Analysis of X-inactivation status in a Rett syndrome natural history study cohort

BACKGROUND: Rett syndrome (RTT) is a rare neurodevelopmental disorder associated with pathogenic MECP2 variants. Because the MECP2 gene is subject to X-chromosome inactivation (XCI), factors including MECP2 genotypic variation, tissue differences in XCI, and skewing of XCI all likely contribute to the clinical severity of individuals with RTT. METHODS: We analyzed the XCI patterns from blood samples of 320 individuals and their mothers. It includes individuals with RTT (n = 287) and other syndromes sharing overlapping phenotypes with RTT (such as CDKL5 Deficiency Disorder [CDD, n = 16]). XCI status in each proband/mother duo and the parental origin of the preferentially inactivated X chromosome were analyzed. RESULTS: The average XCI ratio in probands was slightly increased compared to their unaffected mothers (73% vs. 69%, p = .0006). Among the duos with informative XCI data, the majority of individuals with classic RTT had their paternal allele preferentially inactivated (n = 180/220, 82%). In sharp contrast, individuals with CDD had their maternal allele preferentially inactivated (n = 10/12, 83%). Our data indicate a weak positive correlation between XCI skewing ratio and clinical severity scale (CSS) scores in classic RTT patients with maternal allele preferentially inactivated XCI (r CONCLUSION: These results extend our understanding of the pathogenesis of RTT and other syndromes with overlapping clinical features by providing insight into the both XCI and the preferential XCI of parental alleles

Corporate Social Responsibility and Maturity Mismatch of Investment and Financing: Evidence from Polluting and Non-Polluting Companies

We investigate the influence of corporate social responsibility (CSR) on the maturity mismatch of investment and financing from the perspective of both polluting and non-polluting companies. The results reveal that CSR performance can aggravate the maturity mismatch of investment and financing; and the effect can be more serious in the polluting companies. At the same time, we find that CSR makes companies obtain more short-term debt. What is more, polluting companies perform more environmental responsibilities in the form of long-term investments than non-polluting companies. These phenomena exacerbate the maturity mismatch of investment and financing; and this effect is only significant when polluting companies choose CSR mandatory disclosure. The impact of CSR on the maturity mismatch of investment and financing is more apparent in companies with lower value and at smaller scales. We show that companies should not only perform their CSR to maintain a balanced economic and ecological development, but also pay attention to the aggravation of the maturity mismatch of investment and financing.The paper was supported by the following fund project: General project of philosophy and social science research of the Ministry of Education (project no. 18JHQ083).info:eu-repo/semantics/publishedVersio

Gradient Estimation of Two-Stage Continuous Transfer Lines Subject to Operation-Dependent Failures

This paper addresses the gradient estimation of transfer linescomprising two machines separated by a buffer of finite capacity. A continuous flow model is considered, where machines are subject tooperation-dependent failures, i.e., a machine cannot fail when it is idle. Both repair times and failure times may be general, i.e., they need not be exponentially distributed.The system is hybrid in the sense that it hasboth continuous dynamics, as a result of continuous material flow, and discrete events: failures and repairs. The purpose of this paper is to estimate the gradient of the throughput rate with respect to the buffer capacity. Both IPA estimators and SPA estimators are derived. Simulation results show that IPA estimators do not work, contradicting the common belief that IPA always works for continuous flow models

An annotated checklist of the bryophytes of Taita Hills region, Kenya

Based on previous literature and our own collections, we list 288 bryophyte species (145 liverworts, 143 mosses) from the Taita Hills region (including Mt. Kasigau and Maktau Hill) in SE Kenya. New records for Kenya include the liverworts Archilejeunea elobulata Steph., Bazzania nitida (F. Weber) Grolle, Cololejeunea grossepapillosa (Horik.) N. Kitag., Diplasiolejeunea kraussiana (Lindenb.) Steph., D. villaumei Steph., Lejeunea amaniensis E.W. Jones, L. cyathearum E.W. Jones, Lopholejeunea laciniata E.W. Jones, Metzgeria crassipilis (Lindb.) A. Evans, M. nudifrons Steph., Plagiochila boryana (F. Weber) Nees, and P. moenkemeyeri Steph., and the mosses Leucophanes hildebrandtii Müll. Hal. and Neckeromnion lepineanum (Mont.) S. Olsson, Enroth, Huttunen & D. Quandt. A further 22 liverworts and 13 mosses previously known from other parts of Kenya are reported for the first time from the Taita Hills region.Peer reviewe

Two members of the DUF579 family are responsible for arabinogalactan methylation in Arabidopsis.

All members of the DUF579 family characterized so far have been described to affect the integrity of the hemicellulosic cell wall component xylan: GXMs are glucuronoxylan methyltransferases catalyzing 4-O-methylation of glucuronic acid on xylan; IRX15 and IRX15L, although their enzymatic activity is unknown, are required for xylan biosynthesis and/or xylan deposition. Here we show that the DUF579 family members, AGM1 and AGM2, are required for 4-O-methylation of glucuronic acid of a different plant cell wall component, the highly glycosylated arabinogalactan proteins (AGPs)

An unusual xylan in Arabidopsis primary cell walls is synthesised by GUX3, IRX9L, IRX10L and IRX14.

Xylan is a crucial component of many plant primary and secondary cell walls. However, the structure and function of xylan in the dicotyledon primary cell wall is not well understood. Here, we characterized a xylan that is specific to tissues enriched in Arabidopsis primary cell walls. Unlike previously described xylans, this xylan carries a pentose linked 1-2 to the α-1,2-d-glucuronic acid (GlcA) side chains on the β-1,4-Xyl backbone. The frequent and precisely regular spacing of GlcA substitutions every six xylosyl residues along the backbone is also unlike that previously observed in secondary cell wall xylan. Molecular genetics, in vitro assays, and expression data suggest that IRX9L, IRX10L and IRX14 are required for xylan backbone synthesis in primary cell wall synthesising tissues. IRX9 and IRX10 are not involved in the primary cell wall xylan synthesis but are functionally exchangeable with IRX9L and IRX10L. GUX3 is the only glucuronyltransferase required for the addition of the GlcA decorations on the xylan. The differences in xylan structure in primary versus secondary cell walls might reflect the different roles in cross-linking and interaction with other cell wall components.The work presented in this paper was supported by grants from the BBSRC: BB/G016240/1 BBSRC Sustainable Energy Centre Cell Wall Sugars Programme (BSBEC) and grant BB/K005537/1. JCM’s work at the Joint BioEnergy Institute was supported by the Office of Science, Office of Biological and Environmental Research, of the U.S. Department of Energy under Contract No. DE -AC02-05CH11231. NFB was supported by a PhD studentship from the Portuguese Foundation for Science and Technology. AN was supported by a summer studentship award from the Biochemical Society. The authors are grateful to the European Community’s Seventh Framework Programme SUNLIBB (FP7/2007-2013) under the grant agreement no 251132.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/tpj.1289

Thermodynamic, Spectroscopic, and Structural Studies of Complexation of Phenol- and Pyridine-Armed Macrocyclic Ligands with Univalent Metal Ions

Log K, ΔH, and ΔS values for interactions of a series of pyridinoazacrown ethers each bearing a phenol arm (2−6) and two macrocycles each bearing a pyridine arm (7, 8) with Na^+, K^+, Tl^+, and Ag^+ have been determined in absolute methanol at 25 °C by calorimetric titration. In each case, the complex stability has the sequence Na^+ < K^+ < Tl^+ ≪ Ag^+. The phenol-armed macrocycles exhibit selectivity of more than 4 orders of magnitude for Ag^+ over Na^+, K^+, and Tl^+. Attachment of a pendant phenol arm having various substituents to parent macrocycle 1 increases the binding abilities of the resulting ligands. Substituents on the para position of the phenol arm have an appreciable effect on cation-binding constants. Good Hammett correlations are found by plotting log K values vs σ_p for interactions of five phenol-armed macrocyclic ligands (2−6) with Na^+, K^+, and Tl^+. The complexation has been characterized by means of ^1H NMR and UV−visible spectroscopic, and X-ray crystallographic methods. The crystal data for Na^+−3:  formula, [Na(C_(23)H_(28.5)N_3O_5)](ClO_4)_(0.5); space group, P^1̄; a = 9.400(9) Å, b = 11.467(10) Å, c = 12.281(11) Å, α = 77.22(7)°, β = 87.73(7)°, γ = 86.39(7)°, V = 1288(2) Å^3, and Z = 2. The study indicates that the phenol OH group of 2−6 is capable of forming an intramolecular hydrogen bond with the macroring nitrogen atom and that the complexation in absolute methanol generally does not deprotonate these phenols. In the crystal structure of the Na^+−3 complex, the Na^+ is coordinated to all seven of the donor atoms of the ligand and two Na^+−3 complexes join together to form a dimer. The dimer contains an intermolecular hydrogen bond formed between the phenol hydrogen atom of one ligand and the phenolate group of a centrosymmetrically related ligand and two π−π stacking interactions between the electron-deficient pyridine ring of one molecule and the electron-rich phenol ring of the other

Retrieving landscape freeze/thaw state fromSoil Moisture Active Passive (SMAP) radar and radiometer measurements

Over one-third of the global land area undergoes a seasonal transition between predominantly frozen and non-frozen conditions each year, with the land surface freeze/thaw (FT) state a significant control on hydrological and biospheric processes over northern land areas and at high elevations. The NASA Soil Moisture Active Passive (SMAP) mission produced a daily landscape FT product at 3-km spatial resolution derived from ascending and descending orbits of SMAP high-resolution L-band (1.4 GHz) radar measurements. Following the failure of the SMAP radar in July 2015, coarser (36-km) footprint SMAP radiometer inputs were used to develop an alternative daily passive microwave freeze/thaw product. In this study, in situ observations are used to examine differences in the sensitivity of the 3-km radar versus the 36-km radiometer measurements to the landscape freeze/thaw state during the period of overlapping instrument operation. Assessment of the retrievals at high-latitude SMAP core validation sites showed excellent agreement with in situ flags, exceeding the 80% SMAP mission accuracy requirement. Similar performance was found for the radar and radiometer products using both air temperature and soil temperature derived FT reference flags. There was a tendency for SMAP thaw retrievals to lead the surface flags due to the influence of wet snow cover conditions on both the radar and radiometer signal. Comparison with other satellite derived FT products showed those derived from passive measurements (SMAP radiometer; Aquarius radiometer; Advanced Microwave Scanning Radiometer - 2) retrieved less frozen area than the active products (SMAP radar; Aquarius radar)

The Arabidopsis thaliana nucleotide sugar transporter GONST2 is a functional homolog of GONST1.

Glycosylinositolphosphorylceramides (GIPCs) are the predominant lipid in the outer leaflet of the plasma membrane. Characterized GIPC glycosylation mutants have severe or lethal plant phenotypes. However, the function of the glycosylation is unclear. Previously, we characterized Arabidopsis thaliana GONST1 and showed that it was a nucleotide sugar transporter which provides GDP-mannose for GIPC glycosylation. gonst1 has a severe growth phenotype, as well as a constitutive defense response. Here, we characterize a mutant in GONST1's closest homolog, GONST2. The gonst2-1 allele has a minor change to GIPC headgroup glycosylation. Like other reported GIPC glycosylation mutants, gonst1-1gonst2-1 has reduced cellulose, a cell wall polymer that is synthesized at the plasma membrane. The gonst2-1 allele has increased resistance to a biotrophic pathogen Golovinomyces orontii but not the necrotrophic pathogen Botrytis cinerea. Expression of GONST2 under the GONST1 promoter can rescue the gonst1 phenotype, indicating that GONST2 has a similar function to GONST1 in providing GDP-D-Man for GIPC mannosylation

Golgi-localized STELLO proteins regulate the assembly and trafficking of cellulose synthase complexes in Arabidopsis.

As the most abundant biopolymer on Earth, cellulose is a key structural component of the plant cell wall. Cellulose is produced at the plasma membrane by cellulose synthase (CesA) complexes (CSCs), which are assembled in the endomembrane system and trafficked to the plasma membrane. While several proteins that affect CesA activity have been identified, components that regulate CSC assembly and trafficking remain unknown. Here we show that STELLO1 and 2 are Golgi-localized proteins that can interact with CesAs and control cellulose quantity. In the absence of STELLO function, the spatial distribution within the Golgi, secretion and activity of the CSCs are impaired indicating a central role of the STELLO proteins in CSC assembly. Point mutations in the predicted catalytic domains of the STELLO proteins indicate that they are glycosyltransferases facing the Golgi lumen. Hence, we have uncovered proteins that regulate CSC assembly in the plant Golgi apparatus.The work presented in this paper was supported by grants from the BBSRC: BB/G016240/1 BBSRC Sustainable Energy Centre Cell Wall Sugars Programme (BSBEC) and the European Community’s Seventh Framework Programme SUNLIBB (FP7/2007-2013) under the grant agreement n° 251132 to PD. The UK 850 MHz solid-state NMR Facility was funded by EPSRC and BBSRC, as well as the University of Warwick including via part funding through Birmingham Science City Advanced Materials Projects 1 and 2 supported by Advantage West Midlands (AWM) and the European Regional Development Fund (ERDF); we thank Dinu Iuga for experimental assistance, and Chris Somerville for helpful discussions and suggesting the name STELLO. The authors acknowledge LNBio and LNLS for providing X-ray beam time (proposal GAR 15208), and the Sainsbury Laboratory Cambridge University for imaging facilities. TV was supported by an EMBO long-term fellowship (ALTF 711-2012) and by postdoctoral funding from the Philomathia Foundation. HEM was supported by an EMBO Long Term Fellowship (ALTF-1246-2013) and an NSERC Postdoctoral Fellowship (PDF-454454-2014). SP and YZ were supported by the Max-Planck Gesellschaft, and SP was also supported by a R@MAP Professor position at UoM. We thank the Biological Optical Microscopy Platform (BOMP) at University of Melbourne, and Tom Simmons and Rita Marques for assistance on sugar analyses.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms11656