Circadian rhythms are physiological and behavioural cycles generated by an endogenous biological clock, the suprachiasmatic nucleus. The circadian system influences the majority of physiological processes, including sleep-wake homeostasis. Impaired sleep and alertness are common symptoms of neurodegenerative disorders, and circadian dysfunction might exacerbate the disease process. The pathophysio

The complexity of the human brain derives from the intricate interplay of molecular instructions during development. Here we systematically investigated gene expression changes in the prenatal human striatum and cerebral cortex during development from post-conception weeks 2 to 20. We identified tissue-specific gene coexpression networks, differentially expressed genes and a minimal set of bimodal

BACKGROUND: There is currently little evidence regarding the selection of patients for clinical trials in Parkinson's Disease (PD), especially those involving experimental therapies delivered using invasive techniques.OBJECTIVE: Understanding which patients are recruited will increase awareness of issues regarding parity of access to clinical trials and have an impact on the wider applicability of

Cognitive impairment is common in Parkinson's disease (PD), and many patients will eventually develop a dementia, which has a devastating impact on the patient and their family. As such, there has been much interest in identifying a prodromal state to inform prognosis and facilitate earlier management, similar to the concept of 'MCI' in the Alzheimer's field. However, grouping the early cognitive

The endogenous reparative capacity of the adult human brain is low, and chronic neurodegenerative disorders of the central nervous system represent one of the greatest areas of unmet clinical need in the developing world. Novel therapeutic strategies to treat them include: (i) growth factor delivery to boost endogenous repair and (ii) replacement cell therapy, including replacing dopaminergic neur

Parkinson's disease is associated with multiple cognitive impairments and increased risk of dementia, but the extent of these deficits varies widely among patients. The ICICLE-PD study was established to define the characteristics and prevalence of cognitive change soon after diagnosis, in a representative cohort of patients, using a multimodal approach. Specifically, we tested the 'Dual Syndrome'

Noradrenergic dysfunction may play a significant role in cognition in Parkinson's disease due to the early degeneration of the locus coeruleus. Converging evidence from patient and animal studies points to the role of noradrenaline in dopaminergically insensitive aspects of the parkinsonian dysexecutive syndrome, yet the direct effects of noradrenergic enhancement have not to date been addressed.

OBJECTIVE: Huntington disease (HD) is caused by a genetically encoded pathological protein (mutant huntingtin [mHtt]), which is thought to exert its effects in a cell-autonomous manner. Here, we tested the hypothesis that mHtt is capable of spreading within cerebral tissue by examining genetically unrelated fetal neural allografts within the brains of patients with advancing HD.METHODS: The presen

SynopsisOptimized structures describing key features of the potential energy surface for water exchange at three planar d8 centers have been calculated using ab initio density functional theory. The local density approximation (LDA), including relativistic corrections for Pt, gives good agreement with the available experimental ground state structural data. LDA binding energies together with expli

SynopsisVarious protolytic species of thiols RSH (thioglycolic acid, l-cysteine, dl-penicillamine, and glutathione) in rapid equilibria with each other reduce trans-[Pt(CN)4Cl2]2- in parallel, halide-bridged electron transfer reactions. A linear Brønsted correlation between the reactivity of the thiolate anions RS- and their basicity is observed. The mechanism derived might be used as a model for

SynopsisReduction of gold(III) complexes by thiocyanate takes place via rapid substitutions at gold(III), followed by intramolecular, slower reductive elimination through attack by outer-sphere thiocyanate. A transition state with an S−S interaction between attacking and coordinated thiocyanate is suggested for the redox process.AbstractAbstract ImageKinetics for reactions between thiocyanate and SynopsisReduction of gold(III) complexes by thiocyanate takes place via rapid substitutions at gold(III), followed by intramolecular, slower reductive elimination through attack by outer-sphere thiocyanate. A transition state with an S−S interaction between attacking and coordinated thiocyanate is suggested for the redox process.AbstractAbstract ImageKinetics for reactions between thiocyanate and

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SynopsisReversible formation and proton-assisted aquation of 1:1 monodentate carboxylate complexes of palladium(II) takes place via a transition state stabilized by hydrogen bonding in an activation process strongly dominated by bond making. Volume profiles have been established through high-pressure kinetic measurements.AbstractAbstract ImageKinetics and equilibria for reversible formation of 1:1SynopsisReversible formation and proton-assisted aquation of 1:1 monodentate carboxylate complexes of palladium(II) takes place via a transition state stabilized by hydrogen bonding in an activation process strongly dominated by bond making. Volume profiles have been established through high-pressure kinetic measurements.AbstractKinetics and equilibria for reversible formation of 1:1 monodentate c

Autoxidation of SO2(aq) in the presence of manganese(II) is one of the important pathways for sulfuric acid formation in atmospheric clouds and fogs. Recent experimental results indicating that the catalyzed reaction takes place via a complex free-radical mechanism are discussed. Previous literature is reviewed in the light of this mechanism. Under atmospheric conditions of low total concentrationAutoxidation of SO2(aq) in the presence of manganese(II) is one of the important pathways for sulfuric acid formation in atmospheric clouds and fogs. Recent experimental results indicating that the catalyzed reaction takes place via a complex free-radical mechanism are discussed. Previous literature is reviewed in the light of this mechanism. Under atmospheric conditions of low total concentration

Reduction of [AuCl4]- and trans-[Au(CN)2X2]- (X = Cl, Br) by sulfur(IV) as SO2.nH2O, HSO3-, and SO3(2-) has been studied at 25-degrees-C in aqueous solution with ionic strength 1.0 M and 0 < pH < 2.3 by use of stopped-flow spectrophotometry. Redox takes place directly without initial substitution at the gold(III) centers with stoichiometry Au(III):S(IV) = 1:1 and with Au(I) complexes and HSO4- as

This paper reports the results of a production experiment that explores the prosodic realization of focus in Hungarian, a language that is characterized by obligatory syntactic focus marking. Our study investigates narrow focus in sentences in which focus is unambiguously marked by syntactic means, comparing it to broad focus sentences. Potential independent effects of the salience (textual givenn

The Swedish National Innovation Council (NIC) was created by the Prime Minister (Stefan Löfven) in February 2015, and it has now been operating for 18 months. It is personally chaired by the Prime Minister, which is unusual for such councils in other countries. Another atypical characteristic of the Swedish NIC is its dominant and wide focus on innovation rather than on research (for which there i