Gender specific decrease of a set of circulating Nacylphosphatidyl ethanolamines (NAPEs) in the plasma of Parkinson’s disease patients

Introduction: Current markers of Parkinson's disease (PD) fail to detect the early progression of disease state. Conversely, current omics techniques allow the investigation of hundreds of molecules potentially altered by disease conditions. Based on evidence previously collected by our group in a mouse model of PD, we speculated that a particular set of circulating lipids might be significantly altered by the pathology. Objectives: The aim of current study was to evaluate the potential of a particular set of N-acyl-phosphatidylethanolamines (NAPEs) as potential non-invasive plasma markers of ongoing neurodegeneration from Parkinson's disease in human subjects. Methods: A panel of seven NAPEs were quantified by LC-MS/MS in the plasma of 587 individuals (healthy controls, n = 319; Parkinson's disease, n = 268); Random Forest classification and statistical modeling was applied to compare Parkinson's disease versus controls. All p-values obtained in different tests were corrected for multiplicity by controlling the false discovery rate (FDR). Results: The results indicate that this panel of NAPEs is able to distinguish female PD patients from the corresponding healthy controls. Further to this, the observed downregulation of these NAPEs is in line with the results in plasma of a mouse model of Parkinson's (6-OHDA). Conclusions: In the current study we have shown the downregulation of NAPEs in plasma of PD patients and we thus speculate that these lipids might serve as candidate biomarkers for PD. We also suggest a molecular mechanism, explaining our findings, which involves gut microbiota

CHESTNUT: Improve serendipity in movie recommendation by an Information Theory-based collaborative filtering approach

The term serendipity has been understood narrowly in the Recommender System. Applying a user-centered approach, user-friendly serendipitous recommender systems are expected to be developed based on a good understanding of serendipity. In this paper, we introduce CHESTNUT , a memory-based movie collaborative filtering system to improve serendipity performance. Relying on a proposed Information Theory-based algorithm and previous study, we demonstrate a method of successfully injecting insight, unexpectedness and usefulness, which are key metrics for a more comprehensive understanding of serendipity, into a practical serendipitous runtime system. With lightweight experiments, we have revealed a few runtime issues and further optimized the same. We have evaluated CHESTNUT in both practicability and effectiveness , and the results show that it is fast, scalable and improves serendip-ity performance significantly, compared with mainstream memory-based collaborative filtering. The source codes of CHESTNUT are online at https://github.com/unnc-idl-ucc/CHESTNUT/

Fructan and its relationship to abiotic stress tolerance in plants

Numerous studies have been published that attempted to correlate fructan concentrations with freezing and drought tolerance. Studies investigating the effect of fructan on liposomes indicated that a direct interaction between membranes and fructan was possible. This new area of research began to move fructan and its association with stress beyond mere correlation by confirming that fructan has the capacity to stabilize membranes during drying by inserting at least part of the polysaccharide into the lipid headgroup region of the membrane. This helps prevent leakage when water is removed from the system either during freezing or drought. When plants were transformed with the ability to synthesize fructan, a concomitant increase in drought and/or freezing tolerance was confirmed. These experiments indicate that besides an indirect effect of supplying tissues with hexose sugars, fructan has a direct protective effect that can be demonstrated by both model systems and genetic transformation

Interrelations between substrate cycles and de novo synthesis of pyrimidine deoxyribonucleoside triphosphates in 3T6 cells.

Degradation of pyrimidine deoxyribonucleoside triphosphates plays a major role in the regulation of their pool sizes in 3T6 cells. During normal growth, these cells excrete deoxyribonucleosides (mostly deoxyuridine) into the medium. When DNA strand elongation is inhibited, de novo synthesis of dCTP and dTTP continues, followed by degradation of the deoxyribonucleotides. We now demonstrate that inhibition of de novo synthesis with hydroxyurea stops degradation of deoxyribonucleotides. We now demonstrate that inhibition of de novo synthesis with hydroxyurea stops degradation of deoxyribonucleotides and leads to an influx of deoxyuridine from the medium. This effect appears to be caused by a large drop in the size of the intracellular dUMP pool. We propose that substrate cycles, involving phosphorylation of deoxyribonucleosides by kinases and dephosphorylation of deoxyribonucleoside 5'-phosphates by a nucleotidase, participate in the regulation of the size of pyrimidine deoxyribonucleoside triphosphate pools by directing the flow of deoxyribonucleosides across the cell membrane. While kinases are regulated mainly by allosteric effects, the activity of the nucleotidase appears to be regulated by substrate concentration

Regulation of pyrimidine deoxyribonucleotide metabolism by substrate cycles in dCMP deaminase-deficient V79 hamster cells.

A mutant V79 hamster fibroblast cell line lacking the enzyme dCMP deaminase was used to study the regulation of deoxynucleoside triphosphate pools by substrate cycles between pyrimidine deoxyribosides and their 5'-phosphates. Such cycles were suggested earlier to set the rates of cellular import and export of deoxyribosides, thereby influencing pool sizes (V. Bianchi, E. Pontis, and P. Reichard, Proc. Natl. Acad. Sci. USA 83:986-990, 1986). While normal V79 cells derived more than 80% of their dTTP from CDP reduction via deamination of dCMP, the mutant cells had to rely completely on UDP reduction for de novo synthesis of dTTP, which became limiting for DNA synthesis. Because of the allosteric properties of ribonucleotide reductase, CDP reduction was not diminished, leading to a large expansion of the dCTP pool. The increase of this pool was kept in check by a shift in the balance of the deoxycytidine/dCMP cycle towards the deoxynucleoside, leading to massive excretion of deoxycytidine. In contrast, the balance of the deoxyuridine/dUMP cycle was shifted towards the nucleotide, facilitating import of extracellular deoxynucleosides

Uterine rupture in pregnancy: two case reports and review of literature

Rupture of a gravid uterus is an obstetric emergency. Risks factors include a scarred uterus but also spontaneous rupture of an un- scarred uterus during pregnancy is possible. The authors present two cases of a spontaneous complete uterine rupture during pregnancy. The first case had only a past history of dilatation and curettage for abortion; the second case had a past history of dilatation and curettage for abortion and a monolateral laparoscopic salpingectomy for ectopic pregnancy. They presented with abdominal pain and after ultrasound scan, uterine ruptures were diagnosed. These cases show that there should be a high index of suspicious of uterine rupture in a gravid woman with a history of curettage for the possible presence of misunderstood uterine scar and in women with a past history of salpingectomy with or without corneal resection. Appropriate counseling and close follow-up might help to avoid such obstetrical catastrophes. To provide more insight into the possible risk factors for prelabor uterine rupture in pregnancy, a literature review was performe