20 research outputs found
Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli
Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts. Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins. Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets
Anticipation in entrepreneurship
Entrepreneurship is a forward looking activity that embodies implicit imaginaries. If we remove the notion of a future from the field of entrepreneurship, field would cease to exist as its whole rationale is prospective. Entrepreneurship creates future value (Schumpeter 1934) through creative destruction; in uncertain contexts (Knight 1923) and with ‘alertness’ to opportunity (Kirzner 1982). Entrepreneurial opportunity em-braces anticipation as imaginative reason, strategically employed and motivated by aspiration. Entrepreneurial effectuation is concerned with the controllable aspects of an unpredictable future. Entrepreneuring is a process (Steyaert 2007) producing ontological emergence. Entrepreneurship is expressed in action and produces change. Nadin observes that anticipation relates to the perception of change (Nadin 2010) and is always expressed in action (Nadin 2015). Entrepreneurial identity is sig-nificant and the models embodied in an anticipatory system are what comprise its individuality; what distinguish it uniquely from other sys-tems. A change in these models is a change of identity (Rosen et al. 2012, p370). Entrepreneurship is relational and is coupled with other ac-tors in the environment, generating a sense of shared anticipation, or anticipatory coupling. Anticipatory coupling as a social phenomenon seems ripe for further research. Being emplaced, entrepreneuring practice involve sensing and anticipation (Antonacopoulou and Fuller 2019). Although anticipation is a natural activity, the effectiveness of anticipation can be improved through greater awareness in each of these sets of processes, among others. We suggest that the dynamics of emergence require anticipations of multiple forms of value. Seeing entrepreneurship from an anticipatory standpoint brings more to the fore the nature of values in practice. Further research can help reveal the anticipatory work is done in entrepreneurship to maintain the anticipatory capacity of the enterprise and of the interdependent relationships that maintain the enterprise
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference