Self-Organization and Regulation of Intrinsically Disordered Proteins with Folded N-Termini

How do mostly disordered proteins coordinate the specific assembly of very large signal transduction protein complexes? A newly emerging hypothesis may provide some clues towards a molecular mechanism

Research on Markets for Inventions and Implications for R&D Allocation Strategies

Several streams of literature have examined the phenomenon of “markets for inventions”, that is, the trade of elements of knowledge which are “disembodied” from individuals, organizations, and products. The aims of this paper are to bring together the various streams of research in this area and discuss their major assumptions and limitations, in order to provide a comprehensive framework for understanding the phenomenon, and identify promising paths for future research. We start our review by identifying the object of market exchange—that is, an invention whose knowledge has been codified and disembodied from individuals, organizations, or artifacts. We then identify those factors that enable firms to trade inventions, distinguishing between institutional-, firm-, and industry-level factors. We close our analysis of the extant literature by discussing the implications of markets for inventions for firm behavior and performance. Against this background, we highlight an important avenue for future research. A neglected implication of the development of invention markets is that firms are confronted with a wide variety of technological paths from which to choose, because the opportunity to acquire technologies on the market offers them a greater variety that can their internal R&D departments. However, the streams of research on markets for inventions and on R&D allocation strategies have been surprisingly disconnected so far. Hence, in the final section, we start to establish and explore the link between these literatures, and to identify a research agenda in this domain

Influence of Surgical Approach and Fixation on Complications in Talus Fractures: A Multicenter Review.

Fractures of the talus are infrequent injuries often associated with substantial morbidity and imperfect outcomes. We undertook a retrospective review of talus fractures at several level 1 trauma centers in order to identify common treatment patterns and potential predictors of complications. All cases of talar fractures meeting inclusion criteria at our institution were reviewed. 54 of 103 talus fractures met inclusion criteria. 33 (61.1%) involved the talar neck, 13 (24.1%) the talar body, and 6 (9.2%) involved the lateral process. The most common etiology was motor vehicle accidents, accounting for 27 (50.0%). Mean follow up was 13.6 months (range 8-52 months). 37 (68.5%) fractures were fixated with screws, and 17 (31.5%) were fixated with a plate construct. Single and dual incisions were used in 63.0% and 25.9% of cases, respectively. Complications were seen in 46.3% of cases, with post-traumatic osteoarthritis being the most common complication (35.1%). Avascular necrosis occurred in 4 (7.4%) patients. No independent variables met the statistical threshold to be associated with complications. The present data alludes to possibility of over-reporting complications due to historical literature and the need for further studies

Patient Reported Outcomes Following Triple Arthrodesis for Adult Acquired Flat Foot Deformity: Minimum Two Year Follow Up.

The aim of this study is to analyze patient reported outcomes following this procedure as well as any demographics that may confer prognostic capability. A retrospective analysis was conducted of patients that underwent Triple Arthrodesis at our facility from 2014-2021. Patients were selected if they underwent an isolated triple arthrodesis. All cases included either a gastrocnemius recession versus a percutaneous tendo-achilles lengthening depending on the patient\u27s Silverskiold examination. The electronic medical record was utilized to collect basic patient demographics, previous foot and ankle surgeries, hardware failures, additional procedures, and surgical complications. To evaluate outcomes, we compared Patient Reported Outcomes Measurement Information System (PROMIS) survey scores with the general population and pre-operative vs. post-operative Visual Analog Scale (VAS) scores. Foot Function Index (FFI) scores and scores were utilized as a validation tool for our results. One hundred and thirty two patients met the criteria for our study with a total of 50 participants completing the PROMIS and FFI surveys. The average time point at which the outcomes were collected was 5.50 years postoperatively, ranging from 1.65 to 7.57 years. The average PROMIS physical function was 38.35, pain interference was 61.52, and depression was 49.82 for this population. The mean FFI scores were 58.56 for pain, 60.07 for disability, 48.07 for activity limitation. There was a significant decrease in preoperative and postoperative VAS scores from 5.4 to 2.55 (

Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL

Hepatocyte growth factor (HGF; scatter factor) is a multipotent protein with mitogenic, motogenic, and developmental functions. Upon activation, the HGF-receptor c-Met binds and phosphorylates the multisite docking protein Gab1. Besides binding motifs for phosphatidylinositol 3-kinase and Grb2, Gab 1 contains multiple Tyr-X-X-Pro (YXXP) motifs which, when phosphorylated, are potential binding sites for the adapter proteins c-Crk and Crk-like (CRKL). Stimulation of human embryonic kidney cells (HEK293) with HGF leads to Gab1 association with CRKL. The Gab1-CRKL interaction requires both, the SH2 domain of CRKL and the region containing the YXXP motifs in Gab1. CRKL binds via its first SH3 domain to several downstream signal transducers, including C3G an activator of the small GTPase Rap1. Indeed, Rap1 was rapidly activated after HGF stimulation of HEK293 cells. Rap1 activation through HGF was suppressed through transfection of a truncated C3G protein which only contains the SH3-binding motifs of C3G. Transfection of nonmutated Gab1 led to a strong increase of Rap1·GTP in the absence of HGF. In contrast, transfection of the GabΔYXXP mutant abolished the elevation of Rap1·GTP by HGF. A replating assay indicated that HGF decreases the adhesion of HEK293 cells. The results presented here delineate a novel signaling pathway from HGF to the GTPase Rap1 which depends on the interaction of the adapter protein CRKL with the exchange factor C3G and could be linked to cell migration

Be creative but not so much. Decreasing benefits of creativity in clustered firms

Several previous studies have investigated creativity as an enhancer of innovation, their results showing that there is a positive relationship between the organizational creative climate and innovation. However, no research has been conducted on whether there is a saturation point beyond which an increase in creativity makes innovation performance decrease. In this article, we question the traditional positive relationship between creativity and innovation, and suggest that such a relationship is not linear, but has instead an inverted U-shape due to a saturation effect. We have developed a conceptual model to explain innovation performance considering creativity and network centrality, and it has been tested in the ceramic industrial cluster in Spain. Empirical findings support the inverted U-shaped relationship between creativity and innovation. The implications of these results in relation to creativity and innovation theory and practices are discussed