Computational approaches to shed light on molecular mechanisms in biological processes

Computational approaches based on Molecular Dynamics simulations, Quantum Mechanical methods and 3D Quantitative Structure-Activity Relationships were employed by computational chemistry groups at the University of Milano-Bicocca to study biological processes at the molecular level. The paper reports the methodologies adopted and the results obtained on Aryl hydrocarbon Receptor and homologous PAS proteins mechanisms, the properties of prion protein peptides, the reaction pathway of hydrogenase and peroxidase enzymes and the defibrillogenic activity of tetracyclines. © Springer-Verlag 2007

Vitamin D deficiency and infertility : insights from in vitro fertilization cycles

Context: Vitamin D deficiency has been proven to affect fertility in mammals, but data in human is less convincing. In particular, data on in vitro fertilization (IVF), an attractive model to draw information on this topic, are sparse and conflicting.Objective: Our objective was to investigate IVF outcome in women with deficient 25-hydroxyvitamin D [25 (OH)D] serum levels (30 ng/mL) had the highest chances of pregnancy.Conclusions: VitaminDis an emerging factor influencing female fertility and IVF outcome. Additional studies are pressingly needed to confirm a causal relationship and to investigate the potential therapeutic benefits of vitamin D supplementation

Uterine artery Doppler pulsatility index at 11-38 weeks in ICSI pregnancies with egg donation

BACKGROUND: Uterine artery Doppler pulsatility index (UtA-PI) may be different in pregnancies with egg donation (ICSI-ED) as compared to conceptions with autologous intra-cytoplasmatic sperm injection (autologous ICSI) and to spontaneous conceptions (SC). METHODS: One hundred and ninety-four pregnant women with different modes of conception (MC) were prospectively evaluated: 53 ICSI-ED, 36 autologous ICSI and 105 SC. To evaluate the effects of different MC on PI, multivariable linear regression (MLR) models predicting UtA-PI were fitted after adjustment for maternal age, body mass index, race, parity, smoking status and gestational age. RESULTS: In the first trimester, at MLR, autologous ICSI was not associated with a significantly different UtA-PI [estimate (EST) 0.01; 95% confidence interval (CI) -0.19, 0.2; P=0.9] when compared to SC. Conversely, MC by ICSI-ED was associated with lower first trimester UtA-PI (EST -0.32; CI -0.55, -0.08; P=0.01) when compared to SC. At MLR, MC by autologous ICSI and by ICSI-ED were not associated with significant differences in the second and third trimester UtA-PI when compared to SC. CONCLUSION: ICSI-ED conception presented lower UtA-PI when compared to SC at 11+0-13+6 weeks but not at later assessments. Correction of UtA-PI measurement specifying the origin of oocyte may be useful in first trimester screening

Risk of miscarriage in women with endometriosis: insights from in vitro fertilization cycles

Objective: To evaluate whether women with endometriosis achieving singleton pregnancies with IVF face an increased risk of miscarriage. Design: Matched case-control study. Setting: Infertility units. Patient(s): Women achieving singleton pregnancies with the use of IVF were considered. Cases were women with a history of surgery for endometriosis and those who were documented the presence of ovarian endometriomas at the time of the IVF cycle (n = 313). Controls were matched to cases by age (\ub16 months), type of cycle (fresh or frozen cycle). and study period (n = 313). Intervention(s): Retrospective review of women undergoing IVF. Main Outcome Measure(s): Rate of miscarriage before 12 weeks' gestation. Result(s): The number of miscarriages in women with and without endometriosis was similar, being 48 (15%) and 60 (19%), respectively. The odds ratio of miscarriage in affected women was 0.76 (95% confidence interval 0.50-1.16). The odds ratio adjusted for body mass index (BMI), parity, duration of infertility, and male factor infertility was 0.81 (95% confidence interval 0.53-1.25). Subgroup analyses according to the type of cycle, the number of embryos transferred, the presence of endometriomas, and the history of surgery for endometriosis did not document any subgroup at significant increased risk of miscarriage. Conclusion(s): The risk of miscarriage is not increased in women with endometriosis achieving pregnancy with the use of IVF

DNA-binding protects p53 from interactions with cofactors involved in transcription-independent functions

Binding-induced conformational changes of a protein at regions distant from the binding site may play crucial roles in protein function and regulation. The p53 tumour suppressor is an example of such an allosterically regulated protein. Little is known, however, about how DNA binding can affect distal sites for transcription factors. Furthermore, the molecular details of how a local perturbation is transmitted through a protein structure are generally elusive and occur on timescales hard to explore by simulations. Thus, we employed state-of-the-art enhanced sampling atomistic simulations to unveil DNA-induced effects on p53 structure and dynamics that modulate the recruitment of cofactors and the impact of phosphorylation at Ser215. We show that DNA interaction promotes a conformational change in a region 3 nm away from the DNA binding site. Specifically, binding to DNA increases the population of an occluded minor state at this distal site by more than 4-fold, whereas phosphorylation traps the protein in its major state. In the minor conformation, the interface of p53 that binds biological partners related to p53 transcription-independent functions is not accessible. Significantly, our study reveals a mechanism of DNA-mediated protection of p53 from interactions with partners involved in the p53 transcription-independent signalling. This also suggests that conformational dynamics is tightly related to p53 signalling

Noto Station Status Report

The Noto VLBI station was fully operational in 2012, and the upgrade projects could be restarted, involving mainly the receiver area. Another important improvement was the activation of the 1 Gbps network

Genetic variation in FABP4 and evaluation of its effects on beef cattle fat content

FABP4 is a protein primarily expressed in adipocytes and macrophages that plays a key role in fatty acid trafficking and lipid hydrolysis. FABP4 gene polymorphisms have been associated with meat quality traits in cattle, mostly in Asian breeds under feedlot conditions. The objectives of this work were to characterize FABP4 genetic variation in several worldwide cattle breeds and evaluate possible genotype effects on fat content in a pasture-fed crossbred (Angus-Hereford-Limousin) population. We re-sequenced 43 unrelated animals from nine cattle breeds (Angus, Brahman, Creole, Hereford, Holstein, Limousin, Nelore, Shorthorn, and Wagyu) and obtained 22 single nucleotide polymorphisms (SNPs) over 3,164 bp, including four novel polymorphisms. Haplotypes and linkage disequilibrium analyses showed a high variability. Five SNPs were selected to perform validation and association studies in our crossbred population. Four SNPs showed well-balanced allele frequencies (minor frequency > 0.159), and three showed no significant deviations from Hardy-Weinberg proportions. SNPs showed significant effects on backfat thickness and fatty acid composition (P < 0.05). The protein structure of one of the missense SNPs was analyzed to elucidate its possible effect on fat content in our studied population. Our results revealed a possible blockage of the fatty acid binding site by the missense mutation.Instituto de Genética Veterinari