Chronic renal homograft function. Correlation with histology and lymphocyte antigen matching

Renal function was studied in twenty-nine of thirty-four surviving renal allograft recipients from an initial group of sixty-four patients two years after transplantation. Mean clearances of inulin and PAH were, respectively, greater than and equal to half the donors' initial predicted clearances. Minimum urine osmolality during water diuresis was greater, and maximum urine osmolality during hydropenia was less than normal, an effect attributable partly to enhanced solute load in a single transplanted kidney. Patients with compatible donor-recipient lymphocyte antigens demonstrated statistically better function than those with one or more incompatibilities, although there was a definite degree of overlap between the two groups. In contrast, little correlation could be demonstrated between the cumulative histopathology and renal clearances. Renal function in patients with compatible donors was statistically greater than half the donors' initial predicted function. Serial increase in renal clearances was documented in one patient with a compatible donor. Serial decreases were demonstrated in two patients with incompatible donors. These findings suggest that hypertrophy of the denervated, transplanted kidney occurs when immune reaction is minimal. © 1967

Drifter observations in the summer time Bay of Biscay slope current

During the summer of 2012, 20 surface drifters drogued at 50 m depth were deployed on the continental slope to the north of the Bay of Biscay. Initially after release the drifters all crossed the slope, with 14 continuing equatorward, parallel to the slope following an absolute dynamic topography feature and 6 returning to the slope, in an eddy, visible in chlorophyll-a maps. Lagrangian statistics show an anisotropic flow field that becomes less tied to the absolute dynamic topography and increasingly dominated by diffusion and eddy processes. A weaker tie to the absolute dynamic topography allowed for total of 8 of the drifters crossed from the deep water onto the shelf, showing pathways for flow across the slope. A combination of drifter trajectories, absolute dynamic topography and chlorophyll-a concentration maps have been used to show that small anticyclonic eddies, tied to the complex slope topography provide a mechanism for on shelf transport. During the summer, the presence of these eddies can be seen in surface chlorophyll-a maps

Dissecting the Active Site of the Collagenolytic Cathepsin L3 Protease of the Invasive Stage of Fasciola hepatica

Background: A family of secreted cathepsin L proteases with differential activities is essential for host colonization and survival in the parasitic flatworm Fasciola hepatica. While the blood feeding adult secretes predominantly FheCL1, an enzyme with a strong preference for Leu at the S2 pocket of the active site, the infective stage produces FheCL3, a unique enzyme with collagenolytic activity that favours Pro at P2. Methodology/Principal Findings: Using a novel unbiased multiplex substrate profiling and mass spectrometry methodology (MSP-MS), we compared the preferences of FheCL1 and FheCL3 along the complete active site cleft and confirm that while the S2 imposes the greatest influence on substrate selectivity, preferences can be indicated on other active site subsites. Notably, we discovered that the activity of FheCL1 and FheCL3 enzymes is very different, sharing only 50% of the cleavage sites, supporting the idea of functional specialization. We generated variants of FheCL1 and FheCL3 with S2 and S3 residues by mutagenesis and evaluated their substrate specificity using positional scanning synthetic combinatorial libraries (PS-SCL). Besides the rare P2 Pro preference, FheCL3 showed a distinctive specificity at the S3 pocket, accommodating preferentially the small Gly residue. Both P2 Pro and P3 Gly preferences were strongly reduced when Trp67 of FheCL3 was replaced by Leu, rendering the enzyme incapable of digesting collagen. In contrast, the inverse Leu67Trp substitution in FheCL1 only slightly reduced its Leu preference and improved Pro acceptance in P2, but greatly increased accommodation of Gly at S3. Conclusions/Significance: These data reveal the significance of S2 and S3 interactions in substrate binding emphasizing the role for residue 67 in modulating both sites, providing a plausible explanation for the FheCL3 collagenolytic activity essential to host invasion. The unique specificity of FheCL3 could be exploited in the design of specific inhibitors selectively directed to specific infective stage parasite proteinases. © 2013 Corvo et al

Climate variability of southern Chile since the Last Glacial Maximum : a continuous sedimentological record from Lago Puyehue (40°S)

Author Posting. © Springer, 2007. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Journal of Paleolimnology 39 (2008): 179-195, doi:10.1007/s10933-007-9117-y.This paper presents a multi-proxy climate record of an 11 m long core collected in Lago Puyehue (southern Chile, 40°S) and extending back to 18,000 cal yr BP. The multi-proxy analyses include sedimentology, mineralogy, grain size, geochemistry, loss-on-ignition, magnetic susceptibility and radiocarbon datings. Results demonstrate that sediment grain size is positively correlated with the biogenic sediment content and can be used as a proxy for lake paleoproductivity. On the other hand, the magnetic susceptibility signal is correlated with the aluminium and titanium concentrations and can be used as a proxy for the terrigenous supply. Temporal variations of sediment composition evidence that, since the last glacial maximum, the Chilean Lake District was characterized by 3 abrupt climate changes superimposed on a long-term climate evolution. These rapid climate changes are: (1) an abrupt warming at the end of the last glacial maximum at 17,300 cal yr BP; (2) a 13,100-12,300 cal yr BP cold event, ending rapidly and interpreted as the local counter part of the Younger Dryas cold period, and (3) a 3400-2900 cal yr BP climatic instability synchronous with a period of low solar activity. The timing of the 13,100-12,300 cold event is compared with similar records in both hemispheres and demonstrates that this southern hemisphere climate change lags behind the northern hemisphere Younger Dryas cold period by 500 to 1000 years.This research is supported by the Belgian OSTC project EV/12/10B "A continuous Holocene record of ENSO variability in southern Chile"

Towards precision medicine for hypertension: a review of genomic, epigenomic, and microbiomic effects on blood pressure in experimental rat models and humans

Compelling evidence for the inherited nature of essential hypertension has led to extensive research in rats and humans. Rats have served as the primary model for research on the genetics of hypertension resulting in identification of genomic regions that are causally associated with hypertension. In more recent times, genome-wide studies in humans have also begun to improve our understanding of the inheritance of polygenic forms of hypertension. Based on the chronological progression of research into the genetics of hypertension as the "structural backbone," this review catalogs and discusses the rat and human genetic elements mapped and implicated in blood pressure regulation. Furthermore, the knowledge gained from these genetic studies that provide evidence to suggest that much of the genetic influence on hypertension residing within noncoding elements of our DNA and operating through pervasive epistasis or gene-gene interactions is highlighted. Lastly, perspectives on current thinking that the more complex "triad" of the genome, epigenome, and the microbiome operating to influence the inheritance of hypertension, is documented. Overall, the collective knowledge gained from rats and humans is disappointing in the sense that major hypertension-causing genes as targets for clinical management of essential hypertension may not be a clinical reality. On the other hand, the realization that the polygenic nature of hypertension prevents any single locus from being a relevant clinical target for all humans directs future studies on the genetics of hypertension towards an individualized genomic approach

Computational exploration of molecular receptive fields in the olfactory bulb reveals a glomerulus-centric chemical map

© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Progress in olfactory research is currently hampered by incomplete knowledge about chemical receptive ranges of primary receptors. Moreover, the chemical logic underlying the arrangement of computational units in the olfactory bulb has still not been resolved. We undertook a large-scale approach at characterising molecular receptive ranges (MRRs) of glomeruli in the dorsal olfactory bulb (dOB) innervated by the MOR18-2 olfactory receptor, also known as Olfr78, with human ortholog OR51E2. Guided by an iterative approach that combined biological screening and machine learning, we selected 214 odorants to characterise the response of MOR18-2 and its neighbouring glomeruli. We found that a combination of conventional physico-chemical and vibrational molecular descriptors performed best in predicting glomerular responses using nonlinear Support-Vector Regression. We also discovered several previously unknown odorants activating MOR18-2 glomeruli, and obtained detailed MRRs of MOR18-2 glomeruli and their neighbours. Our results confirm earlier findings that demonstrated tunotopy, that is, glomeruli with similar tuning curves tend to be located in spatial proximity in the dOB. In addition, our results indicate chemotopy, that is, a preference for glomeruli with similar physico-chemical MRR descriptions being located in spatial proximity. Together, these findings suggest the existence of a partial chemical map underlying glomerular arrangement in the dOB. Our methodology that combines machine learning and physiological measurements lights the way towards future high-throughput studies to deorphanise and characterise structure-activity relationships in olfaction.Peer reviewe

Performance of selection hyper-heuristics on the extended HyFlex domains

Selection hyper-heuristics perform search over the space of heuristics by mixing and controlling a predefined set of low level heuristics for solving computationally hard combinatorial optimisation problems. Being reusable methods, they are expected to be applicable to multiple problem domains, hence performing well in cross-domain search. HyFlex is a general purpose heuristic search API which separates the high level search control from the domain details enabling rapid development and performance comparison of heuristic search methods, particularly hyper-heuristics. In this study, the performance of six previously proposed selection hyper-heuristics are evaluated on three recently introduced extended HyFlex problem domains, namely 0–1 Knapsack, Quadratic Assignment and Max-Cut. The empirical results indicate the strong generalising capability of two adaptive selection hyper-heuristics which perform well across the ‘unseen’ problems in addition to the six standard HyFlex problem domains

Understanding the chronology and occupation dynamics of oversized pit houses in the southern Brazilian highlands

A long held view about the occupation of southern proto-Je pit house villages of the southern Brazilian highlands is that these sites represent cycles of long-term abandonment and reoccupation. However, this assumption is based on an insufficient number of radiocarbon dates for individual pit houses. To address this problem, we conducted a programme of comprehensive AMS radiocarbon dating and Bayesian modelling at the deeply stratified oversized pit Houe 1, Baggio 1 site (Cal. A.D. 1395-1650), Campo Belo do Sul, Santa Catarina, Brazil. The straigraphy of House 1 revealed an unparalleled sequence of twelve well preserved floors evidencing a major change in occupation dynamics including five completely burnt collapsed roofs. The results of the radiocarbon dating allowed us to understand for the first time the occupation dynamics of an oversized pit house in the southern Brazilian highlands. The Bayesian model demonstrates that House 1 was occupied for over two centuries with no evidence of major periods of abandonment, calling into question previous models of long-term abandonment. In addition, the House 1 sequence allowed us to tie transformations in ceramic style and lithic technology to an absolute chronology. Finally, we can provide new evidence that the emergence of oversized domestic structures is a relatively recent phenomenon among the southern proto-Je. As monumental pit houses start to be bulit, small pit houses continue to be inhabited, evidencing emerging disparities in domestic architecture after AD 1000. Our research shows the importance of programmes of intensive dating of individual structures to understand occupation dynamcis and site permanence, and challenges long held assumptions that the southern Brazilian highlands were home to marginal cultures in the context of lowland South America

Gate-Controlled Ionization and Screening of Cobalt Adatoms on a Graphene Surface

We describe scanning tunneling spectroscopy (STS) measurements performed on individual cobalt (Co) atoms deposited onto backgated graphene devices. We find that Co adatoms on graphene can be ionized by either the application of a global backgate voltage or by the application of a local electric field from a scanning tunneling microscope (STM) tip. Large screening clouds are observed to form around Co adatoms ionized in this way, and we observe that some intrinsic graphene defects display a similar behavior. Our results provide new insight into charged impurity scattering in graphene, as well as the possibility of using graphene devices as chemical sensors.Comment: 19 pages, 4 figure