarily point to impairments in top-down attention. Our simulations suggest that limited changes in the inhibitory synaptic strength and variations in top-down attention signal affect the model's attentional behaviors in the same way. So, limited deficits in the inhibitory strength may be alleviated by appropriate change in top-down attention biasing. Nevertheless, our model proposes that this compensation is not possible for very high and very low values of the inhibitory strength.     

Crocin and Metformin suppress metastatic breast cancer progression via VEGF and MMP9 downregulations: in vitro and in vivo studies

Metastatic breast cancer remains a serious health concern and numerous investigations recommended medicinal plants as a complementary therapy. Crocin is one of the known anticancer bio-component. Recently, the inhibitory effect of metformin has been studied on the various aspects of cancer. However, no study reported their combination effects on metastatic breast cancer. In the present study, we have assessed their anti-metastatic effects on in vitro and in vivo breast cancer models. Using MTT assay, scratch, and adhesion tests, we have evaluated the cytotoxic, anti-invasive and anti-adhesion effects of crocin and metformin on 4T1 cell line, respectively. Their protective effects and MMP9 as well as VEGF protein expression levels (Western blotting) investigated in the 4T1 murine breast cancer model. Our results showed that both crocin and metformin reduced cell viability, delayed scratch healing and inhibited the cell adhesion, in vitro. While crocin alone restored the mice’s weight reduction, crocin, metformin, and their combination significantly reduced the tumor volume size and enhanced animal survival rate in murine breast cancer model, responses that were associated with VEGF and MMP9 down-regulation. These findings suggest that a combination of crocin and metformin could serve as a novel therapeutic approach to enhance the effectiveness of metastatic breast cancer therapy.

     

Application of nanoparticles in cancer therapy with an emphasis on cell cycle

Owing to their unique characteristics, nanoparticles (NPs) could be incorporated into valuable therapeutic modalities for different diseases; however, there are many concerns about risk factors in human applications. NPs carry therapeutic chemicals that could improve the outcome of cancer therapies. Nowadays, NPs are being recognized as important and strategic agents in treatment of several disorders due to their unique properties in targeting malignant cells in tumor sites. Numerous investigations have shown that the majority of chemotherapeutic agents can be modified through entrapment in submicron colloidal systems. Still, there are problems and limitations in application of NPs in cancer therapy. The aim of the present study is to focus on potential NPs usage in cancer treatment with an emphasis on the cell cycle of malignant cells.