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Differential Transduction Following Basal Ganglia Administration of Distinct Pseudotyped AAV Capsid Serotypes in Nonhuman Primates

We examined the transduction efficiency of different adeno-associated virus (AAV) capsid serotypes encoding for green fluorescent protein (GFP) flanked by AAV2 inverted terminal repeats in the nonhuman primate basal ganglia as a prelude to translational studies, as well as clinical trials in patients with Parkinson's disease (PD). Six intact young adult cynomolgus monkeys received a single 10 mu l

The Primacy of Right. On the Triad of Liberty, Equality and Virtue in Wollstonecraft's Political Thought

I argue along the following lines: For Wollstonecraft, liberty is independence in two different spheres, one presupposing the other. On the one hand, liberty is independence in relation to others, in the sense of not being vulnerable to their whim or arbitrary will. Call this social, or political, liberty. For liberty understood in this way, infringements do not require individual instances of int

Changes in key hypothalamic neuropeptide populations in Huntington disease revealed by neuropathological analyses.

Huntington disease (HD) is a fatal neurodegenerative disorder caused by expansion of a CAG repeat in the HD gene. Degeneration concentrating in the basal ganglia has been thought to account for the characteristic psychiatric symptoms, cognitive decline and motor dysfunction. However, the homeostatic control of emotions and metabolism are disturbed early in HD, and focused studies have identified a

Gene therapy for dopamine replacement.

Dopamine replacement for Parkinson's disease (PD) have seen three major iterations of improvements since the introduction of l-3,4-dihydroxyphenylalanine (l-DOPA) pharmacotherapy: dopamine receptor agonists, ex vivo gene transfer for cell transplantation and most recently in vivo gene therapy. In this chapter, we describe the principles behind viral vector-mediated enzyme replacement in PD. We foc

Mutant huntingtin causes metabolic imbalance by disruption of hypothalamic neurocircuits.

In Huntington's disease (HD), the mutant huntingtin protein is ubiquitously expressed. The disease was considered to be limited to the basal ganglia, but recent studies have suggested a more widespread pathology involving hypothalamic dysfunction. Here we tested the hypothesis that expression of mutant huntingtin in the hypothalamus causes metabolic abnormalities. First, we showed that bacterial a

Optimized adeno-associated viral vector-mediated striatal DOPA delivery restores sensorimotor function and prevents dyskinesias in a model of advanced Parkinson's disease.

Viral vector-mediated gene transfer utilizing adeno-associated viral vectors has recently entered clinical testing as a novel tool for delivery of therapeutic agents to the brain. Clinical trials in Parkinson's disease using adeno-associated viral vector-based gene therapy have shown the safety of the approach. Further efforts in this area will show if gene-based approaches can rival the therapeut

Water and Risk: Developing sustainable and resilient communities

Key Messages • Sweden has an ideal opportunity to become a more important effect, reflecting the views of several Swedish organisations active international partner in DRR and resilience activities, originating in this area. from its strong history of donor support and long engagement • Acting on this opportunity would enable timely Swedish in DRR. contributions to the increasing global debate on

Beating the training obsession: making capacity development for disaster risk management matter

The last ten years have seen a sharp increase in externally supported capacity development initiatives for disaster risk management. However, not all of them have generated sustainable results. The purpose of this paper is to scrutinize the current focus on training as the main tool for capacity development in the context of disaster risk management, and to argue for the necessity to address capac

Identification and citation of digital research resources

Environmental research infrastructures are often built on a large number of distributed observational or experimental sites, run by hundreds of scientists and technicians, financially supported and administrated by a large number of institutions. It becomes very important to acknowledge the data sources and their providers. There is also a strong need for common data citation tracking systems that

Mammographic tumour appearance is related to clinicopathological factors and surrogate molecular breast cancer subtype

Mammographic tumour appearance may provide prognostic useful information. For example, spiculation indicates invasiveness, but also better survival compared to tumours with other appearances. We aimed to study the relationship between mammographic tumour appearance and established clinicopathological factors, including surrogate molecular breast cancer subtypes, in the large Malmö Diet and Cancer

Coherent Bragg imaging of 60 nm Au nanoparticles under electrochemical control at the NanoMAX beamline

Nanoparticles are essential electrocatalysts in chemical production, water treatment and energy conversion, but engineering efficient and specific catalysts requires understanding complex structure-reactivity relations. Recent experiments have shown that Bragg coherent diffraction imaging might be a powerful tool in this regard. The technique provides three-dimensional lattice strain fields from w

Prognostic impact of circulating tumor cell apoptosis and clusters in serial blood samples from patients with metastatic breast cancer in a prospective observational cohort

Background: Presence of circulating tumor cells (CTCs) is a validated prognostic marker in metastatic breast cancer. Additional prognostic information may be obtained by morphologic characterization of CTCs. We explored whether apoptotic CTCs, CTC clusters and leukocytes attached to CTCs are associated with breast cancer subtype and prognosis at base-line (BL) and in follow-up (FU) blood samples i

Myoepithelium assessment with p63 immunostaining in formalinfixed paraffin-embedded breast cancer tissue pre-treated with RNA-later

Objective: To assessmyoepithelium with p63 in fresh breast cancer (BC)tissue samples collected in RNA later for further analysis with NextGeneration Sequencing (NGS) technique. For a better understanding ofthe NGS bulk-analysis, a central part of the sample in RNA-later isformalin-fixed paraffin-embedded to score relative cellularity in % onhematoxylin-eosin (HE) staining (% of invasive cancer, ca

Quality of up to 35 years old archival breast cancer tissue in paraffinblocks for estrogen receptor evaluation

Objective: Estrogen receptor (ER) positive breast cancer (BC) can havean insidious course with disease-relapse decades after primary surgery.New analysis performed on archived formalin-fixed paraffin-embedded(FFPE) tissue are important for disease-management in late BC-relapseand an important tool in BC-research. However, although loss of immunoreactivityin tissue slides after sectioning has been

Carbonaceous aerosol source apportionment using the Aethalometer model -evaluation by radiocarbon and levoglucosan analysis at a rural background site in southern Sweden

With the present demand on fast and inexpensive aerosol source apportionment methods, the Aethalometer model was evaluated for a full seasonal cycle (June 2014–June 2015) at a rural atmospheric measurement station in southern Sweden by using radiocarbon and levoglucosan measurements. By utilizing differences in absorption of UV and IR, the Aethalometer model apportions carbon mass into wood burnin