Metabolomics to understand placental biology: Where are we now?

Metabolomics, the application of analytical chemistry methodologies to survey the chemical composition of a biological system, is used to globally profile and compare metabolites in one or more groups of samples. Given that metabolites are the terminal end-products of cellular metabolic processes, or 'phenotype' of a cell, tissue, or organism, metabolomics is valuable to the study of the maternal-fetal interface as it has the potential to reveal nuanced complexities of a biological system as well as differences over time or between individuals. The placenta acts as the primary site of maternal-fetal exchange, the success of which is paramount to growth and development of offspring during pregnancy and beyond. Although the study of metabolomics has proven moderately useful for the screening, diagnosis, and understanding of the pathophysiology of pregnancy complications, the placental metabolome in the context of a healthy pregnancy remains poorly characterized and understood. Herein, we discuss the technical aspects of metabolomics and review the current literature describing the placental metabolome in human and animal models, in the context of health and disease. Finally, we highlight areas for future opportunities in the emerging field of placental metabolomics.

Transition to turbulence in driven active matter.

A Lorenz-like model was set up recently to study the hydrodynamic instabilities in a driven active matter system. This Lorenz model differs from the standard one in that all three equations contain nonlinear terms. The additional nonlinear term comes from the active matter contribution to the stress tensor. In this work, we investigate the nonlinear properties of this Lorenz model both analytically and numerically. The significant feature of the model is the passage to chaos through a complete set of period-doubling bifurcations above the Hopf point for Schmidt numbers above a critical value. Interestingly enough, at these Schmidt numbers a strange attractor and stable fixed points coexist beyond the homoclinic point. At the Hopf point, the strange attractor disappears leaving a high-period periodic orbit. This periodic state becomes the expected limit cycle through a set of bifurcations and then undergoes a sequence of period-doubling bifurcations leading to the formation of a strange attractor. This is the first situation where a Lorenz-like model has shown a set of consecutive period-doubling bifurcations in a physically relevant transition to turbulence.

Work probability distribution for a ferromagnet with long-ranged and short-ranged correlations.

Work fluctuations and work probability distributions are fundamentally different in systems with short-ranged versus long-ranged correlations. Specifically, in systems with long-ranged correlations the work distribution is extraordinarily broad compared to systems with short-ranged correlations. This difference profoundly affects the possible applicability of fluctuation theorems like the Jarzynski fluctuation theorem. The Heisenberg ferromagnet, well below its Curie temperature, is a system with long-ranged correlations in very low magnetic fields due to the presence of Goldstone modes. As the magnetic field is increased the correlations gradually become short ranged. Hence, such a ferromagnet is an ideal system for elucidating the changes of the work probability distribution as one goes from a domain with long-ranged correlations to a domain with short-ranged correlations by tuning the magnetic field. A quantitative analysis of this crossover behavior of the work probability distribution and the associated fluctuations is presented.

First-trimester reference centiles of fetal biometry in Indian population.

AIM AND OBJECTIVE: To create crown-rump length (CRL)-based biometric chart for fetus in the first trimester among the Indian population. MATERIAL AND METHODS: Cross-sectional data were obtained from 400 singleton pregnancies between 11 and 14 weeks gestation with a normal outcome. Linear regression models were constructed; the mean and SD were derived as a function of CRL. RESULTS: There was a positive correlation of CRL with nuchal translucency (NT) (y = 0.0102x + 0.6307 R2 = 0.1177), biparietal diameter (BPD) (BPD = 0.032*CRL +0.185 R2 = 0.765), occipito-frontal diameter (OFD), lateral ventricular diameter (LV), abdominal circumference (AC) (AC = 0.944*CRL +9.684 R2 = 0.668), femur length (FL) (FL = 0.222*CRL -4.734 R2 = 0.661), fetal weight (FW) (FW = 1.328*CRL -10.41 R2 = 0.662). The regression models and centile charts of NT, BPD, OFD, LV, AC, and FW were constructed. Taking FW as the independent variable, a linear equation of BPD, AC, and FL to calculate weight was constructed. CONCLUSIONS: The first-trimester centile charts of fetal parameters can be used as a reference for Indian population in the determination of gestational age or other adverse outcomes.

Turing-Hopf instabilities through a combination of diffusion, advection, and finite size effects.

We show that in a reaction diffusion system on a two-dimensional substrate with advection in the confined direction, the drift (advection) induced instability occurs through a Hopf bifurcation, which can become a double Hopf bifurcation. The box size in the direction of the drift is a vital parameter. Our analysis involves reduction to a low dimensional dynamical system and constructing amplitude equations.

Control of H-dimer formation of acridine orange using nano clay platelets.

Acridine orange (AO) forms dimer even in aqueous solution. In layer-by-layer (LbL) film of AO dimeric sites predominate over monomeric sites. This communication reports the control of H-dimer of AO in LbL film by incorporating nano clay platelets. This was studied by using UV-Vis absorption spectroscopy. Atomic force microscopic (AFM) image of the LbL film was taken to confirm the presence of nano clay platelets in the LbL film.

Toxicity assessment on trophoblast cells for some environment polluting chemicals and 17ß-estradiol.

The identification of reproductive toxicants is a major scientific challenge for human health. We investigated the effects of a selected group of environmental polluting chemicals mostly provided with estrogenic activity on the human trophoblast cell lines BeWo and HTR-8/SVneo. Cells were exposed for 24h to various concentrations (from 0.1 pM to 1 mM) of atrazine (ATR), diethylstilbestrol (DES), para-nonylphenol (p-NP), resveratrol (RES) and 17 ß-estradiol (E2) and assayed for cell viability and human beta-Chorionic Gonadotropin (ß-hCG) secretion. Decrease of cell viability as respect to control, vehicle-treated, cultures was obtained for all chemicals in the concentration range of 1 µM-1 mM in both cell types. A parallel decrease of ß-hCG secretion was observed in BeWo cells, at 1 µM-1 mM concentrations, with the only exception of ATR which caused an increase at concentrations up to 1mM. ß-hCG release was also unexpectedly inhibited by ATR, DES, p-NP and RES at non-toxic (pM-nM) concentrations. These findings raise concern about the negative, potential effects of various environmental polluting chemicals on pregnancy success and fetal health.

Factors affecting the first service conception rate of cows in smallholder dairy farms in Bangladesh.

The successful outcome of an insemination is a combination of both male and female fertility-linked factors. We investigated the first service conception rate of cows at artificial insemination (AI) in the smallholder dairy farms in Bangladesh. Frozen straws were prepared from ejaculates of Bos indicus (n = 7) and Bos indicus × Bos taurus (n = 7) AI bulls. Fertility was determined from 6101 first services in cows that were performed by 18 technicians in four regions between April 2004 and March 2005. Pregnancy was diagnosed by rectal palpation between 60 and 90 days post-insemination. The Asian version of Artificial Insemination Database Application (AIDA ASIA) was used for bulls-, cows- and AI-related data recording, and later retrieved for analysis. The mean ± SD number of inseminations performed from individual bulls and their conception rates were 436.0 ± 21.6 and 50.7 ± 1.9%, respectively. Logistic regression demonstrated body condition scores (BCS), heat detection signs, months of AI and their interactions had greatest effects (odds ratios: 1.24-16.65, p < 0.04-0.001) on first service conception rate in cows. Fertility differed (p < 0.02-0.001) between the regions, previous calving months, months of AI, BCS, parity and heat detection signs of cows. Inseminations based on mounting activity (n = 2352), genital discharge (n = 3263) and restlessness and/or other signs (n = 486) yielded a conception rate of 53.6%, 48.8% and 50.1%, respectively (p < 0.05). Conception rate between technicians ranged between 43.4% and 58.6% (p < 0.05). The days interval from calving to first service (overall mean ± SD = 153.4 ± 80.6) had relationship (p < 0.001) with BCS, months of previous calving and parity of the cows. Fertility at AI in smallholder farms can be improved by training farmers on nutrition and reproductive management of the cows.

Estimation of malaria mortality of A District in India during 2010 by using three models.

There is no standard method for estimating annual malaria deaths in India. The degree of under-reporting in routine system is uncertain with a varied picture of 10, 15, 25 and 200 times as found in different studies/models. During October 2010 a community based cross-sectional survey was conducted by National Vector Borne Disease Control Programme (NVBDCP) in 32 villages of West Garo Hills district of Meghalaya. 'Gap filling', 'fever survey' and 'verbal autopsy' models, developed in NVBDCP were used on the data obtained from two surveys done simultaneously: 'fever survey' with 2 weeks recall period and 'death survey' with one year recall period. Inputs from demographic and epidemiological data of the district were also given. During 2010, the district has reported 32 malaria deaths. Degrees of under-reporting found in the study were 6.93, 7.53 and 12 times in three models respectively. The first two models yielded closer estimates. But, verbal autopsy model gave inflated value as the method was unreliable for diagnosing malaria deaths. First two models, if found to be replicable, can be incorporated in NVBDCP activities to evaluate malaria control measures at district level. Verbal autopsy model may be used after concordance study in those districts where Pf malaria cases occur but no death is reported.

Periodic orbits in glycolytic oscillators: from elliptic orbits to relaxation oscillations.

We consider the Sel'kov model of glycolytic oscillator for a quantitative study of the limit cycle oscillations in the system. We identify a region of parameter space where perturbation theory holds and use both Linstedt Poincaré technique and harmonic balance to obtain the shape and frequency of the limit cycle. The agreement with the numerically obtained result is excellent. We also find a different extreme, where the limit cycle is of the relaxation oscillator variety, has a large time period and it is seen that, as a particular parameter in the model is varied, the time period increases indefinitely. We characterize this divergence numerically. A calculational method is devised to capture the divergence approximately.

Micellar shape driven counterion binding. Small-angle neutron scattering study of AOT micelle.

Sodium dioctylsulfosuccinate (AOT) micelle has a special counterion binding behavior in aqueous electrolyte medium, viz., the counterion binding constant (ß) abruptly increases by 2-fold at about 0.015 mol dm(-3) NaCl concentration (c*), but not in sodium salicylate (NaSa) solution. Since counterions affect the structure and performance of ionic surfactants, ascertaining the cause for the sudden shift in the ß value of AOT micelle is of fundamental importance. In this study the special counterion binding behavior of AOT micelle has been ascertained at 40 °C by carrying out surface tension, zeta potential, and fluorescence emission (pyrene probe) measurements. The results of the small-angle neutron scattering experiment carried out at 40 °C showed that at c* the shape of AOT micelle changes from prolate spheroid to rodlike in NaCl solution, but not in NaSa solution, thus establishing micellar shape change as responsible for the abrupt change in ß value. The absence of sudden shift in ß of AOT micelle in NaSa solution is attributed to the binding of salicylate coanion to AOT micelle through hydrophobic interaction.

Expression and localization of ATP binding cassette transporter A1 (ABCA1) in first trimester and term human placenta.

ATP binding cassette transporter A1 (ABCA1) is a membrane transporter which performs cellular efflux of cholesterol and phospholipid. ABCA1's cholesterol transporting role in human placenta appears to be crucial for normal fetal development. Despite the critical importance of cholesterol in fetal development, expression of ABCA1 in the human placenta throughout gestation and its specific cellular localization have not been known yet. We therefore investigated ABCA1 expression in human placenta at first trimester and term by western blot and quantitative real-time PCR (qRT-PCR) analysis. Furthermore, its localization was investigated by immunohistochemistry and confocal microscopy. Expression of ABCA1 did not differ significantly between first trimester and term placenta at both protein and mRNA levels. Immunohistochemical data demonstrated that ABCA1 was widely localized in the villous and extravillous cytotrophoblast as well as in some stromal and endothelial cells. Confocal microscopy imaging data showed that ABCA1 was localized largely at the basolateral and to some extent at the apical side of first trimester villous cytotrophoblast cell membranes. Placental expression of ABCA1 throughout the gestation and its specific cellular localization indicate that this transporter may play an important role in materno-fetal cholesterol transfer.

Homocysteine and lipoprotein (a) correlation in ischemic stroke patients.

BACKGROUND: Homocysteine and Lipoprotein (a) have been recognized as risk factors for coronary heart disease. However, their role in ischemic stroke is still not defined. Therefore the present study was undertaken to evaluate their levels and relationship in patients of ischemic stroke. METHODS: The study was conducted in consecutive patients admitted with a diagnosis of acute ischaemic stroke and age and sex matched healthy controls. Plasma homocysteine and serum l lipoprotein (a) levels were determined in the fasting venous blood samples using ELISA and immunoturbidimetric assay respectively. RESULTS: 66 patients with ischaemic stroke (30 males, 36 females) of mean age 54.43+/-1.97 years and 72 controls (39 males, 33 females) of mean age 53.86+/-1.88 years were studied. Mean plasma homocysteine levels in the stroke patients and control groups were 28.40+/-2.08 micromol/L and 11.16+/-1.09 micromol/L respectively (p<0.001). Odds ratio for raised homocysteine levels in stroke cases was 15.7. Plasma homocysteine levels showed a positive correlation with smoking (Pearson's correlation coefficient=0.324 and p-value of 0.008), (Odds ratio=5.71). Serum Lipoprotein (a) levels in stroke cases and control group were 57.33+/-4.40 mg/dl and 23.46+/-1.09 mg/dl respectively, (p<0.001), (Odds Ratio=8.62). A positive correlation was also observed between Homocysteine and Lipoprotein (a) levels with Pearson's correlation coefficient of 0.75 and p-value<0.001. CONCLUSIONS: Raised homocysteine and serum lipoprotein (a) levels were found to be independently associated with ischemic stroke with a significant positive correlation between the two parameters. Elevated homocysteine levels may modulate the toxicity of lipoprotein (a) in ischemic stroke.

Effects of nondenumerable fixed points in finite dynamical systems.

The motion of a spinning soccer ball brings forth the possible existence of a whole class of finite dynamical systems where there may be a nondenumerably infinite number of fixed points. They defy the very traditional meaning of the fixed point that a point on the fixed point in the phase space should remain there forever, for, a fixed point can evolve as well! Under such considerations one can argue that a free-kicked soccer ball should be nonchaotic.

Aripiprazole versus typicals for schizophrenia.

BACKGROUND: Aripiprazole is a relatively new antipsychotic drug, said to be the prototype of a new third generation of antipsychotics; the so-called dopamine-serotonin system stabilisers. In this review we examine how the efficacy and tolerability of aripiprazole differs from that of typical antipsychotics. OBJECTIVES: To evaluate the effects of aripiprazole compared with other typical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group Trials Register (May 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. SELECTION CRITERIA: We included all randomised trials comparing aripiprazole with typical antipsychotics in people with schizophrenia or schizophrenia-like psychosis. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model. We have contacted representatives of Bristol Myers Squibb pharmaceuticals (UK) for additional and missing data. MAIN RESULTS: We included nine randomised trials involving 3122 people comparing aripiprazole with typical antipsychotic drugs. None of the studies reported on relapse - our primary outcome of interest. Attrition from studies was high and data reporting poor. Participants given aripiprazole were comparable to those receiving typical drugs in improving global state and mental state. Aripiprazole provided a significant advantage over typical antipsychotics in terms of fewer occurrences of extra-pyramidal symptom (n=968, 3 RCT, RR 0.46 CI 0.3 to 0.9, NNT 13 CI 17 to 10), and particularly akathisia (n=897, 3 RCT, RR 0.39 CI 0.3 to 0.6, NNT 11 CI 14 to 9). Fewer participants given aripiprazole developed hyperprolactinaemia (n=300, 1 RCT, RR 0.07 CI 0.03 to 0.2, NNT 2 CI 3 to 1) and raised fasting blood glucose (n=360, 1 RCT, RR 0.65 CI 0.5 to 0.9, NNT 8 CI 14 to 6). Aripiprazole presented a lesser risk of sinus tachycardia (n=289, 1 RCT, RR 0.09 CI 0.01 to 0.8, NNT 22 CI 63 to 13) and blurred vision (n=308, 1 RCT, RR 0.19 CI 0.1 to 0.7, NNT 14 CI 25 to 10); but enhanced risk of occurrence of dizziness (n=957, 3 RCTs, RR 1.88 CI 1.1 to 3.2, NNH 20 CI 33 to 14) and nausea (n=957, 3 RCTs, RR 3.03 CI 1.5 to 6.1, NNH 17 CI 25 to 13). Attrition rates were high in both groups, although significantly more participants in the aripiprazole group completed the study in the long term (n=1294, 1 RCT, RR 0.81 CI 0.8 to 0.9 NNT 8 CI 5 to 14). AUTHORS' CONCLUSIONS: Aripiprazole is not much different from typical antipsychotic drugs with respect to efficacy. However it presents significant advantages in terms of tolerability due to its favourable adverse effects profile. This might enhance its effectiveness in encouraging compliance. Clearly reported pragmatic short, medium and long term randomised controlled trials are required to replicate and validate these findings and determine the position of aripiprazole in everyday clinical practice.

Crossbred bull selection for bigger scrotum and shorter age at puberty with potentials for better quality semen.

Shortening age at puberty of crossbred breeding bull is an important issue in the tropics. This study aimed at selecting crossbred bulls at earliest possible age with bigger scrotum and potential for donating quality semen. One hundred and 31 pre-joining crossbred bulls of Central Artificial Insemination Laboratory, Saver, Dhaka were examined. The bulls being trained by seeing semen collection from mature bulls were allowed ejaculation into the artificial vagina at homosexual mount during a 20 min time at three occasions, every three months. Eighty one of 131 bulls produced at least one ejaculate during the study and their mean +/- SD age and scrotal circumference (SC) were 20.3 +/- 4.7 months and 28.2 +/-2.7 cm, respectively. Bulls' body weight, body condition score (BCS) and SC influenced the attainment of their puberty (p < 0.05). Bull's body weight had positive effects on scrotal circumference and ejaculate volume (p < 0.05). Scrotal circumference positively influenced the percentages of normal spermatozoa (p < 0.05). Scrotal skin-fold thickness negatively influenced the proportion of spermatozoa with normal head (p < 0.05). Based on age at first ejaculate and SC, 29.6% bulls (n = 24) were selected by cluster analysis. Selected bulls had mean +/- SD age 17.9 +/- 2.2 months, body weight 287.3 +/-48.6 kg, SC 30.5 +/- 1.5 cm, ejaculate volume 3.4 +/- 1.3 ml, sperm motility 50.8 +/- 17.2%, total spermatozoa per ejaculate 2541.9 +/- 1699.2 million and normal spermatozoa 81.5 +/-14.5%. The selected pubertal bull group was different from the unselected pubertal bulls at MANOVA (p < 0.0001). About 30% of pubertal crossbred bulls can be selected with shorter age and larger scrotum at puberty under conditions prevailed in Bangladesh.

Study of genetic, metabolic and inflammatory risk factors in patients of acute ischemic stroke.

Stroke is the third leading cause of death and foremost cause of disability. Based on studies in CAD patients, a focus has been shifted on genetic and inflammatory markers as risk factors for stroke besides deranged lipid profile. The present study was aimed to ascertain the role of Lipoprotein (a), C-Reactive protein (CRP) levels and lipids in patients of ischemic stroke. The study was done in 82 subjects including 40 Computerized Tomography (CT) proven patients of ischemic stroke and 42 age and sex matched controls. Complete biochemical parameters including lipid profile were carried out on autoanalyzer using standard kits and reagents. Lipoprotein (a) [Lp(a)] was determined by immunoturbidimetric assay. Atherogenic indices (Total cholesterol/ HDL, LDL/HDL and Lipid Tetrad Index) were calculated using these lipid parameters. The CRP levels were measured semi-quantitatively by latex agglutination test method. Out of 40 stroke patients, 38 had abnormalities in lipid profile (As per ATP III guidelines). A significant difference was seen in serum cholesterol, LDL cholesterol and atherogenic indices between the patients and controls. The difference in CRP levels in cases and control subjects was highly significant (4.78±0.72 mg/dl vs 0.76 ±0.70, p<0.001). 96.5% of patients with raised CRP had abnormal lipid levels also. CRP levels in stroke patients showed significant correlation with total cholesterol and LDL (p<0.001), Lp (a) (p=0.002) and atherogenic indices (p<0.05). Raised CRP levels in stroke patients were significantly associated with large territory infarcts, severe disability and poor functional outcome (p<0.05).Genetic [Lp(a)], metabolic (deranged Lipid profile) and inflammatory factors (CRP) together are instrumental in causing cerebrovascular arteriosclerosis leading to ischaemic stroke and can be used as important markers to identify patients at risk of severe stroke and to institute aggressive preventive strategies.

Global persistence exponent in critical dynamics: finite-size-induced crossover.

We extend the definition of a global order parameter to the case of a critical system confined between two infinite parallel plates separated by a distance L. For a quench to the critical point we study the persistence property of the global order parameter and show that there is a crossover behavior characterized by a nonuniversal exponent which depends on the ratio of the system size to a dynamic length scale.