Drug Development.

Background: Efforts to genetically reverse C9orf72 pathology have been hampered by our incomplete understanding of the regulation of this complex locus.

Method: We generated five different genomic excisions at the C9orf72 locus in a patient-derived iPSC line and a WT line (11 total isogenic lines), and examined gene expression and pathological hallmarks of C9 FTD/ALS in motor neurons differentiated from these lines. Comparing the excisions in these isogenic series removed the confounding effects of different genomic backgrounds and allowed us to probe the effects of specific genomic changes.

The relationship between COMT, proline, and negative symptoms in clinical high risk and recent psychosis onset.

Individuals at clinical high-risk (CHR) of developing psychosis, as well as patients with recent psychosis onset (RO), experience significant negative symptoms that detrimentally impact daily-life functioning and are associated with poor outcomes, even in those who do not convert to psychosis. Targeting negative symptoms may thus hold promise for the treatment of CHR and RO patients. Building from previous findings we examined whether the catechol-O-methyltransferase (COMT) ValMet functional polymorphism and fasting peripheral proline concentration predicts the severity of negative symptoms experienced by adolescents and young adults at CHR or those with RO.

Small cell lung cancer associated small bowel obstruction, a diagnostic conundrum: A case report.

Small cell lung cancer (SCLC), a neuroendocrine aggressive subtype of lung cancer, is associated with paraneoplastic disorders in about 9% of patients. In this report, we describe a middle-aged man who presented with chronic bowel obstruction caused by chronic intestinal pseudo-obstruction (CIPO) due to SCLC.

Zfp106 binds to G-quadruplex RNAs and inhibits RAN translation and formation of RNA foci caused by G4C2 repeats.

Expansion of intronic GGGGCC repeats in the gene causes amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Transcription of the expanded repeats results in the formation of RNA-containing nuclear foci and altered RNA metabolism. In addition, repeat-associated non-AUG (RAN) translation of the expanded GGGGCC-repeat sequence results in the production of highly toxic dipeptide-repeat (DPR) proteins.