Improving startups through excellence initiatives: addressing circular economy and innovation.

This study analyses how startups implement circular business models supported by innovation and Industry 4.0, in which strategic stakeholders for value creation are to be found in this specific business ecosystem. The theoretical framework of circular business models supported by innovation was used for analysing the startups based on some assumptions of stakeholder theory. Fifty-one startups were selected, which correspond to the unit of analysis for this study on the improvement of supply chains through circular business models supported by innovation aimed at sustainability in organizations. We conducted a multiple case study whose results suggest that: (i) circularity is strategic for the business to assume its commitment to a sustainable development agenda, especially regarding pollution prevention and proactive action; (ii) visionary entrepreneurs are actively engaged with circular economy practices and technological innovation to promote a circular flow for their business ecosystem; (iii) Industry 4.0 is still incipient, but it is synergistic and beneficial for a successful circular economy in startups; and (iv) primary stakeholders are the activators of circular cycles in the startups surveyed. The present study contributes to the literature in four ways by: (i) presenting a framework which brings together exploratory theoretical propositions on strategic stakeholders for startups, innovative capabilities and assumptions of circular business models; (ii) validating exploratory theoretical propositions with 51 startups; (iii) providing lessons learned so far by the startups which are in line with the assumptions of circular business models for triggering their innovation capabilities and promoting Industry 4.0; (iv) providing an original typology of circular economy assumptions and technological innovations adopted by startups. The originality of this study lies in presenting useful insights for motivating managers to: (i) invest in circular business to become one of the first entrants and earn extra profits; (ii) make investments in circular business and technological innovations to obtain efficiency, practicality and process optimization; (iii) internalize Industry 4.0 technologies concomitantly with technological innovations and circular economy to generate systemic effects; (iv) integrate relevant stakeholders of the business ecosystem to generate a synergistic and effective effect for sustainable development.

The Ca(2+)-binding protein calretinin is selectively enriched in a subpopulation of the epithelial rests of Malassez.

During tooth development, the inner and outer enamel epithelia fuse by mitotic activity to produce a bilayered epithelial sheath termed Hertwig's epithelial root sheath (HERS). The epithelial rests of Malassez (ERM) are the developmental residues of HERS and remain in the adult periodontal ligament (PDL). Although the cellular regulation of the Ca(2+)-binding proteins parvalbumin, calbindin-D28k, and calretinin has been reported in the inner and outer enamel epithelia during tooth development, an involvement of Ca(2+)-binding proteins in the ERM has not so far been characterized. Among the three Ca(2+)-binding proteins tested (calbindin D28k, parvalbumin, calretinin), we have only been able to detect calretinin in a subpopulation of adult rat molar ERM, by using quantitative immunohistochemical and confocal immunofluorescence techniques. TrkA (a marker for ERM) is present in numerous epithelial cell clusters, whereas calretinin has been localized in the cytosol and perinuclear region of a subpopulation of TrkA-positive cells. We conclude that, in inner and outer enamel epithelial cells, Ca(2+) is regulated by calbindin, parvalbumin, and calretinin during tooth development, whereas in the ERM of adult PDL, Ca(2+) is regulated only by calretinin. The expression of Ca(2+)-binding proteins is restricted in a developmental manner in the ERM.

The constitutive activation of extracellular signal-regulated kinase 1 and 2 in periodontal ligament nerve fibers.

BACKGROUND: The extracellular signal-regulated kinases 1 and 2 (ERK1/2) have been implicated in the inflammation-dependent sensitization of nociceptors. Because the periodontal ligament (PDL) contains numerous nociceptors and mechanoceptors, phosphorylation of ERK1/2 was investigated in nerve fibers of the PDL to elucidate the role of constitutive local activation of ERK1/2 in peripheral sensitization. METHODS: Decalcified free-floating sections of rat molars with PDL were incubated using total (t)-ERK1/2 and phosphorylated (p)-ERK1/2 antibodies. For identification of nerve fibers in the PDL, double staining was performed using protein gene product 9.5 (PGP 9.5) with p-ERK1/2. To test whether p-ERK1/2 activated in sensory and mechanoreceptive terminals, double incubations were performed using p-ERK1/2 with calcitonin gene-related peptide (CGRP) and with calretinin. Labeled nerve fibers were quantified by the point-counting method. RESULTS: In cervical, midroot, and apical zones of the PDL, t-ERK1/2- and p-ERK1/2-labeled nerve fibers were found in close association with blood vessels. The p-ERK1/2-labeled free nerve fibers were often detected in cervical and apical areas of the PDL. In nerve fibers of the PDL, p-ERK1/2 was colocalized with PGP 9.5, CGRP, and calretinin. CONCLUSIONS: The perivascular distribution of t-ERK1/2 and p-ERK1/2 in nerve fibers in the PDL is compatible with a role for the constitutive activation of ERK1/2 in the neural regulation of blood vessels in the PDL. The colocalizations of p-ERK1/2 with CGRP and calretinin indicate that ERK1/2 is constitutively activated in a subpopulation of sensory and mechanoreceptive nerve terminals in the PDL.

The early history of the transmissible spongiform encephalopathies exemplified by scrapie.

Transmissible spongiform encephalopathies (TSE) is a group of diseases that is unique in comprising disorders that can occur sporadically, are hereditary and/or infectious. The transmissible pathogen--the prion--is distinct from all other pathogens in being devoid of nucleic acids. During the elucidation of these disorders, many different--and contradictory--theories have been put forward. Early researchers, mostly driven by the economic impact of these diseases on sheep farming, engaged in heavy disputes concerning heredity vs. infectivity of scrapie. Following the experimental demonstration of scrapie's infectivity during the 20th century, research focused on the characterization of the nature of the transmissible agent. The current work comprehensively summarizes the available early literature on TSE research. A review of the historical literature is presented, describing the efforts in breeding, transmission experiments, and theories about the nature of the infectious agent.

Prion protein (PrP) in human teeth: an unprecedented pointer to PrP's function.

Although prion protein's (PrP) involvement in transmission of degenerative neurological diseases has been subjected to considerable scrutiny, its physiological role is still obscure. The distribution of PrP in dental tissues was investigated using three different methods: immunohistochemistry, cell culture, and scanning electron microscopy. PrP knockout mice were found to have marked anomalies in dentin structure. In human teeth, cementoblasts and odontoblasts showed prominent staining for PrP at levels comparable to those of nerve fibers. Epithelial rests of Malassez, which are remnants of a cell type formerly forming enamel, were also positive. Thus, all PrP-positive cells in human dentition are in some way involved in calcified tissue formation. This suggests a previously undetected function of prion protein in healthy vertebrates as evidenced by an obvious phenotype in PrP knockout mice. Periodontal and pulpal tissue exposed by disease or trauma might represent a clinically relevant entry point for prions incorporated orally and thus a possible mode of infection.

The Basal phosphorylation sites of endothelial nitric oxide synthase at serine (Ser)1177, Ser116, and threonine (Thr)495 in rat molar epithelial rests of Malassez.

BACKGROUND: The epithelial rests of Malassez (ERM) are derived from the Hertwig's epithelial root sheath during tooth development. The ERM contain endothelial nitric oxide synthase (eNOS), but the existence of phosphorylation site/s of eNOS in the ERM is unclear. METHODS: Rat molars with periodontium were perfusion- and post-fixed, decalcified, and frozen-sectioned. Free-floating sections were incubated using antisera against total eNOS, eNOS phosphorylated at serine (Ser)1177, Ser116, and threonine (Thr)495. The signal intensities of t-eNOS, p-eNOS at Ser1177 and Ser116 in the ERM were measured by densitometry and statistically analyzed. RESULTS: In the ERM, localization of total eNOS and the phosphorylation sites of eNOS at Ser1177 and Ser116 were detected, while a basal localization of eNOS phosphorylated at Thr495 in the ERM was undetectable. For p-eNOS at Ser116 regional differences in phosphorylation were detected. CONCLUSIONS: The basal production of NO by eNOS in the ERM is modulated by phosphorylation of eNOS at Ser1177 and Ser116 residues, while the basal activity of the eNOS is not influenced by phosphorylation of eNOS at Thr495 residue. This provides evidence that phosphorylation plays a key role for regulation of the catalytic activity of eNOS.