Triggering of inflammatory response by myeloperoxidase-oxidized LDL.

The oxidation theory proposes that LDL oxidation is an early event in atherosclerosis and that oxidized LDL contributes to atherogenesis in triggering inflammation. In contrast to the copper-modified LDL, there are few studies using myeloperoxidase-modified LDL (Mox-LDL) as an inflammation inducer. Our aim is to test whether Mox-LDL could constitute a specific inducer of the inflammatory response. Albumin, which is the most abundant protein in plasma and which is present to an identical concentration of LDL in the intima, was used for comparison. The secretion of IL-8 by endothelial cells (Ea.hy926) and TNF-alpha by monocytes (THP-1) was measured in the cell medium after exposure of these cells to native LDL, native albumin, Mox-LDL, or Mox-albumin. We observed that Mox-LDL induced a 1.5- and 2-fold increase (ANOVA; P < 0.001) in IL-8 production at 100 microg/mL and 200 microg/mL, respectively. The incubation of THP-1 cells with Mox-LDL (100 microg/mL) increased the production of TNF-alpha 2-fold over the control. Native LDL, albumin, and Mox-albumin showed no effect in either cellular types. The myeloperoxidase-modified LDL increase in cytokine release by endothelial and monocyte cells and by firing both local and systemic inflammation could induce atherogenesis and its development.     

Detailed role of microRNA-mediated regulation of PI3K/AKT axis in human tumors

The regulation of signal transmission and biological processes, such as cell proliferation, apoptosis, metabolism, migration, and angiogenesis are greatly influenced by the PI3K/AKT signaling pathway. Highly conserved endogenous non-protein-coding RNAs known as microRNAs (miRNAs) have the ability to regulate gene expression by inhibiting mRNA translation or mRNA degradation. MiRNAs serve key role in PI3K/AKT pathway as upstream or downstream target, and aberrant activation of this pathway contributes to the development of cancers. A growing body of research shows that miRNAs can control the PI3K/AKT pathway to control the biological processes within cells. The expression of genes linked to cancers can be controlled by the miRNA/PI3K/AKT axis, which in turn controls the development of cancer. There is also a strong correlation between the expression of miRNAs linked to the PI3K/AKT pathway and numerous clinical traits. Moreover, PI3K/AKT pathway-associated miRNAs are potential biomarkers for cancer diagnosis, therapy, and prognostic evaluation. The role and clinical applications of the PI3K/AKT pathway and miRNA/PI3K/AKT axis in the emergence of cancers are reviewed in this article.     

Improved PC1/3 production through recombinant expression in insect cells and larvae

Protein convertase 1/3 is a serine endoproteinase present in the regulated secretory pathway of endocrine and neuroendocrine cells. It is responsible for the processing of numerous prohormones and proneuropeptides into their biologically active moieties, often following cleavage at pairs of basic residues. The determination of its three-dimensional structure, as well as the understanding of its enzymatic properties, would greatly benefit from the production and availability of large amounts of recombinant enzyme. We report herein improvements in the production of PC1/3 by expressing recombinant mutated forms in both insect cells (Spodoptera frugiperda, Sf9 cells) and larvae (Trichoplusia ni commonly referred to as cabbage looper). On one hand, we deleted the last 135 COOH-terminal residues of mPC1/3 and, on the other hand, we replaced the signal peptide of mPC1/3 by the viral glycoprotein gp67 signal peptide. These modifications were shown to improve markedly (up to 125%) the secretion into the Sf9 cells medium and the amount of enzymatic activity recovered when compared to the original vector. Moreover, intracoelemic injection of the vectors into insect larvae led to the production and purification of enzymatically active enzyme at a level of 30 microg/larva in the case of mPC1/3 and to the production of a high amount of another enzymatically active convertase, PC7. The optimal viral titer for infection of larvae was determined to be 10(6)pfu/ml. Taking into account the purification protocol combined with the ease and efficiency of using larvae, it should now be possible to meet the needs for biochemical and structural studies.     

Environmental conditions affect spatial genetic structures and dispersal patterns in a solitary rodent

The study of the spatial distribution of relatives in a population under contrasted environmental conditions provides critical insights into the flexibility of dispersal behaviour and the role of environmental conditions in shaping population relatedness and social structure. Yet few studies have evaluated the effects of fluctuating environmental conditions on relatedness structure of solitary species in the wild. The aim of this study was to determine the impact of interannual variations in environmental conditions on the spatial distribution of relatives [spatial genetic structure (SGS)] and dispersal patterns of a wild population of eastern chipmunks (Tamias striatus), a solitary rodent of North America. Eastern chipmunks depend on the seed of masting trees for reproduction and survival. Here, we combined the analysis of the SGS of adults with direct estimates of juvenile dispersal distance during six contrasted years with different dispersal seasons, population sizes and seed production. We found that environmental conditions influences the dispersal distances of juveniles and that male juveniles dispersed farther than females. The extent of the SGS of adult females varied between years and matched the variation in environmental conditions. In contrast, the SGS of males did not vary between years. We also found a difference in SGS between males and females that was consistent with male‐biased dispersal. This study suggests that both the dispersal behaviour and the relatedness structure in a population of a solitary species can be relatively labile and change according to environmental conditions.     

Singlet Oxygen-Mediated Oxidation during UVA Radiation Alters the Dynamic of Genomic DNA Replication

UVA radiation (320–400 nm) is a major environmental agent that can exert its deleterious action on living organisms through absorption of the UVA photons by endogenous or exogenous photosensitizers. This leads to the production of reactive oxygen species (ROS), such as singlet oxygen (¹O₂) and hydrogen peroxide (H₂O₂), which in turn can modify reversibly or irreversibly biomolecules, such as lipids, proteins and nucleic acids. We have previously reported that UVA-induced ROS strongly inhibit DNA replication in a dose-dependent manner, but independently of the cell cycle checkpoints activation. Here, we report that the production of ¹O₂ by UVA radiation leads to a transient inhibition of replication fork velocity, a transient decrease in the dNTP pool, a quickly reversible GSH-dependent oxidation of the RRM1 subunit of ribonucleotide reductase and sustained inhibition of origin firing. The time of recovery post irradiation for each of these events can last from few minutes (reduction of oxidized RRM1) to several hours (replication fork velocity and origin firing). The quenching of ¹O₂ by sodium azide prevents the delay of DNA replication, the decrease in the dNTP pool and the oxidation of RRM1, while inhibition of Chk1 does not prevent the inhibition of origin firing. Although the molecular mechanism remains elusive, our data demonstrate that the dynamic of replication is altered by UVA photosensitization of vitamins via the production of singlet oxygen.     

Barriers in Referring Neonatal Patients to Perinatal Palliative Care: A French Multicenter Survey

BackgroundWhen an incurable fetal condition is detected, some women (or couples) would rather choose to continue with the pregnancy than opt for termination of pregnancy for medical reasons, which, in France, can be performed until full term. Such situations are frequently occurring and sometimes leading to the implementation of neonatal palliative care. The objectives of this study were to evaluate the practices of perinatal care french professionals in this context; to identify the potential obstacles that might interfere with the provision of an appropiate neonatal palliative care; and, from an opposite perspective, to determine the criteria that led, in some cases, to offer this type of care for prenatally diagnosed lethal abnormality.MethodsWe used an email survey sent to 434 maternal-fetal medicine specialists (MFMs) and fetal care pediatric specialists (FCPs) at 48 multidisciplinary centers for prenatal diagnosis (MCPD).ResultsForty-two multidisciplinary centers for prenatal diagnosis (87.5%) took part. In total, 102 MFMs and 112 FCPs completed the survey, yielding response rate of 49.3%. One quarter of professionals (26.2%) estimated that over 20% of fetal pathologies presenting in MCPD could correspond to a diagnosis categorized as lethal (FCPs versus MFMs: 24% vs 17.2%, p = 0.04). The mean proportion of fetal abnormalities eligible for palliative care at birth was estimated at 19.30% (± 2.4) (FCPs versus MFMs: 23.4% vs 15.2%, p = 0.029). The degree of diagnostic certainty appears to be the most influencing factor (98.1%, n = 207) in the information provided to the pregnant woman with regard to potential neonatal palliative care. The vast majority of professionals, 92.5%, supported considering the practice of palliative care as a regular option to propose antenatally.ConclusionsOur study reveals the clear need for training perinatal professionals in perinatal palliative care and for the standardization of practices in this field.     

Decreased Risk of Ventilator-Associated Pneumonia in Sepsis Due to Intra-Abdominal Infection

Rationale

Experimental studies suggest that intra-abdominal infection (IAI) induces biological alterations that may affect the risk of lung infection.

Objectives

To investigate the potential effect of IAI at ICU admission on the subsequent occurrence of ventilator-associated pneumonia (VAP).

Methods

We used data entered into the French prospective multicenter Outcomerea database in 1997–2011. Consecutive patients who had severe sepsis and/or septic shock at ICU admission and required mechanical ventilation for more than 3 days were included. Patients with acute pancreatitis were not included.

Measurements and Main Results

Of 2623 database patients meeting the inclusion criteria, 290 (11.1%) had IAI and 2333 (88.9%) had other infections. The IAI group had fewer patients with VAP (56 [19.3%] vs. 806 [34.5%], P<0.01) and longer time to VAP (5.0 vs.10.5 days; P<0.01). After adjustment on independent risk factors for VAP and previous antimicrobial use, IAI was associated with a decreased risk of VAP (hazard ratio, 0.62; 95% confidence interval, 0.46–0.83; P<0.0017). The pathogens responsible for VAP were not different between the groups with and without IAI (Pseudomonas aeruginosa, 345 [42.8%] and 24 [42.8%]; Enterobacteriaceae, 264 [32.8%] and 19 [34.0%]; and Staphylococcus aureus, 215 [26.7%] and 17 [30.4%], respectively). Crude ICU mortality was not different between the groups with and without IAI (81 [27.9%] and 747 [32.0%], P = 0.16).

Conclusions

In our observational study of mechanically ventilated ICU patients with severe sepsis and/or septic shock, VAP occurred less often and later in the group with IAIs compared to the group with infections at other sites.     

Mother–offspring distances reflect sex differences in fine‐scale genetic structure of eastern grey kangaroos

Natal dispersal affects life history and population biology and causes gene flow. In mammals, dispersal is usually male‐biased so that females tend to be philopatric and surrounded by matrilineal kin, which may lead to preferential associations among female kin. Here we combine genetic analyses and behavioral observations to investigate spatial genetic structure and sex‐biased dispersal patterns in a high‐density population of mammals showing fission–fusion group dynamics. We studied eastern grey kangaroos (Macropus giganteus) over 2 years at Wilsons Promontory National Park, Australia, and found weak fine‐scale genetic structure among adult females in both years but no structure among adult males. Immature male kangaroos moved away from their mothers at 18–25 months of age, while immature females remained near their mothers until older. A higher proportion of male (34%) than female (6%) subadults and young adults were observed to disperse, although median distances of detected dispersals were similar for both sexes. Adult females had overlapping ranges that were far wider than the maximum extent of spatial genetic structure found. Female kangaroos, although weakly philopatric, mostly encounter nonrelatives in fission–fusion groups at high density, and therefore kinship is unlikely to strongly affect sociality.     

Ascending curbs of progressively higher height increases forward trunk flexion along with upper extremity mechanical and muscular demands in manual wheelchair users with a spinal cord injury

High upper extremity (U/E) demands are required when manual wheelchair users (MWUs) with spinal cord injury (SCI) ascend curbs; this may contribute to the risk of developing U/E musculoskeletal impairments. The aim of this study was to compare movement strategies (kinematics), mechanical loads (kinetics) and muscular demand (EMG) at the non-dominant U/E among 15 MWUs with SCI when ascending curbs of 4 cm (3 trials), 8 cm (3 trials) and 12 cm high (3 trials) from a starting line set 3 m before the curb. Biomechanical data was collected during three trials for each height. The curb ascent task was divided into three adjustment phases: caster pop, rear-wheel ascent and post-ascent. The greatest effort was generated by the shoulder flexors and internal rotators as well as the elbow flexors. A significant difference (p < 0.0167) between the curb heights was found for most outcome measures studied: movement excursion, net joint moments and muscular utilization ratio (MUR) of the main muscles increased with the higher curb heights, mainly around the shoulder joint. These results provide insight that aside from adhering to a highly structured training method for wheelchair curb ascent, rehabilitation professionals need to propose task-specific strength training programs based on the demands documented in this study and continue to advocate for physically accessible environments.     

The first non‐marine ostracod fauna from the Lower Barremian dysodiles of Lebanon

Dysodiles are finely laminated sedimentary rocks rich in organic matter and in exceptionally well‐preserved fossils, hence their petroleum and palaeontological interest. However, few studies focused on the dysodiles of Lebanon, leaving their palaeontological content and their depositional environment largely unknown. Our previous investigations show a variety of well‐preserved lacustrine fossils including ichthyofauna, chelonians, insects, plant debris, gastropods, palynomorphs and ostracods. The present study focuses on the ostracods of five sampling localities from the Lower Barremian of Lebanon. Being the most abundant fossils, ostracods raise some taphonomic and palaeoecological questions that may help us understand the depositional environment and enrich the story of these Early Barremian lakes. Faunal differences between the sampled sections provide clues to the specific characteristics of each lake. The abundance of ‘butterfly’ preservation of carapaces, together with the association of adults and juveniles, indicates calm depositional environments without post‐mortem transport. The assemblages comprise ostracods with known swimming ability (Cyprois and Zonocypris) or that are thought to have been swimmers (Cypridea), while non‐swimmers are absent, suggesting that nektobenthonic ostracods must have lived only in the shallow margins of the lakes or among floating vegetation because hypolimnion conditions were hostile to benthos. This study provides different scenarios on how this fauna ended up preserved in the laminated lake sediments.