Modifiers of C9orf72 dipeptide repeat toxicity connect nucleocytoplasmic transport defects to FTD/ALS.

C9orf72 mutations are the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Dipeptide repeat proteins (DPRs) produced by unconventional translation of the C9orf72 repeat expansions cause neurodegeneration in cell culture and in animal models. We performed two unbiased screens in Saccharomyces cerevisiae and identified potent modifiers of DPR toxicity, including karyopherins and effectors of Ran-mediated nucleocytoplasmic transport, providing insight into potential disease mechanisms and therapeutic targets.

Co-existence of intact stemness and priming of neural differentiation programs in mES cells lacking Trim71.

Regulatory networks for differentiation and pluripotency in embryonic stem (ES) cells have long been suggested to be mutually exclusive. However, with the identification of many new components of these networks ranging from epigenetic, transcriptional, and translational to even post-translational mechanisms, the cellular states of pluripotency and early differentiation might not be strictly bi-modal, but differentiating stem cells appear to go through phases of simultaneous expression of stemness and differentiation genes. Translational regulators such as RNA binding proteins (RBPs) and micro RNAs (miRNAs) might be prime candidates for guiding a cell from pluripotency to differentiation.

Controllable Tuning Plasmonic Coupling with Nanoscale Oxidation.

The nanoparticle on mirror (NPoM) construct is ideal for the strong coupling of localized plasmons because of its simple fabrication and the nanometer-scale gaps it offers. Both of these are much harder to control in nanoparticle dimers. Even so, realizing controllable gap sizes in a NPoM remains difficult and continuous tunability is limited.

Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro.

Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely used to culture neurons.

Polo-like kinase 3 is associated with improved overall survival in cholangiocarcinoma.

Background & Aims: Cholangiocarcinomas (CCA) paradoxically express the death ligand TRAIL and thus, are dependent on effective survival signals to circumvent apoptosis. Hedgehog signalling exerts major survival signals in CCA by regulating serine/threonine kinase polo-like kinase (PLK)2. We here aimed to examine the role of PLK1/2/3 expression for CCA tumour biology.

Unfolding the contents of sub-nm plasmonic gaps using normalising plasmon resonance spectroscopy.

Plasmonic coupling of gold nanoparticles to a gold surface creates intense plasmonic hot spots with large electromagnetic field-enhancements within the cavity formed by the two metallic surfaces. The localised field in such structures is extremely sensitive to morphological fluctuations and subtle changes in the dielectric properties of the cavity contents. Here, we present an optical method that pins down the properties of the gap contents with high sensitivity, termed normalising plasmon resonance (NPR) spectroscopy.

Screening and brief intervention for substance misuse: Does it reduce aggression and HIV-related risk behaviours?

Purpose: To explore whether reducing substance misuse through a brief motivational intervention also reduces aggression and HIV risk behaviours.

Methods: Participants were enrolled in a randomized controlled trial in primary care if they screened positive for substance misuse. Substance misuse was assessed using the Alcohol, Smoking and Substance Involvement Screening Test; aggression, using a modified version of the Explicit Aggression Scale; and HIV risk, through a count of common risk behaviours.

Isolation and characterization of unhydrolyzed oligosaccharides from switchgrass (Panicum virgatum, L.) xylan after exhaustive enzymatic treatment with commercial enzyme preparations.

Switchgrass (Panicum virgatum, L.) is a potential renewable source of carbohydrates for use in microbial conversion to biofuels. Xylan comprises approximately 30% of the switchgrass cell wall.

Triacetic acid lactone production in industrial Saccharomyces yeast strains.

Triacetic acid lactone (TAL) is a potential platform chemical that can be produced in yeast. To evaluate the potential for industrial yeast strains to produce TAL, the g2ps1 gene encoding 2-pyrone synthase was transformed into 13 industrial yeast strains of varied genetic background. TAL production varied 63-fold between strains when compared in batch culture with glucose.

Monitoring morphological changes in 2D monolayer semiconductors using atom-thick plasmonic nanocavities.

Nanometer-sized gaps between plasmonically coupled adjacent metal nanoparticles enclose extremely localized optical fields, which are strongly enhanced. This enables the dynamic investigation of nanoscopic amounts of material in the gap using optical interrogation. Here we use impinging light to directly tune the optical resonances inside the plasmonic nanocavity formed between single gold nanoparticles and a gold surface, filled with only yoctograms of semiconductor.

Disease recurrence in localized scleroderma: a retrospective analysis of 344 patients with paediatric- or adult-onset disease.

Background: Localized scleroderma (LoS) is characterized by a phase of disease activity followed by remission. However, disease recurrences occur. Knowledge concerning these recurrences can help prompt treatment, thereby preventing disease damage.

Significant life events and their impact on alcohol and drug use: a qualitative study.

This study used a life-course perspective to identify and understand life events related to long-term alcohol and other drug (AOD) use trajectories across the life span. Using a purposive sample, we conducted semi-structured telephone interviews with 48 participants (n = 30 abstinent and 18 non-abstinent) from a longitudinal study of AOD outcomes 15 years following outpatient AOD treatment. A content analysis was conducted using ATLAS.

Structural characterization of (1→2)-β-xylose-(1→3)-α-arabinose-containing oligosaccharide products of extracted switchgrass (Panicum virgatum, L.) xylan after exhaustive enzymatic treatment with α-arabinofuranosidase and β-endo-xylanase.

Switchgrass (Panicum virgatum, L.) is a potential dedicated biomass crop for use in biocatalytic conversion systems to biofuels. Nearly 30% of switchgrass cell wall material is xylan.

Advising depression patients to reduce alcohol and drug use: factors associated with provider intervention in outpatient psychiatry.

Background And Objectives: Mental health clinicians have an important opportunity to help depression patients reduce co-occurring alcohol and drug use. This study examined demographic and clinical patient characteristics and service factors associated with receiving a recommendation to reduce alcohol and drug use from providers in a university-based outpatient psychiatry clinic.

Methods: The sample consisted of 97 participants ages 18 and older who reported hazardous drinking (≥3 drinks/occasion), illegal drug use (primarily cannabis) or misuse of prescription drugs, and who scored ≥15 on the Beck Depression Inventory-II (BDI-II).

Costs of care for persons with opioid dependence in commercial integrated health systems.

Background: When used in general medical practices, buprenorphine is an effective treatment for opioid dependence, yet little is known about how use of buprenorphine affects the utilization and cost of health care in commercial health systems.

Methods: The objective of this retrospective cohort study was to examine how buprenorphine affects patterns of medical care, addiction medicine services, and costs from the health system perspective. Individuals with two or more opioid-dependence diagnoses per year, in two large health systems (System A: n = 1836; System B: n = 4204) over the time span 2007-2008 were included.

Platelet-derived growth factor primes cancer-associated fibroblasts for apoptosis.

Desmoplastic malignancies such as cholangiocarcinoma (CCA) are characterized by a dense stroma containing an abundance of myofibroblasts termed cancer-associated fibroblasts (CAF). The CAF phenotype represents an "activated state" in which cells are primed for cell death triggered by BH3 mimetics. Accordingly, this primed state may be therapeutically exploited.

Development of realistic environmental release factors based on measured data: approach and lessons from the EU metal industry.

The assessment of environmental exposure and risks associated with the production or use of a substance on an industrial site includes the estimation of the releases to the environment. In the absence of measured release data on the specific substance, a risk assessor would rely on default release factors to the environmental compartments as developed in international, national, or regional context. Because a wide variety of substances, processes, and uses has to be covered, default release factors are as a rule conservative, usually leading to significant overprediction of releases and hence to overpredicted environmental exposure concentrations and risks.

Effectiveness of nurse-practitioner-delivered brief motivational intervention for young adult alcohol and drug use in primary care in South Africa: a randomized clinical trial.

Aims: To assess the effectiveness of brief motivational intervention for alcohol and drug use in young adult primary care patients in a low-income population and country.

Methods: A randomized controlled trial in a public-sector clinic in Delft, a township in the Western Cape, South Africa recruited 403 patients who were randomized to either single-session, nurse practitioner-delivered Brief Motivational Intervention plus referral list or usual care plus referral list, and followed up at 3 months.

Results: Although rates of at-risk alcohol use and drug use did not differ by treatment arm at follow-up, patients assigned to the Brief Motivational Intervention had significantly reduced scores on ASSIST (Alcohol, Smoking and Substance Involvement Screening Test) for alcohol-the most prevalent substance.

Comparison of health care needs of child family members of adults with alcohol or drug dependence versus adults with asthma or diabetes.

Objective: To compare the health problems, preventive care utilization, and medical costs of child family members (CFMs) of adults diagnosed with alcohol or drug dependence (AODD) to CFMs of adults diagnosed with diabetes or asthma.

Methods: Child family members of adults diagnosed with AODD between 2002 and 2005 and CFMs of matched adults diagnosed with diabetes or asthma were followed up to 7 years after diagnosis of the index adult. Logistic regression was used to determine whether the CFMs of AODD adults were more likely to be diagnosed with medical conditions, or get preventive care, than the CFMs of adults with asthma or diabetes.

Nonlinear superchiral meta-surfaces: tuning chirality and disentangling non-reciprocity at the nanoscale.

Circularly polarized light is incident on a nanostructured chiral meta-surface. In the nanostructured unit cells whose chirality matches that of light, superchiral light is forming and strong optical second harmonic generation can be observed.

Metal and nutrient dynamics in decomposing tree litter on a metal contaminated site.

In a forest on sandy, metal polluted soil, we examined effects of six tree species on litter decomposition rates and accompanied changes in metal (Cd, Zn) and nutrient (base cations, N, C) amounts. Decomposition dynamics were studied by means of a litterbag experiment lasting for 30 months. The decomposition peak occurred within the first year for all tree species, except for aspen.