How long is a hillslope?

Hillslope length is a fundamental attribute of landscapes, intrinsically linked to drainage density, landslide hazard, biogeochemical cycling and hillslope sediment transport. Existing methods to estimate catchment average hillslope lengths include inversion of drainage density or identification of a break in slope–area scaling, where the hillslope domain transitions into the fluvial domain. Here we implement a technique which models flow from point sources on hilltops across pixels in a digital elevation model (DEM), based on flow directions calculated using pixel aspect, until reaching the channel network, defined using recently developed channel extraction algorithms. Through comparisons between these measurement techniques, we show that estimating hillslope length from plots of topographic slope versus drainage area, or by inverting measures of drainage density, systematically underestimates hillslope length. In addition, hillslope lengths estimated by slope–area scaling breaks show large variations between catchments of similar morphology and area. We then use hillslope length–relief structure of landscapes to explore nature of sediment flux operating on a landscape. Distinct topographic forms are predicted for end-member sediment flux laws which constrain sediment transport on hillslopes as being linearly or nonlinearly dependent on hillslope gradient. Because our method extracts hillslope profiles originating from every ridgetop pixel in a DEM, we show that the resulting population of hillslope length–relief measurements can be used to differentiate between linear and nonlinear sediment transport laws in soil mantled landscapes. We find that across a broad range of sites across the continental United States, topography is consistent with a sediment flux law in which transport is nonlinearly proportional to topographic gradient

Hypermethioninaemia due to methionine adenosyltransferase I/III (MAT I/III) deficiency: diagnosis in an expanded neonatal screening programme

The Expanded Newborn Screening Program (MS/MS) in the region of Galicia (NW Spain) was initiated in 2000 and includes the measurement of methionine levels in dried blood spots. Between June 2000 and June 2007, 140 818 newborns were analysed, and six cases of persistent hypermethioninaemia were detected: one homocystinuria due to cystathionine β-synthase (CβS) deficiency, and five methionine adenosyltransferase I/III (MAT I/III) deficiencies. The five cases of MAT I/III deficiency represent an incidence of 1/28 163 newborns. In these five patients, methionine levels in dried blood spots ranged from 50 to 147 μmol/L. At confirmation of the persistence of the hypermethioninaemia in a subsequent plasma sample, plasma methionine concentrations were moderately elevated in 4 of the 5 patients (mean 256 μmol/L), while total homocysteine (tHcy) was normal; the remaining patient showed plasma methionine of 573 μmol/L and tHcy of 22.8 μmol/L. All five patients were heterozygous for the same dominant mutation, R264H in the MAT1A gene. With a diet not exceeding recommended protein requirements for their age, all patients maintained methionine levels below 300 μmol/L. Currently, with a mean of 2.5 years since diagnosis, the patients are asymptomatic and show developmental quotients within the normal range. Our results show a rather high frequency of hypermethioninaemia due to MAT I/III deficiency in the Galician neonatal population, indicating a need for further studies to evaluate the impact of persistent isolated hypermethioninaemia in neonatal screening programmes

Newborn Screening for Homocystinuria Revealed a High Frequency of MAT I/III Deficiency in Iberian Peninsula

Acessível em: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4375120/Homocystinuria due to cystathionine β-synthase deficiency or "classical homocystinuria" is a rare autosomal recessive condition resulting in altered sulfur metabolism with elevated methionine and homocysteine in plasma and homocystine in urine. This condition is characterized by a high clinical heterogeneity, which contributes to late clinical diagnosis, usually only made after irreversible damage has occurred. Treatment is effective if started before clinical symptoms. The analysis of methionine levels by tandem mass spectrometry (MS/MS) allows the newborn screening for homocystinuria, but false-positive results can be frequently obtained and lead to the unwanted identification of methionine adenosyl transferase (MAT I/III) deficiency. This latter condition is biochemically characterized by isolated persistent hypermethioninemia, accompanied in some individuals with slightly elevated levels of homocysteine in plasma. A dominant form of MAT I/III deficiency, associated with mutation p.R264H, seems to be very frequent in the Iberian Peninsula and usually has a clinically benign course. Both these metabolic disorders are screened in Galicia and Portugal since the introduction of the MS/MS technology, in 2000 and 2004, respectively, resulting in the identification of three patients with classical homocystinuria and 44 patients with MAT I/III deficiency. All but one heterozygous parent of MAT I/III patients, identified with the p.R264H mutation, are healthy adults around the age of 30/40. The implementation of a second-tier test for homocysteine in dried blood spots would considerably reduce the number of MAT I/III-deficient patients identified and improve the specificity and positive predictive value for classical homocystinuria screening

Biochemical basis for the dominant inheritance of hypermethioninemia associated with the R264H mutation of the MAT1A gene. A monomeric methionine adenosyltransferase with tripolyphosphatase activity

Methionine adenosyltransferase (MAT) catalyzes the synthesis of S-adenosylmethionine (AdoMet), the main alkylating agent in living cells. Additionally, in the liver, MAT is also responsible for up to 50% of methionine catabolism. Humans with mutations in the gene MAT1A, the gene that encodes the catalytic subunit of MAT I and III, have decreased MAT activity in liver, which results in a persistent hypermethioninemia without homocystinuria. The hypermethioninemic phenotype associated with these mutations is inherited as an autosomal recessive trait. The only exception is the dominant mild hypermethioninemia associated with a G-A transition at nucleotide 791 of exon VII. This change yields a MAT1A-encoded subunit in which arginine 264 is replaced by histidine. Our results indicate that in the homologous rat enzyme, replacement of the equivalent arginine 265 by histidine (R265H) results in a monomeric MAT with only 0.37% of the AdoMet synthetic activity. However the tripolyphosphatase activity is similar to that found in the wild type (WT) MAT and is inhibited by PP(i). Our in vivo studies demonstrate that the R265H MAT I/III mutant associates with the WT subunit resulting in a dimeric R265H-WT MAT unable to synthesize AdoMet. Tripolyphosphatase activity is maintained in the hybrid MAT, but is not stimulated by methionine and ATP, indicating a deficient binding of the substrates. Our data indicate that the active site for tripolyphosphatase activity is functionally active in the monomeric R265H MAT I/III mutant. Moreover, our results provide a molecular mechanism that might explain the dominant inheritance of the hypermethioninemia associated with the R264H mutation of human MAT I/III

Abnormal hypermethylation at imprinting control regions in patients with S-adenosylhomocysteine hydrolase (AHCY) deficiency

S-adenosylhomocysteine hydrolase (AHCY) deficiency is a rare autosomal recessive disorder in methionine metabolism caused by mutations in the AHCY gene. Main characteristics are psychomotor delay including delayed myelination and myopathy (hypotonia, absent tendon reflexes etc.) from birth, mostly associated with hypermethioninaemia, elevated serum creatine kinase levels and increased genome wide DNA methylation. The prime function of AHCY is to hydrolyse and efficiently remove S-adenosylhomocysteine, the by-product of transmethylation reactions and one of the most potent methyltransferase inhibitors. In this study, we set out to more specifically characterize DNA methylation changes in blood samples from patients with AHCY deficiency. Global DNA methylation was increased in two of three analysed patients. In addition, we analysed the DNA methylation levels at differentially methylated regions (DMRs) of six imprinted genes (MEST, SNRPN, LIT1, H19, GTL2 and PEG3) as well as Alu and LINE1 repetitive elements in seven patients. Three patients showed a hypermethylation in up to five imprinted gene DMRs. Abnormal methylation in Alu and LINE1 repetitive elements was not observed. We conclude that DNA hypermethylation seems to be a frequent but not a constant feature associated with AHCY deficiency that affects different genomic regions to different degrees. Thus AHCY deficiency may represent an ideal model disease for studying the molecular origins and biological consequences of DNA hypermethylation due to impaired cellular methylation status

Heteroepitaxial growth of ferromagnetic MnSb(0001) films on Ge/Si(111) virtual substrates

Molecular beam epitaxial growth of ferromagnetic MnSb(0001) has been achieved on high quality, fully relaxed Ge(111)/Si(111) virtual substrates grown by reduced pressure chemical vapor deposition. The epilayers were characterized using reflection high energy electron diffraction, synchrotron hard X-ray diffraction, X-ray photoemission spectroscopy, and magnetometry. The surface reconstructions, magnetic properties, crystalline quality, and strain relaxation behavior of the MnSb films are similar to those of MnSb grown on GaAs(111). In contrast to GaAs substrates, segregation of substrate atoms through the MnSb film does not occur, and alternative polymorphs of MnSb are absent

Quasar accretion disk sizes from continuum reverberation mapping in the DES standard-star fields

Measurements of the physical properties of accretion disks in active galactic nuclei are important for better understanding the growth and evolution of supermassive black holes. We present the accretion disk sizes of 22 quasars from continuum reverberation mapping with data from the Dark Energy Survey (DES) standard star fields and the supernova C fields. We construct continuum lightcurves with the \textit{griz} photometry that span five seasons of DES observations. These data sample the time variability of the quasars with a cadence as short as one day, which corresponds to a rest frame cadence that is a factor of a few higher than most previous work. We derive time lags between bands with both JAVELIN and the interpolated cross-correlation function method, and fit for accretion disk sizes using the JAVELIN Thin Disk model. These new measurements include disks around black holes with masses as small as $\sim10^7$ $M_{\odot}$, which have equivalent sizes at 2500\AA \, as small as $\sim 0.1$ light days in the rest frame. We find that most objects have accretion disk sizes consistent with the prediction of the standard thin disk model when we take disk variability into account. We have also simulated the expected yield of accretion disk measurements under various observational scenarios for the Large Synoptic Survey Telescope Deep Drilling Fields. We find that the number of disk measurements would increase significantly if the default cadence is changed from three days to two days or one day.Comment: 33 pages, 24 figure

Search for squarks and gluinos with the ATLAS detector in final states with jets and missing transverse momentum using √s=8 TeV proton-proton collision data

A search for squarks and gluinos in final states containing high-p T jets, missing transverse momentum and no electrons or muons is presented. The data were recorded in 2012 by the ATLAS experiment in s√=8 TeV proton-proton collisions at the Large Hadron Collider, with a total integrated luminosity of 20.3 fb−1. Results are interpreted in a variety of simplified and specific supersymmetry-breaking models assuming that R-parity is conserved and that the lightest neutralino is the lightest supersymmetric particle. An exclusion limit at the 95% confidence level on the mass of the gluino is set at 1330 GeV for a simplified model incorporating only a gluino and the lightest neutralino. For a simplified model involving the strong production of first- and second-generation squarks, squark masses below 850 GeV (440 GeV) are excluded for a massless lightest neutralino, assuming mass degenerate (single light-flavour) squarks. In mSUGRA/CMSSM models with tan β = 30, A 0 = −2m 0 and μ > 0, squarks and gluinos of equal mass are excluded for masses below 1700 GeV. Additional limits are set for non-universal Higgs mass models with gaugino mediation and for simplified models involving the pair production of gluinos, each decaying to a top squark and a top quark, with the top squark decaying to a charm quark and a neutralino. These limits extend the region of supersymmetric parameter space excluded by previous searches with the ATLAS detector