Curious enough to start up? How epistemic curiosity and entrepreneurial alertness influence entrepreneurship orientation and intention

Epistemic curiosity as the desire to acquire new knowledge and ideas is considered as an important attribute for successful entrepreneurs among practitioners, yet there is lacking empirical evidence of epistemic curiosity having an effect on entrepreneurial outcomes. This study aims to put a spotlight on epistemic curiosity as a predictor for entrepreneurial intentions and orientation. We found that epistemic curiosity has a stronger influence on entrepreneurial outcomes in comparison to the Big Five personality trait openness to experience, which is a widely used and conceptually related predictor for entrepreneurship. Furthermore, we found evidence for a mediating role of entrepreneurial alertness which gives further insights about how personality influences the ability to recognize business opportunities and leads to the formation of entrepreneurship orientation and intentions. Our findings contribute to the field of entrepreneurship research by emphasizing that epistemic curiosity may be one of the most important personality indicators for the emergence of entrepreneurial intentions and behavior

Expression und Charakterisierung des Andes-Virus L-Proteins

Andes virus (ANDV) is a member of the genus Hantavirus. Little is known about structure and function of the hantaviral L protein. Sequence alignments revealed a putative RNA-dependent RNA polymerase domain in the center and an endonuclease at the N terminus. Studying hantaviral L proteins is difficult, because recombinant L protein expression in mammalian cells is very ineffective. Deletion analysis revealed that the N terminus determine the low-expression phenotype. This work demonstrates that ANDV L protein expression can be rescued upon mutation of catalytic amino acids and further conserved residues of the putative endonuclease domain. In addition, wild-type ANDV L rather than expressible L mutants suppressed the level of mRNA and reduces protein expression. Expressible ANDV L mutants colocalized with the cellular processing (P) bodies, ANDV N and NSs protein, but not with the glycoprotein Gc. This work suggests that ANDV L protein possesses an endonuclease at the N terminus suppressing the level of its own as well as heterologous mRNAs upon recombinant expression in mammalian cells

Gold nanoparticle-mediated laser stimulation causes a complex stress signal in neuronal cells

Gold nanoparticle mediated laser stimulation of neuronal cells allows for cell activation on a single-cell level. It could therefore be considered an alternative to classical electric neurostimulation. The physiological impact of this new approach has not been intensively studied so far. Here, we investigate the targeted cell's reaction to a laser stimulus based on its calcium response. A complex cellular reaction involving multiple sources has been revealed. © 2017 SPIE-OSA

Cardiac myxomas: Short- and long-term follow-up

Background: Cardiac myxomas are the most frequently encountered benign intracardiac tumors, that, if left untreated, are inexorably progressive and potentially fatal. Patients with cardiac myxoma can be treated only by surgical removal. This study summarizes our experience over 22 years with these tumors. Methods: Fifty seven patients (M/F: 14/43, age: 57.9 ± 14.6 years) with cardiac myxomas underwent surgical resection at our institution. There were 82.4% left atrial myxomas, 14.0% right atrial myxomas, 3.6% biatrial myxomas. The duration of symptoms prior to surgery ranged from 6 to 1,373 days (median 96 days). The surgical approach comprised complete wide excision. The diagnostic methods, incidence of thromboembolic complications, valve degeneration, surgical repair techniques, recurrence and re-operation were reviewed and the Kaplan-Meier survival curve was calculated. Results: There were no in-hospital deaths. Hospital stay amounted to a mean of 13.7 ± 6.9 days. Late follow-up was available for 54 (94.7%) patients for a median 7.5 years after surgery (23 days to 21.4 years). Fifty two patients are alive, while five patients had died after a mean interval of 6.3 years. Cause of death was cardiac in 40% of the patients (n = 2) and non-cardiac in the other 60% (n = 3). Conclusions: Surgical excision of cardiac myxoma carries a low operative risk and gives excellent short-term and long-term results. Surgical excision of the tumor appears to be curative, with few recurrences at long-term follow-up. After diagnosis, surgery should be performed urgently, in order to prevent complications such as embolic events or obstruction of the mitral orifice. Follow-up examination, including echocardiography, should be performed regularly

Using Rasch Analysis to Develop the Communication Confidence Rating Scale for Aphasia (CCRSA)

The Communication Confidence Rating Scale for Aphasia (CCRSA) was developed to measure the construct of confidence in communication abilities. Using eight items from the ASHA-Quality of Communication Life Scale, the CCRSA was developed and administered to 21 individuals with aphasia before and after therapy. Psychometric properties of the CCRSA were investigated using rating scale (Rasch) analysis. Preliminary reliability and sensitivity of the CCRSA support its use in assessing self-report of communication confidence. Results indicate that modification of the scale is warranted. Further evaluation of communication confidence is required with larger and more diverse samples

Gld2 activity is regulated by phosphorylation in the N-terminal domain

The de-regulation of microRNAs (miRNAs) is associated with multiple human diseases, yet cellular mechanisms governing miRNA abundance remain largely elusive. Human miR-122 is required for Hepatitis C proliferation, and low miR-122 abundance is associated with hepatic cancer. The adenylyltransferase Gld2 catalyses the post-transcriptional addition of a single adenine residue (A + 1) to the 3ʹ-end of miR-122, enhancing its stability. Gld2 activity is inhibited by binding to the Hepatitis C virus core protein during HepC infection, but no other mechanisms of Gld2 regulation are known. We found that Gld2 activity is regulated by site-specific phosphorylation in its disordered N-terminal domain. We identified two phosphorylation sites (S62, S110) where phosphomimetic substitutions increased Gld2 activity and one site (S116) that markedly reduced activity. Using mass spectrometry, we confirmed that HEK 293 cells readily phosphorylate the N-terminus of Gld2. We identified protein kinase A (PKA) and protein kinase B (Akt1) as the kinases that site-specifically phosphorylate Gld2 at S116, abolishing Gld2-mediated nucleotide addition. The data demonstrate a novel phosphorylation-dependent mechanism to regulate Gld2 activity, revealing tumour suppressor miRNAs as a previously unknown target of Akt1-dependent signalling

Structural analysis of PLD3 reveals insights into the mechanism of lysosomal 5′ exonuclease-mediated nucleic acid degradation

The phospholipase D (PLD) family is comprised of enzymes bearing phospholipase activity towards lipids or endo- and exonuclease activity towards nucleic acids. PLD3 is synthesized as a type II transmembrane protein and proteolytically cleaved in lysosomes, yielding a soluble active form. The deficiency of PLD3 leads to the slowed degradation of nucleic acids in lysosomes and chronic activation of nucleic acid-specific intracellular toll-like receptors. While the mechanism of PLD phospholipase activity has been extensively characterized, not much is known about how PLDs bind and hydrolyze nucleic acids. Here, we determined the high-resolution crystal structure of the luminal N-glycosylated domain of human PLD3 in its apo- and single-stranded DNA-bound forms. PLD3 has a typical phospholipase fold and forms homodimers with two independent catalytic centers via a newly identified dimerization interface. The structure of PLD3 in complex with an ssDNA-derived thymidine product in the catalytic center provides insights into the substrate binding mode of nucleic acids in the PLD family. Our structural data suggest a mechanism for substrate binding and nuclease activity in the PLD family and provide the structural basis to design immunomodulatory drugs targeting PLD3

Directed evolution of a biterminal bacterial display scaffold enhances the display of diverse peptides

Bacterial cell-surface display systems coupled with quantitative screening methods offer the potential to expand protein engineering capabilities. To more fully exploit this potential, a unique bacterial surface display scaffold was engineered to display peptides more efficiently from the surface exposed C- and N-termini of a circularly permuted outer membrane protein. Using directed evolution, efficient membrane localization of a circularly permuted OmpX (CPX) display scaffold was rescued, thereby improving the presentation of diverse passenger peptides on the cell surface. Random and targeted mutagenesis directed towards linkers joining the native N- and C-termini of OmpX coupled with screening by FACS yielded an enhanced CPX (eCPX) variant which localized to the outer membrane as efficiently as the non-permuted parent. Interestingly, enhancing substitutions coincided with a C-terminal motif conserved in outer membrane proteins. Surface localization of various passenger peptides and mini-proteins was expedited using eCPX relative to that achieved with the parent scaffold. The new variant also permitted simultaneous display and labeling of distinct peptides on structurally adjacent C- and N-termini, thus enabling display level normalization during library screening and the display of bidentate or dimeric peptides. Consequently, the evolved scaffold, eCPX, expands the range of applications for bacterial display. Finally, this approach provides a route to improve the performance of cell-surface display vectors for protein engineering and design