Reconstruction and Validation of RefRec: A Global Model for the Yeast Molecular Interaction Network

Molecular interaction networks establish all cell biological processes. The networks are under intensive research that is facilitated by new high-throughput measurement techniques for the detection, quantification, and characterization of molecules and their physical interactions. For the common model organism yeast Saccharomyces cerevisiae, public databases store a significant part of the accumulated information and, on the way to better understanding of the cellular processes, there is a need to integrate this information into a consistent reconstruction of the molecular interaction network. This work presents and validates RefRec, the most comprehensive molecular interaction network reconstruction currently available for yeast. The reconstruction integrates protein synthesis pathways, a metabolic network, and a protein-protein interaction network from major biological databases. The core of the reconstruction is based on a reference object approach in which genes, transcripts, and proteins are identified using their primary sequences. This enables their unambiguous identification and non-redundant integration. The obtained total number of different molecular species and their connecting interactions is ∼67,000. In order to demonstrate the capacity of RefRec for functional predictions, it was used for simulating the gene knockout damage propagation in the molecular interaction network in ∼590,000 experimentally validated mutant strains. Based on the simulation results, a statistical classifier was subsequently able to correctly predict the viability of most of the strains. The results also showed that the usage of different types of molecular species in the reconstruction is important for accurate phenotype prediction. In general, the findings demonstrate the benefits of global reconstructions of molecular interaction networks. With all the molecular species and their physical interactions explicitly modeled, our reconstruction is able to serve as a valuable resource in additional analyses involving objects from multiple molecular -omes. For that purpose, RefRec is freely available in the Systems Biology Markup Language format

Auditory Feedback Control of Vocal Pitch during Sustained Vocalization: A Cross-Sectional Study of Adult Aging

Background: Auditory feedback has been demonstrated to play an important role in the control of voice fundamental frequency (F0), but the mechanisms underlying the processing of auditory feedback remain poorly understood. It has been well documented that young adults can use auditory feedback to stabilize their voice F0 by making compensatory responses to perturbations they hear in their vocal pitch feedback. However, little is known about the effects of aging on the processing of audio-vocal feedback during vocalization. Methodology/Principal Findings: In the present study, we recruited adults who were between 19 and 75 years of age and divided them into five age groups. Using a pitch-shift paradigm, the pitch of their vocal feedback was unexpectedly shifted 650 or 6100 cents during sustained vocalization of the vowel sound/u/. Compensatory vocal F0 response magnitudes and latencies to pitch feedback perturbations were examined. A significant effect of age was found such that response magnitudes increased with increasing age until maximal values were reached for adults 51–60 years of age and then decreased for adults 61–75 years of age. Adults 51–60 years of age were also more sensitive to the direction and magnitude of the pitch feedback perturbations compared to younger adults. Conclusion: These findings demonstrate that the pitch-shift reflex systematically changes across the adult lifespan. Understanding aging-related changes to the role of auditory feedback is critically important for our theoretica

The socio-psychological challenges of succession in family firms: The implications of collective psychological ownership

One of the most distinct challenges that family businesses face is succession. Several researchers have recognized that it is not a single event, but a process associated with social and psychological challenges. This article advances knowledge on these challenges drawing on the theory of collective psychological ownership (CPO). More precisely, we present the socio-psychological challenges in succession, and the main factors related to them and discuss how CPO affects this relationship. This work serves as an analytical framework for future research on the topic.Post-print / Final draf