The Endometrial Transcription Landscape of MRKH Syndrome.

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome (OMIM 277000) is characterized by agenesis of the uterus and upper part of the vagina in females with normal ovarian function. While genetic causes have been identified for a small subset of patients and epigenetic mechanisms presumably contribute to the pathogenic unfolding, too, the etiology of the syndrome has remained largely enigmatic. A comprehensive understanding of gene activity in the context of the disease is crucial to identify etiological components and their potential interplay. So far, this understanding is lacking, primarily due to the scarcity of samples and suitable tissue. In order to close this gap, we profiled endometrial tissue of uterus rudiments in a large cohort of MRKH patients using RNA-seq and thereby provide a genome-wide view on the altered transcription landscape of the MRKH syndrome. Differential and co-expression analyses of the data identified cellular processes and candidate genes that converge on a core network of interconnected regulators that emerge as pivotal for the perturbed expression space. With these results and browsable access to the rich data through an online tool we seek to accelerate research to unravel the underlying biology of the syndrome.

The Challenge and Opportunity to Diagnose Parkinson's Disease in Midlife.

Parkinson's disease (PD) is the most common neurodegenerative movement disorder that affects extensive regions of the nervous system. Its current clinical diagnosis is based on motor symptoms that appear late during disease progression when substantial proportions of the nigrostriatal dopaminergic neuron population are lost already. Although disturbances in sleep and other biofunctions often surface years prior to motor impairments and point to a long prodromal phase, these phenotypic signs in a person's midlife lack predictive power. They do, however, signal the unfolding of the disease and suggest molecular correlates that begin deviating early on. Revealing such trajectories, hence, promises not only a better understanding of prodromal PD but may also enable a much-needed earlier diagnosis. A nexus that may harbor such molecular trajectories is the epigenome as key etiological factors of PD-genetics, age, and environment-influence this substrate. An earlier diagnosis would also allow earlier interventions and lifestyle adjustments to improve brain function and reduce symptoms. In this review, we describe the challenges of diagnosing PD early on and highlight the opportunities that may arise from steering research efforts towards comprehensive interrogations of molecular layers during the long-time neglected midlife phase. In particular, we emphasize how existing cohorts of at-risk individuals, available animal models, and suitable markers may come together and aid in revealing molecular trajectories that offer diagnostic utility for PD in its prodromal stage.

Self-conscious emotions and depression: rumination explains why shame but not guilt is maladaptive.

Feelings of shame and guilt are factors associated with depression. However, studies simultaneously investigating shame and guilt suggest that only shame has a strong unique effect, although it is not yet clear which psychological processes cause shame and not shame-free guilt to be related to depression. The authors hypothesized that shame, in contrast to guilt, elicits rumination, which then leads to depression. Therefore, in this study we investigated event-related shame and guilt, event-related rumination, and depression among 149 mothers and fathers following family breakup due to marital separation. Data were analyzed using latent variable modeling. The results confirm that shame but not guilt has a strong unique effect on depression. Moreover, the results show that the effect of shame is substantially mediated by rumination. The results are discussed against the background of self-discrepancies and self-esteem.

The effects of DNIC-type inhibition on temporal summation compared to single pulse processing: does sex matter?

A few experimental observations have suggested that diffuse noxious inhibitory control (DNIC)-type inhibition acts preferentially on the pain system if this is in a sensitised state, e.g. after slow temporal summation (wind-up). However, firm evidence is still missing. Furthermore, sex-related factors, which seem to affect temporal summation as well as DNIC effects, might thus also modulate the interaction of these two processes. To answer these questions, we investigated 40 young and pain-free subjects (20 female and 20 male). The conditioning stimulus in our DNIC paradigm was realized by immersion of the hand into a water tub containing either 42 degrees C (non-painful heat) or 46 degrees C (painful heat) hot water. The test stimuli were either single pulses or series of five pulses (0.5 Hz repetition frequency) produced by a pressure algometer. The VAS ratings for the last stimulus in the series were significantly higher than for the single pulse (temporal summation). The ratings were significantly reduced by the 42 degrees C conditioning stimulus and even more by the 46 degrees C conditioning stimulus, suggesting DNIC-like inhibition. This was equally true both for the single pulse and for the series of pulses. Sex differences were not observed for temporal summation, DNIC inhibition or for the interaction of the two processes, although women exhibited significantly lower pressure pain thresholds and higher ratings for the tonic heat stimuli. In conclusion, DNIC-type inhibition apparently does not preferentially act on a sensitised pain system after slow temporal summation. Considering the sex of the subjects does not change this insight.