Deciphering Cell Lineage Specification during Male Sex Determination with Single-Cell RNA Sequencing

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Data analysis issues for allele-specific expression using Illumina's GoldenGate assay

Background  

High-throughput measurement of allele-specific expression (ASE) is a relatively new and exciting application area for array-based technologies. In this paper, we explore several data sets which make use of Illumina's GoldenGate BeadArray technology to measure ASE. This platform exploits coding SNPs to obtain relative expression measurements for alleles at approximately 1500 positions in the genome.     

Progesterone signaling in human myometrium through two novel membrane G protein-coupled receptors: potential role in functional progesterone withdrawal at term

Progestin withdrawal is a crucial event for the onset of labor in many mammalian species. However, in humans the mechanism of a functional progestin withdrawal is unclear, because progestin concentrations do not drop in maternal plasma preceding labor. We report the presence of two novel functional membrane progestin receptors (mPRs), mPRalpha and mPRbeta, in human myometrium that are differentially modulated during labor and by steroids in vitro. The mPRs are coupled to inhibitory G proteins, resulting in a decline in cAMP levels and increased phosphorylation of myosin light chain, both of which facilitate myometrial contraction. Activation of mPRs leads to transactivation of PR-B, the first evidence for cross-talk between membrane and nuclear PRs. Progesterone activation of the mPRs leads also to a decrease of the steroid receptor coactivator 2. Our data indicate the presence of a novel signaling pathway mediated by mPRs that may result in a functional progestin withdrawal, shifting the balance from a quiescent state to one of contraction.     

Efforts to Explain and Control the Prolonged Thermophilic Period in Two-phase Olive Oil Mill Sludge Composting

The aim of this paper was to evaluate the use of different bulking agents in different ratios as a means to control, optimise and eventually reduce the duration of the thermophilic period in two-phase olive oil mill sludge (OOMS) composting. The bulking agents used were: (i) olive tree leaves (OTL), (ii) olive tree shredded branches (OTB) and (iii) woodchips (WDC). The selection of these materials was based on their abundance and availability on the island of Crete, the southernmost point of Greece. The ratios studied were: Pile 1, OOMS:OTL in 1:1 v/v; Pile 2, OOMS:WDC in 1:1.5 v/v; Pile 3, OOMS:OTL in 1:2 v/v; Pile 4, OOMS:OTL:OTB in 1:1:1 v/v; and Pile 5, OOMS:OTL:OTB in 1:1:2 v/v. The composting system used was that of windrows with the volume of each pile approximately 20–25 m³. The experiments took place over two consecutive years. A composting turner was used and turnings were performed at one and two week intervals. In each pile a variety of physiochemical parameters were monitored. Temperature remained high in all five trials. Piles 1, 2, 3, 4 and 5 temperatures recorded values of above 50 °C for 106, 158, 160, 175 and 183 days, respectively. Volumes were reduced by approximately 67%, 62%, 63%, 80% and 84%, respectively. Temperature remained high, mainly due to the presence in large amounts of oily substances which during their complete oxidation release important amounts of energy and aid the cometabolism of more stable molecules such as lignin. This process is better described as the slow “burning” of a “fuel” mixture in an “engine” than composting. This approach is based on the extensive similarities of this process to that of crude oil sludge or similar waste composting.     

Controlled disorder in plant light-harvesting complex II explains its photoprotective role

The light-harvesting antenna of photosystem II (PSII) has the ability to switch rapidly between a state of efficient light use and one in which excess excitation energy is harmlessly dissipated as heat, a process known as qE. We investigated the single-molecule fluorescence intermittency of the main component of the PSII antenna (LHCII) under conditions that mimic efficient use of light or qE, and we demonstrate that weakly fluorescing states are stabilized under qE conditions. Thus, we propose that qE is explained by biological control over the intrinsic dynamic disorder in the complex-the frequencies of switching establish whether the population of complexes is unquenched or quenched. Furthermore, the quenched states were accompanied by two distinct spectral signatures, suggesting more than one mechanism for energy dissipation in LHCII.     

Long- and Short-Term Selective Forces on Malaria Parasite Genomes

Plasmodium parasites, the causal agents of malaria, result in more than 1 million deaths annually. Plasmodium are unicellular eukaryotes with small ∼23 Mb genomes encoding ∼5200 protein-coding genes. The protein-coding genes comprise about half of these genomes. Although evolutionary processes have a significant impact on malaria control, the selective pressures within Plasmodium genomes are poorly understood, particularly in the non-protein-coding portion of the genome. We use evolutionary methods to describe selective processes in both the coding and non-coding regions of these genomes. Based on genome alignments of seven Plasmodium species, we show that protein-coding, intergenic and intronic regions are all subject to purifying selection and we identify 670 conserved non-genic elements. We then use genome-wide polymorphism data from P. falciparum to describe short-term selective processes in this species and identify some candidate genes for balancing (diversifying) selection. Our analyses suggest that there are many functional elements in the non-genic regions of these genomes and that adaptive evolution has occurred more frequently in the protein-coding regions of the genome.     

Vancomycin Treatment of Infective Endocarditis Is Linked with Recently Acquired Obesity

Background

Gut microbiota play a major role in digestion and energy conversion of nutrients. Antibiotics, such as avoparcin (a vancomycin analogue), and probiotics, such as Lactobacillus species, have been used to increase weight in farm animals. We tested the effect of antibiotics given for infective endocarditis (IE) on weight gain (WG).

Methodology/Principal Findings

Forty-eight adults with a definite diagnosis of bacterial IE (antibiotic group) were compared with forty-eight age-matched controls without IE. Their body mass index (BMI) was collected at one month before the first symptoms and one year after hospital discharge. The BMI increased significantly and strongly in vancomycin-plus-gentamycin–treated patients (mean [±SE] kg/m², +2.3 [0.9], p = 0.03), but not in controls or in patients treated with other antibiotics. Seventeen patients had a BMI increase of ≥10%, and five of the antibiotic group developed obesity. The treatment by vancomycin-plus-gentamycin was an independent predictor of BMI increase of ≥10% (adjusted OR, 6.7; 95% CI, 1.37–33.0; p = 0.02), but not treatment with other antibiotics. Weight gain was particularly high in male patients older than 65 who did not undergo cardiac surgery. Indeed, all three vancomycin-treated patients with these characteristics developed obesity.

Conclusions/Significance

A major and significant weight gain can occur after a six-week intravenous treatment by vancomycin plus gentamycin for IE with a risk of obesity, especially in males older than 65 who have not undergone surgery. We speculate on the role of the gut colonization by Lactobacillus sp, a microorganism intrinsically resistant to vancomycin, used as a growth promoter in animals, and found at a high concentration in the feces of obese patients. Thus, nutritional programs and weight follow-up should be utilized in patients under such treatment.