Inhibition of tryptophan 2,3-dioxygenase impairs DNA damage tolerance and repair in glioma cells.

Expression of tryptophan 2,3-dioxygenase (TDO) is a determinant of malignancy in gliomas through kynurenine (KYN) signaling. We report that inhibition of TDO activity attenuated recovery from replication stress and increased the genotoxic effects of bis-chloroethylnitrosourea (BCNU). Activation of the Chk1 arm of the replication stress response (RSR) was reduced when TDO activity was blocked prior to BCNU treatment, whereas phosphorylation of serine 33 (pS33) on replication protein A (RPA) was enhanced-indicative of increased fork collapse.

Disfluency Characteristics of 4- and 5-Year-Old Children Who Stutter and Their Relationship to Stuttering Persistence and Recovery.

Purpose The purpose of this study is to document disfluency behaviors expressed by 4- and 5-year-old children who stutter and to identify whether stuttering characteristics at this age are predictive of later stuttering recovery or persistence. Method We analyzed spontaneous speech samples from 47 children diagnosed with developmental stuttering when they were 4-5 years old. Based on their eventual diagnosis made the final year of participation in the longitudinal study when the children were 6-9 years old, the children were divided into two groups: children who eventually recovered from stuttering ( = 29) and children who were persisting ( = 18).

What Are Predictors for Persistence in Childhood Stuttering?

Over the past 10 years, we (the Purdue Stuttering Project) have implemented longitudinal studies to examine factors related to persistence and recovery in early childhood stuttering. Stuttering develops essentially as an impairment in speech sensorimotor processes that is strongly influenced by dynamic interactions among motor, language, and emotional domains. Our work has assessed physiological, behavioral, and clinical features of stuttering within the motor, linguistic, and emotional domains.

Hemodynamics of speech production: An fNIRS investigation of children who stutter.

Stuttering affects nearly 1% of the population worldwide and often has life-altering negative consequences, including poorer mental health and emotional well-being, and reduced educational and employment achievements. Over two decades of neuroimaging research reveals clear anatomical and physiological differences in the speech neural networks of adults who stutter. However, there have been few neurophysiological investigations of speech production in children who stutter.

Aberrant Kynurenine Signaling Modulates DNA Replication Stress Factors and Promotes Genomic Instability in Gliomas.

Metabolism of the essential amino acid L-tryptophan (TRP) is implicated in a number of neurological conditions including depression, neurodegenerative diseases, and cancer. The TRP catabolite kynurenine (KYN) has recently emerged as an important neuroactive factor in brain tumor pathogenesis, with additional studies implicating KYN in other types of cancer. Often highlighted as a modulator of the immune response and a contributor to immune escape for malignant tumors, it is well-known that KYN has effects on the production of the coenzyme nicotinamide adenine dinucleotide (NAD(+)), which can have a direct impact on DNA repair, replication, cell division, redox signaling, and mitochondrial function.