Distinct Type of Transmission Barrier Revealed by Study of Multiple Prion Determinants of Rnq1

Prions are self-propagating protein conformations. Transmission of the prion state between non-identical proteins, e.g. between homologous proteins from different species, is frequently inefficient. Transmission barriers are attributed to sequence differences in prion proteins, but their underlying mechanisms are not clear. Here we use a yeast Rnq1/[PIN+]-based experimental system to explore the nature of transmission barriers. [PIN+], the prion form of Rnq1, is common in wild and laboratory yeast strains, where it facilitates the appearance of other prions. Rnq1's prion domain carries four discrete QN-rich regions. We start by showing that Rnq1 encompasses multiple prion determinants that can independently drive amyloid formation in vitro and transmit the [PIN+] prion state in vivo. Subsequent analysis of [PIN+] transmission between Rnq1 fragments with different sets of prion determinants established that (i) one common QN-rich region is required and usually sufficient for the transmission; (ii) despite identical sequences of the common QNs, such transmissions are impeded by barriers of different strength. Existence of transmission barriers in the absence of amino acid mismatches in transmitting regions indicates that in complex prion domains multiple prion determinants act cooperatively to attain the final prion conformation, and reveals transmission barriers determined by this cooperative fold

A comprehensive overview of radioguided surgery using gamma detection probe technology

The concept of radioguided surgery, which was first developed some 60 years ago, involves the use of a radiation detection probe system for the intraoperative detection of radionuclides. The use of gamma detection probe technology in radioguided surgery has tremendously expanded and has evolved into what is now considered an established discipline within the practice of surgery, revolutionizing the surgical management of many malignancies, including breast cancer, melanoma, and colorectal cancer, as well as the surgical management of parathyroid disease. The impact of radioguided surgery on the surgical management of cancer patients includes providing vital and real-time information to the surgeon regarding the location and extent of disease, as well as regarding the assessment of surgical resection margins. Additionally, it has allowed the surgeon to minimize the surgical invasiveness of many diagnostic and therapeutic procedures, while still maintaining maximum benefit to the cancer patient. In the current review, we have attempted to comprehensively evaluate the history, technical aspects, and clinical applications of radioguided surgery using gamma detection probe technology

The Aging Overactive Bladder: a Review of Aging-Related Changes from the Brain to the Bladder

Purpose of reviewTo understand the current literature on age-related neural and detrusor changes associated with overactive bladder symptoms.Recent findingsRecent functional magnetic resonance imaging (fMRI) studies have unveiled an age-related decrease in the neural control of continence, represented in the insula, anterior cingulate cortex (ACC) and prefrontal cortex (PFC). Older individuals with overactive bladder symptoms also demonstrate heightened activation of the ACC with low volumes, representing increased bladder sensitivity or sense of urgency. At the level of the bladder, age-related changes in the urothelium, neurotransmitters/receptors (both muscarinic and purinergic), and inflammation [including nerve growth factor (NGF), monocyte chemoattractant protein-1 (MCP-1) and oxidative stress] are also associated with overactive bladder.SummaryOveractive bladder among older adults is a complex condition incorporating physiologic age-related changes from the brain to the bladder and beyond