The legacy effect of synthetic N fertiliser.

Unlabelled: Cumulative crop recovery of synthetic fertiliser nitrogen (N) over several cropping seasons (legacy effect) generally receives limited attention. The increment in crop N uptake after the first-season uptake from fertiliser can be expressed as a fraction (∆RE) of the annual N application rate. This study aims to quantify ∆RE using data from nine long-term experiments (LTEs).

Differentiation Drives Widespread Rewiring of the Neural Stem Cell Chaperone Network.

Neural stem and progenitor cells (NSPCs) are critical for continued cellular replacement in the adult brain. Lifelong maintenance of a functional NSPC pool necessitates stringent mechanisms to preserve a pristine proteome. We find that the NSPC chaperone network robustly maintains misfolded protein solubility and stress resilience through high levels of the ATP-dependent chaperonin TRiC/CCT.

Superresolution Fluorescence Imaging of Mutant Huntingtin Aggregation in Cells.

Fluorescence-based nanoscopy methods (also known as "superresolution" microscopy) have substantially expanded our options to examine the distributions of molecules inside cells with nanometer-scale resolution and molecular specificity. In the biophysical analysis of aggregation-prone misfolded proteins and peptides, this has enabled the visualization of distinct populations of aggregated species such as fibrillar assemblies within intact neuronal cells, well below previous limits of sensitivity and resolution. With the Huntington's disease protein, polyglutamine-expanded mutant huntingtin, as an example, we provide sample preparation and imaging protocols for superresolution microscopy down to the ~30 nm-level.

Delayed emergence of subdiffraction-sized mutant huntingtin fibrils following inclusion body formation.

Aberrant aggregation of improperly folded proteins is the hallmark of several human neurodegenerative disorders, including Huntington's Disease (HD) with autosomal-dominant inheritance. In HD, expansion of the CAG-repeat-encoded polyglutamine (polyQ) stretch beyond ~40 glutamines in huntingtin (Htt) and its N-terminal fragments leads to the formation of large (up to several μm) globular neuronal inclusion bodies (IBs) over time. We report direct observations of aggregating Htt exon 1 in living and fixed cells at enhanced spatial resolution by stimulated emission depletion (STED) microscopy and single-molecule super-resolution optical imaging.

The Copper Metabolism MURR1 domain protein 1 (COMMD1) modulates the aggregation of misfolded protein species in a client-specific manner.

The Copper Metabolism MURR1 domain protein 1 (COMMD1) is a protein involved in multiple cellular pathways, including copper homeostasis, NF-κB and hypoxia signalling. Acting as a scaffold protein, COMMD1 mediates the levels, stability and proteolysis of its substrates (e.g.

Sorting out the trash: the spatial nature of eukaryotic protein quality control.

Failure to maintain protein homeostasis is associated with aggregation and cell death, and underies a growing list of pathologies including neurodegenerative diseases, aging, and cancer. Misfolded proteins can be toxic and interfere with normal cellular functions, particularly during proteotoxic stress. Accordingly, molecular chaperones, the ubiquitin-proteasome system (UPS) and autophagy together promote refolding or clearance of misfolded proteins.

Spatial sequestration of misfolded proteins by a dynamic chaperone pathway enhances cellular fitness during stress.

The extensive links between proteotoxic stress, protein aggregation and pathologies ranging from ageing to neurodegeneration underscore the importance of understanding how cells manage protein misfolding. Using live-cell imaging, we determine the fate of stress-induced misfolded proteins from their initial appearance until their elimination. Upon denaturation, misfolded proteins are sequestered from the bulk cytoplasm into dynamic endoplasmic reticulum (ER)-associated puncta that move and coalesce into larger structures in an energy-dependent but cytoskeleton-independent manner.

Processing consequences of superfluous and missing prosodic breaks in auditory sentence comprehension.

This ERP study investigates whether a superfluous prosodic break (i.e., a prosodic break that does not coincide with a syntactic break) has more severe processing consequences during auditory sentence comprehension than a missing prosodic break (i.

Liver-specific Commd1 knockout mice are susceptible to hepatic copper accumulation.

Canine copper toxicosis is an autosomal recessive disorder characterized by hepatic copper accumulation resulting in liver fibrosis and eventually cirrhosis. We have identified COMMD1 as the gene underlying copper toxicosis in Bedlington terriers. Although recent studies suggest that COMMD1 regulates hepatic copper export via an interaction with the Wilson disease protein ATP7B, its importance in hepatic copper homeostasis is ill-defined.

The copper-transporting capacity of ATP7A mutants associated with Menkes disease is ameliorated by COMMD1 as a result of improved protein expression.

Menkes disease (MD) is an X-linked recessive disorder characterized by copper deficiency resulting in a diminished function of copper-dependent enzymes. Most MD patients die in early childhood, although mild forms of MD have also been described. A diversity of mutations in the gene encoding of the Golgi-resident copper-transporting P(1B)-type ATPase ATP7A underlies MD.

Pitch accents in context: how listeners process accentuation in referential communication.

We investigated whether listeners are sensitive to (mis)matching accentuation patterns with respect to contrasts in the linguistic and visual context, using Event-Related Potentials. We presented participants with displays of two pictures followed by a spoken reference to one of these pictures (e.g.

The role of prosodic breaks and pitch accents in grouping words during on-line sentence processing.

The present study addresses the question whether accentuation and prosodic phrasing can have a similar function, namely, to group words in a sentence together. Participants listened to locally ambiguous sentences containing object- and subject-control verbs while ERPs were measured. In Experiment 1, these sentences contained a prosodic break, which can create a certain syntactic grouping of words, or no prosodic break.

Cu,Zn superoxide dismutase maturation and activity are regulated by COMMD1.

The maturation and activation of the anti-oxidant Cu,Zn superoxide dismutase (SOD1) are highly regulated processes that require several post-translational modifications. The maturation of SOD1 is initiated by incorporation of zinc and copper ions followed by disulfide oxidation leading to the formation of enzymatically active homodimers. Our present data indicate that homodimer formation is a regulated final step in SOD1 maturation and implicate the recently characterized copper homeostasis protein COMMD1 in this process.

The interplay between prosody and syntax in sentence processing: the case of subject- and object-control verbs.

This study addresses the question whether prosodic information can affect the choice for a syntactic analysis in auditory sentence processing. We manipulated the prosody (in the form of a prosodic break; PB) of locally ambiguous Dutch sentences to favor one of two interpretations. The experimental items contained two different types of so-called control verbs (subject and object control) in the matrix clause and were syntactically disambiguated by a transitive or by an intransitive verb.

Nuclear-cytosolic transport of COMMD1 regulates NF-kappaB and HIF-1 activity.

Copper metabolism MURR1 domain1 (COMMD1) is a novel inhibitor of the transcription factors NF-kappaB and HIF-1, which play important roles in inflammation and tumor growth, respectively. In this study, we identified two highly conserved nuclear export signals (NESs) in COMMD1 and revealed that these NESs were essential and sufficient to induce maximal nuclear export of COMMD1. Inhibition of CRM1-mediated nuclear export by Leptomycin B resulted in nuclear accumulation of COMMD1.

Role of transition metals in the pathogenesis of amyotrophic lateral sclerosis.

ALS (amyotrophic lateral sclerosis) is a devastating progressive neurodegenerative disorder resulting in selective degeneration of motor neurons in brain and spinal cord and muscle atrophy. In approx. 2% of all cases, the disease is caused by a mutation in the Cu,Zn-superoxide dismutase (SOD1) gene.

Relevance of animal models for understanding mammalian copper homeostasis.

As a trace element, copper has a crucial role in mammalian metabolism, but it can be toxic in excess. The importance of a balanced copper homeostasis is illustrated by several copper-associated disorders in man, such as Menkes and Wilson disease, and in a wide variety of animal models (eg, mice, dogs, and sheep). Proteins involved in controlling copper metabolism have been well studied in yeast and in vitro.

Sentence processing in the visual and auditory modality: do comma and prosodic break have parallel functions?

Two Event-Related Potential (ERP) studies contrast the processing of locally ambiguous sentences in the visual and the auditory modality. These sentences are disambiguated by a lexical element. Before this element appears in a sentence, the sentence can also be disambiguated by a boundary marker: a comma in the visual modality, or a prosodic break in the auditory modality.

Discourse structure and relative clause processing.

Studies in several languages have shown that subject-relative clauses are easier to process than object-relative clauses. Mak, Vonk, and Schriefers (2006) have proposed the topichood hypothesis to account for the preference for subject-relative clauses. This hypothesis claims that the entity in the relative clause that is most topicworthy will be chosen as the subject.

Coherence-driven resolution of referential ambiguity: a computational model.

We present a computational model that provides a unified account of inference, coherence, and disambiguation. It simulates how the build-up of coherence in text leads to the knowledge-based resolution of referential ambiguity. Possible interpretations of an ambiguity are represented by centers of gravity in a high-dimensional space.

Spelling consistency affects reading in young Dutch readers with and without dyslexia.

Lexical-decision studies with experienced English and French readers have shown that visual-word identification is not only affected by pronunciation inconsistency of a word (i.e., multiple ways to pronounce a spelling body), but also by spelling inconsistency (i.

Discourse, syntax, and prosody: the brain reveals an immediate interaction.

Speech is structured into parts by syntactic and prosodic breaks. In locally syntactic ambiguous sentences, the detection of a syntactic break necessarily follows detection of a corresponding prosodic break, making an investigation of the immediate interplay of syntactic and prosodic information impossible when studying sentences in isolation. This problem can be solved, however, by embedding sentences in a discourse context that induces the expectation of either the presence or the absence of a syntactic break right at a prosodic break.

Processing the noun phrase versus sentence coordination ambiguity: thematic information does not completely eliminate processing difficulty.

When faced with the noun phrase (NP) versus sentence (S) coordination ambiguity as in, for example, The thief shot the jeweller and the cop ...

Predicting without modeling: a critique of Trabasso and Bartolone (2003).

T. Trabasso and J. Bartolone (2003) used a computational model of narrative text comprehension to account for empirical findings.

Constitutive expression of a murine interferon alpha gene in hamster cells and characterization of its protein product.

The coding part of a murine interferon alpha (MuIFN-alpha) gene was cloned into an expression plasmid containing the simian virus 40 early promoter and the rabbit beta-globin polyadenylation signal. This construct was transfected into Chinese hamster ovary cells, together with a plasmid containing the Ecogpt gene as a selection marker. Resulting colonies were assayed for constitutive interferon production and analysed for integration of MuIFN-alpha genes.