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Author: Christian G Huber (154)


Feb
2018

Despite decades of accumulated knowledge about proteins and their post-translational modifications (PTMs), numerous questions remain regarding their molecular composition and biological function. One of the most fundamental queries is the extent to which the combinations of DNA-, RNA- and PTM-level variations explode the complexity of the human proteome. Here, we outline what we know from current databases and measurement strategies including mass spectrometry-based proteomics.

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Nov
2017

Detecting and quantifying post-translational modifications (PTMs) in full-length proteins is a challenge, especially in the case of spontaneously occurring, nonenzymatic PTMs. Such a PTM is the formation of succinimide (Snn) in a protein that occurs spontaneously in prone primary sequences and leads typically to an equilibrium between Snn and its hydrolysis products isoaspartate (isoAsp) and aspartate. In order to detect these modifications in proteins by NMR spectroscopy, chemical shift assignments of reference compounds are required.

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Dec
2017

Aggressive behavior and violence in psychiatric patients have often been quoted to justify more restrictive settings in psychiatric facilities. However, the effects of open vs. locked door policies on aggressive incidents remain unclear.

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Mar
2018

People suffering from schizophrenia-spectrum disorders often endorse a reduced quality of life (QoL) as compared to the general population. There appears to be a lack of studies for rural catchment areas for this patient population. We conducted a cross-sectional study with 94 people with schizophrenia-spectrum disorders in a mainly rural alpine area.

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Aug
2017

Oxidation of biopharmaceuticals may affect their bioactivity, serum half-life, and (bio)chemical stability. The Fc domain of IgG monoclonal antibodies (mAbs) contains two methionine residues which are susceptible to oxidation. Here, we present a middle-down approach employing the cysteine protease IdeS under reducing conditions to obtain three mAb subunits of approximately 25 kDa: Fc/2, Fd', and LC.

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Aug
2017

HPA axis functioning plays an important role in the etiology of schizophrenia spectrum disorders (SSD). However, only few studies have examined HPA axis responsivity to psychosocial stress in SSD, and results are heterogeneous. Furthermore, childhood trauma is known to influence psychopathology and treatment outcome in SSD, but studies on the influence of childhood trauma on stress related HPA axis activity are missing.

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Sep
2017

Although elderly people have many serious dental issues and are in need of prosthesis, few opt for dental implants. The aim of this study was to investigate barriers that prevent elderly people from receiving dental implants. Specifically, we examined (i) whether the message was delivered before or after the interview had an impact, and (ii) whether it did matter who delivered the message.

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Apr
2017

Perceptions of dangerousness are an influential component of mental health stigma and can be driven by the display of psychiatric symptoms and the use of psychiatric service institutions. Yet, no previous study compared symptoms and service use associated perceptions of dangerousness. Therefore, we conducted a representative survey (N = 2,207) in the canton of Basel-Stadt, Switzerland.

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Mar
2017

The objective is to investigate the relationship between psychopathology measured by the positive and negative syndrome scale (PANSS) and concurrent global assessment of functioning (GAF) and subjective well-being under neuroleptics (SWN) in patients with schizophrenia spectrum disorder (SSD) regarding severity of illness and disease phase. We analyzed a sample of 202 SSD patients consisting of first episode psychosis (FEP) and multiple episode psychosis (MEP) patients followed up to 12 months using linear mixed models. All PANSS syndromes except excitement were associated with GAF scores (positive syndrome: p < 0.

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Mar
2017

Cancer represents heterogeneous and aberrantly proliferative manifestations composed of (epi)genetically and phenotypically distinct cells with a common clonal origin. Cancer stem cells (CSC) make up a rare subpopulation with the remarkable capacity to initiate, propagate and spread a malignant disease. Furthermore, CSC show increased therapy resistance, thereby contributing to disease relapse.

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Dec
1969

Substance use treatment is often performed inside locked wards. We investigate the effects of adopting a policy of open-door treatment for a substance use treatment and dual diagnosis ward.
This is a prospective open-label study investigating 3-month study periods before opening (P1), immediately after (P2), and 1 year after the first period (P3).

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Dec
1969

People who suffer from severe mental illness often present with histories of abuse during childhood. Alcohol use disorders is a common co-morbidity of survivors of childhood abuse and neglect. This study analyzes the effects of stressful childhood experiences, a proxy for trauma, on the frequency of alcohol consumption and the utilization of health care services in a population of people with severe mental illness.

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Feb
2017

An ongoing debate concerns acceptability, benefits, and shortcomings of coercive treatment such as assisted outpatient treatment (AOT). The hypothesis that involuntary commitment to outpatient treatment may lead to a better clinical outcome for a subgroup of persons with severe mental illness (SMI) is controversial. Nonetheless, positive effects of AOT may be mediated by an increased availability of healthcare resources or increased service use.

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Jun
2017

Background There is evidence for two different types and/or sources of mental illness stigma, namely the display of psychiatric symptoms and the use of psychiatric service institutions. However, no current study has compared the two. Furthermore, gaps exist in our knowledge of both types of stigma.

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Dec
1969

There is evidence that exposure to social stress plays a crucial role in the onset and relapse of schizophrenia; however, the reaction of patients with schizophrenia spectrum disorder (SSD) to experimentally induced social stress is not yet fully understood.
Original research published between January 1993 and August 2015 was included in this systematic literature research. Social stress paradigms, reporting subjective responses to stress measures, plasma or saliva cortisol, or heart rate (HR) in patients with SSD were included.

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Dec
1969

The rapidly increasing number of engineered nanoparticles (NPs), and products containing NPs, raises concerns for human exposure and safety. With this increasing, and ever changing, catalogue of NPs it is becoming more difficult to adequately assess the toxic potential of new materials in a timely fashion. It is therefore important to develop methods which can provide high-throughput screening of biological responses.

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Dec
1969

Bacterial collagenases differ considerably in their structure and functions. The collagenases ColH and ColG from Clostridium histolyticum and ColA expressed by Clostridium perfringens are well-characterized collagenases that cleave triple-helical collagen, which were therefore termed as ´true´ collagenases. ColA from Bacillus cereus (B.

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Aug
2016

Untargeted metabolomics aims at obtaining quantitative information on the highest possible number of low-molecular biomolecules present in a biological sample. Rather small changes in mass spectrometric spectrum acquisition parameters may have a significant influence on the detectabilities of metabolites in untargeted global-scale studies by means of high-performance liquid chromatography-mass spectrometry (HPLC-MS). Employing whole cell lysates of human renal proximal tubule cells, we present a systematic global-scale study of the influence of mass spectrometric scan parameters and post-acquisition data treatment on the number and intensity of metabolites detectable in whole cell lysates.

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Dec
1969

Our study aimed to explore the effects of different types of adverse childhood experiences (e.g. domestic violence, early loss, parental dysfunction, sexual and physical abuse) as well as experiences of sexual and physical abuse in adulthood on dissociative symptoms in adult patients with schizophrenia-spectrum disorders.

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Aug
2016

Plant cell wall polymers are synthesized by glycosyltransferases using nucleotide sugars as substrates. Most UDP-sugars are synthesized from UDP-glucose via de novo pathways but salvage pathways work in parallel to recycle sugars, which have been released during cell wall polymer and glycoprotein turnover. Here we report on the cloning and biochemical analysis of two arabinokinases in Arabidopsis.

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Dec
1969

Agitation, aggression, and violence are increased in psychotic disorders. Additionally, an earlier age at onset may be associated with aggressive behavior. However, the relationship of age at onset, an agitated-aggressive syndrome as measured with the Positive And Negative Syndrome Scale for Schizophrenia - Excited Component (PANSS-EC), and its potential correlates in first-episode psychosis (FEP) has not been studied.

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Aug
2016

Spouses of cancer patients play a crucial role in deciding on therapeutic choices. The aim of our study was to assess their role in counseling for radical prostatectomy.
We analyzed 30 videotaped preoperative consultations prior to radical prostatectomy.

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Nov
2015

Gold nanoparticles (AuNPs) are a popular choice for use in medical and biomedical research applications. With suitable functionalisation AuNPs can be applied in drug delivery systems, or can aid in disease diagnosis. One such functionalisation is with chitosan, which enables efficient interaction and permeation of cellular membranes, providing an effective adjuvant.

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Dec
2015

Heroin addiction is a severe relapsing brain disorder associated with impaired cognitive control, including deficits in attention allocation. The thalamus has a high density of opiate receptors and is critically involved in orchestrating cortical activity during cognitive control. However, there have been no studies on how acute heroin treatment modulates thalamic activity.

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Sep
2015

The characterization and absolute quantification of protein biopharmaceuticals and their product-related impurities, e.g., oxidation variants, is essential due to their potential impact on biological activity and immunogenicity.

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Jul
2015

Untargeted metabolomics has the potential to improve the predictivity of in vitro toxicity models and therefore may aid the replacement of expensive and laborious animal models. Here we describe a long term repeat dose nephrotoxicity study conducted on the human renal proximal tubular epithelial cell line, RPTEC/TERT1, treated with 10 and 35 μmol·liter(-1) of chloroacetaldehyde, a metabolite of the anti-cancer drug ifosfamide. Our study outlines the establishment of an automated and easy to use untargeted metabolomics workflow for HPLC-high resolution mass spectrometry data.

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Dec
2015

The present study was performed in an attempt to develop an in vitro integrated testing strategy (ITS) to evaluate drug-induced neurotoxicity. A number of endpoints were analyzed using two complementary brain cell culture models and an in vitro blood-brain barrier (BBB) model after single and repeated exposure treatments with selected drugs that covered the major biological, pharmacological and neuro-toxicological responses. Furthermore, four drugs (diazepam, cyclosporine A, chlorpromazine and amiodarone) were tested more in depth as representatives of different classes of neurotoxicants, inducing toxicity through different pathways of toxicity.

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May
2015

Inter-cellular communication with stromal cells is vital for cancer cells. Molecules involved in the communication are potential drug targets. To identify them systematically, we applied a systems level analysis that combined reverse network engineering with causal effect estimation.

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Apr
2015

MS-based proteomics and metabolomics are rapidly evolving research fields driven by the development of novel instruments, experimental approaches, and analysis methods. Monolithic analysis tools perform well on single tasks but lack the flexibility to cope with the constantly changing requirements and experimental setups. Workflow systems, which combine small processing tools into complex analysis pipelines, allow custom-tailored and flexible data-processing workflows that can be published or shared with collaborators.

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Dec
2015

The neural mechanisms of heroin addiction are still incompletely understood, even though modern neuroimaging techniques offer insights into disease-related changes in vivo. While changes on cortical structure have been reported in heroin addiction, evidence from subcortical areas remains underrepresented. Functional imaging studies revealed that the brain reward system and particularly the nucleus accumbens (NAcc) play a pivotal role in the pathophysiology of drug addiction.

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Dec
2014

Levothyroxine as active pharmaceutical ingredient of formulations used for the treatment of hypothyroidism is distributed worldwide and taken by millions of people. An important issue in terms of compound stability is its capability to react with ambient oxygen, especially in case of long term compound storage at elevated temperature. In this study we demonstrate that ultrahigh-performance liquid chromatography coupled to UV spectrometry and high-resolution mass spectrometry (UHPLC-UV-HRMS) represent very useful approaches to investigate the influence of ambient oxygen on the degradation kinetics of levothyroxine in the solid state at enhanced degradation conditions.

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Dec
2015

Cisplatin is one of the most widely used chemotherapeutic agents for the treatment of solid tumours. The major dose-limiting factor is nephrotoxicity, in particular in the proximal tubule. Here, we use an integrated omics approach, including transcriptomics, proteomics and metabolomics coupled to biokinetics to identify cell stress response pathways induced by cisplatin.

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Aug
2016

Despite increasing interest in global mental health training opportunities, only a few psychiatry residency programs offer global mental health training experiences in developing countries and even fewer programs offer it in other first-world countries. The authors developed a global mental health elective giving US psychiatry residents the opportunity to visit Switzerland to study and experience the mental health care system in this European country. This elective focuses on four major learning objectives: (1) the system of training and curriculum of postgraduate psychiatry education in Switzerland, (2) clinical and organizational aspects of Swiss mental health, (3) administrative aspects of Swiss mental health care delivery, and (4) scholarly activity.

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Jul
2014

Change of treatment policy from closed to open ward settings has been shown to reduce coercive measures. The aim of the current study was to examine the effects of the change from closed to open wards on the frequency of seclusion and forced medication in a hospital-wide setting.
2-year, longitudinal observational study with 2838 inpatient cases.

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Dec
1969

The current paper presents literature relevant to the relationship of religiosity, spirituality, and personal beliefs with mental health and, in particular, anxiety disorders as an empirical narrative review, providing an overview on the most important and clinically relevant research results on the topic. The relationship between religiosity/spirituality, personal beliefs (ie, magical ideation and paranormal beliefs), and mental health has lately been studied extensively, and results have indicated significant associations among these variables. However, scientific approaches to this field are complex and multidimensional, partly leading to poor operationalization, incomparable data, and contradictory results.

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Apr
2014

We assessed both current maladaptive personality traits (MPTs) and, retrospectively, premorbid MPTs in patients with schizophrenia spectrum disorders (SSDs). This was to examine whether the patients had the impression that their personality had changed and which traits were affected. We also wanted to determine whether the perceived changes could be explained by SSD psychopathology.

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Sep
2014

Stressful childhood experiences (SCE) are associated with many different health outcomes, such as psychiatric symptoms, physical illnesses, alcohol and drug abuse, and victimization experiences. Lesbian, gay, bisexual, and transgender (LGBT) people are at risk to be victims of SCE and show higher prevalence of SCE when compared with heterosexual controls.
This review analyzed systematically 73 articles that addressed different types of SCE in sexual minority populations and included items of household dysfunction.

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May
2014

An analytical workflow was developed for the absolute quantification of uridine diphosphate (UDP)-sugars in plant material in order to compare their metabolism both in wild-type Arabidopsis thaliana and mutated plants (ugd2,3) possessing genetic alterations within the UDP-glucose dehydrogenase genes involved in UDP-sugar metabolism. UDP-sugars were extracted from fresh plant material by chloroform-methanol-water extraction and further purified by solid-phase extraction with a porous graphitic carbon adsorbent with extraction efficiencies between 80 ± 5 % and 90 ± 5 %. Quantitative determination of the UDP-sugars was accomplished through HPLC separation with a porous graphitic carbon column (Hypercarb(TM)) which was interfaced to electrospray ionization Orbitrap mass spectrometry.

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Mar
2014

Nitration of the major birch pollen allergen Bet v 1 alters the immune responses toward this protein, but the underlying chemical mechanisms are not yet understood. Here we address the efficiency and site-selectivity of the nitration reaction of recombinant protein samples of Bet v 1.0101 with different nitrating agents relevant for laboratory investigations (tetranitromethane, TNM), for physiological processes (peroxynitrite, ONOO(-)), and for the health effects of environmental pollutants (nitrogen dioxide and ozone, O₃/NO₂).

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Jan
2014

The characterization of proteins modified with poly(ethylene glycol) (PEG), such as recombinant human granulocyte-colony stimulating factor (PEGylated rhG-CSF or pegfilgrastim), by electrospray ionization-mass spectrometry (ESI-MS) constitutes a challenge due to the overlapping protein charge state pattern and PEG polydispersity. In order to minimize spectral overlaps, charge reduction by means of the addition of amine was applied. Method development for direct-infusion measurements, carried out on an ESI-time-of-flight (ESI-TOF) instrument, demonstrated the potential of triethylamine (TEA) for shifting the charge state pattern toward lower-charged species and of formic acid (FA) for causing higher charging.

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Feb
2014

De novo sequencing is a popular technique in proteomics for identifying peptides from tandem mass spectra without having to rely on a protein sequence database. Despite the strong potential of de novo sequencing algorithms, their adoption threshold remains quite high. We here present a user-friendly and lightweight graphical user interface called DeNovoGUI for running parallelized versions of the freely available de novo sequencing software PepNovo+, greatly simplifying the use of de novo sequencing in proteomics.

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Mar
2015

To compare ward atmosphere, safety, therapeutic hold, and patients' coherence on closed, recently opened, and open psychiatric wards.
Ward atmosphere on two closed, two recently opened, and two permanently open wards was examined using the Essen Climate Evaluation Schema (EssenCES), and structural as well as clinical data were extracted.
Global ward atmosphere (p < 0.

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Dec
1969

Helminth infections and allergy have evolutionary and clinical links. Infection with the nematode Ascaris lumbricoides induces IgE against several molecules including invertebrate pan-allergens. These antibodies influence the pathogenesis and diagnosis of allergy; therefore, studying parasitic and non-parasitic allergens is essential to understand both helminth immunity and allergy.

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Dec
1969

Structure and function are closely related in the healthy human brain. In patients with chronic heroin exposure, brain imaging studies have identified long-lasting changes in gray matter (GM) volume. More recently, we showed that acute application of heroin in dependent patients results in hypoperfusion of fronto-temporal areas compared with the placebo condition.

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