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2.
Chemistry ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31574177

RESUMO

Though alkali metal NacNac (ß-diketiminate) complexes have been utilised in synthesis as NacNac-transfer agents, studies of them in their own right with small molecules are exceptionally rare. Here, the lithium compound of the common 2,6-diisopropylphenyl-ß-methyldiketiminate [NacNac(Dipp, Me)] ligand is investigated with carbon dioxide and isocyanates. In all four cases reaction occurs at the backbone γ-C atom of the NacNac ligand, which redistributes electronically into a diimine. Insertion of CO2 gives an eight-atom carboxylate (Li2 O4 C2 ) ring at the γ-C site in a dimer. Insertion of tBuNCO gives a secondary amide at the γ-C site in a monomer with TMEDA chelating lithium. Double insertion of tBuNCO and (adventitious) oxygen gives a dimer with a (LiO)2 central core involving the latter source. Insertion of less bulky (iPrNCO) gives a dimer with dimerisation through the C=O bonds of the emergent secondary amide function.

3.
Nat Commun ; 10(1): 4451, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31575864

RESUMO

TCR-gene-transfer is an efficient strategy to produce therapeutic T cells of defined antigen specificity. However, there are substantial variations in the cell surface expression levels of human TCRs, which can impair the function of engineered T cells. Here we demonstrate that substitutions of 3 amino acid residues in the framework of the TCR variable domains consistently increase the expression of human TCRs on the surface of engineered T cells.The modified TCRs mediate enhanced T cell proliferation, cytokine production and cytotoxicity, while reducing the peptide concentration required for triggering effector function up to 3000-fold. Adoptive transfer experiments in mice show that modified TCRs control tumor growth more efficiently than wild-type TCRs. Our data indicate that simple variable domain modifications at a distance from the antigen-binding loops lead to increased TCR expression and improved effector function. This finding provides a generic platform to optimize the efficacy of TCR gene therapy in humans.

4.
Adv Mater ; 31(43): e1902407, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31512304

RESUMO

Molecular vibrations play a critical role in the charge transport properties of weakly van der Waals bonded organic semiconductors. To understand which specific phonon modes contribute most strongly to the electron-phonon coupling and ensuing thermal energetic disorder in some of the most widely studied high-mobility molecular semiconductors, state-of-the-art quantum mechanical simulations of the vibrational modes and the ensuing electron-phonon coupling constants are combined with experimental measurements of the low-frequency vibrations using inelastic neutron scattering and terahertz time-domain spectroscopy. In this way, the long-axis sliding motion is identified as a "killer" phonon mode, which in some molecules contributes more than 80% to the total thermal disorder. Based on this insight, a way to rationalize mobility trends between different materials and derive important molecular design guidelines for new high-mobility molecular semiconductors is suggested.

5.
Mol Ecol ; 28(19): 4422-4438, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31486145

RESUMO

Nearly all animal species have utilized photoperiod to cue seasonal behaviours and life history traits. We investigated photoperiod responses in keystone species, Daphnia magna, to identify molecular processes underlying ecologically important behaviours and traits using functional transcriptomic analyses. Daphnia magna were photoperiod-entrained immediately posthatch to a standard control photoperiod of 16 light/ 8 dark hours (16L:8D) relative to shorter (4L:20D, 8L:16D, 12L:12L) and longer (20L:4D) day length photoperiods. Short-day photoperiods induced significantly increased light-avoidance behaviours relative to controls. Correspondingly, significant differential transcript expression for genes involved in glutamate signalling was observed, a critical signalling pathway in arthropod light-avoidance behaviour. Additionally, period circadian protein and proteins coding F-box/LRR-repeat domains were differentially expressed which are recognized to establish circadian rhythms in arthropods. Indicators of metabolic rate increased in short-day photoperiods which corresponded with broadscale changes in transcriptional expression across system-level energy metabolism pathways. The most striking observations included significantly decreased neonate production at the shortest day length photoperiod (4L:20D) and significantly increased male production across short-day and equinox photoperiods (4L:20D, 8L:16D and 12L:12D). Transcriptional expression consistent with putative mechanisms of male production was observed including photoperiod-dependent expression of transformer-2 sex-determining protein and small nuclear ribonucleoprotein particles (snRNPs) which control splice variant expression for genes like transformer. Finally, increased transcriptional expression of glutamate has also been shown to induce male production in Daphnia pulex via photoperiod-sensitive mechanisms. Overall, photoperiod entrainment affected molecular pathways that underpin critical behavioural and life history traits in D. magna providing fundamental insights into biological responses to this primary environmental cue.

6.
Integr Environ Assess Manag ; 15(6): 1021-1028, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31393089

RESUMO

Although advanced materials (AdMs) are beneficial in many applications, questions remain as to whether they are more or less sustainable than the conventional materials that they may replace. Currently, there is no available tool to provide clarity to these questions. Traditional approaches for evaluating the sustainability of a chemical or material are usually not standardized, and as a result, the metrics used in sustainability measurements are subjective and often vary from assessor to assessor. Additionally, sustainability characterizations resulting from these approaches are typically presented qualitatively and are often vaguely drawn, making it difficult to confidently and transparently conclude that 1 material is more sustainable than another. This paper aims to address these gaps by enabling stakeholders involved in the production, use, or governance of AdMs to assess the sustainability of AdMs in a consistent, objective, and quantitative way using a multicriteria decision analysis (MCDA)-based model. The model proposed herein adapts a triple-bottom-line (TBL) framework from the Institution of Chemical Engineers (IChemE) and incorporates criteria weights identified through a stakeholder values assessment conducted by surveying AdM practitioners. Results from the stakeholder values assessment show that the perceived importance of the economic component of the TBL varies the most across stakeholders, and that practitioners providing responses from the perspective of a nongovernmental environmental advocacy group or a regulator of AdMs such as the United States Environmental Protection Agency were more likely to score and weigh economic indicators lower and environmental indicators higher compared to when responding from a business owner perspective. The resulting MCDA-based model allows stakeholders to assess the sustainability of an AdM or AdM-enabled product and compare it to product alternatives, predict how other stakeholders might score a product by identifying the extent to which components of the TBL are valued by other stakeholders, and identify which subcriteria contribute most to an improvement in a product's sustainability score. Integr Environ Assess Manag 2019;00:1-8. © 2019 SETAC.

7.
Chem Commun (Camb) ; 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31347619

RESUMO

The scandium Cp/COT hybrid sandwich compound [(η5-C5H5)Sc(η8-C8H8)] is resistant to metallation via conventional alkyllithium and lithium amide bases. In this work, clean, selective, stoichiometric and high-yielding mono- and dimetallation is accomplished using tandem trans-metal-trapping (TMT) involving LiTMP and iBu2AlTMP with deprotonation occurring selectively at the Cp and Cp/COT rings respectively, providing the first examples of selective metallation of a sandwich complex featuring a group 3 element.

8.
Angew Chem Int Ed Engl ; 58(35): 12291-12296, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31260154

RESUMO

Synthesized, isolated, and characterized by X-ray crystallography and NMR spectroscopic studies, lithium phosphidoaluminate iBu3 AlPPh2 Li(THF)3 has been tested as a catalyst for hydrophosphination of alkynes, alkenes, and carbodiimides. Based on the collective evidence of stoichiometric reactions, NMR monitoring studies, kinetic analysis, and DFT calculations, a mechanism involving deprotonation, alkyne insertion, and protonolysis is proposed for the [iBu3 AlHLi]2 aluminate catalyzed hydrophosphination of alkynes with diphenylphosphine. This study enhances further the development of transition-metal-free, atom-economical homogeneous catalysis using common sustainable main-group metals.

9.
Nat Commun ; 10(1): 3106, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31308374

RESUMO

Immune responses need to be controlled tightly to prevent autoimmune diseases, yet underlying molecular mechanisms remain partially understood. Here, we identify biallelic mutations in three patients from two unrelated families in differentially expressed in FDCP6 homolog (DEF6) as the molecular cause of an inborn error of immunity with systemic autoimmunity. Patient T cells exhibit impaired regulation of CTLA-4 surface trafficking associated with reduced functional CTLA-4 availability, which is replicated in DEF6-knockout Jurkat cells. Mechanistically, we identify the small GTPase RAB11 as an interactor of the guanine nucleotide exchange factor DEF6, and find disrupted binding of mutant DEF6 to RAB11 as well as reduced RAB11+CTLA-4+ vesicles in DEF6-mutated cells. One of the patients has been treated with CTLA-4-Ig and achieved sustained remission. Collectively, we uncover DEF6 as player in immune homeostasis ensuring availability of the checkpoint protein CTLA-4 at T-cell surface, identifying a potential target for autoimmune and/or cancer therapy.

10.
Environ Toxicol Chem ; 38(10): 2326-2336, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31233239

RESUMO

Activated carbon-amended bed sediments reduced total polychlorinated biphenyl (PCB) accumulation in 3 functionally different marine species, sandworms (Alitta virens), hard clams (Mercenaria mercenaria), and sheepshead minnows (Cyprinodon variegatus), during both clean and contaminated ongoing sediment inputs. Mesocosm experiments were conducted for 90 d to evaluate native, field-aged bed sediment PCBs, and ongoing input PCBs added 3 times a week. Simulated in situ remediation applied an activated carbon dose equal to the native organic carbon content that was premixed into the bed sediment for 1 mo. The highest bioaccumulation of native PCBs was in worms that remained in and directly ingested the sediment, whereas the highest bioaccumulation of the input PCBs was in fish that were exposed to the water column. When periodic PCB-contaminated sediment inputs were introduced to the water column, the activated carbon remedy had minimal effect on the input PCBs, whereas the native bed PCBs still dominated bioaccumulation in the control (no activated carbon). Therefore, remediation of only the local bedded sediment in environmental systems with ongoing contaminant inputs may have lower efficacy for fish and other pelagic and epibenthic organisms. While ongoing inputs continue to obscure remedial outcomes at contaminated sediment sites, the present study showed clear effectiveness of activated carbon amendment remediation on native PCBs despite these inputs but no remediation effectiveness for the input-associated PCBs (at least within the present study duration). Environ Toxicol Chem 2019;38:2326-2336. Published 2019 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

11.
Angew Chem Int Ed Engl ; 58(37): 12898-12902, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31243862

RESUMO

A wide range of polyfunctional diaryl- and diheteroarylzinc species were prepared in toluene within 10 min to 5 h through an I/Zn or Br/Zn exchange reaction using bimetallic reagents of the general formula R'2 Zn⋅2 LiOR (R'=sBu, tBu, pTol). Highly sensitive functional groups, such as a triazine, a ketone, an aldehyde, or a nitro group, were tolerated in these exchange reactions, enabling the synthesis of a plethora of functionalized (hetero)arenes after quenching with various electrophiles. Insight into the constitution and reactivity of these bimetallic mixtures revealed the formation of highly active lithium diorganodialkoxyzincates of type [R'2 Zn(OR)2 Li2 ].

12.
Sci Immunol ; 4(35)2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31152091

RESUMO

CTLA-4 is a critical negative regulator of the immune system and a major target for immunotherapy. However, precisely how it functions in vivo to maintain immune homeostasis is not clear. As a highly endocytic molecule, CTLA-4 can capture costimulatory ligands from opposing cells by a process of transendocytosis (TE). By restricting costimulatory ligand expression in this manner, CTLA-4 controls the CD28-dependent activation of T cells. Regulatory T cells (Tregs) constitutively express CTLA-4 at high levels and, in its absence, show defects in TE and suppressive function. Activated conventional T cells (Tconv) are also capable of CTLA-4-dependent TE; however, the relative use of this mechanism by Tregs and Tconv in vivo remains unclear. Here, we set out to characterize both the perpetrators and cellular targets of CTLA-4 TE in vivo. We found that Tregs showed constitutive cell surface recruitment of CTLA-4 ex vivo and performed TE rapidly after TCR stimulation. Tregs outperformed activated Tconv at TE in vivo, and expression of ICOS marked Tregs with this capability. Using TCR transgenic Tregs that recognize a protein expressed in the pancreas, we showed that the presentation of tissue-derived self-antigen could trigger Tregs to capture costimulatory ligands in vivo. Last, we identified migratory dendritic cells (DCs) as the major target for Treg-based CTLA-4-dependent regulation in the steady state. These data support a model in which CTLA-4 expressed on Tregs dynamically regulates the phenotype of DCs trafficking to lymph nodes from peripheral tissues in an antigen-dependent manner.

13.
Acta Crystallogr C Struct Chem ; 75(Pt 6): 633-642, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31166914

RESUMO

The structures of seven divalent metal cation compounds of Ponceau Xylidine {PX; systematic name of dication: 4-[2-(3,4-dimethylphenyl)hydrazin-1-ylidene]-3-oxo-3,4-dihydronaphthalene-2,7-disulfonate}, also known as Acid Red 26, CI 16150, and of five divalent metal cation compounds of Crystal Scarlet {CS; systematic name of dication: 8-[2-(naphthalen-1-yl)hydrazin-1-ylidene]-7-oxo-7,8-dihydronaphthalene-1,3-disulfonate}, also known as Acid Red 44, CI 16250, are presented. These are hexaaquamagnesium(II) PX dimethylformamide (DMF) monosolvate, [Mg(H2O)6](C18H14N2O7S2)·C3H7NO, (I); heptaaquacalcium(II) PX 2.5-hydrate, [Ca(H2O)7](C18H14N2O7S2)·2.5H2O, (II); catena-poly[aqua(µ-DMF)tris(DMF)bis(µ3-PX)distrontium(II)], [Sr(C18H14N2O7S2)(C3H7NO)2(H2O)0.5]n, (III); the transition-metal series hexaaquametal(II) PX DMF monosolvate, [M(H2O)6](C18H14N2O7S2)·C3H7NO, where M (metal) = Co, (IV), Ni, (V), Cu, (VI), and Zn, (VII); heptaaquacalcium(II) CS monohydrate, [Ca(H2O)7](C20H13N2O7S2)·H2O, (VIII); octaaquastrontium(II) CS monohydrate, [Sr(H2O)8](C20H13N2O7S2)·H2O, (IX); catena-poly[[triaqua(DMF)barium(II)]-µ-CS], [Ba(C20H13N2O7S2)(C3H7NO)(H2O)3]n, (X); tetrakis(DMF)(CS)copper(II) monohydrate, [Cu(C20H13N2O7S2)(C3H7NO)4]·H2O, (XI); and catena-poly[[[aquatris(DMF)zinc(III)]-µ-CS] diethyl ether hemisolvate], {[Zn(C20H13N2O7S2)(C3H7NO)3(H2O)]·0.5C4H10O}n, (XII). In all cases, the structures obtained were solvates with dimethylformamide (DMF) and/or water present. The disulfonated naphthalene-based azo anions adopt hydrazone tautomeric forms. The structures of the Mg salt and of four transition-metal forms (M = Co, Ni, Cu and Zn) of PX are found to form an isostructural series. All have solvent-separated ion-pair (SSIP) type structures and the formula [M(H2O)6][PX]·DMF. The Ca salt of PX also has an SSIP structure, but has a higher hydration state, [Ca(H2O)7][PX]·2.5H2O. In contrast, the Sr salt of PX, [Sr(PX)(DMF)2(H2O)0.5]n forms a one-dimensional coordination polymer. Both the Ca and the Sr salt of CS have an SSIP structure, namely [Ca(H2O)7][CS]·H2O and [Sr(H2O)8][CS]·H2O, whilst the heavier Ba analogue, [Ba(CS)(DMF)(H2O)3]n, forms a one-dimensional coordination polymer. Unlike PX, two CS structures containing transition metals are found to be coordination complexes, [Cu(CS)(DMF)4]·H2O and {[Zn(CS)(DMF)3(H2O)]·0.5Et2O}n. This suggests that CS is a better ligand than PX for transition metals. The Cu complex forms discrete molecules with Cu in a square-pyramidal environment, whilst the Zn species is a one-dimensional coordination polymer based on octahedral Zn centres.

14.
Dalton Trans ; 48(23): 8122-8130, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31045196

RESUMO

Main group bimetallic complexes, while being increasingly used in stoichiometric deprotonation and metal-halogen exchange reactions, have not yet made a significant impact in catalytic applications. This paper explores the ability of alkali metal magnesiates to catalyse the intermolecular hydroamination of alkynes and alkenes using sytrene and diphenylacetylene as principle setting model substrates. By systematically studying the role of the alkali-metal and the formulation of the heterobimetallic precatalyst, this study establishes higher order potassium magnesiate [(PMDETA)2K2Mg(CH2SiMe3)4] (7) as a highly effective system capable of catalysing hydroamination of styrene and diphenylacetylene with several amines while operating at room temperature. This high reactivity contrasts with the complete lack of catalytic ability of neutral Mg(CH2SiMe3)2, even when harsher reaction conditions are employed (24 h, 80 °C). A pronounced alkali metal effect is also uncovered proving that the alkali metal (Li, Na, or K) is not a mere spectating counterion. Through stoichiometric reactions, and structural and spectroscopic (DOSY NMR) investigations we shed some light on the potential reaction pathway as well as the constitution of key intermediates. This work suggests that the enhanced catalytic activity of 7 can be rationalised in terms of the superior nucleophilic power of the formally dianionic magnesiate {Mg(NR2)4}2- generated in situ during the hydroamination process, along with the ability of potassium to engage in π-interactions with the unsaturated organic substrate, enhancing its susceptibility towards a nucleophilic attack by the amide anion.

15.
Risk Anal ; 39(8): 1783-1795, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30908695

RESUMO

Novel materials with unique or enhanced properties relative to conventional materials are being developed at an increasing rate. These materials are often referred to as advanced materials (AdMs) and they enable technological innovations that can benefit society. Despite their benefits, however, the unique characteristics of many AdMs, including many nanomaterials, are poorly understood and may pose environmental safety and occupational health (ESOH) risks that are not readily determined by traditional risk assessment methods. To assess these risks while keeping up with the pace of development, technology developers and risk assessors frequently employ risk-screening methods that depend on a clear definition for the materials that are to be assessed (e.g., engineered nanomaterial) as well as a method for binning materials into categories for ESOH risk prioritization. The term advanced material lacks a consensus definition and associated categorization or grouping system for risk screening. In this study, we aim to establish a practitioner-driven definition for AdMs and a practitioner-validated framework for categorizing AdMs into conceptual groupings based on material characteristics. Results from multiple workshops and interviews with practitioners provide consistent differentiation between AdMs and conventional materials, offer functional nomenclature for application science, and provide utility for future ESOH risk assessment prioritization. The definition and categorization framework established here serve as a first step in determining if and when there is a need for specific ESOH and regulatory screening for an AdM as well as the type and extent of risk-related information that should be collected or generated for AdMs and AdM-enabled technologies.

16.
J Phys Chem A ; 123(14): 3185-3193, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30896170

RESUMO

Small organic conjugated systems displaying one-dimensional stacking motifs in the solid state that facilitate charge propagation are highly desirable. Noncovalent interactions, although weak, can synergistically provide those supramolecular architectures with large binding energies and associated thermal integrity. Amongst the plethora of intermolecular interactions contributing toward the overall lattice energy and stability of the charge-propagation supramolecular architectures, H-bonding interactions are well-known to play a pivotal role. Despite their critical contribution, the positions of hydrogen atoms in X-ray crystallographic data are parameterized, which can lead to significant changes in the computed intermolecular interactions. Herein, we report for the first time an analysis of the role that the optimization of the H atoms in X-ray structures has in the computed intermolecular interactions energies in diketopyrrolopyrroles (DPPs). A large dataset comprising 94 dimer pairs from 19 different DPP-based systems, including three pigment analogues, was employed. In total, more than 1400 H-X chemical bonds were considered and optimized using the M06-2X density functional at the 6-311G(d) level. Intermolecular interactions were computed for the H-optimized geometries and compared to those from nonoptimized counterparts. We report that in 35 out of the 94 dimer pairs investigated (37%), the computed intermolecular interactions were at least 2.5 kJ mol-1 larger on progression to the H-optimized geometries. In turn, lower computed values were yielded upon H-optimization computed for 8 out of the 94 dimer pairs (8%), with one case exhibiting a difference greater than 2.5 kJ mol-1. In line with the negligible changes to electron density and wavefunction overlap, the computed changes on the transfer integrals for the hole and electron were always lower than 1 kJ mol-1. The observed changes to computed intermolecular interactions can play a critical role in determining the thermal integrity of the supramolecular structures and charge propagation channels, and thus in the absence of neutron diffraction data, H atoms should be optimized prior to computation. We envisage that the results herein will be of interest to the extensive scientific community devoted to the understanding of intermolecular interactions in organic conjugated systems and the realization of superior charge-transfer-mediating materials, and given the plethora of intermolecular interactions investigated, the results are not solely limited to DPP-based architectures.

17.
Chem Commun (Camb) ; 55(30): 4339-4342, 2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30911746

RESUMO

A series of new Mg(ii) amides featuring a bulky ß-diketiminate backstop ligand, has been synthesised. These complexes are demonstrated to be excellent sources of nucleophilic amides that can participate in rapid C-F activation of several fluoroarenes at room temperature or using microwave assistance, leading to the installment of synthetically important C-N bonds via nucleophilic substitution.

18.
Acta Crystallogr C Struct Chem ; 75(Pt 3): 359-371, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30833533

RESUMO

An efficient approach for the regioselective synthesis of (5-amino-3-methylsulfanyl-1H-1,2,4-triazol-1-yl)(2-fluorophenyl)methanone, C10H9FN4OS, (3), from the N-acylation of 3-amino-5-methylsulfanyl-1H-1,2,4-triazole, (1), with 2-fluorobenzoyl chloride has been developed. Heterocyclic amide (3) was used successfully as a strategic intermediate for the preparation of 2-fluoro-N-(3-methylsulfanyl-1H-1,2,4-triazol-5-yl)benzamide, C10H9FN4OS, (4), through a microwave-assisted Fries rearrangement under catalyst- and solvent-free conditions. Theoretical studies of the prototropy process of (1) and the Fries rearrangement of (3) to provide (4), involving the formation of an intimate ion pair as the key step, were carried out by density functional theory (DFT) calculations. The crystallographic analysis of the intermolecular interactions and the energy frameworks based on the effects of the different molecular conformations of (3) and (4) are described.

19.
Kidney Int ; 95(4): 914-928, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30773290

RESUMO

Approximately 500 monogenic causes of chronic kidney disease (CKD) have been identified, mainly in pediatric populations. The frequency of monogenic causes among adults with CKD has been less extensively studied. To determine the likelihood of detecting monogenic causes of CKD in adults presenting to nephrology services in Ireland, we conducted whole exome sequencing (WES) in a multi-centre cohort of 114 families including 138 affected individuals with CKD. Affected adults were recruited from 78 families with a positive family history, 16 families with extra-renal features, and 20 families with neither a family history nor extra-renal features. We detected a pathogenic mutation in a known CKD gene in 42 of 114 families (37%). A monogenic cause was identified in 36% of affected families with a positive family history of CKD, 69% of those with extra-renal features, and only 15% of those without a family history or extra-renal features. There was no difference in the rate of genetic diagnosis in individuals with childhood versus adult onset CKD. Among the 42 families in whom a monogenic cause was identified, WES confirmed the clinical diagnosis in 17 (40%), corrected the clinical diagnosis in 9 (22%), and established a diagnosis for the first time in 16 families referred with CKD of unknown etiology (38%). In this multi-centre study of adults with CKD, a molecular genetic diagnosis was established in over one-third of families. In the evolving era of precision medicine, WES may be an important tool to identify the cause of CKD in adults.

20.
Environ Toxicol Chem ; 38(6): 1221-1230, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30790342

RESUMO

There are limited acute toxicity test methods for native North American marine species that are considered zooplankton for their entire life cycle. Examples of standardized marine zooplankton methods include mussel, bivalve, and echinoderm development tests that use a relatively short-lived planktonic larval stage, chronic life-cycle toxicity tests using epibenthic copepods, and a 24-h Acartia tonsa copepod test method. The objectives of the present study were to: 1) develop and evaluate a novel, 48-h acute toxicity test method using the marine North American copepod Pseudodiaptomus pelagicus that is planktonic for its entire life cycle, and 2) determine the sensitivity of P. pelagicus relative to commonly tested marine toxicity test species. The average (±1 standard deviation) median lethal concentrations (LC50s) for copper (Cu), phenanthrene, and un-ionized ammonia were 32 ± 15 µg/L, 161 ± 51 µg/L, and 1.08 ± 0.30 mg NH3 /L, respectively. These results placed P. pelagicus on the more sensitive end of Cu and phenanthrene species sensitivity distributions. The copepod was less sensitive to un-ionized ammonia than commonly tested marine species. This finding suggests that the acute P. pelagicus test method will allow a focus on assessing the impacts of persistent contaminants of concern with less confounding impact from naturally occurring ammonia released to the water from sources such as suspended sediments. Environ Toxicol Chem 2019;38:1221-1230. Published 2019 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

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