The ability to acquire large-scale recordings of neuronal activity in awake and unrestrained animals is needed to provide new insights into how populations of neurons generate animal behavior. We ...present an instrument capable of recording intracellular calcium transients from the majority of neurons in the head of a freely behaving Caenorhabditis elegans with cellular resolution while simultaneously recording the animal’s position, posture, and locomotion. This instrument provides whole-brain imaging with cellular resolution in an unrestrained and behaving animal. We use spinning-disk confocalmicroscopy to capture 3D volumetric fluorescent images of neurons expressing the calcium indicator GCaMP6s at 6 head-volumes/s. A suite of three cameras monitor neuronal fluorescence and the animal’s position and orientation. Custom software tracks the 3D position of the animal’s head in real time and two feedback loops adjust a motorized stage and objective to keep the animal’s head within the field of view as the animal roams freely. We observe calcium transients from up to 77 neurons for over 4 min and correlate this activity with the animal’s behavior. We characterize noise in the system due to animal motion and show that, across worms, multiple neurons show significant correlations with modes of behavior corresponding to forward, backward, and turning locomotion.
Numerous uremic solutes are derived from the action of colon microbes. Two such solutes, indoxyl sulfate and p-cresol sulfate, have been associated with adverse outcomes in renal failure. This study ...tested whether increasing dietary fiber in the form of resistant starch would lower the plasma levels of these solutes in patients on hemodialysis.
Fifty-six patients on maintenance hemodialysis were randomly assigned to receive supplements containing resistant starch (n=28) or control starch (n=28) daily for 6 weeks in a study conducted between October 2010 and May 2013. Of these, 40 patients (20 in each group) completed the study and were included in the final analysis. Plasma indoxyl sulfate and p-cresol sulfate levels were measured at baseline and week 6.
Increasing dietary fiber for 6 weeks significantly reduced the unbound, free plasma level of indoxyl sulfate (median -29% 25th percentile, 75th percentile, -56, -12 for fiber versus -0.4% -20, 34 for control, P=0.02). The reduction in free plasma levels of indoxyl sulfate was accompanied by a reduction in free plasma levels of p-cresol sulfate (r=0.81, P<0.001). However, the reduction of p-cresol sulfate levels was of lesser magnitude and did not achieve significance (median -28% -46, 5 for fiber versus 4% -28, 36 for control, P=0.05).
Increasing dietary fiber in hemodialysis patients may reduce the plasma levels of the colon-derived solutes indoxyl sulfate and possibly p-cresol sulfate without the need to intensify dialysis treatments. Further studies are required to determine whether such reduction provides clinical benefits.
Advances in optical neuroimaging techniques now allow neural activity to be recorded with cellular resolution in awake and behaving animals. Brain motion in these recordings pose a unique challenge. ...The location of individual neurons must be tracked in 3D over time to accurately extract single neuron activity traces. Recordings from small invertebrates like C. elegans are especially challenging because they undergo very large brain motion and deformation during animal movement. Here we present an automated computer vision pipeline to reliably track populations of neurons with single neuron resolution in the brain of a freely moving C. elegans undergoing large motion and deformation. 3D volumetric fluorescent images of the animal's brain are straightened, aligned and registered, and the locations of neurons in the images are found via segmentation. Each neuron is then assigned an identity using a new time-independent machine-learning approach we call Neuron Registration Vector Encoding. In this approach, non-rigid point-set registration is used to match each segmented neuron in each volume with a set of reference volumes taken from throughout the recording. The way each neuron matches with the references defines a feature vector which is clustered to assign an identity to each neuron in each volume. Finally, thin-plate spline interpolation is used to correct errors in segmentation and check consistency of assigned identities. The Neuron Registration Vector Encoding approach proposed here is uniquely well suited for tracking neurons in brains undergoing large deformations. When applied to whole-brain calcium imaging recordings in freely moving C. elegans, this analysis pipeline located 156 neurons for the duration of an 8 minute recording and consistently found more neurons more quickly than manual or semi-automated approaches.
Modern drug discovery is contingent on identifying lead compounds and rapidly synthesizing analogues. The use of a common pharmacophore to direct multiple and divergent C-H functionalizations of lead ...compounds is a particularly attractive approach. Herein, we demonstrate the viability of late-stage diversification through the divergent C-H functionalization of sulfonamides, an important class of pharmacophores found in nearly 200 drugs currently on the market, including the non-steroidal anti-inflammatory blockbuster drug celecoxib. We developed a set of six categorically different sulfonamide C-H functionalization reactions (olefination, arylation, alkylation, halogenation, carboxylation, and carbonylation), each representing a distinct handle for further diversification to reach a large number of analogues. We then performed late-stage, site-selective diversification of a sulfonamide drug candidate containing multiple potentially reactive C-H bonds to synthesize directly novel celecoxib analogues as potential cyclooxygenase-II (COX-2)-specific inhibitors. Together with other recently developed practical directing groups, such as CONHOMe and CONHC(6)F(5), sulfonamide directing groups demonstrate that the auxiliary approach established in asymmetric catalysis can be equally effective in developing broadly useful C-H activation reactions.
The Northern and Southern Patagonian Ice Fields (NPI and SPI) in South America are the largest bodies of ice in the Southern hemisphere outside of Antarctica and the largest contributors to eustatic ...sea level rise (SLR) in the world, per unit area. Here we exploit swath processed CryoSat-2 interferometric data to produce maps of surface elevation change at sub-kilometer spatial resolution over the Ice Fields for six glaciological years between April 2011 and March 2017. Mass balance is calculated independently for nine sub-regions, including six individual glaciers larger than 300 km2. Overall, between 2011 and 2017 the Patagonian Ice Fields have lost mass at a combined rate of 21.29 ± 1.98 Gt a−1, contributing 0.059 ± 0.005 mm a−1 to SLR. We observe widespread thinning on the Ice Fields, particularly north of 49° S. However the pattern of surface elevation change is highly heterogeneous, partly reflecting the importance of dynamic processes on the Ice Fields. The Jorge Montt glacier (SPI), whose tidewater terminus is approaching floatation, retreated ~2.5 km during our study period and lost mass at the rate of 2.20 ± 0.38 Gt a−1 (4.64 ± 0.80 mwe a−1). In contrast with the general pattern of retreat and mass loss, Pio XI, the largest glacier in South America, is advancing and gaining mass at 0.67 ± 0.29 Gt a−1 rate.
•CS2 swath altimetry captures elevation change patterns over complex topography.•Ice dynamics plays important role in driving strong mass losses on the ice fields.•Pio XI, the only glacier with positive mass balance, advanced at both its termini.•Between 2011 and 2017 the Patagonian ice fields lost 21.29 ± 1.98 Gt a−1.•Mass loss is 24% (42%) higher compared to the period 2000–2012/14 (1975–2000).
Review and analysis of 1332 gas chromatography (GC) n-alkane traces of oils from the Cooper and Eromanga basins indicate the shape of any GC trace profile is primarily controlled by the degree of ...organic maturity (early, peak or late) at which the oils were expelled from the parent source rock, rather than indicating the depositional environment, and hence organic composition, of that source rock. The depositional environment of a source rock may still be inferred, however, from the position of the n-alkane maximum on the GC traces of early expulsion oils in association with the pour point of the oil. Departures of GC trace profiles from the standard early, peak or late expulsion profiles can indicate mixing of oils of different maturities, while variations in the GC trace profiles of oils within adjacent reservoir units may indicate phase separation of the parent liquid, or possible seal breach by an accumulation that exceeds the capacity of its overlying seal.
KEY POINTS
GC trace profiles of 1332 oils from across the Cooper and Eromanga basins of central Australia have been reviewed.
Organic maturity, rather than organic composition, of the parent source rock controls the shape of any GC trace profile.
All early maturity oils display a consistent GC trace profile shape that is different from all peak maturity oils and different again from all late maturity oils.
Depositional environment of the source rocks within a basin can be inferred from the relative pour points of the resultant oils.
In an exploratory, block-randomised, parallel, double-blind, single-centre, placebo-controlled superiority study (ISRCTN12562026, funded by Cultech Ltd), 220 Bulgarian participants (30 to 65 years ...old) with BMI 25-34.9 kg/m
received Lab4P probiotic (50 billion/day) or a matched placebo for 6 months. Participants maintained their normal diet and lifestyle. Primary outcomes were changes in body weight, BMI, waist circumference (WC), waist-to-height ratio (WtHR), blood pressure and plasma lipids. Secondary outcomes were changes in plasma C-reactive protein (CRP), the diversity of the faecal microbiota, quality of life (QoL) assessments and the incidence of upper respiratory tract infection (URTI). Significant between group decreases in body weight (1.3 kg, p < 0.0001), BMI (0.045 kg/m
, p < 0.0001), WC (0.94 cm, p < 0.0001) and WtHR (0.006, p < 0.0001) were in favour of the probiotic. Stratification identified greater body weight reductions in overweight subjects (1.88%, p < 0.0001) and in females (1.62%, p = 0.0005). Greatest weight losses were among probiotic hypercholesterolaemic participants (-2.5%, p < 0.0001) alongside a significant between group reduction in small dense LDL-cholesterol (0.2 mmol/L, p = 0.0241). Improvements in QoL and the incidence rate ratio of URTI (0.60, p < 0.0001) were recorded for the probiotic group. No adverse events were recorded. Six months supplementation with Lab4P probiotic resulted in significant weight reduction and improved small dense low-density lipoprotein-cholesterol (sdLDL-C) profiles, QoL and URTI incidence outcomes in overweight/obese individuals.
An Enlarged Profile of Uremic Solutes Tanaka, Hisae; Sirich, Tammy L; Plummer, Natalie S ...
PloS one,
08/2015, Letnik:
10, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Better knowledge of the uremic solutes that accumulate when the kidneys fail could lead to improved renal replacement therapy. This study employed the largest widely available metabolomic platform to ...identify such solutes. Plasma and plasma ultrafiltrate from 6 maintenance hemodialysis (HD) patients and 6 normal controls were first compared using a platform combining gas and liquid chromatography with mass spectrometry. Further studies compared plasma from 6 HD patients who had undergone total colectomy and 9 with intact colons. We identified 120 solutes as uremic including 48 that had not been previously reported to accumulate in renal failure. Combination of the 48 newly identified solutes with those identified in previous reports yielded an extended list of more than 270 uremic solutes. Among the solutes identified as uremic in the current study, 9 were shown to be colon-derived, including 6 not previously identified as such. Literature search revealed that many uremic phenyl and indole solutes, including most of those shown to be colon-derived, come from plant foods. Some of these compounds can be absorbed directly from plant foods and others are produced by colon microbial metabolism of plant polyphenols that escape digestion in the small intestine. A limitation of the metabolomic method was that it underestimated the elevation in concentration of uremic solutes which were measured using more quantitative assays.
In response to the urgent need for improved mapping of global biomass and the lack of any current space systems capable of addressing this need, the BIOMASS mission was proposed to the European Space ...Agency for the third cycle of Earth Explorer Core missions and was selected for Feasibility Study (Phase A) in March 2009. The objectives of the mission are 1) to quantify the magnitude and distribution of forest biomass globally to improve resource assessment, carbon accounting and carbon models, and 2) to monitor and quantify changes in terrestrial forest biomass globally, on an annual basis or better, leading to improved estimates of terrestrial carbon sources (primarily from deforestation); and terrestrial carbon sinks due to forest regrowth and afforestation. These science objectives require the mission to measure above-ground forest biomass from 70° N to 56° S at spatial scale of 100–200
m, with error not exceeding ±
20% or ±
10
t
ha
−
1
and forest height with error of ±
4
m. To meet the measurement requirements, the mission will carry a P-Band polarimetric SAR (centre frequency 435
MHz with 6
MHz bandwidth) with interferometric capability, operating in a dawn-dusk orbit with a constant incidence angle (in the range of 25°–35°) and a 25–45
day repeat cycle. During its 5-year lifetime, the mission will be capable of providing both direct measurements of biomass derived from intensity data and measurements of forest height derived from polarimetric interferometry. The design of the BIOMASS mission spins together two main observational strands: (1) the long heritage of airborne observations in tropical, temperate and boreal forest that have demonstrated the capabilities of P-band SAR for measuring forest biomass; (2) new developments in recovery of forest structure including forest height from Pol-InSAR, and, crucially, the resistance of P-band to temporal decorrelation, which makes this frequency uniquely suitable for biomass measurements with a single repeat-pass satellite. These two complementary measurement approaches are combined in the single BIOMASS sensor, and have the satisfying property that increasing biomass reduces the sensitivity of the former approach while increasing the sensitivity of the latter. This paper surveys the body of evidence built up over the last decade, from a wide range of airborne experiments, which illustrates the ability of such a sensor to provide the required measurements.
At present, the BIOMASS P-band radar appears to be the only sensor capable of providing the necessary global knowledge about the world's forest biomass and its changes. In addition, this first chance to explore the Earth's environment with a long wavelength satellite SAR is expected to make yield new information in a range of geoscience areas, including subsurface structure in arid lands and polar ice, and forest inundation dynamics.
► The BIOMASS mission aims to provide global forest biomass maps using P-band SAR images. ► Forest biomass is derived using radar intensity, PolInSAR and tomographic techniques. ► The mission will help quantify the terrestrial contribution to the global carbon cycle.
This study investigates the performances of four major global Leaf Area Index (LAI) products at 1/11.2° spatial sampling and a monthly time step: ECOCLIMAP climatology, GLOBCARBON (from ...SPOT/VEGETATION and ATSR/AATSR), CYCLOPES (from SPOT/VEGETATION) and MODIS Collection 4 (main algorithm, from MODIS/TERRA). These products were intercompared during the 2001–2003 period over the BELMANIP network of sites. Their uncertainty was assessed by comparison with 56 LAI reference maps derived from ground measurements. CYCLOPES and MODIS depict realistic spatial variations at continental scale, while ECOCLIMAP poorly captures surface spatial heterogeneity, and GLOBCARBON tends to display erratic variations. ECOCLIMAP and GLOBCARBON show the highest frequency of successful retrievals while MODIS and CYCLOPES retrievals are frequently missing in winter over northern latitudes and over the equatorial belt. CYCLOPES and MODIS describe consistent temporal profiles over most vegetation types, while ECOCLIMAP does not show any interannual variations, and GLOBCARBON can exhibit temporal instability during the growing season over forests. The CYCLOPES, MODIS, and GLOBCARBON LAI values agree better over croplands and grasslands than over forests, where differences in vegetation structure representation between algorithms and surface reflectance uncertainties lead to substantial discrepancies between products. CYCLOPES does not reach high enough LAI values to properly characterize forests. In contrast, the other products have sufficient dynamic range of LAI to describe the global variability of LAI. Overall, CYCLOPES is the most similar product to the LAI reference maps. However, more accurate ground measurements and better representation of the global and seasonal variability of vegetation are required to refine this result.
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