Human fertilization in vivo and in vitro requires the CatSper channel to initiate sperm hyperactivation.

The infertility of many couples rests on an enigmatic dysfunction of the man's sperm. To gain insight into the underlying pathomechanisms, we assessed the function of the sperm-specific multisubunit CatSper-channel complex in the sperm of almost 2,300 men undergoing a fertility workup, using a simple motility-based test. We identified a group of men with normal semen parameters but defective CatSper function.

Human Coxsackie- and adenovirus receptor is a putative target of neutrophil elastase-mediated shedding.

Background: During viral-induced myocarditis, immune cells migrate towards the site of infection and secrete proteases, which in turn can act as sheddases by cleaving extracellular domains of transmembrane proteins. We were interested in the shedding of the Coxsackie- and adenovirus receptor (CAR) that acts as an entry receptor for both eponymous viruses, which cause myocarditis. CAR shedding by secreted immune proteases could result in a favourable outcome of myocarditis as CAR's extracellular domain would be removed from the cardiomyocytes' surface leading to decreased susceptibility to ongoing viral infections.

Analysis of the cerebellar molecular stress response led to first evidence of a role for FKBP51 in brain FKBP52 expression in mice and humans.

As the cerebellar molecular stress response is understudied, we assessed protein expression levels of hypothalamic-pituitary-adrenal (HPA) axis regulators and neurostructural markers in the cerebellum of a male PTSD mouse model and of unstressed vs. stressed male FK506 binding protein 51 () knockout (KO) vs. wildtype mice.

Naturally occurring variants in the transmembrane and cytoplasmic domains of the human Coxsackie- and adenovirus receptor have no impact on virus internalisation.

The Coxsackie- and adenovirus receptor (CAR) mediates homophilic cell-cell contacts and susceptibility to both human pathogenic viruses through its membrane-distal immunoglobulin domain. In the present study, we screened five missense variants of the human CAR gene for their influence on adenovector or Coxsackievirus entry into Chinese hamster ovary cells. The CAR variants facilitated virus internalisation to a similar extent as wild type CAR.

Whole Genome Sequencing of 39 Invasive Streptococcus pneumoniae Sequence Type 199 Isolates Revealed Switches from Serotype 19A to 15B.

Streptococcus pneumoniae is a major pathogen that causes different invasive pneumococcal diseases (IPD). The pneumococcal polysaccharide capsule is a main virulence factor. More than 94 capsule types have been described, but only a limited number of capsule types accounted for the majority of IPD cases before the introduction of pneumococcal vaccines.

Identification and characterization of HPA-axis reactivity endophenotypes in a cohort of female PTSD patients.

Analysis of the function of the hypothalamic-pituitary-adrenal (HPA)-axis in patients suffering from posttraumatic stress disorder (PTSD) has hitherto produced inconsistent findings, inter alia in the Trier Social Stress Test (TSST). To address these inconsistencies, we compared a sample of 23 female PTSD patients with either early life trauma (ELT) or adult trauma (AT) or combined ELT and AT to 18 age-matched non-traumatized female healthy controls in the TSST which was preceded by intensive baseline assessments. During the TSST, we determined a variety of clinical, psychological, endocrine and cardiovascular parameters as well as expression levels of four HPA-axis related genes.

A role for synapsin in FKBP51 modulation of stress responsiveness: Convergent evidence from animal and human studies.

Both the molecular co-chaperone FKBP51 and the presynaptic vesicle protein synapsin (alternatively spliced from SYN1-3) are intensively discussed players in the still insufficiently explored pathobiology of psychiatric disorders such as major depression, schizophrenia and posttraumatic stress disorder (PTSD). To address their still unknown interaction, we compared the expression levels of synapsin and five other neurostructural and HPA axis related marker proteins in the prefrontal cortex (PFC) and the hippocampus of restrained-stressed and unstressed Fkbp5 knockout mice and corresponding wild-type littermates. In addition, we compared and correlated the gene expression levels of SYN1, SYN2 and FKBP5 in three different online datasets comprising expression data of human healthy subjects as well as of predominantly medicated patients with different psychiatric disorders.

Less common genotype variants of TP53 polymorphisms are associated with poor outcome in adult patients with adrenocortical carcinoma.

Context: The Li-Fraumeni tumor syndrome is strongly associated with adrenocortical carcinoma (ACC) and is caused by germline mutations in TP53 in 70% of cases. Also, TP53 polymorphisms have been shown to influence both cancer risk and clinical outcome in several tumor entities. We, therefore, investigated TP53 polymorphisms in a cohort of adult patients with ACC.

Therapeutic Action of Fluoxetine is Associated with a Reduction in Prefrontal Cortical miR-1971 Expression Levels in a Mouse Model of Posttraumatic Stress Disorder.

MicroRNAs (miRNA) are a class of small non-coding RNAs that have recently emerged as epigenetic modulators of gene expression in psychiatric diseases like schizophrenia and major depression. So far, miRNAs have neither been studied in patients suffering from posttraumatic stress disorder (PTSD) nor in PTSD animal models. Here, we present the first study exploring the connection between miRNAs and PTSD.

Long-lasting hippocampal synaptic protein loss in a mouse model of posttraumatic stress disorder.

Despite intensive research efforts, the molecular pathogenesis of posttraumatic stress disorder (PTSD) and especially of the hippocampal volume loss found in the majority of patients suffering from this anxiety disease still remains elusive. We demonstrated before that trauma-induced hippocampal shrinkage can also be observed in mice exhibiting a PTSD-like syndrome. Aiming to decipher the molecular correlates of these trans-species posttraumatic hippocampal alterations, we compared the expression levels of a set of neurostructural marker proteins between traumatized and control mice at different time points after their subjection to either an electric footshock or mock treatment which was followed by stressful re-exposure in several experimental groups.

Intranasally administered neuropeptide S (NPS) exerts anxiolytic effects following internalization into NPS receptor-expressing neurons.

Experiments in rodents revealed neuropeptide S (NPS) to constitute a potential novel treatment option for anxiety diseases such as panic and post-traumatic stress disorder. However, both its cerebral target sites and the molecular underpinnings of NPS-mediated effects still remain elusive. By administration of fluorophore-conjugated NPS, we pinpointed NPS target neurons in distinct regions throughout the entire brain.

TP53 germline mutations in adult patients with adrenocortical carcinoma.

Context: Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with germline mutations in TP53. According to the Chompret criteria for LFS, any patient with adrenocortical cancer (ACC), irrespective of age and family history, is at high risk for a TP53 germline mutation. However, whereas such mutations have been detected with high frequency in childhood ACC, a large cohort of adult patients with ACC has never been investigated for TP53 germline mutations.

FK506 binding protein 5 shapes stress responsiveness: modulation of neuroendocrine reactivity and coping behavior.

Background: The Hsp90 cochaperone FK506 binding protein 5 (FKBP5) is an established regulator of the glucocorticoid receptor (GR), and numerous genetic studies have linked it to stress-related diseases such as major depression or posttraumatic stress disorder. However, translational studies including genetic animal models are lacking.

Methods: Mice deficient of FKBP5 were generated and analyzed in comparison with wildtype littermates.

Reduced hippocampus volume in the mouse model of Posttraumatic Stress Disorder.

Some, but not all studies in patients with posttraumatic stress disorder (PTSD), report reduced hippocampus (HPC) volume. In particular it is unclear, whether smaller hippocampal volume represents a susceptibility factor for PTSD rather than a consequence of the trauma. To gain insight into the relationship of brain morphology and trauma exposure, we investigated volumetric and molecular changes of the HPC in a mouse model of PTSD by means of in vivo Manganese Enhanced Magnetic Resonance Imaging (MEMRI) and ex vivo ultramicroscopic measurements.