Pre-eclampsia and fetal growth restriction arise from disorders of placental development and have some shared mechanistic features. Initiation is often rooted in the maldevelopment of a ...maternal-placental blood supply capable of providing for the growth requirements of the fetus in later pregnancy, without exerting undue stress on maternal body systems. Here, we review normal development of a placental bed with a safe and adequate blood supply and a villous placenta-blood interface from which nutrients and oxygen can be extracted for the growing fetus. We consider disease mechanisms that are intrinsic to the maternal environment, the placenta or the interaction between the two. Systemic signalling from the endocrine placenta targets the maternal endothelium and multiple organs to adjust metabolism for an optimal pregnancy and later lactation. This signalling capacity is skewed when placental damage occurs and can deliver a dangerous pathogenic stimulus. We discuss the placental secretome including glycoproteins, microRNAs and extracellular vesicles as potential biomarkers of disease. Angiomodulatory mediators, currently the only effective biomarkers, are discussed alongside non-invasive imaging approaches to the prediction of disease risk. Identifying the signs of impending pathology early enough to intervene and ameliorate disease in later pregnancy remains a complex and challenging objective.
Working memory (WM) has limited capacity. This leaves attention with the important role of allowing into storage only the most relevant information. It is increasingly evident that attention is ...equally crucial for prioritizing representations within WM as the importance of individual items changes. Retrospective prioritization has been proposed to result from a focus of internal attention highlighting one of several representations. Here, we suggest an updated model, in which prioritization acts in multiple steps: first orienting towards and selecting a memory, and then reconfiguring its representational state in the service of upcoming task demands. Reconfiguration sets up an optimized perception–action mapping, obviating the need for sustained attention. This view is consistent with recent literature, makes testable predictions, and links WM with task switching and action preparation.
Abstract
Bone marrow fat infiltration is one of the hallmarks of aging and osteoporotic bones. Marrow adipocytes produce substantial amounts of palmitic acid (PA). PA is toxic to bone-forming ...osteoblasts in vitro, affecting their differentiation, function, and survival. Since rapamycin (RAP)-induced inhibition of target of rapamycin complex 1 (mTORC1) activates autophagy and prevents apoptosis, we hypothesized that RAP may preserve osteoblast viability and reduce PA-induced lipotoxicity. Normal human osteoblasts were incubated with RAP in the presence of a lipotoxic concentration of PA or vehicle for 24 and 48 hours. Expression of LC3 protein levels and the phosphorylation of the direct mTORC1 target p70S6K1-T389 were quantified by Western blot. Lysosomes and autophagosomes were studied using confocal fluorescence imaging, lysotracker, and live-cell imaging. RAP reduced PA-induced apoptosis. In addition, PA-induced autophagosome formation increased substantially over the time-course, an effect that was significantly regulated by the presence of RAP in the media. In addition, LC3I/II ratios were higher in PA-induced cells with RAP whereas p70S6K1-T389 were lower in PA and RAP together. In summary, this study highlights the role of the RAP-sensitive mTORC1 pathway in normal human osteoblasts under lipotoxic conditions. RAP-associated therapies could, potentially, be targeted for specific roles in osteoporosis and aging bone.
Obesity increases the risk for developing gestational diabetes mellitus (GDM) and preeclampsia (PE), which both associate with increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular ...disease (CVD) in women in later life. In the general population, metabolic syndrome (MetS) associates with T2DM and CVD. The impact of maternal MetS on pregnancy outcomes, in nulliparous pregnant women, has not been investigated.
Low-risk, nulliparous women were recruited to the multi-centre, international prospective Screening for Pregnancy Endpoints (SCOPE) cohort between 11 November 2004 and 28 February 2011. Women were assessed for a range of demographic, lifestyle, and metabolic health variables at 15 ± 1 weeks' gestation. MetS was defined according to International Diabetes Federation (IDF) criteria for adults: waist circumference ≥80 cm, along with any 2 of the following: raised trigycerides (≥1.70 mmol/l ≥150 mg/dl), reduced high-density lipoprotein cholesterol (<1.29 mmol/l <50 mg/dl), raised blood pressure (BP) (i.e., systolic BP ≥130 mm Hg or diastolic BP ≥85 mm Hg), or raised plasma glucose (≥5.6 mmol/l). Log-binomial regression analyses were used to examine the risk for each pregnancy outcome (GDM, PE, large for gestational age LGA, small for gestational age SGA, and spontaneous preterm birth sPTB) with each of the 5 individual components for MetS and as a composite measure (i.e., MetS, as defined by the IDF). The relative risks, adjusted for maternal BMI, age, study centre, ethnicity, socioeconomic index, physical activity, smoking status, depression status, and fetal sex, are reported. A total of 5,530 women were included, and 12.3% (n = 684) had MetS. Women with MetS were at an increased risk for PE by a factor of 1.63 (95% CI 1.23 to 2.15) and for GDM by 3.71 (95% CI 2.42 to 5.67). In absolute terms, for PE, women with MetS had an adjusted excess risk of 2.52% (95% CI 1.51% to 4.11%) and, for GDM, had an adjusted excess risk of 8.66% (95% CI 5.38% to 13.94%). Diagnosis of MetS was not associated with increased risk for LGA, SGA, or sPTB. Increasing BMI in combination with MetS increased the estimated probability for GDM and decreased the probability of an uncomplicated pregnancy. Limitations of this study are that there are several different definitions for MetS in the adult population, and as there are none for pregnancy, we cannot be sure that the IDF criteria are the most appropriate definition for pregnancy. Furthermore, MetS was assessed in the first trimester and may not reflect pre-pregnancy metabolic health status.
We did not compare the impact of individual metabolic components with that of MetS as a composite, and therefore cannot conclude that MetS is better at identifying women at risk. However, more than half of the women who had MetS in early pregnancy developed a pregnancy complication compared with just over a third of women who did not have MetS. Furthermore, while increasing BMI increases the probability of GDM, the addition of MetS exacerbates this probability. Further studies are required to determine if individual MetS components act synergistically or independently.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mechanical interactions are fundamental to biology. Mechanical forces of chemical origin determine motility and adhesion on the cellular scale, and govern transport and affinity on the molecular ...scale. Biological sensing in the mechanical domain provides unique opportunities to measure forces, displacements and mass changes from cellular and subcellular processes. Nanomechanical systems are particularly well matched in size with molecular interactions, and provide a basis for biological probes with single-molecule sensitivity. Here we review micro- and nanoscale biosensors, with a particular focus on fast mechanical biosensing in fluid by mass- and force-based methods, and the challenges presented by non-specific interactions. We explain the general issues that will be critical to the success of any type of next-generation mechanical biosensor, such as the need to improve intrinsic device performance, fabrication reproducibility and system integration. We also discuss the need for a greater understanding of analyte-sensor interactions on the nanoscale and of stochastic processes in the sensing environment.
Delineating regions is an important first step in understanding the evolution and biogeography of faunas. However, quantitative approaches are often limited at a global scale, particularly in the ...marine realm. Reef fishes are the most diversified group of marine fishes, and compared to most other phyla, their taxonomy and geographical distributions are relatively well known. Based on 169 checklists spread across all tropical oceans, the present work aims to quantitatively delineate biogeographical entities for reef fishes at a global scale. Four different classifications were used to account for uncertainty related to species identification and the quality of checklists. The four classifications delivered converging results, with biogeographical entities that can be hierarchically delineated into realms, regions and provinces. All classifications indicated that the Indo-Pacific has a weak internal structure, with a high similarity from east to west. In contrast, the Atlantic and the Eastern Tropical Pacific were more strongly structured, which may be related to the higher levels of endemism in these two realms. The "Coral Triangle", an area of the Indo-Pacific which contains the highest species diversity for reef fishes, was not clearly delineated by its species composition. Our results show a global concordance with recent works based upon endemism, environmental factors, expert knowledge, or their combination. Our quantitative delineation of biogeographical entities, however, tests the robustness of the results and yields easily replicated patterns. The similarity between our results and those from other phyla, such as corals, suggests that our approach may be of broad utility in describing and understanding global marine biodiversity patterns.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Atomic masses of tritium and helium-3 Myers, E G; Wagner, A; Kracke, H ...
Physical review letters,
2015-Jan-09, Letnik:
114, Številka:
1
Journal Article
Recenzirano
Odprti dostop
By measuring the cyclotron frequency ratios of (3)He(+) to HD(+) and T(+) to HD(+), and using HD(+) as a mass reference, we obtain new atomic masses for (3)He and T. Our results are M(3)He=3.016 029 ...322 43(19) u and MT=3.016 049 281 78(19) u, where the uncertainty includes an uncertainty of 0.12 nu in the mass reference. Allowing for cancellation of common systematic errors, we find the Q value for tritium β decay to be (MT-M(3)He)c(2)=18 592.01(7) eV. This allows an improved test of systematics in measurements of tritium β decay that set limits on neutrino mass.
We present experimental results from the first systematic study of performance scaling with drive parameters for a magnetoinertial fusion concept. In magnetized liner inertial fusion experiments, the ...burn-averaged ion temperature doubles to 3.1 keV and the primary deuterium-deuterium neutron yield increases by more than an order of magnitude to 1.1 × 1013 (2 kJ deuterium-tritium equivalent) through a simultaneous increase in the applied magnetic field (from 10.4 to 15.9 T), laser preheat energy (from 0.46 to 1.2 kJ), and current coupling (from 16 to 20 MA). Individual parametric scans of the initial magnetic field and laser preheat energy show the expected trends, demonstrating the importance of magnetic insulation and the impact of the Nernst effect for this concept. A drive-current scan shows that present experiments operate close to the point where implosion stability is a limiting factor in performance, demonstrating the need to raise fuel pressure as drive current is increased. Simulations that capture these experimental trends indicate that another order of magnitude increase in yield on the Z facility is possible with additional increases of input parameters.
We investigate use of nanomechanical torsional resonators for frequency-shift-based infrared (IR) thermal sensing. Nanoscale torsion rods, ∼1 μm long and 50–100 nm in diameter, provide both ...extraordinary thermal isolation and excellent angular displacement and torque sensitivities, of order ∼10–7 rad·Hz–1/2 and ∼10–22 (N·m) Hz–1/2, respectively. Furthermore, these nanorods act as linear torsional springs, yielding a maximum angular displacement of 3.6° and a dynamic range of over 100 dB; this exceeds the performance of flexural modes by as much as 5 orders of magnitude. These attributes lead to superior noise performance for torsional-mode sensing. We demonstrate the operational principles of torsional-mode IR detection, attaining an uncooled noise equivalent temperature difference (NETD) of 390 mK. By modeling the fundamental noise processes, we project that further reduction of device size can significantly improve thermal responsivity; a room-temperature NETD below 10 mK appears feasible.
THE CIRCUITRY OF THE DENTATE GYRUS (DG) OF THE HIPPOCAMPUS IS UNIQUE COMPARED TO OTHER HIPPOCAMPAL SUBFIELDS BECAUSE THERE ARE TWO GLUTAMATERGIC PRINCIPAL CELLS INSTEAD OF ONE: granule cells, which ...are the vast majority of the cells in the DG, and the so-called "mossy cells." The distinctive appearance of mossy cells, the extensive divergence of their axons, and their vulnerability to excitotoxicity relative to granule cells has led to a great deal of interest in mossy cells. Nevertheless, there is no consensus about the normal functions of mossy cells and the implications of their vulnerability. There even seems to be some ambiguity about exactly what mossy cells are. Here we review initial studies of mossy cells, characteristics that define them, and suggest a practical definition to allow investigators to distinguish mossy cells from other hilar neurons even if all morphological and physiological information is unavailable due to technical limitations of their experiments. In addition, hypotheses are discussed about the role of mossy cells in the DG network, reasons for their vulnerability and their implications for disease.
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