The contribution of preclinical magnetic resonance imaging and spectroscopy to Huntington's disease.

Huntington's disease is an inherited disorder characterized by psychiatric, cognitive, and motor symptoms due to degeneration of medium spiny neurons in the striatum. A prodromal phase precedes the onset, lasting decades. Current biomarkers include clinical score and striatal atrophy using Magnetic Resonance Imaging (MRI).

Longitudinal MRI and 1H-MRS study of SCA7 mouse forebrain reveals progressive multiregional atrophy and early brain metabolite changes indicating early neuronal and glial dysfunction.

SpinoCerebellar Ataxia type 7 (SCA7) is an inherited disorder caused by CAG triplet repeats encoding polyglutamine expansion in the ATXN7 protein, which is part of the transcriptional coactivator complex SAGA. The mutation primarily causes neurodegeneration in the cerebellum and retina, as well as several forebrain structures. The SCA7140Q/5Q knock-in mouse model recapitulates key disease features, including loss of vision and motor performance.

Antisense oligonucleotide-mediated disruption of HTT caspase-6 cleavage site ameliorates the phenotype of YAC128 Huntington disease mice.

In Huntington disease, cellular toxicity is particularly caused by toxic protein fragments generated from the mutant huntingtin (HTT) protein. By modifying the HTT protein, we aim to reduce proteolytic cleavage and ameliorate the consequences of mutant HTT without lowering total HTT levels. To that end, we use an antisense oligonucleotide (AON) that targets HTT pre-mRNA and induces partial skipping of exon 12, which contains the critical caspase-6 cleavage site.

Long term worsening of amyloid pathology, cerebral function, and cognition after a single inoculation of beta-amyloid seeds with Osaka mutation.

Alzheimer's disease (AD) is characterized by intracerebral deposition of abnormal proteinaceous assemblies made of amyloid-β (Aß) peptides or tau proteins. These peptides and proteins induce synaptic dysfunctions that are strongly correlated with cognitive decline. Intracerebral infusion of well-defined Aβ seeds from non-mutated Aβ or Aβ peptides can increase Aβ depositions several months after the infusion.

Longitudinal multimodal MRI characterization of a knock-in mouse model of Huntington's disease reveals early gray and white matter alterations.

Pathogenesis of the inherited neurodegenerative disorder Huntington's disease (HD) is progressive with a long presymptomatic phase in which subtle changes occur up to 15 years before the onset of symptoms. Thus, there is a need for early, functional biomarker to better understand disease progression and to evaluate treatment efficacy far from onset. Recent studies have shown that white matter may be affected early in mutant HTT gene carriers.

Broad Influence of Mutant Ataxin-3 on the Proteome of the Adult Brain, Young Neurons, and Axons Reveals Central Molecular Processes and Biomarkers in SCA3/MJD Using Knock-In Mouse Model.

Spinocerebellar ataxia type 3 (SCA3/MJD) is caused by CAG expansion mutation resulting in a long polyQ domain in mutant ataxin-3. The mutant protein is a special type of protease, deubiquitinase, which may indicate its prominent impact on the regulation of cellular proteins levels and activity. Yet, the global model picture of SCA3 disease progression on the protein level, molecular pathways in the brain, and neurons, is largely unknown.

Fluid Dynamics of the Open Port Interface for High-Speed Nanoliter Volume Sampling Mass Spectrometry.

The open port interface (OPI) coupled to an atmospheric pressure ion source is used to capture, dilute, focus, and transport nanoliter volume sample droplets for high-speed mass spectrometric analysis. For typical applications, the system has been optimized to achieve 1 Hz nanoliter volume sample transfer rates while simultaneously diluting the sample >1000-fold to minimize sample matrix-induced ionization suppression. Geometric, flow, and dispensing alterations to the system presented here demonstrate that sample transfer rates for the OPI of at least 15 Hz are possible.

Zero Echo Time O-MRI Reveals Decreased Cerebral Metabolic Rate of Oxygen Consumption in a Murine Model of Amyloidosis.

The cerebral metabolic rate of oxygen consumption (CMRO) is a key metric to investigate the mechanisms involved in neurodegeneration in animal models and evaluate potential new therapies. CMRO can be measured by direct O magnetic resonance imaging (O-MRI) of HO signal changes during inhalation of O-labeled oxygen gas. In this study, we built a simple gas distribution system and used 3D zero echo time (ZTE-)MRI at 11.

Monitoring mechanical stimulation for optimal tendon tissue engineering: A mechanical and biological multiscale study.

To understand the effect of mechanical stimulation on cell response, bone marrow stromal cells were cultured on electrospun scaffolds under two distinct mechanical conditions (static and dynamic). Comparison between initial and final mechanical and biological properties of the cell-constructs were conducted over 14 days for both culturing conditions. As a result, mechanically stimulated constructs, in contrast to their static counterparts, showed evident mechanical-induced cell orientation, an effective aligned collagen and tenomodulin extracellular matrix.

Simulating age-related limitations among students and health professionals: a scoping review.

The use of simulation in health training has increased significantly in recent years. In geriatrics/gerontology, the simulation of age-related limitations enables users to experience the functional and sensory limitations that older people live with. The objective of this scoping review is to identify and describe studies exploring the effects of age-simulation on students and health professionals.

[Aging-simulation experience among students and health professionals: a scoping review].

Unlabelled: The use of simulation in health training increased significantly in recent years. In geriatrics/gerontology, the aging-simulation experience allows to feel the functional and sensory limitations lived by older persons.

Objective: The objective of this scoping review is to identify and describe studies exploring the effects of the aging-simulation experience on students and health professionals.

Conformational transitions of the serotonin 5-HT receptor.

The serotonin 5-HT receptor is a pentameric ligand-gated ion channel (pLGIC). It belongs to a large family of receptors that function as allosteric signal transducers across the plasma membrane; upon binding of neurotransmitter molecules to extracellular sites, the receptors undergo complex conformational transitions that result in transient opening of a pore permeable to ions. 5-HT receptors are therapeutic targets for emesis and nausea, irritable bowel syndrome and depression.

Estimation of water quality by UV/Vis spectrometry in the framework of treated wastewater reuse.

The aim of this study is to investigate the potential of ultraviolet/visible (UV/Vis) spectrometry as a complementary method for routine monitoring of reclaimed water production. Robustness of the models and compliance of their sensitivity with current quality limits are investigated. The following indicators are studied: total suspended solids (TSS), turbidity, chemical oxygen demand (COD) and nitrate.

Bdf1 Bromodomains Are Essential for Meiosis and the Expression of Meiotic-Specific Genes.

Bromodomain and Extra-terminal motif (BET) proteins play a central role in transcription regulation and chromatin signalling pathways. They are present in unicellular eukaryotes and in this study, the role of the BET protein Bdf1 has been explored in Saccharomyces cerevisiae. Mutation of Bdf1 bromodomains revealed defects on both the formation of spores and the meiotic progression, blocking cells at the exit from prophase, before the first meiotic division.

How much does nasal cavity morphology matter? Patterns and rates of olfactory airflow in phyllostomid bats.

The morphology of the nasal cavity in mammals with a good sense of smell includes features that are thought to improve olfactory airflow, such as a dorsal conduit that delivers odours quickly to the olfactory mucosa, an enlarged olfactory recess at the back of the airway, and a clear separation of the olfactory and respiratory regions of the nose. The link between these features and having a good sense of smell has been established by functional examinations of a handful of distantly related mammalian species. In this paper, we provide the first detailed examination of olfactory airflow in a group of closely related species that nevertheless vary in their sense of smell.

The role of the olfactory recess in olfactory airflow.

The olfactory recess - a blind pocket at the back of the nasal airway - is thought to play an important role in mammalian olfaction by sequestering air outside of the main airstream, thus giving odorants time to re-circulate. Several studies have shown that species with large olfactory recesses tend to have a well-developed sense of smell. However, no study has investigated how the size of the olfactory recess relates to air circulation near the olfactory epithelium.

Mmi1 RNA surveillance machinery directs RNAi complex RITS to specific meiotic genes in fission yeast.

RNA interference (RNAi) silences gene expression by acting both at the transcriptional and post-transcriptional levels in a broad range of eukaryotes. In the fission yeast Schizosaccharomyces pombe the RNA-Induced Transcriptional Silencing (RITS) RNAi complex mediates heterochromatin formation at non-coding and repetitive DNA. However, the targeting and role of RITS at other genomic regions, including protein-coding genes, remain unknown.

RNAi-mediated immunity provides strong protection against the negative-strand RNA vesicular stomatitis virus in Drosophila.

Activation of innate antiviral responses in multicellular organisms relies on the recognition of structural differences between viral and cellular RNAs. Double-stranded (ds)RNA, produced during viral replication, is a well-known activator of antiviral defenses and triggers interferon production in vertebrates and RNAi in invertebrates and plants. Previous work in mammalian cells indicates that negative-strand RNA viruses do not appear to generate dsRNA, and that activation of innate immunity is triggered by the recognition of the uncapped 5' ends of viral RNA.

Biological activity of the Agrobacterium rhizogenes-derived trolC gene of Nicotiana tabacum and its functional relation to other plast genes.

Agrobacterium rhizogenes induces hairy roots through the activity of three essential T-DNA genes, rolA, rolB, and rolC, whereas the orf13 gene acts as an accessory root-inducing gene. rolB, rolC, and orf13 belong to the highly diverged plast gene family with remotely related representatives in the endomycorrhizal basidiomycete Laccaria bicolor. Nicotiana glauca and N.

Post-transcriptional regulation of miR-27 in murine cytomegalovirus infection.

In mammals, microRNAs (miRNAs) can play diverse roles in viral infection through their capacity to regulate both host and viral genes. Recent reports have demonstrated that specific miRNAs change in expression level upon infection and can impact viral production and infectivity. It is clear that miRNAs are an integral component of viral-host interactions, and it is likely that both host and virus contain mechanisms to regulate miRNA expression and/or activity.

Low-pressure membrane integrity tests for drinking water treatment: A review.

Low-pressure membrane systems, including microfiltration (MF) and ultrafiltration (UF) membranes, are being increasingly used in drinking water treatments due to their high level of pathogen removal. However, the pathogen will pass through the membrane and contaminate the product if the membrane integrity is compromised. Therefore, an effective on-line integrity monitoring method for MF and UF membrane systems is essential to guarantee the regulatory requirements for pathogen removal.

Evaluation of water treatment plant UV reactor efficiency against Cryptosporidium parvum oocyst infectivity in immunocompetent suckling mice.

Aim: To assess the efficiency of a medium-pressure UV reactor under full-scale water treatment plant (WTP) conditions on the infectivity of Cryptosporidium parvum oocysts in an Naval Medical Research Institute (NMRI) suckling mice infectivity model.

Methods And Results: Six/seven-day-old mice were administered orally 2-10x10(4)Cryptosporidium parvum oocysts. Compared with nonirradiated oocysts, 40 mJ cm(-2) UV irradiation of ingested oocysts resulted 7 days later in a 3.