By tethering their circular genomes (episomes) to host chromatin, DNA tumor viruses ensure retention and segregation of their genetic material during cell divisions. Despite functional genetic and crystallographic studies, there is little information addressing the 3D structure of these tethers in cells, issues critical for understanding persistent infection by these viruses. Here, we have applied direct stochastic optical reconstruction microscopy (dSTORM) to establish the nanoarchitecture of tethers within cells latently infected with the oncogenic human pathogen, Kaposi's sarcoma-associated herpesvirus (KSHV). Each KSHV tether comprises a series of homodimers of the latency-associated nuclear antigen (LANA) that bind with their C termini to the tandem array of episomal terminal repeats (TRs) and with their N termini to host chromatin. Superresolution imaging revealed that individual KSHV tethers possess similar overall dimensions and, in aggregate, fold to occupy the volume of a prolate ellipsoid. Using plasmids with increasing numbers of TRs, we found that tethers display polymer power law scaling behavior with a scaling exponent characteristic of active chromatin. For plasmids containing a two-TR tether, we determined the size, separation, and relative orientation of two distinct clusters of bound LANA, each corresponding to a single TR. From these data, we have generated a 3D model of the episomal half of the tether that integrates and extends previously established findings from epifluorescent, crystallographic, and epigenetic approaches. Our findings also validate the use of dSTORM in establishing novel structural insights into the physical basis of molecular connections linking host and pathogen genomes.
Neurogenic Thoracic Outlet Syndrome (NTOS) is a rare, but controversial syndrome in relation to its diagnosis, treatment modality, and approaches in case of surgical treatment. In the English literature, there are sparse studies dealing with these aspects. We conducted a PubMed 2000-2017 literature review and found a total of 3953 cases reported with NTOS. The clinical characteristics, etiology, electrophysiological and radiological work-up and treatment options were reviewed and reported. It seems that, as far as surgical indication criteria are concerned, there is a consensus for NTOS in its motor deficit stage and its techniques are generally well established. This review showed that differential diagnosis, radiological, and electrophysiological criteria for correct diagnosis of NTOS are not controversial. However, surgical indications and types of approaches and techniques reflect the surgeon’s affiliation with specialties dealing with NTOS (vascular, plastic, hand, orthopedic or neurosurgeons), and the surgeon’s experience with this specific and rare syndrome.
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