IAP antagonist Grim mediates cell death through divergent pathways

Apoptosis is an evolutionarily conserved process, carried out through proteolytic cascades that lead to activation of cysteinyl aspartate-specific proteases (caspases), which in turn cause cell self-destruction. While caspases are activated upon various death stimuli or developmental cues, inhibitor of apoptosis (IAPs) can prevent caspase-mediated cell death, not only through direct binding and inhibition, but also by directly ubiquitinating caspases, which inactivates them or targets them for degradation. In flies and mammals, cell death is facilitated or enhanced by the accumulation of “IAP antagonists”, which promote cell death by utilizing their N-terminal IAP binding motifs (IBMs) to interact with IAPs, to displace caspases from IAP-binding, and to promote IAPs autoubiquitination. Herein, we demonstrate that a Drosophila IAP antagonist, Grim, induces cell death through divergent mechanisms: an IBM-dependent pathway, requiring a crosstalk with Drosophila IAP1 (DIAP1), and an IBM-independent manner, involving Grim’s C-terminus for translational repression. We discovered that Grim is a target for caspase-mediated cleavage at Grim’s C-terminus (Asp132). Grim loses its only lysine (Lys 136) after cleavage, but acquires a longer half-life due to inability of DIAP1 to ubiquitinate it, which in turn leads to greater cell death. This novel regulation allows increased levels of Grim to efficiently kill through an IBM-dependent mechanism that derepresses caspase inhibition. However, in addition to IBM-dependent cell death, Grim is able to induce caspase activation independent of its IBM. In our studies, we have demonstrated that IBM-independent cell death requires Grim’s C-terminal domain as well as the characteristic Grim Helix 3 (GH3) domain. Importantly, Grim’s C-terminus localizes Grim to distinct cytoplasmic granules, i.e. P-bodies, where translation is repressed due to the accumulation of protein components that regulate mRNA translation or stability. Knockdown of a P-body-localized translational repressor, Me31B, largely reduced IBM-independent cell death. Taken together, IBM-independent cell death occurs, at least in part, through Me31B-mediated translational repression, requiring the localization of Grim to P-bodies via Grim’s C-terminus. Overall, we have discovered that the interplay between caspases and the proteasome system creates an intricate regulatory system for maintaining Grim at low levels in the cell under normal conditions. Once needed, Grim levels accumulate rapidly and induce cell death efficiently through IBM-dependent destruction of DIAP1 and derepression of caspases as well as through IBM-independent translational repression.Cellular and Molecular Biolog

Laparoscopic resection of perforated duodenal diverticulum – A case report and literature review

AbstractBackgroundDuodenum diverticulum is the most common site for diverticular disease of small intestine. Most of duodenal diverticulum are asymptomatic, but complicated or perforated duodenal diverticulum is rare. Nonoperative management is attractive in selected patients, because of higher surgical complications. We suggest the use of a minimally invasive operative method as an alternative approach for the management of complicated duodenal diverticulum, especially when conservative treatment has failed.Case presentationA 67-year-old female was admitted to Emergency Department with sudden onset of severe right upper abdominal pain and fever (38.2°C) lasted 8h. Abdominal computed tomographic imaging was performed and a perforated duodenal diverticulum with right-sided anterior pararenal space free air and fluid retention was identified. After assessment and resuscitation, proper treatment modality was selected taking in consideration type, location and complication of duodenal diverticulum. A emergency laparoscopic duodenal diverticulectomy with intraabdominal drainage was performed. Postoperative period was uneventful and patient was discharged on the 10th postoperative day. English literatures discussing laparoscopic management for complicated duodenal diverticulum were carefully reviewed.ConclusionsLaparoscopic approach showed less complication, shorted hospital stay and better outcome in comparison to conservative, or open surgery. Laparoscopic approach is safe and feasible in selected cases of complicated duodenal diverticulum (laterally located and protruding duodenal diverticulum). With advances in laparoscopic instruments and techniques, complicated duodenal diverticulums can be managed safely by laparoscopically

On the boundary of the numerical range of a matrix

AbstractA characterization of real matrices is given for which a diagonal entry of a matrix is a boundary point of its numerical range

Cultivating Social Capital through Interactivity on Social Network Sites

The Internet has changed from an information tool to a social tool. More and more people use social networking sites such as Facebook to build and maintain numerous interpersonal relationships. The benefits of online social interaction can be manifested in bridging and bonding social capital. This study examined how the four dimensions of perceived interactivity (control, synchronicity, surveillance, and social bandwidth) affected users’ bridging and bonding social capital. Moreover, this study also assessed how the effects of perceived interactivity on bridging and bonding social capital were mediated by communication quality and social relationship support. This study recruited 422 respondents to participate in the survey. The first results showed that three out of four dimensions of perceived interactivity (control, synchronicity, and social bandwidth) positively influenced bridging and bonding social capital, whereas perceived surveillance negatively affected bridging social capital. Moreover, they have a stronger effect on bridging than on bonding social capital. The second findings revealed that the relationships between the two dimensions of perceived interactivity (synchronicity and social bandwidth) and bridging social capital were mediated by social relationship support

Investigating New Forms of Single-handed Physical Phone Interaction with Finger Dexterity

With phones becoming more powerful and such an essential part of our lives, manufacturers are creating new device forms and interactions to better support even more diverse functions. A common goal is to enable a larger input space and expand the input vocabulary using new physical phone interactions other than touchscreen input. This thesis explores how utilizing our hand and finger dexterity can expand physical phone interactions. To understand how we can physically manipulate a phone using the fine motor skills of finger, we identify and evaluate single-handed "dexterous gestures". Four manipulations are defined: shift, spin (yaw axis), rotate (roll axis) and flip (pitch axis), with a formative survey showing all except flip have been performed for various reasons. A controlled experiment examines the speed, behaviour, and preference of manipulations in the form of dexterous gestures, by considering two directions and two movement magnitudes. Using a heuristic recognizer for spin, rotate, and flip, a one-week usability experiment finds increased practice and familiarity improve the speed and comfort of dexterous gestures. With the confirmation that users can loosen their grip and perform gestures with finger dexterity, we investigate the performance of one-handed touch input on the side of a mobile phone. An experiment examines grip change and subjective preference when reaching for side targets using different fingers. Two following experiments examine taps and flicks using the thumb and index finger in a new two-dimensional input space. We simulate a side-touch sensor with a combination of capacitive sensing and motion tracking to distinguish touches on the lower, middle, or upper edges. We further focus on physical phone interaction with a new phone form factor by exploring and evaluating single-handed folding interactions suitable for "modern flip phones": smartphones with a bendable full screen touch display. Three categories of interactions are identified: only-fold, touch-enhanced fold, and fold-enhanced touch; in which gestures are created using fold direction, fold magnitude, and touch position. A prototype evaluation device is built to resemble current flip phones, but with a modified spring system to enable folding in both directions. A study investigates performance and preference for 30 fold gestures, revealing which are most promising. Overall, our exploration shows that users can loosen their grip to physically interact with phones in new ways, and these interactions could be practically integrated into daily phone applications

Personal space in libraries: the influence of lighting on choice

A quasi-experimental study conducted in Ames Public Library, Ames, Iowa was used to evaluate whether lighting would be the main element influencing library users\u27 choice of study space, or the greater influence could be the need for personal privacy. The study had 15 study carrel seats; each study carrel had a small built-in bookshelf and side dividers to provide an individual user space. The experiment was composed of two parts: the first part (the control setting) was conducted under existing library lighting conditions, and the second part (the test setting) incorporated four additional desk light fixtures into the space. The survey questionnaire and observations were distributed and conducted for investigating the possible changes in seating pattern related to the additional light fixtures. Cross-tabs, chi-square, independent-sample T-Test, and one-way ANOVA in SPSS statistical program (version 11.0) were used to investigate five research questions which examine the major hypothesis of this study does lighting significantly affect choice of study space. The result supported the hypothesis and suggested lighting does not only provide library users the visual illuminations to check out books, and also it is an important element for determining the functional and efficient work surface that would influence users\u27 choice on where they like to work. Even though 70 to 80 percent of library users and the building standard codes suggests the light is bright enough in general, the placement of the additional task light fixtures will be another helpful tool to create a more aesthetically pleasing and comfortable reading space for all library users