Characterising the dynamics of placental glycogen stores in the mouse.

INTRODUCTION: The placenta performs a range of functions to support fetal growth. In addition to facilitating nutrient transport, the placenta also stores glucose as glycogen, which is thought to maintain fetal glucose supply during late gestation. However, evidence to support such a role is currently lacking. Similarly, our understanding of the dynamics of placental glycogen metabolism in normal mouse pregnancy is limited. METHODS: We quantified the placental glycogen content of wild type C57BL/6JOlaHsd mouse placentas from mid (E12.5) to late (E18.5) gestation, alongside characterising the temporal expression pattern of genes encoding glycogenesis and glycogenolysis pathway enzymes. To assess the potential of the placenta to produce glucose, we investigated the spatiotemporal expression of glucose 6-phosphatase by qPCR and in situ hybridisation. Separate analyses were undertaken for placentas of male and female conceptuses to account for potential sexual dimorphism. RESULTS: Placental glycogen stores peak at E15.5, having increased over 5-fold from E12.5, before declining by a similar extent by E18.5. Glycogen stores were 17% higher in male placentas than in females at E15.5. Expression of glycogen branching enzyme (Gbe1) was reduced ~40% towards term. Expression of the glucose 6-phosphatase isoform G6pc3 was enriched in glycogen trophoblast cells and increased towards term. DISCUSSION: Reduced expression of Gbe1 suggests a decline in glycogen branching towards term. Expression of G6pc3 by glycogen trophoblasts is consistent with an ability to produce and release glucose from glycogen stores. However, the ultimate destination of the glucose generated from placental glycogen remains to be elucidated.Centre for Trophoblast Researc

An Exact Formula for the Average Run Length to False Alarm of the Generalized Shiryaev-Roberts Procedure for Change-Point Detection under Exponential Observations

We derive analytically an exact closed-form formula for the standard minimax Average Run Length (ARL) to false alarm delivered by the Generalized Shiryaev-Roberts (GSR) change-point detection procedure devised to detect a shift in the baseline mean of a sequence of independent exponentially distributed observations. Specifically, the formula is found through direct solution of the respective integral (renewal) equation, and is a general result in that the GSR procedure's headstart is not restricted to a bounded range, nor is there a "ceiling" value for the detection threshold. Apart from the theoretical significance (in change-point detection, exact closed-form performance formulae are typically either difficult or impossible to get, especially for the GSR procedure), the obtained formula is also useful to a practitioner: in cases of practical interest, the formula is a function linear in both the detection threshold and the headstart, and, therefore, the ARL to false alarm of the GSR procedure can be easily computed.Comment: 9 pages; Accepted for publication in Proceedings of the 12-th German-Polish Workshop on Stochastic Models, Statistics and Their Application

Major Element Composition of Sediments in Terms of Weathering and Provenance: Implications for Crustal Recycling

The elemental composition of a sediment is set by the composition of its protolithand modified by weathering, sorting, and diagenesis. An important problem is deconvolving these contributions to a sediment’s composition to arrive at information about processesthat operate on the Earth’s surface. We approach this problem by developing a predictive andinvertible model of sedimentary major-element composition. We compile a dataset of sedimentary rock, river sediment, soil, and igneous rock compositions. Principal componentanalysis of the dataset shows that most variation can be simplified to a small number of variables. We thus show that any sediment’s composition can be described with just two vectorsof igneous evolution and weathering. We hence define a model for sedimentary compositionas a combination of these processes. A 1:1 correspondence is observed between predictionsand independent data. The log-ratios ln(K 2 O/MgO) and ln(Al 2 O 3 /Na 2 O) are found to besimple proxies for respectively the model’s protolith and weathering indices. Significant deviations from the model can be explained by sodium-calcium exchange. Using this approach,we show that the major-element composition of the upper continental crust has been modified by weathering and we calculate the amount of each element that it must have lost tomodify it to its present composition. By extrapolating modern weathering rates over the ageof the crust we conclude that it has not retained a significant amount of the necessarily produced weathering restite. This restite has likely been subducted into the mantle, indicating acrust-to-mantle recycling rate of 1.33 ± 0.89 × 10 13 kg yr −1 .</p

Scale‐dependent flow directions of rivers and the importance of subplate support

Large rivers play crucial roles in determining locations of civilization, biodiversity, and efflux to the oceans. The paths they take across Earth's surface vary with scale. At long‐wavelengths rivers can have simple flow paths. At smaller scales, in meanders for example, their paths change rapidly as a consequence of lithology, biota, and other environmental variables. It is not straightforward to identify the scales at which river planforms are set. We overcome these issues by developing a spectral (wavelet) methodology to map flow‐directions as a function of distance and scale. This methodology allows short‐wavelength features (e.g., meanders) to be filtered from river flow‐paths. With short‐wavelength structure removed, the flow‐directions of rivers in Western USA correlate with long‐wavelength gravity anomalies suggesting control by subplate support. This relationship is replicated by an ensemble of landscape evolution models. These results combined suggest that drainage at large scales, O(103) km, is set by subplate support

Scale Dependence of Dark Energy Antigravity

We investigate the effects of negative pressure induced by dark energy (cosmological constant or quintessence) on the dynamics at various astrophysical scales. Negative pressure induces a repulsive term (antigravity) in Newton's law which dominates on large scales. Assuming a value of the cosmological constant consistent with the recent SnIa data we determine the critical scale $r_c$ beyond which antigravity dominates the dynamics ($r_c \sim 1Mpc$) and discuss some of the dynamical effects implied. We show that dynamically induced mass estimates on the scale of the Local Group and beyond are significantly modified due to negative pressure. We also briefly discuss possible dynamical tests (eg effects on local Hubble flow) that can be applied on relatively small scales (a few $Mpc$) to determine the density and equation of state of dark energy.Comment: Contributed talk at the 2nd Hellenic Cosmology Workshop at NOA (Athens) Jan. 2001.To appear in the proceedings. Based on work done in collaboration with M. Axenides and E. Florato

Mitochondria directly donate their membrane to form autophagosomes during a novel mechanism of parkin-associated mitophagy

BACKGROUND: Autophagy (macroautophagy), a cellular process of “self-eating”, segregates damaged/aged organelles into vesicles, fuses with lysosomes, and enables recycling of the digested materials. The precise origin(s) of the autophagosome membrane is unclear and remains a critical but unanswered question. Endoplasmic reticulum, mitochondria, Golgi complex, and the plasma membrane have been proposed as the source of autophagosomal membranes. FINDINGS: Using electron microscopy, immunogold labeling techniques, confocal microscopy, and flow cytometry we show that mitochondria can directly donate their membrane material to form autophagosomes. We expand upon earlier studies to show that mitochondria donate their membranes to form autophagosomes during basal and drug-induced autophagy. Moreover, electron microscopy and immunogold labeling studies show the first physical evidence of mitochondria forming continuous structures with LC3-labeled autophagosomes. The mitochondria forming these structures also stain positive for parkin, indicating that these mitochondrial-formed autophagosomes represent a novel mechanism of parkin-associated mitophagy. CONCLUSIONS: With the on-going debate regarding autophagosomal membrane origin, this report demonstrates that mitochondria can donate membrane materials to form autophagosomes. These structures may also represent a novel form of mitophagy where the mitochondria contribute to the formation of autophagosomes. This novel form of parkin-associated mitophagy may be a more efficient bio-energetic process compared with de novo biosynthesis of a new membrane, particularly if the membrane is obtained, at least partly, from the organelle being targeted for later degradation in the mature autolysosome

Extensive dissolution of live pteropods in the Southern Ocean

The carbonate chemistry of the surface ocean is rapidly changing with ocean acidification, a result of human activities. In the upper layers of the Southern Ocean, aragonite—a metastable form of calcium carbonate with rapid dissolution kinetics—may become undersaturated by 2050 (ref. 2). Aragonite undersaturation is likely to affect aragonite-shelled organisms, which can dominate surface water communities in polar regions. Here we present analyses of specimens of the pteropod Limacina helicina antarctica that were extracted live from the Southern Ocean early in 2008. We sampled from the top 200m of the water column, where aragonite saturation levels were around 1, as upwelled deep water is mixed with surface water containing anthropogenic CO2. Comparing the shell structure with samples from aragonite-supersaturated regions elsewhere under a scanning electron microscope, we found severe levels of shell dissolution in the undersaturated region alone. According to laboratory incubations of intact samples with a range of aragonite saturation levels, eight days of incubation in aragonite saturation levels of 0.94– 1.12 produces equivalent levels of dissolution. As deep-water upwelling and CO2 absorption by surface waters is likely to increase as a result of human activities2,4, we conclude that upper ocean regions where aragonite-shelled organisms are affected by dissolution are likely to expand