Action and reaction: Chlamydophila pneumoniae proteome alteration in a persistent infection induced by iron deficiency

Chlamydophila pneumoniae is an obligate intracellular pathogen implicated in a variety of acute and chronic diseases. Long-term infections are associated with a persistent life stage, in which bacteria can stay for years. They are less accessible to antibiotic treatment but still prone to sustain an inflammatory response. Different in vitro models have been established to mimic and characterize chlamydial persistency. For C. pneumoniae and Chlamydia trachomatis, altered metabolic activities and changed antigenic profiles compared to acute infections have been reported. Most studies including transcriptome and proteome analyses describe persistency induced by IFNγ treatment. Here, we use iron depletion of the infected cell culture that also leads into persistent infection. We describe differently regulated proteins found by subtractive proteome analysis comparing two early stages of infection with and without addition of the iron chelator deferoxamine-mesylate. While only one bacterial protein was up-regulated during iron deficiency up to 24 h post infection (p.i.), 11 were found to be up-regulated and eight to be down-regulated from 24-48 h p.i. Two down-regulated proteins could be identified by peptide mass fingerprinting as thioredoxin reductase and chromosome partitioning protein (ParB). The latter is involved in chromosome segregation. Thus, using a comparative approach we identified on a proteome level down-regulation of ParB in persistent chlamydial forms, which is in agreement with previous results describing changes in cell division and atypical altered morphology of persistent Chlamydiae

Toward a global consensus on outcome measures for clinical trials in tinnitus: Report from the first international meeting of the COMiT initiative, November 14, 2014, Amsterdam, the Netherlands

In Europe alone, over 70 million people experience tinnitus; for seven million people, it creates a debilitating condition. Despite its enormous socioeconomic relevance, progress in successfully treating the condition is somewhat limited. The European Union has approved funding to create a pan-European tinnitus research collaboration network (2014-2018). The goal of one working group is to establish an international standard for outcome measurements in clinical trials of tinnitus. Importantly, this would enhance tinnitus research by informing sample-size calculations, enabling meta-analyses, and facilitating the identification of tinnitus subtypes, ultimately leading to improved treatments. The first meeting followed a workshop on "Agreed Standards for Measurement: An International Perspective" with invited talks on clinimetrics and existing international initiatives to define core sets for outcome measurements in hearing loss (International classification of functioning, disability, and health core sets for hearing loss) and eczema (Harmonizing outcome measures for eczema). Both initiatives have taken an approach that clearly distinguishes the specification of what to measure from that of how to measure it. Meeting delegates agreed on taking a step-wise roadmap for which the first output would be a consensus on what outcome domains are essential for all trials. The working group seeks to embrace inclusivity and brings together clinicians, tinnitus researchers, experts on clinical research methodology, statisticians, and representatives of the health industry. People who experience tinnitus are another important participant group. This meeting report is a call to those stakeholders across the globe to actively participate in the initiative. © 2015 The Author(s)

Genetics of tinnitus: An emerging area for molecular diagnosis and drug development

Subjective tinnitus is the perception of sound in the absence of external or bodily-generated sounds. Chronic tinnitus is a highly prevalent condition affecting over 70 million people in Europe. A wide variety of comorbidities, including hearing loss, psychiatric disorders, neurodegenerative disorders, and temporomandibular joint (TMJ) dysfunction, have been suggested to contribute to the onset or progression of tinnitus; however, the precise molecular mechanisms of tinnitus are not well understood and the contribution of genetic and epigenetic factors remains unknown. Human genetic studies could enable the identification of novel molecular therapeutic targets, possibly leading to the development of novel pharmaceutical therapeutics. In this article, we briefly discuss the available evidence for a role of genetics in tinnitus and consider potential hurdles in designing genetic studies for tinnitus. Since multiple diseases have tinnitus as a symptom and the supporting genetic evidence is sparse, we propose various strategies to investigate the genetic underpinnings of tinnitus, first by showing evidence of heritability using concordance studies in twins, and second by improving patient selection according to phenotype and/or etiology in order to control potential biases and optimize genetic data output. The increased knowledge resulting from this endeavor could ultimately improve the drug development process and lead to the preventive or curative treatment of tinnitus. © 2016 Lopez-Escamez, Bibas, Cima, Van de Heyning, Knipper, Mazurek, Szczepek and Cederroth