Tedizolid HCl Nematode species display remarkable versatilit

Nematode species display remarkable versatility in relation to the diverse trophic niches that they occupy and display substantial diversity at morphological levels of the intestine (Munn and Greenwood, 1984). Hence, while many basic intestinal cell characteristics are likely to be broadly conserved, other characteristics may markedly vary among different nematode lineages and species. Orthologous protein families conserved among phylogenetically diverse nematode species have been investigated (Mitreva et al., 2011), while only modest attempts have been made to deduce characteristics of nematode intestinal Tedizolid HCl that are conserved among, and potentially ancestral to, all nematodes (Yin et al., 2008). The selection of species investigated was critical for success in this research (Fig. 1). Using RNA from dissected intestines we directly identified the genes expressed in the adult intestine of three parasitic nematode species of livestock: Trichuris suis, Ascaris suum and Haemonchus contortus. Each of these is a soil transmitted pathogen with model applications to other phylogenetically related pathogens of humans and animals. Each of these species, referred to here as ‘core species’, is a member of a different and diverse nematode taxonomic clade (I, III and V, respectively (Blaxter et al., 1998)), and each core species occupies a distinct trophic niche (epithelial layer of the swine cecum, swine small intestinal lumen and blood feeder at the abomasal mucosa of small ruminants, respectively), likely requiring diverse adaptations for success (Fig. 1). Therefore, intestinal cell proteins and functions conserved among these phylogenetically and biologically diverse nematodes are likely to reflect basic features ancestral to many or all nematodes. Beyond these considerations, the relatively large size of the adult worms of each of the core species supports dissection to obtain intestinal tissue and RNA, which is otherwise difficult for most nematode species.
Materials & Methods
Results
Discussion Biological characteristics unique, by comparison to other tissues, to the intestine of parasitic nematodes have led to promising new approaches for therapies to treat and control infections caused by these pathogens of humans, animals and possibly plants (Jasmer et al., 1993, 2000, 2007; Smith, 1993; Hu et al., 2010, 2012; Kao et al., 2011). Despite the promising advances, research on the intestine has been impeded by a poor understanding of the protein constituents that comprise the intestinal proteome and perform functions essential for survival of nematodes. While it is expected that many intestinal cell characteristics will be conserved among nematodes, expectations of high functional diversity among the many and varied nematode species are raised simply by considering the broad diversity in intestinal morphology and trophic niches inhabited by nematodes. Until now, viewpoints on relative conservation and diversity of intestinal cell proteins among species have been difficult to generate. Research presented here has made a major step in establishing quantitative measures on conservation and diversity of intestinal functions and in a pan-Nematoda context. These advances led to establishment of an extensive database that pinpoints protein sites with application towards development of new therapies against many pathogenic nematodes.
Author Contributions
Acknowledgments This study was supported by the National Institute of General Medicine Science GrantR01GM097435 to M.M. The authors would like to thank McDonnell Genome Institute staff and faculty for their technical assistance related to data generation. The authors declare that they have no competing interests.
Introduction Acute kidney injury (AKI) is a common clinical problem associated with an increasing prevalence, high morbidity, mortality, and prolonged length of hospitalization (Hsu et al., 2007; Lameire et al., 2005; Xue et al., 2006). AKI is also a risk factor for progression to chronic kidney disease (CKD) (Siew and Deger, 2012; Lo et al., 2009; Wald et al., 2009; Ferenbach and Bonventre, 2015; Canaud and Bonventre, 2015). Global or local ischemia contributes to the pathogenesis of AKI which complicates various clinical conditions. Ischemia-reperfusion injury (IRI) is also a risk factor for delayed graft function and chronic allograft nephropathy (Wirthensohn and Guder, 1986; Brezis et al., 1984; Fletcher et al., 2009). As the options to prevent AKI are few and its prognosis is poor, novel interventional strategies are needed. Episodes of nonlethal ischemia can precondition the kidney protecting it against subsequent ischemia (Park et al., 2001; Joo et al., 2006; Ali et al., 2007; Bonventre, 2002). It would be highly desirable to mimic ischemic preconditioning with pharmaceutical intervention. While there are studies reporting that agents, such as high mobility group box 1 (HMGB1) (Wu et al., 2014), isoflurane (Su et al., 2014), inhibitors of hypoxia inducible transcription factor (HIF) or carbon monoxide (Bernhardt et al., 2006) given to animals prior to the ischemic event are protective, in most studies the agents are administered close to the time of IRI. Furthermore the effects are not keep in sustained if given more than a few hours prior to the IRI, nor are the mechanisms understood.