Layer-specific fMRI responses to excitatory and inhibitory neuronal activities in the olfactory bulb

High-resolution functional magnetic resonance imaging (fMRI) detects localized neuronal activity via the hemodynamic response, but it is unclear whether it accurately identifies neuronal activity specific to individual layers. To address this issue, we preferentially evoked neuronal activity in superficial, middle, and deep layers of the rat olfactory bulb: the glomerular layer by odor (5% amyl acetate), the external plexiform layer by electrical stimulation of the lateral olfactory tract (LOT), and the granule cell layer by electrical stimulation of the anterior commissure (AC), respectively. Electrophysiology, laser-Doppler flowmetry of cerebral blood flow (CBF), and blood oxygenation level-dependent (BOLD) and cerebral blood volume-weighted (CBV) fMRI at 9.4 T were performed independently. We found that excitation of inhibitory granule cells by stimulating LOT and AC decreased the spontaneous multi-unit activities of excitatory mitral cells and subsequently increased CBF, CBV, and BOLD signals. Odor stimulation also increased the hemodynamic responses. Furthermore, the greatest CBV fMRI responses were discretely separated into the same layers as the evoked neuronal activities for all three stimuli, whereas BOLD was poorly localized with some exception to the poststimulus undershoot. In addition, the temporal dynamics of the fMRI responses varied depending on the stimulation pathway, even within the same layer. These results indicate that the vasculature is regulated within individual layers and CBV fMRI has a higher fidelity to the evoked neuronal activity compared with BOLD. Our findings are significant for understanding the neuronal origin and spatial specificity of hemodynamic responses, especially for the interpretation of laminar-resolution fMRI. © 2015 the authors115151sciescopu

New first trimester crown-rump length's equations optimized by structured data collection from a French general population

--- Objectives --- Prior to foetal karyotyping, the likelihood of Down's syndrome is often determined combining maternal age, serum free beta-HCG, PAPP-A levels and embryonic measurements of crown-rump length and nuchal translucency for gestational ages between 11 and 13 weeks. It appeared important to get a precise knowledge of these scan parameters' normal values during the first trimester. This paper focused on crown-rump length. --- METHODS --- 402 pregnancies from in-vitro fertilization allowing a precise estimation of foetal ages (FA) were used to determine the best model that describes crown-rump length (CRL) as a function of FA. Scan measures by a single operator from 3846 spontaneous pregnancies representative of the general population from Northern France were used to build a mathematical model linking FA and CRL in a context as close as possible to normal scan screening used in Down's syndrome likelihood determination. We modeled both CRL as a function of FA and FA as a function of CRL. For this, we used a clear methodology and performed regressions with heteroskedastic corrections and robust regressions. The results were compared by cross-validation to retain the equations with the best predictive power. We also studied the errors between observed and predicted values. --- Results --- Data from 513 spontaneous pregnancies allowed to model CRL as a function of age of foetal age. The best model was a polynomial of degree 2. Datation with our equation that models spontaneous pregnancies from a general population was in quite agreement with objective datations obtained from 402 IVF pregnancies and thus support the validity of our model. The most precise measure of CRL was when the SD was minimal (1.83mm), for a CRL of 23.6 mm where our model predicted a 49.4 days of foetal age. Our study allowed to model the SD from 30 to 90 days of foetal age and offers the opportunity of using Zscores in the future to detect growth abnormalities. --- Conclusion --- With powerful statistical tools we report a good modeling of the first trimester embryonic growth in the general population allowing a better knowledge of the date of fertilization useful in the ultrasound screening of Down's syndrome. The optimal period to measure CRL and predict foetal age was 49.4 days (9 weeks of gestational age). Our results open the way to the detection of foetal growth abnormalities using CRL Zscores throughout the first trimester

Obesity-induced insulin resistance in human skeletal muscle is characterised by defective activation of p42/p44 MAP kinase

Insulin resistance (IR), an impaired cellular, tissue and whole body response to insulin, is a major pathophysiological defect of type 2 diabetes mellitus. Although IR is closely associated with obesity, the identity of the molecular defect(s) underlying obesity-induced IR in skeletal muscle remains controversial; reduced post-receptor signalling of the insulin receptor substrate 1 (IRS1) adaptor protein and downstream effectors such as protein kinase B (PKB) have previously been implicated. We examined expression and/or activation of a number of components of the insulin-signalling cascade in skeletal muscle of 22 healthy young men (with body mass index (BMI) range, 20–37 kg/m2). Whole body insulin sensitivity (M value) and body composition was determined by the hyperinsulinaemic (40 mU. min−1.m−2.), euglycaemic clamp and by dual energy X-ray absorptiometry (DEXA) respectively. Skeletal muscle (vastus lateralis) biopsies were taken before and after one hour of hyperinsulinaemia and the muscle insulin signalling proteins examined by western blot and immunoprecipitation assay. There was a strong inverse relationship between M-value and BMI. The most striking abnormality was significantly reduced insulin-induced activation of p42/44 MAP kinase, measured by specific assay, in the volunteers with poor insulin sensitivity. However, there was no relationship between individuals' BMI or M-value and protein expression/phosphorylation of IRS1, PKB, or p42/44 MAP kinase protein, under basal or hyperinsulinaemic conditions. In the few individuals with poor insulin sensitivity but preserved p42/44 MAP kinase activation, other signalling defects were evident. These findings implicate defective p42/44 MAP kinase signalling as a potential contributor to obesity-related IR in a non-diabetic population, although clearly multiple signalling defects underlie obesity associated IR

Agroecosystem energy transitions in the old and new worlds: trajectories and determinants at the regional scale

Energy efficiency in biomass production is a major challenge for a future transition to sustainable food and energy provision. This study uses methodologically consistent data on agroecosystem energy flows and different metrics of energetic efficiency from seven regional case studies in North America (USA and Canada) and Europe (Spain and Austria) to investigate energy transitions in Western agroecosystems from the late nineteenth to the late twentieth centuries. We quantify indicators such as external final energy return on investment (EFEROI, i.e., final produce per unit of external energy input), internal final EROI (IFEROI, final produce per unit of biomass reused locally), and final EROI (FEROI, final produce per unit of total inputs consumed). The transition is characterized by increasing final produce accompanied by increasing external energy inputs and stable local biomass reused. External inputs did not replace internal biomass reinvestments, but added to them. The results were declining EFEROI, stable or increasing IFEROI, and diverging trends in FEROI. The factors shaping agroecosystem energy profiles changed in the course of the transition: Under advanced organic and frontier agriculture of the late nineteenth and early twentieth centuries, population density and biogeographic conditions explained both agroecosystem productivity and energy inputs. In industrialized agroecosystems, biogeographic conditions and specific socio-economic factors influenced trends towards increased agroecosystem specialization. The share of livestock products in a region's final produce was the most important factor determining energy returns on investment

9/11-Related Experiences and Tasks of Landfill and Barge Workers: Qualitative Analysis from the World Trade Center Health Registry

<p>Abstract</p> <p>Background</p> <p>Few studies have documented the experiences of individuals who participated in the recovery and cleanup efforts at the World Trade Center Recovery Operation at Fresh Kills Landfill, on debris loading piers, and on transport barges after the September 11, 2001 terrorist attack.</p> <p>Methods</p> <p>Semi-structured telephone interviews were conducted with a purposive sample of workers and volunteers from the World Trade Center Health Registry. Qualitative methods were used to analyze the narratives.</p> <p>Results</p> <p>Twenty workers and volunteers were interviewed. They described the transport of debris to the Landfill via barges, the tasks and responsibilities associated with their post-9/11 work at the Landfill, and their reflections on their post-9/11 experiences. Tasks included sorting through debris, recovering human remains, searching for evidence from the terrorist attacks, and providing food and counseling services. Exposures mentioned included dust, fumes, and odors. Eight years after the World Trade Center disaster, workers expressed frustration about poor risk communication during recovery and cleanup work. Though proud of their contributions in the months after 9/11, some participants were concerned about long-term health outcomes.</p> <p>Conclusions</p> <p>This qualitative study provided unique insight into the experiences, exposures, and concerns of understudied groups of 9/11 recovery and cleanup workers. The findings are being used to inform the development of subsequent World Trade Center Health Registry exposure and health assessments.</p

Retinal Structures and Visual Cortex Activity are Impaired Prior to Clinical Vision Loss in Glaucoma

Glaucoma is the second leading cause of blindness worldwide and its pathogenesis remains unclear. In this study, we measured the structure, metabolism and function of the visual system by optical coherence tomography and multi-modal magnetic resonance imaging in healthy subjects and glaucoma patients with different degrees of vision loss. We found that inner retinal layer thinning, optic nerve cupping and reduced visual cortex activity occurred before patients showed visual field impairment. The primary visual cortex also exhibited more severe functional deficits than higher-order visual brain areas in glaucoma. Within the visual cortex, choline metabolism was perturbed along with increasing disease severity in the eye, optic radiation and visual field. In summary, this study showed evidence that glaucoma deterioration is already present in the eye and the brain before substantial vision loss can be detected clinically using current testing methods. In addition, cortical cholinergic abnormalities are involved during trans-neuronal degeneration and can be detected non-invasively in glaucoma. The current results can be of impact for identifying early glaucoma mechanisms, detecting and monitoring pathophysiological events and eye-brain-behavior relationships, and guiding vision preservation strategies in the visual system, which may help reduce the burden of this irreversible but preventable neurodegenerative disease. © The Author(s) 2016111121sciescopu

Diffusion of MMPs on the Surface of Collagen Fibrils: The Mobile Cell Surface – Collagen Substratum Interface

Remodeling of the extracellular matrix catalyzed by MMPs is central to morphogenetic phenomena during development and wound healing as well as in numerous pathologic conditions such as fibrosis and cancer. We have previously demonstrated that secreted MMP-2 is tethered to the cell surface and activated by MT1-MMP/TIMP-2-dependent mechanism. The resulting cell-surface collagenolytic complex (MT1-MMP)2/TIMP-2/MMP-2 can initiate (MT1-MMP) and complete (MMP-2) degradation of an underlying collagen fibril. The following question remained: What is the mechanism of substrate recognition involving the two structures of relatively restricted mobility, the cell surface enzymatic complex and a collagen fibril embedded in the ECM? Here we demonstrate that all the components of the complex are capable of processive movement on a surface of the collagen fibril. The mechanism of MT1-MMP movement is a biased diffusion with the bias component dependent on the proteolysis of its substrate, not adenosine triphosphate (ATP) hydrolysis. It is similar to that of the MMP-1 Brownian ratchet we described earlier. In addition, both MMP-2 and MMP-9 as well as their respective complexes with TIMP-1 and -2 are capable of Brownian diffusion on the surface of native collagen fibrils without noticeable dissociation while the dimerization of MMP-9 renders the enzyme immobile. Most instructive is the finding that the inactivation of the enzymatic activity of MT1-MMP has a detectable negative effect on the cell force developed in miniaturized 3D tissue constructs. We propose that the collagenolytic complex (MT1-MMP)2/TIMP-2/MMP-2 represents a Mobile Cell Surface – Collagen Substratum Interface. The biological implications of MT1-MMP acting as a molecular ratchet tethered to the cell surface in complex with MMP-2 suggest a new mechanism for the role of spatially regulated peri-cellular proteolysis in cell-matrix interactions

From vineyards to feedlots: a fund-flow scanning of sociometabolic transition in the Vallès County (Catalonia) 1860-1956-1999

We analyse the changes to agricultural metabolism in four municipalities of Vallès County (Catalonia, Iberia) by accounting for their agroecosystemfunds and flows during the socioecological transition from organic to industrial farming between the late nineteenth and twentieth centuries. The choice of three different stages in this transition allows us to observe the transformation of its funds and flows over time, the links established between them and the effect on their energy profiles.We emphasize the relevance of the integration and consistency of agroecosystem funds for energy efficiency in agriculture and their role as underlying historical drivers of this socioecological transition. While readjustment to market conditions and availability and affordability of external inputs are considered the main drivers of the transition, we also highlight the role of societal energy and nutritional transitions. An analysis of advanced organic agriculture c. 1860 reveals the great effort required to reproduce soil fertility and livestock from the internal recirculation of biomass. Meanwhile, a balance between land produce and livestock densities enabled the integration of funds, with a positive impact on energy performance. The adoption of fossil fuels and synthetic fertilizers c. 1956 reduced somewhat the pressure exerted on the land by overcoming the former dependence on local biomass flows to reproduce the agroecosystem. Yet external inputs diminished sustainability. Partial dependence on external markets existed congruently with internal crop diversity and the predominance of organic over industrial farm management. A shift towards animal production and consumption led to a new specialization process c. 1999 that resulted in crop homogenization and agroecological landscape disintegration. The energy returns of this linear feed-food livestock bioconversion declined compared to earlier mixed farming. Huge energy flows driven by a globalized economy ran through this agroecosystem, provoking deep impacts at both a local and external scale