Investigation on silent bacterial infections in specimens from pregnant women affected by spontaneous miscarriage

Miscarriage is one of the main complications occurring in pregnancy. The association between adverse pregnancy outcomes and silent bacterial infections has been poorly investigated. Ureaplasma parvum and urealiticum, Mycoplasma genitalium and hominis and Chlamydia trachomatis DNA sequences have been investigated by polymerase chain reaction (PCR) methods in chorionic villi tissues and peripheral blood mononuclear cells (PBMCs) from females with spontaneous abortion (SA, n = 100) and females who underwent voluntary interruption of pregnancy (VI, n = 100). U. parvum DNA was detected in 14% and 15% of SA and VI, respectively, with a mean of bacterial DNA load of 1.3 × 10⁻¹ copy/cell in SA and 2.8 × 10 ⁻³ copy/cell in VI; U. urealiticum DNA was detected in 3% and 2% of SA and VI specimens, respectively, with a mean DNA load of 3.3 × 10⁻³ copy/cell in SA and 1.6 × 10⁻³ copy/cell in VI; M. hominis DNA was detected in 5% of SA specimens with a DNA load of 1.3 × 10⁻⁴ copy/cell and in 6% of VI specimens with a DNA load of 1.4 × 10⁻⁴ copy/cell; C. trachomatis DNA was detected in 3% of SA specimens with a DNA load of 1.5 × 10⁻⁴ copy/cell and in 4% of VI specimens with a mean DNA load of 1.4 × 10⁻⁴ copy/cell. In PBMCs from the SA and VI groups, Ureaplasma spp, Mycoplasma spp and C. trachomatis DNAs were detected with a prevalence of 1%–3%. Bacteria were investigated, for the first time, by quantitative real-time PCR (qPCR) in chorionic villi tissues and PBMCs from women affected by SA and VI. These data may help to understand the role and our knowledge of the silent infections in SA.     

Quantitative phosphoproteomics reveals novel roles of cAMP in plants

3′,5′-cyclic adenosine monophosphate (cAMP) is finally recognized as an essential signaling molecule in plants where cAMP-dependent processes include responses to hormones and environmental stimuli. To better understand the role of 3′,5′-cAMP at the systems level, we have undertaken a phosphoproteomic analysis to elucidate the cAMP-dependent response of tobacco BY-2 cells. These cells overexpress a molecular “sponge” that buffers free intracellular cAMP level. The results show that, firstly, in vivo cAMP dampening profoundly affects the plant kinome and notably mitogen-activated protein kinases, receptor-like kinases, and calcium-dependent protein kinases, thereby modulating the cellular responses at the systems level. Secondly, buffering cAMP levels also affects mRNA processing through the modulation of the phosphorylation status of several RNA-binding proteins with roles in splicing, including many serine and arginine-rich proteins. Thirdly, cAMP-dependent phosphorylation targets appear to be conserved among plant species. Taken together, these findings are consistent with an ancient role of cAMP in mRNA processing and cellular programming and suggest that unperturbed cellular cAMP levels are essential for cellular homeostasis and signaling in plant cells.     

GPU-FS-kNN: A Software Tool for Fast and Scalable kNN Computation Using GPUs

Background

The analysis of biological networks has become a major challenge due to the recent development of high-throughput techniques that are rapidly producing very large data sets. The exploding volumes of biological data are craving for extreme computational power and special computing facilities (i.e. super-computers). An inexpensive solution, such as General Purpose computation based on Graphics Processing Units (GPGPU), can be adapted to tackle this challenge, but the limitation of the device internal memory can pose a new problem of scalability. An efficient data and computational parallelism with partitioning is required to provide a fast and scalable solution to this problem.

Results

We propose an efficient parallel formulation of the k-Nearest Neighbour (kNN) search problem, which is a popular method for classifying objects in several fields of research, such as pattern recognition, machine learning and bioinformatics. Being very simple and straightforward, the performance of the kNN search degrades dramatically for large data sets, since the task is computationally intensive. The proposed approach is not only fast but also scalable to large-scale instances. Based on our approach, we implemented a software tool GPU-FS-kNN (GPU-based Fast and Scalable k-Nearest Neighbour) for CUDA enabled GPUs. The basic approach is simple and adaptable to other available GPU architectures. We observed speed-ups of 50–60 times compared with CPU implementation on a well-known breast microarray study and its associated data sets.

Conclusion

Our GPU-based Fast and Scalable k-Nearest Neighbour search technique (GPU-FS-kNN) provides a significant performance improvement for nearest neighbour computation in large-scale networks. Source code and the software tool is available under GNU Public License (GPL) at https://sourceforge.net/p/gpufsknn/.     

From Recombination Dynamics to Device Performance: Quantifying the Efficiency of Exciton Dissociation,Charge Separation,and Extraction in Bulk Heterojunction Solar Cells with Fluorine‐Substituted Polymer Donors

An original set of experimental and modeling tools is used to quantify the yield of each of the physical processes leading to photocurrent generation in organic bulk heterojunction solar cells, enabling evaluation of materials and processing condition beyond the trivial comparison of device performances. Transient absorption spectroscopy, “the” technique to monitor all intermediate states over the entire relevant timescale, is combined with time‐delayed collection field experiments, transfer matrix simulations, spectral deconvolution, and parametrization of the charge carrier recombination by a two‐pool model, allowing quantification of densities of excitons and charges and extrapolation of their kinetics to device‐relevant conditions. Photon absorption, charge transfer, charge separation, and charge extraction are all quantified for two recently developed wide‐bandgap donor polymers: poly(4,8‐bis((2‐ethylhexyl)oxy)benzo[1,2‐b:4,5‐b′]dithiophene‐3,4‐difluorothiophene) (PBDT[2F]T) and its nonfluorinated counterpart poly(4,8‐bis((2‐ethylhexyl)oxy)benzo[1,2‐b:4,5‐b′]dithiophene‐3,4‐thiophene) (PBDT[2H]T) combined with PC₇₁BM in bulk heterojunctions. The product of these yields is shown to agree well with the devices' external quantum efficiency. This methodology elucidates in the specific case studied here the origin of improved photocurrents obtained when using PBDT[2F]T instead of PBDT[2H]T as well as upon using solvent additives. Furthermore, a higher charge transfer (CT)‐state energy is shown to lead to significantly lower energy losses (resulting in higher V_OC) during charge generation compared to P3HT:PCBM.     

Characterizing the Community Structure of Complex Networks

Background

Community structure is one of the key properties of complex networks and plays a crucial role in their topology and function. While an impressive amount of work has been done on the issue of community detection, very little attention has been so far devoted to the investigation of communities in real networks.

Methodology/Principal Findings

We present a systematic empirical analysis of the statistical properties of communities in large information, communication, technological, biological, and social networks. We find that the mesoscopic organization of networks of the same category is remarkably similar. This is reflected in several characteristics of community structure, which can be used as “fingerprints” of specific network categories. While community size distributions are always broad, certain categories of networks consist mainly of tree-like communities, while others have denser modules. Average path lengths within communities initially grow logarithmically with community size, but the growth saturates or slows down for communities larger than a characteristic size. This behaviour is related to the presence of hubs within communities, whose roles differ across categories. Also the community embeddedness of nodes, measured in terms of the fraction of links within their communities, has a characteristic distribution for each category.

Conclusions/Significance

Our findings, verified by the use of two fundamentally different community detection methods, allow for a classification of real networks and pave the way to a realistic modelling of networks'' evolution.     

Control of human trophoblast function

The trophoblast, i.e. the peripheral part of the human conceptus, exerts a crucial role in implantation and placentation. Both processes properly occur as a consequence of an intimate dialogue between fetal and maternal tissues, fulfilled by membrane ligands and receptors, as well as by hormone and local factor release. During blastocyst implantation, generation of distinct trophoblast cell types begins, namely the villous and the extravillous trophoblast, the former of which is devoted to fetal-maternal exchanges and the latter binds the placental body to the uterine wall. Physiological placentation is characterized by the invasion of the uterine spiral arteries by extravillous trophoblast cells arising from anchoring villi. Due to this invasion, the arterial structure is replaced by amorphous fibrinoid material and endovascular trophoblastic cells. This transformation establishes a low-resistance, high-capacity perfusion system from the radial arteries to the intervillous space, in which the villous tree is embedded. The physiology of pregnancy depends upon the orderly progress of structural and functional changes of villous and extravillous trophoblast, whereas a derangement of such processes can lead to different types of complications of varying degrees of gravity, including possible pregnancy loss and maternal life-threatening diseases. In this review we describe the mechanisms which regulate trophoblast differentiation, proliferation, migration and invasiveness, and the alterations in these mechanisms which lead to pathological conditions. Furthermore, based on the growing evidence that proper inflammatory changes and oxidative balance are needed for successful gestation, we explain the mechanisms by which agents able to influence such processes may be useful in the prevention and treatment of pregnancy disorders.     

Ethnic differences in key candidate genes for spontaneous preterm birth: TNF-alpha and its receptors

OBJECTIVES: Spontaneous preterm birth (PTB) has a significant ethnic disparity with people of African descent having an almost 2-fold higher incidence than those of European descent in the United States. This disparity may be caused by differences in the distribution of genetic risk factors. The objective of this study is to examine genetic differences between African-Americans and European Americans for single nucleotide polymorphisms (SNPs) in candidate genes for PTB. METHODS: We examined patterns of variation in 19 SNPs in 3 candidate genes for preterm birth: TNF-alpha, TNF-receptor 1 and TNF-receptor 2. Allele, genotype and haplotype frequencies were compared between African-Americans (AA) and European-Americans (EA) in cases and controls separately. Both maternal and fetal genotypes were studied, as it is unclear whether one or both of these are important in the etiology of PTB. RESULTS: The vast majority of the SNPs differed significantly between ethnic groups, although there are only a few suggestive results comparing cases and controls within an ethnic group. For TNF-alpha, four of six SNPs; for TNF-R1, 5/6; and for TNF-R2, 6/7 showed significant differences between ethnic groups in either allele and/or genotype frequency. CONCLUSIONS: Our data demonstrate highly significant genetic differences between ethnic groups in genes that may play a role in the risk of PTB.     

Properties of a Bacillus subtilis strain lacking DNA polymerase I

We have isolated a mutant of Bacillussubtilis deficient in DNA polymerase I, denominated polA42, which shows a reduced ability to repair the damage to DNA by UV radiation, MMS and mitomycin C;the ability to perform recombination is not appreciably impaired.DEAE cellulose chromatography allows the separation of polymerases I and II from the parental strain;a simple procedure is also described which allows to separate rapidly the polymerases II and III of the mutant strain. The three separated polymerases have similar catalytic properties but they can be distinguished for their sensitivity to inhibitors: PCMB inhibits polymerases II and III but not polymerase I; HPUra inhibits only polymerase III. All three enzymes are unaffected by nalidixate. The DNA synthesis occurring in cells of the polA42 strain permeabilized with toluene is inhibited by nalidixate, whereas the synthesis occurring in polA⁺ toluenized cells is unaffected by the drug. The polA gene has been mapped by transduction and localized between the phe₁₂ and argA₃ genes.