Paternal low protein diet affects adult offspring cardiovascular and metabolic function in mice

Although the association between maternal periconceptional diet and adult offspring health is well characterised, our understanding of the impact of paternal nutrition at the time of conception on offspring phenotype remains poorly defined. Therefore, we determined the effect of a paternal preconception low protein diet (LPD on adult offspring cardiovascular and metabolic health in mice. Male C57BL/6 mice were fed either normal protein diet (NPD; 18% casein or LPD (9% casein for 7 wk before mating. At birth, a reduced male-to-female ratio (P = 0.03 and increased male offspring weight (P = 0.009 were observed in litters from LPD compared with NPD stud males with no differences in mean litter size. LPD offspring were heavier than NPD offspring at 2 and 3 wk of age (P <0.02. However, no subsequent differences in body weight were observed. Adult male offspring derived from LPD studs developed relative hypotension (decreased by 9.2 mmHg and elevated heart rate (P <0.05, whereas both male and female offspring displayed vascular dysfunction and impaired glucose tolerance relative to NPD offspring. At cull (24 wk, LPD males had elevated adiposity (P = 0.04, reduced heart-to-body weight ratio (P = 0.04, and elevated circulating TNF-α levels (P = 0.015 compared with NPD males. Transcript expression in offspring heart and liver tissue was reduced for genes involved in calcium signaling (Adcy, Plcb, Prkcb and metabolism (Fto in LPD offspring (P <0.03. These novel data reveal the impact of suboptimal paternal nutrition on adult offspring cardiovascular and metabolic homeostasis, and provide some insight into the underlying regulatory mechanisms.

Abnormal systemic and ocular vascular response to temperature provocation in primary open-angle glaucoma patients:a case for autonomic failure?

PURPOSE. To assess systemic and ocular vascular reactivity in response to warm and cold provocation in untreated patients with primary open-angle glaucoma and normal control subjects. METHODS. Twenty-four patients with primary open-angle glaucoma and 22 normal control subjects were subjected to a modified cold pressor test involving immersion of the right hand in 40°C warm water followed by 4°C cold water exposure, and finger and ocular blood flow were assessed by means of peripheral laser Doppler flowmetry and retinal flowmetry, respectively. Finger and body temperature as well as intraocular pressure, systemic blood pressure, systemic pulse pressure, heart rate, and ocular perfusion pressure were also monitored. RESULTS. The patients with glaucoma demonstrated an increase in diastolic blood pressure (P = 0.023), heart rate (P = 0.010), and mean ocular perfusion pressure (P = 0.039) during immersion of the tested hand in 40°C water. During cold provocation, the patients demonstrated a significant decrease in finger (P = 0.0003) and ocular blood flow (the parameter velocity measured at the temporal neuroretinal rim area; P = 0.021). Normal subjects did not demonstrate any blood flow or finger temperature changes during immersion of the tested hand in 40°C water (P > 0.05); however, they exhibited increases in systolic blood pressure (P = 0.034) and pulse pressure (P = 0.0009) and a decrease in finger blood flow (P = 0.0001) during cold provocation. In normal subjects, the ocular blood flow was unchanged during high- and low-temperature challenge. CONCLUSIONS. Cold provocation elicits a different blood pressure, and ocular blood flow response in patients with primary open-angle glaucoma compared with control subjects. These findings suggest a systemic autonomic failure and ocular vascular dysregulation in POAG patients.

Serum-free process development:improving the yield and consistency of human mesenchymal stromal cell production

Background aims: The cost-effective production of human mesenchymal stromal cells (hMSCs) for off-the-shelf and patient specific therapies will require an increasing focus on improving product yield and driving manufacturing consistency. Methods: Bone marrow-derived hMSCs (BM-hMSCs) from two donors were expanded for 36 days in monolayer with medium supplemented with either fetal bovine serum (FBS) or PRIME-XV serum-free medium (SFM). Cells were assessed throughout culture for proliferation, mean cell diameter, colony-forming potential, osteogenic potential, gene expression and metabolites. Results: Expansion of BM-hMSCs in PRIME-XV SFM resulted in a significantly higher growth rate (P < 0.001) and increased consistency between donors compared with FBS-based culture. FBS-based culture showed an inter-batch production range of 0.9 and 5 days per dose compared with 0.5 and 0.6 days in SFM for each BM-hMSC donor line. The consistency between donors was also improved by the use of PRIME-XV SFM, with a production range of 0.9 days compared with 19.4 days in FBS-based culture. Mean cell diameter has also been demonstrated as a process metric for BM-hMSC growth rate and senescence through a correlation (Rp>2p> = 0.8705) across all conditions. PRIME-XV SFM has also shown increased consistency in BM-hMSC characteristics such as per cell metabolite utilization, in vitro colony-forming potential and osteogenic potential despite the higher number of population doublings. Conclusions: We have increased the yield and consistency of BM-hMSC expansion between donors, demonstrating a level of control over the product, which has the potential to increase the cost-effectiveness and reduce the risk in these manufacturing processes.

Productivity- and ocean circulation changes in the sub-Antarctic Atlantic during the last deglaciation and Marine Isotope Stage 3

Millennial-scale climate changes during the last glacial period and deglaciation were accompanied by rapid changes in atmospheric CO2 that remain unexplained. While the role of the Southern Ocean as a 'control valve' on ocean-atmosphere CO2 exchange has been emphasized, the exact nature of this role, in particular the relative contributions of physical (for example, ocean dynamics and air-sea gas exchange) versus biological processes (for example, export productivity), remains poorly constrained. Here we combine reconstructions of bottom-water [O2], export production and 14C ventilation ages in the sub-Antarctic Atlantic, and show that atmospheric CO2 pulses during the last glacial- and deglacial periods were consistently accompanied by decreases in the biological export of carbon and increases in deep-ocean ventilation via southern-sourced water masses. These findings demonstrate how the Southern Ocean's 'organic carbon pump' has exerted a tight control on atmospheric CO2, and thus global climate, specifically via a synergy of both physical and biological processes.

Stable-isotope ratios and accumulation rates of four firn cores from the Dronning Maud Land, Antarctica

Four firn cores were retrieved in 2007 at two ridges in the area of the Ekström Ice Shelf, Dronning Maud Land, coastal East Antarctica, in order to investigate the recent regional climate variability and the potential for future extraction of an intermediate-depth core. Stable water-isotope analysis, tritium content and electrical conductivity were used to date the cores. For the period 1981-2006 a strong and significant correlation between the stable-isotope composition of firn cores in the hinterland and mean monthly air temperatures at Neumayer station was (r=0.54-0.71). No atmospheric warming or cooling trend is inferred from our stable-isotope data for the period 1962-2006. The stable-isotope record of the ice/firn cores could expand well beyond the meteorological record of the region. No significant temporal variation of accumulation rates was detected. However, decreasing accumulation rates were found from coast to hinterland, as well as from east (Halvfarryggen) to west (Søråsen). The deuterium excess (d) exhibits similar differences (higher d at Søråsen, lower d at Halvfarryggen), with a weak negative temporal trend on Halvfarryggen (0.04 per mil/a), probably implying increasing oceanic input. We conclude that Halvfarryggen acts as a natural barrier for moisture-carrying air masses circulating in the region from east to west.

Temperature variabilty in the southeastern Black-Sea during 64-20ka BP

The Eurasian inland propagation of temperature anomalies during glacial millennial-scale climate variability is poorly understood but this knowledge is crucial to understanding hemisphere-wide atmospheric teleconnection patterns and climate mechanisms. Based on biomarkers and geochemical paleothermometers, a pronounced continental temperature variability between 64,000 and 20,000 years ago, coinciding with the Greenland Dansgaard-Oeschger cycles, was determined in a well-dated sediment record from the formerly enclosed Black Sea. Cooling during Heinrich events was not stronger than during other stadials in the Black Sea. This is corroborated by modeling results showing that regular Dansgaard-Oeschger cycles penetrated deeper into the Eurasian continent than Heinrich events. The pattern of coastal ice-rafted detritus suggests a strong dependence on the climate background state, with significantly milder winters during periods of reduced Eurasian ice sheets and an intensified meridional atmospheric circulation.

Organic carbon accumulation in the South Atlantic Ocean

A compilation of 1118 surface sediment samples from the South Atlantic was used to map modern seafloor distribution of organic carbon content in this ocean basin. Using new data on Holocene sedimentation rates, we estimated the annual organic carbon accumulation in the pelagic realm (>3000 m water depth) to be approximately 1.8*10**12 g C/year. In the sediments underlying the divergence zone in the Eastern Equatorial Atlantic (EEA), only small amounts of organic carbon accumulate in spite of the high surface water productivity observed in that area. This implies that in the Eastern Equatorial Atlantic, organic carbon accumulation is strongly reduced by efficient degradation of organic matter prior to its burial. During the Last Glacial Maximum (LGM), accumulation of organic carbon was higher than during the mid-Holocene along the continental margins of Africa and South America (Brazil) as well as in the equatorial region. In the Eastern Equatorial Atlantic in particular, large relative differences between LGM and mid-Holocene accumulation rates are found. This is probably to a great extent due to better preservation of organic matter related to changes in bottom water circulation and not just a result of strongly enhanced export productivity during the glacial period. On average, a two- to three-fold increase in organic carbon accumulation during the LGM compared to mid-Holocene conditions can be deduced from our cores. However, for the deep-sea sediments this cannot be solely attributed to a glacial productivity increase, as changes in South Atlantic deep-water circulation seem to result in better organic carbon preservation during the LGM.

Bounds on end-to-end performance of networks employing erasure control coding

Erasure control coding has been exploited in communication networks with an aim to improve the end-to-end performance of data delivery across the network. To address the concerns over the strengths and constraints of erasure coding schemes in this application, we examine the performance limits of two erasure control coding strategies, forward erasure recovery and adaptive erasure recovery. Our investigation shows that the throughput of a network using an (n, k) forward erasure control code is capped by r =k/n when the packet loss rate p ≤ (te/n) and by k(l-p)/(n-te) when p > (t e/n), where te is the erasure control capability of the code. It also shows that the lower bound of the residual loss rate of such a network is (np-te)/(n-te) for (te/n) < p ≤ 1. Especially, if the code used is maximum distance separable, the Shannon capacity of the erasure channel, i.e. 1-p, can be achieved and the residual loss rate is lower bounded by (p+r-1)/r, for (1-r) < p ≤ 1. To address the requirements in real-time applications, we also investigate the service completion time of different schemes. It is revealed that the latency of the forward erasure recovery scheme is fractionally higher than that of the scheme without erasure control coding or retransmission mechanisms (using UDP), but much lower than that of the adaptive erasure scheme when the packet loss rate is high. Results on comparisons between the two erasure control schemes exhibit their advantages as well as disadvantages in the role of delivering end-to-end services. To show the impact of the bounds derived on the end-to-end performance of a TCP/IP network, a case study is provided to demonstrate how erasure control coding could be used to maximize the performance of practical systems. © 2010 IEEE.

Coding Strategies and Implementations of Compressive Sensing

<p>This dissertation studies the coding strategies of computational imaging to overcome the limitation of conventional sensing techniques. The information capacity of conventional sensing is limited by the physical properties of optics, such as aperture size, detector pixels, quantum efficiency, and sampling rate. These parameters determine the spatial, depth, spectral, temporal, and polarization sensitivity of each imager. To increase sensitivity in any dimension can significantly compromise the others. p><p>This research implements various coding strategies subject to optical multidimensional imaging and acoustic sensing in order to extend their sensing abilities. The proposed coding strategies combine hardware modification and signal processing to exploiting bandwidth and sensitivity from conventional sensors. We discuss the hardware architecture, compression strategies, sensing process modeling, and reconstruction algorithm of each sensing system. p><p>Optical multidimensional imaging measures three or more dimensional information of the optical signal. Traditional multidimensional imagers acquire extra dimensional information at the cost of degrading temporal or spatial resolution. Compressive multidimensional imaging multiplexes the transverse spatial, spectral, temporal, and polarization information on a two-dimensional (2D) detector. The corresponding spectral, temporal and polarization coding strategies adapt optics, electronic devices, and designed modulation techniques for multiplex measurement. This computational imaging technique provides multispectral, temporal super-resolution, and polarization imaging abilities with minimal loss in spatial resolution and noise level while maintaining or gaining higher temporal resolution. The experimental results prove that the appropriate coding strategies may improve hundreds times more sensing capacity. p><p>Human auditory system has the astonishing ability in localizing, tracking, and filtering the selected sound sources or information from a noisy environment. Using engineering efforts to accomplish the same task usually requires multiple detectors, advanced computational algorithms, or artificial intelligence systems. Compressive acoustic sensing incorporates acoustic metamaterials in compressive sensing theory to emulate the abilities of sound localization and selective attention. This research investigates and optimizes the sensing capacity and the spatial sensitivity of the acoustic sensor. The well-modeled acoustic sensor allows localizing multiple speakers in both stationary and dynamic auditory scene; and distinguishing mixed conversations from independent sources with high audio recognition rate.p>

Spontaneous Unfolding and Refolding of FNIII Domains Assayed by Thiol Exchange

<p>Fibronectin (FN) is a large extracellular matrix (ECM) protein that is made up ofp><p>type I (FNI), type II (FNII), & type III (FNIII) domains. It assembles into an insolublep><p>supra-­‐‑molecular structure: the fibrillar FN matrix. FN fibrillogenesis is a cell‐‑mediated process, which is initiated when FN binds to integrins on the cell surface. The FN matrix plays an important role in cell migration, proliferation, signaling & adhesion. Despite decades of research, the FN matrix is one of the least understood supra-­‐‑molecular protein assemblies. There have been several attempts to elucidate the exact mechanism of matrix assembly resulting in significant progress in the field but it is still unclear as to what are FN-­‐‑FN interactions, the nature of these interactions and the domains of FN thatp><p>are in contact with each other. FN matrix fibrils are elastic in nature. Two models have been proposed to explain the elasticity of the fibrils. The first model: the ‘domain unfolding’ model postulates that the unraveling of FNIII domains under tension explains fibril elasticity.p><p>The second model relies on the conformational change of FN from compact to extended to explain fibril elasticity. FN contain 15 FNIII domains, each a 7-­‐‑strand beta sandwich. Earlier work from our lab used the technique of labeling a buried Cys to study the ‘domain unfolding’ model. They used mutant FNs containing a buried Cys in a single FNIII domain and found that 6 of the 15 FNIII domains label in matrix fibrils. Domain unfolding due to tension, matrix associated conformational changes or spontaneous folding and unfolding are all possible explanation for labeling of the buried Cys. The present study also uses the technique of labeling a buried Cys to address whether it is spontaneous folding and unfolding that labels FNIII domains in cell culture. We used thiol reactive DTNB to measure the kinetics of labeling of buried Cys in eleven FN III domains over a wide range of urea concentrations (0-­‐‑9M). The kinetics data were globally fit using Mathematica. The results are equivalent to those of H-­‐‑D exchange, andp><p>provide a comprehensive analysis of stability and unfolding/folding kinetics of eachp><p>domain. For two of the six domains spontaneous folding and unfolding is possibly the reason for labeling in cell culture. For the rest of the four domains it is probably matrix associated conformational changes or tension induced unfolding.p><p>A long-­‐‑standing debate in the protein-­‐‑folding field is whether unfolding ratep><p>constants or folding rate constants correlate to the stability of a protein. FNIII domains all have the same ß sandwich structure but very different stabilities and amino acid sequences. Our study analyzed the kinetics of unfolding and folding and stabilities of eleven FNIII domains and our results show that folding rate constants for FNIII domains are relatively similar and the unfolding rates vary widely and correlate to stability. FN forms a fibrillar matrix and the FN-­‐‑FN interactions during matrix fibril formation are not known. FNI 1-­‐‑9 or the N-­‐‑ terminal region is indispensible for matrix formation and its major binding partner has been shown to be FNIII 2. Earlier work from our lab, using FRET analysis showed that the interaction of FNI 1-­‐‑9 with a destabilized FNIII 2 (missing the G strand, FNIII 2ΔG) reduces the FRET efficiency. This efficiency is restored in the presence of FUD (bacterial adhesion from S. pyogenes) that has been known to interact with FNI 1-­‐‑9 via a tandem ß zipper. In the present study wep><p>use FRET analysis and a series of deletion mutants of FNIII 2ΔG to study the shortest fragment of FNIII 2ΔG that is required to bind FNI 1-­‐‑9. Our results presented here are qualitative and show that FNIII 2ΔC’EFG is the shortest fragment required to bind FNI 1-­‐‑9. Deletion of one more strand abolishes the interaction with FNI 1-­‐‑9.p>

Age determination and clay layer frequencies of sediments of the Black and Red Sea

Paleoenvironmental proxy data for ocean properties, eolian sediment input, and continental rainfall based on high-resolution analyses of sediment cores from the southwestern Black Sea and the northernmost Gulf of Aqaba were used to infer hydroclimatic changes in northern Anatolia and the northern Red Sea region during the last ~7500 years. Pronounced and coherent multicentennial variations in these records reveal patterns that strongly resemble modern temperature and rainfall anomalies related to the Arctic Oscillation/North Atlantic Oscillation (AO/NAO). These patterns suggest a prominent role of AO/NAO-like atmospheric variability during the Holocene beyond interannual to interdecadal timescales, most likely originating from solar output changes.

Organic geochemistry from different DSDP Holes in the subtropical South Atlantic Ocean

Organic matter has been characterized in samples of Pleistocene, Pliocene, and Miocene sediments from seven Deep Sea Drilling Project sites in the subtropical South Atlantic Ocean. Organic carbon concentrations average 0.3% for most samples, and n-alkanoic acid, n-alkanol, and alkane biomarkers indicate extensive microbial reworking of organic matter in these organic-carbon-lean sediments. Samples from the easternmost parts of the South Atlantic contain an average of 4.1% organic carbon and reflect the high productivity associated with the Benguela Current. Lipid biomarkers show less microbial reworking in these sediments. Eolian transport of land-derived hydrocarbons is evident at most of these oceanic locations.

Laminated sediment cores in the Bering Sea

During the last glacial termination, the upper North Pacific Ocean underwent dramatic and rapid changes in oxygenation that lead to the transient intensification of oxygen minimum zones (OMZs), recorded by the widespread occurrence of laminated sediments on circum-Pacific continental margins. We present a new laminated sediment record from the mid-depth (1100 m) northern Bering Sea margin that provides insight into these deglacial OMZ maxima with exceptional, decadal-scale detail. Combined ultrahigh-resolution micro-X-ray-fluorescence (micro-XRF) data and sediment facies analysis of laminae reveal an alternation between predominantly terrigenous and diatom-dominated opal sedimentation. The diatomaceous laminae are interpreted to represent spring/summer productivity events related to the retreating sea ice margin.We identified five laminated sections in the deglacial part of our site. Lamina counts were carried out on these sections and correlated with the Bølling-Allerød and Preboreal phases in the North Greenland Ice Core (NGRIP) oxygen isotope record, indicating an annual deposition of individual lamina couplets (varves). The observed rapid decadal intensifications of anoxia, in particular within the Bølling-Allerød, are tightly coupled to short-term warm events through increases in regional export production. This dependence of laminae formation on warmer temperatures is underlined by a correlation with published Bering Sea sea surface temperature records and d18O data of planktic foraminifera from the Gulf of Alaska. The rapidity of the observed changes strongly implies a close atmospheric teleconnection between North Pacific and North Atlantic regions.We suggest that concomitant increases in export production and subsequent remineralization of organic matter in the Bering Sea, in combination with oxygen-poor waters entering the Being Sea, drove down oxygen concentrations to values below 0.1ml/l and caused laminae preservation. Calculated benthic-planktic ventilation ages show no significant variations throughout the last deglaciation, indicating that changes in formation rates or differing sources of North Pacific mid-depth waters are not prime candidates for strengthening the OMZ at our site. The age models established by our correlation procedure allow for the determination of calendar age control points for the Bølling-Allerød and the Preboreal that are independent of the initial radiocarbon-based chronology. Resulting surface reservoir ages range within 730-990 yr during the Bølling-Allerød, 800-1100 yr in the Younger Dryas, and 765-775 yr for the Preboreal.

Bulk density, and peat and net carbon accumulation of samples from Selwyn lake, Canada

Peat and net carbon accumulation rates in two sub-arctic peat plateaus of west-central Canada have been studied through geochemical analyses and accelerator mass spectrometry (AMS) radiocarbon dating. The peatland sites started to develop around 6600-5900 cal. yr BP and the peat plateau stages are characterized by Sphagnum fuscum peat alternating with rootlet layers. The long-term peat and net carbon accumulation rates for both profiles are 0.30-0.31 mm/yr and 12.5-12.7 gC/m**2/yr, respectively. These values reflect very slow peat accumulation (0.04-0.09 mm/yr) and net carbon accumulation (3.7-5.2 gC/m**2/yr) in the top rootlet layers. Extensive AMS radiocarbon dating of one profile shows that accumulation rates are variable depending on peat plateau stage. Peat accumulation rates are up to six times higher and net carbon accumulation rates up to four times higher in S. fuscum than in rootlet stages. Local fires represented by charcoal remains in some of the rootlet layers result in very low accumulation rates. High C/N ratios throughout most of the peat profiles suggest low degrees of decomposition due to stable permafrost conditions. Hence, original peat accretion has remained largely unaltered, except in the initial stages of peatland development when permafrost was not yet present.

Alkenone accumulation rates, stable carbon isotope record, and sea surface temperature reconstruction for IODP Site 306-U1313

Here we present orbitally-resolved records of terrestrial higher plant leaf wax input to the North Atlantic over the last 3.5 Ma, based on the accumulation of long-chain n-alkanes and n-alkanl-1-ols at IODP Site U1313. These lipids are a major component of dust, even in remote ocean areas, and have a predominantly aeolian origin in distal marine sediments. Our results demonstrate that around 2.7 million years ago (Ma), coinciding with the intensification of the Northern Hemisphere glaciation (NHG), the aeolian input of terrestrial material to the North Atlantic increased drastically. Since then, during every glacial the aeolian input of higher plant material was up to 30 times higher than during interglacials. The close correspondence between aeolian input to the North Atlantic and other dust records indicates a globally uniform response of dust sources to Quaternary climate variability, although the amplitude of variation differs among areas. We argue that the increased aeolian input at Site U1313 during glacials is predominantly related to the episodic appearance of continental ice sheets in North America and the associated strengthening of glaciogenic dust sources. Evolutional spectral analyses of the n-alkane records were therefore used to determine the dominant astronomical forcing in North American ice sheet advances. These results demonstrate that during the early Pleistocene North American ice sheet dynamics responded predominantly to variations in obliquity (41 ka), which argues against previous suggestions of precession-related variations in Northern Hemisphere ice sheets during the early Pleistocene.