Inhibition or knock out of Inducible nitric oxide synthase result in resistance to bleomycin-induced lung injury

Background

In the present study, by comparing the responses in wild-type mice (WT) and mice lacking (KO) the inducible (or type 2) nitric oxide synthase (iNOS), we investigated the role played by iNOS in the development of on the lung injury caused by bleomycin administration. When compared to bleomycin-treated iNOSWT mice, iNOSKO mice, which had received bleomycin, exhibited a reduced degree of the (i) lost of body weight, (ii) mortality rate, (iii) infiltration of the lung with polymorphonuclear neutrophils (MPO activity), (iv) edema formation, (v) histological evidence of lung injury, (vi) lung collagen deposition and (vii) lung Transforming Growth Factor beta1 (TGF-β1) expression.

Methods

Mice subjected to intratracheal administration of bleomycin developed a significant lung injury. Immunohistochemical analysis for nitrotyrosine revealed a positive staining in lungs from bleomycin-treated iNOSWT mice.

Results

The intensity and degree of nitrotyrosine staining was markedly reduced in tissue section from bleomycin-iNOSKO mice. Treatment of iNOSWT mice with of {"type":"entrez-nucleotide","attrs":{"text":"GW274150","term_id":"282552565","term_text":"GW274150"}}GW274150, a novel, potent and selective inhibitor of iNOS activity (5 mg/kg i.p.) also significantly attenuated all of the above indicators of lung damage and inflammation.

Conclusion

Taken together, our results clearly demonstrate that iNOS plays an important role in the lung injury induced by bleomycin in the mice.     

Postnatal PPARδ Activation and Myostatin Inhibition Exert Distinct yet Complimentary Effects on the Metabolic Profile of Obese Insulin-Resistant Mice

Background

Interventions for T2DM have in part aimed to mimic exercise. Here, we have compared the independent and combined effects of a PPARδ agonist and endurance training mimetic ({"type":"entrez-nucleotide","attrs":{"text":"GW501516","term_id":"289075981","term_text":"GW501516"}}GW501516) and a myostatin antibody and resistance training mimetic (PF-879) on metabolic and performance outcomes in obese insulin resistant mice.

Methodology/Principal Findings

Male ob/ob mice were treated for 6 weeks with vehicle, {"type":"entrez-nucleotide","attrs":{"text":"GW501516","term_id":"289075981","term_text":"GW501516"}}GW501516, PF-879, or {"type":"entrez-nucleotide","attrs":{"text":"GW501516","term_id":"289075981","term_text":"GW501516"}}GW501516 in combination with PF-879. The effects of the interventions on body composition, glucose homeostasis, glucose tolerance, energy expenditure, exercise capacity and metabolic gene expression were compared at the end of study. {"type":"entrez-nucleotide","attrs":{"text":"GW501516","term_id":"289075981","term_text":"GW501516"}}GW501516 attenuated body weight and fat mass accumulation and increased the expression of genes of oxidative metabolism. In contrast, PF-879 increased body weight by driving muscle growth and altered the expression of genes involved in insulin signaling and glucose metabolism. Despite their differences, both interventions alone improved glucose homeostasis. Moreover, {"type":"entrez-nucleotide","attrs":{"text":"GW501516","term_id":"289075981","term_text":"GW501516"}}GW501516 more effectively improved serum lipids, and PF-879 uniquely increased energy expenditure, exercise capacity and adiponectin levels. When combined the robust effects of {"type":"entrez-nucleotide","attrs":{"text":"GW501516","term_id":"289075981","term_text":"GW501516"}}GW501516 and/or PF-879 on body weight, adiposity, muscle mass, glycemia, serum lipids, energy expenditure and exercise capacity were highly conserved.

Conclusions/Significance

The data, for the first time, demonstrate postnatal inhibition of myostatin not only promotes gains in muscle mass similar to resistance training,but improves metabolic homeostasis. In several instances, these effects were either distinct from or complimentary to those of {"type":"entrez-nucleotide","attrs":{"text":"GW501516","term_id":"289075981","term_text":"GW501516"}}GW501516. The data further suggest that strategies to increase muscle mass, and not necessarily oxidative capacity, may effectively counter insulin resistance and T2DM.     

Oral administration of GW788388, an inhibitor of transforming growth factor beta signaling, prevents heart fibrosis in Chagas disease

Background

Chagas disease induced by Trypanosoma cruzi (T. cruzi) infection is a major cause of mortality and morbidity affecting the cardiovascular system for which presently available therapies are largely inadequate. Transforming Growth Factor beta (TGFß) has been involved in several regulatory steps of T. cruzi invasion and in host tissue fibrosis. {"type":"entrez-nucleotide","attrs":{"text":"GW788388","term_id":"293585730","term_text":"GW788388"}}GW788388 is a new TGFß type I and type II receptor kinase inhibitor that can be orally administered. In the present work, we studied its effects in vivo during the acute phase of experimental Chagas disease.

Methodology/Principal Findings

Male Swiss mice were infected intraperitoneally with 10⁴ trypomastigotes of T. cruzi (Y strain) and evaluated clinically. We found that this compound given once 3 days post infection (dpi) significantly decreased parasitemia, increased survival, improved cardiac electrical conduction as measured by PR interval in electrocardiography, and restored connexin43 expression. We could further show that cardiac fibrosis development, evaluated by collagen type I and fibronectin expression, could be inhibited by this compound. Interestingly, we further demonstrated that administration of {"type":"entrez-nucleotide","attrs":{"text":"GW788388","term_id":"293585730","term_text":"GW788388"}}GW788388 at the end of the acute phase (20 dpi) still significantly increased survival and decreased cardiac fibrosis (evaluated by Masson''s trichrome staining and collagen type I expression), in a stage when parasite growth is no more central to this event.

Conclusion/Significance

This work confirms that inhibition of TGFß signaling pathway can be considered as a potential alternative strategy for the treatment of the symptomatic cardiomyopathy found in the acute and chronic phases of Chagas disease.     

Schistosoma japonicum Soluble Egg Antigens Facilitate Hepatic Stellate Cell Apoptosis by Downregulating Akt Expression and Upregulating p53 and DR5 Expression

Background

The induction of hepatic stellate cell (HSC) apoptosis has potential as a potent strategy to diminish the progression of liver fibrosis. Previous studies have demonstrated the ability of soluble egg antigens (SEA) from schistosomes to inhibit HSC activation and to induce apoptosis in vitro. In this study, we aimed to explore the mechanism of SEA-induced apoptosis in HSCs.

Methodology/Principal Findings

In this study, we found that SEA could upregulate p53 and DR5 and downregulate the p-Akt. The apoptosis of HSCs induced by SEA could be reduced in HSCs that were treated with p53-specific siRNA and in HSCs that were treated with DR5-specific shRNA. In addition, {"type":"entrez-nucleotide","attrs":{"text":"GW501516","term_id":"289075981","term_text":"GW501516"}}GW501516, which enhances the expression of Akt, could also decrease the SEA-induced HSC apoptosis. We also found that the increased expression of p53 and DR5 induced by SEA through Mdm2 were reduced by {"type":"entrez-nucleotide","attrs":{"text":"GW501516","term_id":"289075981","term_text":"GW501516"}}GW501516.

Conclusions/Significance

Our data suggest that SEA can induce HSC apoptosis by downregulating Akt expression and upregulating p53-dependent DR5 expression.     

Angiopoietin-Like 4 Mediates PPAR Delta Effect on Lipoprotein Lipase-Dependent Fatty Acid Uptake but Not on Beta-Oxidation in Myotubes

Peroxisome proliferator-activated receptor (PPAR) delta is an important regulator of fatty acid (FA) metabolism. Angiopoietin-like 4 (Angptl4), a multifunctional protein, is one of the major targets of PPAR delta in skeletal muscle cells. Here we investigated the regulation of Angptl4 and its role in mediating PPAR delta functions using human, rat and mouse myotubes. Expression of Angptl4 was upregulated during myotubes differentiation and by oleic acid, insulin and PPAR delta agonist {"type":"entrez-nucleotide","attrs":{"text":"GW501516","term_id":"289075981","term_text":"GW501516"}}GW501516. Treatment with {"type":"entrez-nucleotide","attrs":{"text":"GW501516","term_id":"289075981","term_text":"GW501516"}}GW501516 or Angptl4 overexpression inhibited both lipoprotein lipase (LPL) activity and LPL-dependent uptake of FAs whereas uptake of BSA-bound FAs was not affected by either treatment. Activation of retinoic X receptor (RXR), PPAR delta functional partner, using bexarotene upregulated Angptl4 expression and inhibited LPL activity in a PPAR delta dependent fashion. Silencing of Angptl4 blocked the effect of {"type":"entrez-nucleotide","attrs":{"text":"GW501516","term_id":"289075981","term_text":"GW501516"}}GW501516 and bexarotene on LPL activity. Treatment with {"type":"entrez-nucleotide","attrs":{"text":"GW501516","term_id":"289075981","term_text":"GW501516"}}GW501516 but not Angptl4 overexpression significantly increased palmitate oxidation. Furthermore, Angptl4 overexpression did not affect the capacity of {"type":"entrez-nucleotide","attrs":{"text":"GW501516","term_id":"289075981","term_text":"GW501516"}}GW501516 to increase palmitate oxidation. Basal and insulin stimulated glucose uptake, glycogen synthesis and glucose oxidation were not significantly modulated by Angptl4 overexpression. Our findings suggest that FAs-PPARdelta/RXR-Angptl4 axis controls the LPL-dependent uptake of FAs in myotubes, whereas the effect of PPAR delta activation on beta-oxidation is independent of Angptl4.     

Profilin-1 is expressed in human atherosclerotic plaques and induces atherogenic effects on vascular smooth muscle cells

Background

Profilin-1 is an ubiquitous actin binding protein. Under pathological conditions such as diabetes, profilin-1 levels are increased in the vascular endothelium. We recently demonstrated that profilin-1 overexpression triggers indicators of endothelial dysfunction downstream of LDL signaling, and that attenuated expression of profilin-1 confers protection from atherosclerosis in vivo.

Methodology

Here we monitored profilin-1 expression in human atherosclerotic plaques by immunofluorescent staining. The effects of recombinant profilin-1 on atherogenic signaling pathways and cellular responses such as DNA synthesis (BrdU-incorporation) and chemotaxis (modified Boyden-chamber) were evaluated in cultured rat aortic and human coronary vascular smooth muscle cells (VSMCs). Furthermore, the correlation between profilin-1 serum levels and the degree of atherosclerosis was assessed in humans.

Principal Findings

In coronary arteries from patients with coronary heart disease, we found markedly enhanced profilin expression in atherosclerotic plaques compared to the normal vessel wall. Stimulation of rat aortic and human coronary VSMCs with recombinant profilin-1 (10⁻⁶ M) in vitro led to activation of intracellular signaling cascades such as phosphorylation of Erk1/2, p70^S6 kinase and PI3K/Akt within 10 minutes. Furthermore, profilin-1 concentration-dependently induced DNA-synthesis and migration of both rat and human VSMCs, respectively. Inhibition of PI3K (Wortmannin, {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002) or Src-family kinases (SU6656, PP2), but not PLCγ ({"type":"entrez-nucleotide","attrs":{"text":"U73122","term_id":"4098075","term_text":"U73122"}}U73122), completely abolished profilin-induced cell cycle progression, whereas PI3K inhibition partially reduced the chemotactic response. Finally, we found that profilin-1 serum levels were significantly elevated in patients with severe atherosclerosis in humans (p<0.001 vs. no atherosclerosis or control group).

Conclusions

Profilin-1 expression is significantly enhanced in human atherosclerotic plaques compared to the normal vessel wall, and the serum levels of profilin-1 correlate with the degree of atherosclerosis in humans. The atherogenic effects exerted by profilin-1 on VSMCs suggest an auto-/paracrine role within the plaque. These data indicate that profilin-1 might critically contribute to atherogenesis and may represent a novel therapeutic target.     

Co-Depletion of Cathepsin B and uPAR Induces G0/G1 Arrest in Glioma via FOXO3a Mediated p27Kip1 Upregulation

Background

Cathepsin B and urokinase plasminogen activator receptor (uPAR) are both known to be overexpressed in gliomas. Our previous work and that of others strongly suggest a relationship between the infiltrative phenotype of glioma and the expression of cathepsin B and uPAR. Though their role in migration and adhesion are well studied the effect of these molecules on cell cycle progression has not been thoroughly examined.

Methodology/Principal Findings

Cathespin B and uPAR single and bicistronic siRNA plasmids were used to downregulate these molecules in SNB19 and U251 glioma cells. FACS analysis and BrdU incorporation assay demonstrated G0/G1 arrest and decreased proliferation with the treatments, respectively. Immunoblot and immunocyto analysis demonstrated increased expression of p27^Kip1 and its nuclear localization with the knockdown of cathepsin B and uPAR. These effects could be mediated by αVβ3/PI3K/AKT/FOXO pathway as observed by the decreased αVβ3 expression, PI3K and AKT phosphorylation accompanied by elevated FOXO3a levels. These results were further confirmed with the increased expression of p27^Kip1 and FOXO3a when treated with {"type":"entrez-nucleotide","attrs":{"text":"Ly294002","term_id":"1257998346","term_text":"LY294002"}}Ly294002 (10 µM) and increased luciferase expression with the siRNA and {"type":"entrez-nucleotide","attrs":{"text":"Ly294002","term_id":"1257998346","term_text":"LY294002"}}Ly294002 treatments when the FOXO binding promoter region of p27^Kip1 was used. Our treatment also reduced the expression of cyclin D1, cyclin D2, p-Rb and cyclin E while the expression of Cdk2 was unaffected. Of note, the Cdk2-cyclin E complex formation was reduced significantly.

Conclusion/Significance

Our study indicates that cathepsin B and uPAR knockdown induces G0/G1 arrest by modulating the PI3K/AKT signaling pathway and further increases expression of p27^Kip1 accompanied by the binding of FOXO3a to its promoter. Taken together, our findings provide molecular mechanism for the G0/G1 arrest induced by the downregulation of cathepsin B and uPAR in SNB19 and U251 glioma cells.     

Diacylglycerol regulates acute hypoxic pulmonary vasoconstriction via TRPC6

Background

Hypoxic pulmonary vasoconstriction (HPV) is an essential mechanism of the lung that matches blood perfusion to alveolar ventilation to optimize gas exchange. Recently we have demonstrated that acute but not sustained HPV is critically dependent on the classical transient receptor potential 6 (TRPC6) channel. However, the mechanism of TRPC6 activation during acute HPV remains elusive. We hypothesize that a diacylglycerol (DAG)-dependent activation of TRPC6 regulates acute HPV.

Methods

We investigated the effect of the DAG analog 1-oleoyl-2-acetyl-sn-glycerol (OAG) on normoxic vascular tone in isolated perfused and ventilated mouse lungs from TRPC6-deficient and wild-type mice. Moreover, the effects of OAG, the DAG kinase inhibitor {"type":"entrez-nucleotide","attrs":{"text":"R59949","term_id":"830644","term_text":"R59949"}}R59949 and the phospholipase C inhibitor {"type":"entrez-nucleotide","attrs":{"text":"U73122","term_id":"4098075"}}U73122 on the strength of HPV were investigated compared to those on non-hypoxia-induced vasoconstriction elicited by the thromboxane mimeticum U46619.

Results

OAG increased normoxic vascular tone in lungs from wild-type mice, but not in lungs from TRPC6-deficient mice. Under conditions of repetitive hypoxic ventilation, OAG as well as {"type":"entrez-nucleotide","attrs":{"text":"R59949","term_id":"830644","term_text":"R59949"}}R59949 dose-dependently attenuated the strength of acute HPV whereas U46619-induced vasoconstrictions were not reduced. Like OAG, {"type":"entrez-nucleotide","attrs":{"text":"R59949","term_id":"830644","term_text":"R59949"}}R59949 mimicked HPV, since it induced a dose-dependent vasoconstriction during normoxic ventilation. In contrast, {"type":"entrez-nucleotide","attrs":{"text":"U73122","term_id":"4098075"}}U73122, a blocker of DAG synthesis, inhibited acute HPV whereas {"type":"entrez-nucleotide","attrs":{"text":"U73343","term_id":"1688125"}}U73343, the inactive form of {"type":"entrez-nucleotide","attrs":{"text":"U73122","term_id":"4098075"}}U73122, had no effect on HPV.

Conclusion

These findings support the conclusion that the TRPC6-dependency of acute HPV is induced via DAG.     

Genome sequences published outside of Standards in Genomic Sciences, March-April 2012

The purpose of this table is to provide the community with a citable record of publications of ongoing genome sequencing projects that have led to a publication in the scientific literature. While our goal is to make the list complete, there is no guarantee that we may have omitted one or more publications appearing in this time frame. Readers and authors who wish to have publications added to subsequent versions of this list are invited to provide the bibliographic data for such references to the SIGS editorial office.

Phylum Euryarchaeota

• Halococcus hamelinensis, sequence accession PRJNA80845 [1]
• “Methanocella conradii” HZ254, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003243","term_id":"379319823","term_text":"CP003243"}}CP003243 [2]
• Thermococcus litoralis NS-C, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHVB00000000","term_id":"374743520","term_text":"AHVB00000000"}}AHVB00000000 [3]

Phylum Crenarchaeota

• Candidatus Nitrosopumilus salaria” BD31, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AEXL00000000","term_id":"386807666","term_text":"AEXL00000000"}}AEXL00000000 [4]
• Candidatus Nitrosoarchaeum limnia, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHJG00000000","term_id":"367466343","term_text":"AHJG00000000"}}AHJG00000000 [5]

Phylum Deinococcus-Thermus

• Deinococcus gobiensis, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP002536","term_id":"324314064","term_text":"CP002536"}}CP002536 [6]

Phylum Proteobacteria

• Aggregatibacter actinomycetemcomitans strain ANH9381, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003099","term_id":"365745154","term_text":"CP003099"}}CP003099 [7]
• Alishewanella jeotgali, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHTH00000000","term_id":"374571619","term_text":"AHTH00000000"}}AHTH00000000 [8]
• Enterobacter aerogenes KCTC 2190, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP002824","term_id":"334732565","term_text":"CP002824"}}CP002824 [9]
• Escherichia coli O104:H4, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AFOB02000092","term_id":"340739517","term_text":"AFOB02000092"}}AFOB02000092 [10]
• Helicobacter pylori strains 17874, sequence accession PRJNA76569 [11]
• Helicobacter pylori strains P79, sequence accession PRJNA76567 [11]
• Janthinobacterium sp. Strain PAMC 25724, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHHB00000000","term_id":"372292151","term_text":"AHHB00000000"}}AHHB00000000 [12]
• Klebsiella oxytoca KCTC 1686, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003218","term_id":"365906294","term_text":"CP003218"}}CP003218 [13]
• Klebsiella pneumoniae subsp. pneumoniae HS11286, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003200","term_id":"364515570","term_text":"CP003200"}}CP003200 (chromosome), {"type":"entrez-nucleotide","attrs":{"text":"CP003223","term_id":"365803686","term_text":"CP003223"}}CP003223 (plasmid pKPHS1), {"type":"entrez-nucleotide","attrs":{"text":"CP003224","term_id":"365803828","term_text":"CP003224"}}CP003224 (plasmid pKPHS2), {"type":"entrez-nucleotide","attrs":{"text":"CP003225","term_id":"365803989","term_text":"CP003225"}}CP003225 (plasmid pKPHS3), {"type":"entrez-nucleotide","attrs":{"text":"CP003226","term_id":"365804142","term_text":"CP003226"}}CP003226 (plasmid pKPHS4), {"type":"entrez-nucleotide","attrs":{"text":"CP003227","term_id":"365804147","term_text":"CP003227"}}CP003227 (plasmid pKPHS5), {"type":"entrez-nucleotide","attrs":{"text":"CP003228","term_id":"365804153","term_text":"CP003228"}}CP003228 (plasmid pKPHS6) [14]
• Oceanimonas sp. GK1, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003171","term_id":"372983507","term_text":"CP003171"}}CP003171 [15]
• “Pseudogulbenkiania ferrooxidans” Strain 2002, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"NZ_ACIS01000000","term_id":"224827334","term_text":"ref||NZ_ACIS01000000"}}NZ_ACIS01000000 [16]
• Pseudomonas extremaustralis 14-3b, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHIP00000000","term_id":"371721769","term_text":"AHIP00000000"}}AHIP00000000 [17]
• Pseudomonas sp. Strain PAMC 25886, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHHC00000000","term_id":"372002201","term_text":"AHHC00000000"}}AHHC00000000 [18]
• Psychrobacter, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHVZ00000000","term_id":"375126956","term_text":"AHVZ00000000"}}AHVZ00000000 [19]
• Rahnella sp. Strain Y9602, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP002505","term_id":"321165934","term_text":"CP002505"}}CP002505 [20]
• Rhizobium sp. Strain PDO1-076, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHZC00000000","term_id":"375058045","term_text":"AHZC00000000"}}AHZC00000000 [21]
• Rhodospirillum photometricum DSM122, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"HE663493","term_id":"378401447","term_text":"HE663493"}}HE663493 [22]
• “Rickettsia sibirica sibirica”, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHIZ00000000","term_id":"374669031","term_text":"AHIZ00000000"}}AHIZ00000000 [23]
• Rickettsia sibirica subsp. mongolitimonae strain HA-91, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHZB00000000","term_id":"375318263","term_text":"AHZB00000000"}}AHZB00000000 [24]
• Salmonella enterica subsp. enterica Serotype Enteritidis Strain LA5, sequence accession [25]
• Salmonella enterica subsp. enterica Serotype Senftenberg Strain SS209, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CAGQ00000000","term_id":"379987603","term_text":"CAGQ00000000"}}CAGQ00000000 [26]
• Salmonella enterica subsp. enterica Serovar Typhi P-stx-12, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003278","term_id":"374352002","term_text":"CP003278"}}CP003278 (chromosome) and {"type":"entrez-nucleotide","attrs":{"text":"CP003279","term_id":"374356693","term_text":"CP003279"}}CP003279 (plasmid) [27]
• Sphingomonas echinoides ATCC 14820, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHIR00000000","term_id":"366040205","term_text":"AHIR00000000"}}AHIR00000000 [28]
• Strain HIMB55, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGIF00000000","term_id":"374304583","term_text":"AGIF00000000"}}AGIF00000000 [29]
• Vibrio harveyi CAIM 1792, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHHQ00000000","term_id":"374671508","term_text":"AHHQ00000000"}}AHHQ00000000 [30]
• Wolbachia Strain wAlbB, sequence accession {"type":"entrez-nucleotide-range","attrs":{"text":"CAGB01000001 to CAGB01000165","start_term":"CAGB01000001","end_term":"CAGB01000165","start_term_id":"371933004","end_term_id":"371931774"}}CAGB01000001 to CAGB01000165 [31]
• Xanthomonas axonopodis pv. punicae Strain LMG 859, sequence accession {"type":"entrez-nucleotide-range","attrs":{"text":"CAGJ01000001 to CAGJ01000217","start_term":"CAGJ01000001","end_term":"CAGJ01000217","start_term_id":"372556075","end_term_id":"372551622"}}CAGJ01000001 to CAGJ01000217 [32]

Phylum Tenericutes

• Mycoplasma hyorhinis Strain GDL-1, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003231","term_id":"367460291","term_text":"CP003231"}}CP003231 [33]

Phylum Firmicutes

• Bacillus subtilis, sequence accession BGSCID 3A27 through BGSCID 28A4 [34]
• Clostridium difficile Strain CD37, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHJJ00000000","term_id":"371930118","term_text":"AHJJ00000000"}}AHJJ00000000 [35]
• Clostridium perfringens, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AFES00000000","term_id":"380306484","term_text":"AFES00000000"}}AFES00000000 [36]
• Lactobacillus fructivorans KCTC 3543, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AEQY00000000","term_id":"316986063","term_text":"AEQY00000000"}}AEQY00000000 [37]
• Lactococcus lactis IO-1, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AP012281","term_id":"374672113","term_text":"AP012281"}}AP012281 [38]
• Lactobacillus plantarum strain NC8, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGRI00000000","term_id":"376011245","term_text":"AGRI00000000"}}AGRI00000000 [39]
• Paenibacillus dendritiformis C454, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHKH00000000","term_id":"374393106","term_text":"AHKH00000000"}}AHKH00000000 [40]
• Paenibacillus sp. Strain Aloe-11, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGFI00000000","term_id":"374477730","term_text":"AGFI00000000"}}AGFI00000000 [41]
• “Peptoniphilus rhinitidis” 1-13^T, sequence accession {"type":"entrez-nucleotide-range","attrs":{"text":"BAEW01000001 to BAEW01000056","start_term":"BAEW01000001","end_term":"BAEW01000056","start_term_id":"374722129","end_term_id":"374722074"}}BAEW01000001 to BAEW01000056 [42]
• Streptococcus macedonicus ACA-DC 198, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"HE613569","term_id":"372283141","term_text":"HE613569"}}HE613569 and {"type":"entrez-nucleotide","attrs":{"text":"HE613570","term_id":"372285142","term_text":"HE613570"}}HE613570 [43]
• Staphylococcus aureus VC40, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003033","term_id":"374362062","term_text":"CP003033"}}CP003033 [44]
• Streptococcus infantarius subsp. infantarius Strain CJ18, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003295","term_id":"374681091","term_text":"CP003295"}}CP003295 (chromosome), {"type":"entrez-nucleotide","attrs":{"text":"CP003296","term_id":"374682963","term_text":"CP003296"}}CP003296 (plasmid) [45]
• Streptococcus macedonicus ACA-DC 198, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"HE613569","term_id":"372283141","term_text":"HE613569"}}HE613569 (chromosome), {"type":"entrez-nucleotide","attrs":{"text":"HE613570","term_id":"372285142","term_text":"HE613570"}}HE613570 (plasmid pSMA198) [46]

Phylum Actinobacteria

• Actinoplanes sp. SE50/110, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003170","term_id":"359832573","term_text":"CP003170"}}CP003170 [47]
• Amycolatopsis sp. Strain ATCC 39116, sequence accession [48]
• Nocardia cyriacigeorgica GUH-2, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"FO082843","term_id":"374843763","term_text":"FO082843"}}FO082843 [49]
• Salinibacterium sp., sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHWA00000000","term_id":"375323651","term_text":"AHWA00000000"}}AHWA00000000 [50]
• Streptomyces acidiscabies 84-104, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHBF00000000","term_id":"372137622","term_text":"AHBF00000000"}}AHBF00000000 [51]

Non-Bacterial genomes

• Bluetongue Virus Serotype 2, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AJ783905","term_id":"70907482","term_text":"AJ783905"}}AJ783905 (Seg-6) and {"type":"entrez-nucleotide","attrs":{"text":"JQ681257","term_id":"383932043","term_text":"JQ681257"}}JQ681257 (Seg-1), {"type":"entrez-nucleotide","attrs":{"text":"JQ681257","term_id":"383932043","term_text":"JQ681257"}}JQ681257 (Seg-1), {"type":"entrez-nucleotide","attrs":{"text":"JQ681258","term_id":"383932045","term_text":"JQ681258"}}JQ681258 (Seg-2), {"type":"entrez-nucleotide","attrs":{"text":"JQ681259","term_id":"383932047","term_text":"JQ681259"}}JQ681259 (Seg-3), {"type":"entrez-nucleotide","attrs":{"text":"JQ681260","term_id":"383932049","term_text":"JQ681260"}}JQ681260 (Seg-4), {"type":"entrez-nucleotide","attrs":{"text":"JQ681261","term_id":"383932051","term_text":"JQ681261"}}JQ681261 (Seg-5), {"type":"entrez-nucleotide","attrs":{"text":"JQ681262","term_id":"383932053","term_text":"JQ681262"}}JQ681262 (Seg-7), JQ6812563 (Seg-8), JQ6812564 (Seg-9), to {"type":"entrez-nucleotide","attrs":{"text":"JQ681265","term_id":"383932059","term_text":"JQ681265"}}JQ681265 (Seg-10) [52]
• Virus Serotype 1, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AJ585111","term_id":"118420282","term_text":"AJ585111"}}AJ585111 (Seg-2), {"type":"entrez-nucleotide","attrs":{"text":"AJ586659","term_id":"47826214","term_text":"AJ586659"}}AJ586659 (Seg-6), {"type":"entrez-nucleotide","attrs":{"text":"JQ282770","term_id":"383215071","term_text":"JQ282770"}}JQ282770 (Seg-1), {"type":"entrez-nucleotide","attrs":{"text":"JQ282771","term_id":"383215073","term_text":"JQ282771"}}JQ282771 (Seg-3), {"type":"entrez-nucleotide","attrs":{"text":"JQ282772","term_id":"383215075","term_text":"JQ282772"}}JQ282772 (Seg-4), {"type":"entrez-nucleotide","attrs":{"text":"JQ282773","term_id":"383215077","term_text":"JQ282773"}}JQ282773 (Seg-5), {"type":"entrez-nucleotide","attrs":{"text":"JQ282774","term_id":"383215079","term_text":"JQ282774"}}JQ282774 (Seg-7), {"type":"entrez-nucleotide","attrs":{"text":"JQ282775","term_id":"383215081","term_text":"JQ282775"}}JQ282775 (Seg-8), {"type":"entrez-nucleotide","attrs":{"text":"JQ282776","term_id":"383215083","term_text":"JQ282776"}}JQ282776 (Seg-9), and {"type":"entrez-nucleotide","attrs":{"text":"JQ282777","term_id":"383215085","term_text":"JQ282777"}}JQ282777 (Seg-10) [52]
• Chloroplast genome of Erycina pusilla, sequence accession JF_746994 [53]
• Danio rerio, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JQ434101","term_id":"384872525","term_text":"JQ434101"}}JQ434101 [54]
• Enterococcal Bacteriophage SAP6, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JF731128","term_id":"343411857","term_text":"JF731128"}}JF731128 [55]
• Eubenangee virus, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JQ070376","term_id":"383513837","term_text":"JQ070376"}}JQ070376 through {"type":"entrez-nucleotide","attrs":{"text":"JQ070385","term_id":"383513855","term_text":"JQ070385"}}JQ070385 [56]
• Fujian/411-like viruses, sequence accession {"type":"entrez-nucleotide-range","attrs":{"text":"CY087969 to CY088568","start_term":"CY087969","end_term":"CY088568","start_term_id":"380506411","end_term_id":"380507803"}}CY087969 to CY088568 [57]
• Hantavirus Variant of Rio Mamoré Virus, Maripa Virus, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JQ611712","term_id":"384382977","term_text":"JQ611712"}}JQ611712 (segment S), {"type":"entrez-nucleotide","attrs":{"text":"JQ611713","term_id":"384382979","term_text":"JQ611713"}}JQ611713 (segment M), and {"type":"entrez-nucleotide","attrs":{"text":"JQ611714","term_id":"384382981","term_text":"JQ611714"}}JQ611714 (segment L) [58]
• Pata virus, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JQ070386","term_id":"383513857","term_text":"JQ070386"}}JQ070386 through {"type":"entrez-nucleotide","attrs":{"text":"JQ070395","term_id":"383513875","term_text":"JQ070395"}}JQ070395 [59]
• Porcine Circovirus 2, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JQ413808","term_id":"383215164","term_text":"JQ413808"}}JQ413808 [60]
• Porcine Reproductive and Respiratory Syndrome Virus, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JQ326271","term_id":"382929416","term_text":"JQ326271"}}JQ326271 [61]
• Streptococcus mutans Phage M102AD, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"DQ386162","term_id":"88698119","term_text":"DQ386162"}}DQ386162 [62]
• Tilligery virus, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JQ070366","term_id":"383513817","term_text":"JQ070366"}}JQ070366 through {"type":"entrez-nucleotide","attrs":{"text":"JQ070375","term_id":"383513835","term_text":"JQ070375"}}JQ070375 [63]

     

Genome sequences published outside of Standards in Genomic Sciences, January-March 2012

The purpose of this table is to provide the community with a citable record of publications of ongoing genome sequencing projects that have led to a publication in the scientific literature. While our goal is to make the list complete, there is no guarantee that we may have omitted one or more publications appearing in this time frame. Readers and authors who wish to have publications added to subsequent versions of this list are invited to provide the bibliographic data for such references to the SIGS editorial office.

Phylum Crenarchaeota

• Pyrobaculum strain 1860, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003098","term_id":"356640791","term_text":"CP003098"}}CP003098 [1]

Phylum Deinococcus-Thermus

• “Thermus sp.” Strain CCB_US3_UF1, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003126","term_id":"359289533","term_text":"CP003126"}}CP003126 (chromosome), {"type":"entrez-nucleotide","attrs":{"text":"CP003127","term_id":"359291781","term_text":"CP003127"}}CP003127 (plasmid) [2]

Phylum Proteobacteria

• “Achromobacter arsenitoxydans” SY8, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGUF00000000","term_id":"359366799","term_text":"AGUF00000000"}}AGUF00000000 [3]
• Acidovorax sp. Strain NO1, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGTS00000000","term_id":"363417938","term_text":"AGTS00000000"}}AGTS00000000 [4]
• Acinetobacter baumannii AB4857, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHAG00000000","term_id":"371492156","term_text":"AHAG00000000"}}AHAG00000000 [5]
• Acinetobacter baumannii AB5075, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHAH00000000","term_id":"371492114","term_text":"AHAH00000000"}}AHAH00000000 [5]
• Acinetobacter baumannii AB5256, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHAI00000000","term_id":"371492153","term_text":"AHAI00000000"}}AHAI00000000 [5]
• Acinetobacter baumannii AB5711, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHAJ00000000","term_id":"371492197","term_text":"AHAJ00000000"}}AHAJ00000000 [5]
• Aeromonas salmonicida, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGVO00000000","term_id":"356689990","term_text":"AGVO00000000"}}AGVO00000000 [6]
• Aggregatibacter actinomycetemcomitans RHAA1, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHGR00000000","term_id":"359757447","term_text":"AHGR00000000"}}AHGR00000000 [7]
• Agrobacterium tumefaciens 5A, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGVZ00000000","term_id":"358008163","term_text":"AGVZ00000000"}}AGVZ00000000 [8]
• Azoarcus sp. Strain KH32C, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AP012304","term_id":"358635055","term_text":"AP012304"}}AP012304, {"type":"entrez-nucleotide","attrs":{"text":"AP012305","term_id":"358639587","term_text":"AP012305"}}AP012305 [9]
• Burkholderia sp. Strain YI23, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003087","term_id":"357934279","term_text":"CP003087"}}CP003087 (Chromosome 1), {"type":"entrez-nucleotide","attrs":{"text":"CP003088","term_id":"357937049","term_text":"CP003088"}}CP003088 (Chromosome 2), {"type":"entrez-nucleotide","attrs":{"text":"CP003089","term_id":"357938589","term_text":"CP003089"}}CP003089 (Chromosome 3), {"type":"entrez-nucleotide","attrs":{"text":"CP003090","term_id":"357939954","term_text":"CP003090"}}CP003090 (plasmid BYI23_D), {"type":"entrez-nucleotide","attrs":{"text":"CP003091","term_id":"357941606","term_text":"CP003091"}}CP003091 (plasmid BYI23_E) {"type":"entrez-nucleotide","attrs":{"text":"CP003092","term_id":"357941997","term_text":"CP003092"}}CP003092 (plasmid BYI23_F) [10]
• Brucella suis VBI22, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003128","term_id":"358257303","term_text":"CP003128"}}CP003128, {"type":"entrez-nucleotide","attrs":{"text":"CP003129","term_id":"358259429","term_text":"CP003129"}}CP003129 [11]
• Comamonas testosteroni ATCC 11996, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHIL00000000","term_id":"371454882","term_text":"AHIL00000000"}}AHIL00000000 [12]
• “Commensalibacter intestini” A911^T, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGFR00000000","term_id":"353673384","term_text":"AGFR00000000"}}AGFR00000000 [13]
• Edwardsiella ictaluri, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP001600.1","term_id":"238867551","term_text":"CP001600.1"}}CP001600.1 [14]
• Enterobacter cloacae subsp. dissolvens SDM, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGSY00000000","term_id":"357435944","term_text":"AGSY00000000"}}AGSY00000000 [15]
• “Gluconobacter morbifer” G707^T, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGQV00000000","term_id":"356416073","term_text":"AGQV00000000"}}AGQV00000000 [16]
• Legionella dumoffii TEX-KL, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGVT00000000","term_id":"358009168","term_text":"AGVT00000000"}}AGVT00000000 [17]
• Legionella dumoffii NY-23, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGVU00000000","term_id":"358009167","term_text":"AGVU00000000"}}AGVU00000000 [17]
• Legionella pneumophila serogroup 12 Strain 570-CO-H, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003192","term_id":"364506764","term_text":"CP003192"}}CP003192 [18]
• Marinobacterium stanieri S30, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AFPL00000000","term_id":"339778849","term_text":"AFPL00000000"}}AFPL00000000 [19]
• “Marinobacter manganoxydans” MnI7-9, sequence accession {"type":"entrez-nucleotide-range","attrs":{"text":"CP001978 to CP001980","start_term":"CP001978","end_term":"CP001980","start_term_id":"311692891","end_term_id":"311697125"}}CP001978 to CP001980 [20]
• Mesorhizobium alhagi CCNWXJ12-2T, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHAM00000000","term_id":"359256606","term_text":"AHAM00000000"}}AHAM00000000 [21]
• Mesorhizobium amorphae, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGSN00000000","term_id":"355545111","term_text":"AGSN00000000"}}AGSN00000000 [22]
• Methylomicrobium alcaliphilum 20Z, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"FO082060","term_id":"351716053","term_text":"FO082060"}}FO082060 and {"type":"entrez-nucleotide","attrs":{"text":"FO082061","term_id":"351720036","term_text":"FO082061"}}FO082061 [23]
• Mitsuaria sp. Strain H24L5A, sequence accession {"type":"entrez-nucleotide-range","attrs":{"text":"CAFG01000001 to CAFG01000607","start_term":"CAFG01000001","end_term":"CAFG01000607","start_term_id":"354809229","end_term_id":"354808623"}}CAFG01000001 to CAFG01000607 [24]
• Novosphingobium pentaromativorans US6-1, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGFM00000000","term_id":"357601355","term_text":"AGFM00000000"}}AGFM00000000 [25]
• Pantoea ananatis B1-9, sequence accession {"type":"entrez-nucleotide-range","attrs":{"text":"CAEI01000001 to CAEI01000169","start_term":"CAEI01000001","end_term":"CAEI01000169","start_term_id":"344197887","end_term_id":"344197719"}}CAEI01000001 to CAEI01000169 [26]
• Pantoea ananatis LMG 5342, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"HE617160","term_id":"365184443","term_text":"HE617160"}}HE617160 (chromosome), {"type":"entrez-nucleotide","attrs":{"text":"HE617161","term_id":"365188784","term_text":"HE617161"}}HE617161 (pPANA10) [27]
• Pantoea ananatis Strain PA13, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003085","term_id":"354986417","term_text":"CP003085"}}CP003085 and {"type":"entrez-nucleotide","attrs":{"text":"CP003086","term_id":"354685304","term_text":"CP003086"}}CP003086 [28]
• Pseudomonas aeruginosa, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AFXI00000000","term_id":"343788111","term_text":"AFXI00000000"}}AFXI00000000 [29]
• Pseudomonas aeruginosa, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AFXJ00000000","term_id":"343788109","term_text":"AFXJ00000000"}}AFXJ00000000 [29]
• Pseudomonas aeruginosa, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AFXK00000000","term_id":"343788110","term_text":"AFXK00000000"}}AFXK00000000 [29]
• Pseudomonas chlororaphis GP72, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHAY01000000","term_id":"359757954","term_text":"gb||AHAY01000000"}}AHAY01000000 [30]
• Pseudomonas fluorescens F113, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003150","term_id":"359757955","term_text":"CP003150"}}CP003150 [31]
• Pseudomonas fluorescens Wayne 1R, sequence accession {"type":"entrez-nucleotide-range","attrs":{"text":"CADX01000001 to CADX01000090","start_term":"CADX01000001","end_term":"CADX01000090","start_term_id":"354924103","end_term_id":"354924014"}}CADX01000001 to CADX01000090 [32]
• Pseudomonas fluorescens Wood1R, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CAFF01000001","term_id":"354698772","term_text":"CAFF01000001"}}CAFF01000001 to {"type":"entrez-nucleotide","attrs":{"text":"CAFF01001437","term_id":"354697336","term_text":"CAFF01001437"}}CAFF01001437 [32]
• Pseudomonas psychrotolerans L19, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHBD00000000","term_id":"359372666","term_text":"AHBD00000000"}}AHBD00000000 [33]
• Pseudoalteromonas rubra ATCC 29570^T, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHCD00000000","term_id":"540289291","term_text":"AHCD00000000"}}AHCD00000000 [34]
• Pseudomonas stutzeri SDM-LAC, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGSX00000000","term_id":"357435965","term_text":"AGSX00000000"}}AGSX00000000 [35]
• Pseudoxanthomonas spadix BD-a59, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003093","term_id":"357433120","term_text":"CP003093"}}CP003093 [36]
• Rickettsia slovaca, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP002428","term_id":"360041315","term_text":"CP002428"}}CP002428 [37]
• Salmonella enterica serovar Pullorum RKS5078, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003047","term_id":"357204415","term_text":"CP003047"}}CP003047 [38]
• Sinorhizobium meliloti CCNWSX0020, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGVV00000000","term_id":"359507569","term_text":"AGVV00000000"}}AGVV00000000 [39]
• Sphingobium sp. Strain SYK-6, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AP012222","term_id":"345135066","term_text":"AP012222"}}AP012222 and {"type":"entrez-nucleotide","attrs":{"text":"AP012223","term_id":"345138980","term_text":"AP012223"}}AP012223 [40]
• Sphingomonas sp. Strain PAMC 26605, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHIS00000000","term_id":"366040305","term_text":"AHIS00000000"}}AHIS00000000 [41]
• Stenotrophomonas maltophilia RR-10, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGRB00000000","term_id":"359757773","term_text":"AGRB00000000"}}AGRB00000000 [42]
• Strain HIMB30, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGIG00000000","term_id":"349602640","term_text":"AGIG00000000"}}AGIG00000000 [43]
• Taylorella equigenitalis, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003059","term_id":"347973256","term_text":"CP003059"}}CP003059 [44]
• Vibrio campbellii DS40M4, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGIE00000000","term_id":"358251732","term_text":"AGIE00000000"}}AGIE00000000 [45]
• Vibrio fischeri SR5, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHIH00000000","term_id":"371496097","term_text":"AHIH00000000"}}AHIH00000000 [46]
• Yersinia enterocolitica, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGQO00000000","term_id":"351780838","term_text":"AGQO00000000"}}AGQO00000000 [47]

Phylum Tenericutes

• Candidatus Mycoplasma haemominutum, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"HE613254","term_id":"357978897","term_text":"HE613254"}}HE613254 [48]
• Mycoplasma haemocanis strain Illinois, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003199","term_id":"363988676","term_text":"CP003199"}}CP003199 [49]
• Mycoplasma iowae, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGFP00000000","term_id":"349504222","term_text":"AGFP00000000"}}AGFP00000000 [50]
• Mycoplasma pneumoniae Type 2a Strain 309, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AP012303","term_id":"358640274","term_text":"AP012303"}}AP012303 [51]

Phylum Firmicutes

• Bacillus cereus F837/76, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003187","term_id":"364509831","term_text":"CP003187"}}CP003187 (chromosome) {"type":"entrez-nucleotide","attrs":{"text":"CP003188","term_id":"364515227","term_text":"CP003188"}}CP003188 (pF837_55kb), {"type":"entrez-nucleotide","attrs":{"text":"CP003189","term_id":"364515372","term_text":"CP003189"}}CP003189 (pF837_10kb) [52]
• Brevibacillus laterosporus Strain GI-9, sequence accession {"type":"entrez-nucleotide-range","attrs":{"text":"CAGD01000001 to CAGD01000061","start_term":"CAGD01000001","end_term":"CAGD01000061","start_term_id":"359745324","end_term_id":"359745264"}}CAGD01000001 to CAGD01000061 [53]
• Clostridium sporogenes PA 3679, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGAH00000000","term_id":"364889226","term_text":"AGAH00000000"}}AGAH00000000 [54]
• Enterococcus mundtii CRL1656, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AFWZ00000000.1","term_id":"354620965","term_text":"AFWZ00000000.1"}}AFWZ00000000.1 [55]
• Geobacillus thermoleovorans CCB_US3_UF5, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003125","term_id":"359285645","term_text":"CP003125"}}CP003125 [56]
• Lactobacillus curvatus Strain CRL705, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGBU01000000","term_id":"354514905","term_text":"gb||AGBU01000000"}}AGBU01000000 [57]
• Lactobacillus rhamnosus ATCC 8530, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003094","term_id":"355393429","term_text":"CP003094"}}CP003094 [58]
• Lactobacillus rhamnosus R0011, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGKC00000000","term_id":"357540515","term_text":"AGKC00000000"}}AGKC00000000 [59]
• Lactococcus garvieae TB25, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGQX01000000","term_id":"359031556","term_text":"gb||AGQX01000000"}}AGQX01000000 [60]
• Lactococcus garvieae LG9, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGQY01000000","term_id":"359031592","term_text":"gb||AGQY01000000"}}AGQY01000000 [60]
• Lactococcus lactis subsp. cremoris A76, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003132","term_id":"358748197","term_text":"CP003132"}}CP003132 (chromosome), {"type":"entrez-nucleotide","attrs":{"text":"CP003136","term_id":"358750967","term_text":"CP003136"}}CP003136 (pQA505), {"type":"entrez-nucleotide","attrs":{"text":"CP003135","term_id":"358750954","term_text":"CP003135"}}CP003135 (PQA518), {"type":"entrez-nucleotide","attrs":{"text":"CP003134","term_id":"358750911","term_text":"CP003134"}}CP003134 (pQA549), {"type":"entrez-nucleotide","attrs":{"text":"CP003133","term_id":"358750841","term_text":"CP003133"}}CP003133 (pQA554) [61]
• Leuconostoc citreum LBAE C10, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CAGE00000000","term_id":"365487970","term_text":"CAGE00000000"}}CAGE00000000 [62]
• Leuconostoc citreum LBAE C11, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CAGF00000000","term_id":"365512054","term_text":"CAGF00000000"}}CAGF00000000 [62]
• Leuconostoc citreum LBAE E16, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CAGG00000000","term_id":"365528100","term_text":"CAGG00000000"}}CAGG00000000 [62]
• Leuconostoc mesenteroides subsp. mesenteroides Strain J18, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003101","term_id":"948298071","term_text":"CP003101"}}CP003101 [63]
• Paenibacillus peoriae Strain KCTC 3763^T, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGFX00000000","term_id":"359367787","term_text":"AGFX00000000"}}AGFX00000000 [64]
• Pediococcus acidilactici MA18/5M, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGKB00000000","term_id":"357540603","term_text":"AGKB00000000"}}AGKB00000000 [65]
• Pediococcus claussenii ATCC BAA-344^T, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003137","term_id":"361055534","term_text":"CP003137"}}CP003137 (chromosome), {"type":"entrez-nucleotide","attrs":{"text":"CP003138","term_id":"361057275","term_text":"CP003138"}}CP003138 (pPECL-1), {"type":"entrez-nucleotide","attrs":{"text":"CP003139","term_id":"361057278","term_text":"CP003139"}}CP003139 (pPECL-2), {"type":"entrez-nucleotide","attrs":{"text":"CP003140","term_id":"361057281","term_text":"CP003140"}}CP003140 (pPECL-3), {"type":"entrez-nucleotide","attrs":{"text":"CP003141","term_id":"361057302","term_text":"CP003141"}}CP003141 (pPECL-4), {"type":"entrez-nucleotide","attrs":{"text":"CP003142","term_id":"361057319","term_text":"CP003142"}}CP003142 (pPECL-5), {"type":"entrez-nucleotide","attrs":{"text":"CP003143","term_id":"361057355","term_text":"CP003143"}}CP003143 (pPECL-6), {"type":"entrez-nucleotide","attrs":{"text":"CP003144","term_id":"361057377","term_text":"CP003144"}}CP003144 (pPECL-7), {"type":"entrez-nucleotide","attrs":{"text":"CP003145","term_id":"380450589","term_text":"CP003145"}}CP003145 (pPECL-8) [66]
• Staphylococcus aureus M013, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003166","term_id":"359829121","term_text":"CP003166"}}CP003166 [67]
• Staphylococcus aureus subsp. aureus TW20, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"FN433596","term_id":"269939526","term_text":"FN433596"}}FN433596 [68]
• Weissella confusa LBAE C39-2, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CAGH00000000","term_id":"365549261","term_text":"CAGH00000000"}}CAGH00000000 [69]

Phylum Actinobacteria

• Corynebacterium casei, sequence accession {"type":"entrez-nucleotide-range","attrs":{"text":"CAFW01000001 to CAFW01000106","start_term":"CAFW01000001","end_term":"CAFW01000106","start_term_id":"356609265","end_term_id":"356606462"}}CAFW01000001 to CAFW01000106 [70]
• Corynebacterium glutamicum, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGQQ00000000","term_id":"658109743","term_text":"AGQQ00000000"}}AGQQ00000000 [71]
• Leucobacter chromiiresistens, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGCW00000000","term_id":"353529976","term_text":"AGCW00000000"}}AGCW00000000 [72]
• Mycobacterium abscessus, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGQU00000000","term_id":"353453148","term_text":"AGQU00000000"}}AGQU00000000 [73]
• Propionibacterium acnes ST9, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003195","term_id":"365742920","term_text":"CP003195"}}CP003195 [74]
• Propionibacterium acnes ST22, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003196","term_id":"365740656","term_text":"CP003196"}}CP003196 [74]
• Propionibacterium acnes ST27, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP003197","term_id":"365738411","term_text":"CP003197"}}CP003197 [74]
• Saccharomonospora azurea SZMC 14600, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AHBX00000000","term_id":"359740650","term_text":"AHBX00000000"}}AHBX00000000 [75]
• Streptomyces sp. Strain TOR3209, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGNH00000000","term_id":"359357427","term_text":"AGNH00000000"}}AGNH00000000 [76]
• Streptomyces sp. Strain W007, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGSW00000000","term_id":"364010697","term_text":"AGSW00000000"}}AGSW00000000 [77]

Phylum Spirochaetes

• Borrelia valaisiana VS116, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"ABCY02000001","term_id":"224510974","term_text":"ABCY02000001"}}ABCY02000001 (chromosome), {"type":"entrez-nucleotide","attrs":{"text":"CP001439","term_id":"224497263","term_text":"CP001439"}}CP001439 (plasmid Ip17), {"type":"entrez-nucleotide","attrs":{"text":"CP001437","term_id":"224497187","term_text":"CP001437"}}CP001437 (Ip25), {"type":"entrez-nucleotide","attrs":{"text":"CP001440","term_id":"224497290","term_text":"CP001440"}}CP001440 (plasmid Ip 28-3), {"type":"entrez-nucleotide","attrs":{"text":"CP001442","term_id":"224497476","term_text":"CP001442"}}CP001442 (plasmid Ip28-8), {"type":"entrez-nucleotide","attrs":{"text":"CP001436","term_id":"224497148","term_text":"CP001436"}}CP001436 (Ip 36), {"type":"entrez-nucleotide","attrs":{"text":"CP001433","term_id":"224496993","term_text":"CP001433"}}CP001433 (plasmid Ip 54), {"type":"entrez-nucleotide","attrs":{"text":"CP001438","term_id":"224497250","term_text":"CP001438"}}CP001438 (plasmid cp9), {"type":"entrez-nucleotide","attrs":{"text":"CP001432","term_id":"224496964","term_text":"CP001432"}}CP001432 (plasmid cp26), {"type":"entrez-nucleotide","attrs":{"text":"CP001441","term_id":"224497433","term_text":"CP001441"}}CP001441 (plasmid cp32-5), {"type":"entrez-nucleotide","attrs":{"text":"CP001434","term_id":"224497064","term_text":"CP001434"}}CP001434 (plasmid cp32-7), {"type":"entrez-nucleotide","attrs":{"text":"CP001435","term_id":"224497109","term_text":"CP001435"}}CP001435 (plasmid cp32-10) [78]
• “Borrelia bissettii” DN127, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"CP002746","term_id":"342222012","term_text":"CP002746"}}CP002746 (chromosome), {"type":"entrez-nucleotide","attrs":{"text":"CP002756","term_id":"342223236","term_text":"CP002756"}}CP002756 (plasmid Ip12), {"type":"entrez-nucleotide","attrs":{"text":"CP002757","term_id":"342223270","term_text":"CP002757"}}CP002757 (plasmid Ip25), {"type":"entrez-nucleotide","attrs":{"text":"CP002758","term_id":"342223295","term_text":"CP002758"}}CP002758 (plasmid 28-3), {"type":"entrez-nucleotide","attrs":{"text":"CP002759","term_id":"342223320","term_text":"CP002759"}}CP002759 (plasmid Ip 28-4), {"type":"entrez-nucleotide","attrs":{"text":"CP002760","term_id":"342223351","term_text":"CP002760"}}CP002760 (Ip28-7), {"type":"entrez-nucleotide","attrs":{"text":"CP002761","term_id":"342223388","term_text":"CP002761"}}CP002761 (plasmid Ip54), {"type":"entrez-nucleotide","attrs":{"text":"CP002762","term_id":"342223459","term_text":"CP002762"}}CP002762 (plasmid Ip56), {"type":"entrez-nucleotide","attrs":{"text":"CP002755","term_id":"342223223","term_text":"CP002755"}}CP002755 (plasmid cp9), {"type":"entrez-nucleotide","attrs":{"text":"CP002747","term_id":"342222829","term_text":"CP002747"}}CP002747 (plasmid cp26), {"type":"entrez-nucleotide","attrs":{"text":"CP002749","term_id":"342222904","term_text":"CP002749"}}CP002749 (plasmid cp32-3), {"type":"entrez-nucleotide","attrs":{"text":"CP002750","term_id":"342222947","term_text":"CP002750"}}CP002750 (plasmid cp32-4), {"type":"entrez-nucleotide","attrs":{"text":"CP002751","term_id":"342222990","term_text":"CP002751"}}CP002751 (plasmid 32-5), {"type":"entrez-nucleotide","attrs":{"text":"CP002752","term_id":"342223034","term_text":"CP002752"}}CP002752 (plasmid cp32-6), {"type":"entrez-nucleotide","attrs":{"text":"CP002753","term_id":"342223077","term_text":"CP002753"}}CP002753 (plasmid cp32-7), CP0027554 (plasmid cp32-9), {"type":"entrez-nucleotide","attrs":{"text":"CP002748","term_id":"342222857","term_text":"CP002748"}}CP002748 (plasmid cp32-11) [78]
• Borrelia spielmanii A14S, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"ABKB02000001","term_id":"224514548","term_text":"ABKB02000001"}}ABKB02000001 (chromosome), {"type":"entrez-nucleotide","attrs":{"text":"CP001468","term_id":"224497637","term_text":"CP001468"}}CP001468 (plasmid Ip17), {"type":"entrez-nucleotide","attrs":{"text":"CP001471","term_id":"224497796","term_text":"CP001471"}}CP001471 (Ip28-3), {"type":"entrez-nucleotide","attrs":{"text":"CP001470","term_id":"224497745","term_text":"CP001470"}}CP001470 (plasmid Ip28-4), {"type":"entrez-nucleotide","attrs":{"text":"CP001465","term_id":"224497532","term_text":"CP001465"}}CP001465 (plasmid Ip28-2), {"type":"entrez-nucleotide","attrs":{"text":"CP001466","term_id":"224497566","term_text":"CP001466"}}CP001466 (plasmid Ip36), {"type":"entrez-nucleotide","attrs":{"text":"CP001464","term_id":"224497496","term_text":"CP001464"}}CP001464 (plasmid Ip38), {"type":"entrez-nucleotide","attrs":{"text":"CP001469","term_id":"224497671","term_text":"CP001469"}}CP001469 (plasmid Ip54), {"type":"entrez-nucleotide","attrs":{"text":"ABKB02000016","term_id":"224513758","term_text":"ABKB02000016"}}ABKB02000016, {"type":"entrez-nucleotide","attrs":{"text":"ABKB02000020","term_id":"224513743","term_text":"ABKB02000020"}}ABKB02000020 (plasmid cp9), {"type":"entrez-nucleotide","attrs":{"text":"CP001467","term_id":"224497607","term_text":"CP001467"}}CP001467 (plasmid cp26), {"type":"entrez-nucleotide","attrs":{"text":"ABKB02000026","term_id":"224513697","term_text":"ABKB02000026"}}ABKB02000026 (plasmid cp32-3), {"type":"entrez-nucleotide","attrs":{"text":"ABKB02000031","term_id":"224513641","term_text":"ABKB02000031"}}ABKB02000031 (plasmid 32-5), {"type":"entrez-nucleotide","attrs":{"text":"ABKB02000021","term_id":"224513736","term_text":"ABKB02000021"}}ABKB02000021 (plasmid cp32-12), {"type":"entrez-nucleotide","attrs":{"text":"ABKB02000014","term_id":"224513768","term_text":"ABKB02000014"}}ABKB02000014 (unidentified) [78]

Non-Bacterial genomes

• Aspergillus flavus, sequence accession {"type":"entrez-geo","attrs":{"text":"GSE32177","term_id":"32177"}}GSE32177 [79]
• Bacteriophage SPN3UB, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JQ288021","term_id":"378408798","term_text":"JQ288021"}}JQ288021 [80]
• Bamboo mitochondria, sequence accession {"type":"entrez-nucleotide-range","attrs":{"text":"JQ235166 to JQ235179","start_term":"JQ235166","end_term":"JQ235179","start_term_id":"372861916","end_term_id":"372861969"}}JQ235166 to JQ235179 [81]
• Boea hygrometrica chloroplast, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JN107811","term_id":"340549387","term_text":"JN107811"}}JN107811 [82]
• Boea hygrometrica mitochondrial, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JN107812","term_id":"340549473","term_text":"JN107812"}}JN107812 [82]
• Canine Picornavirus, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JN831356","term_id":"377826518","term_text":"JN831356"}}JN831356 [83]
• Chandipura virus (CHPV) CIN0327, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"GU212856.1","term_id":"309261828","term_text":"GU212856.1"}}GU212856.1 [84]
• Chandipura virus (CHPV) CIN0451, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"GU212857.1","term_id":"309261834","term_text":"GU212857.1"}}GU212857.1 [84]
• Chandipura virus (CHPV) CIN0751, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"GU212858.1","term_id":"309261840","term_text":"GU212858.1"}}GU212858.1 [84]
• Chandipura virus (CHPV) CIN0755, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"GU190711.1","term_id":"309099431","term_text":"GU190711.1"}}GU190711.1 [84]
• Chinese Porcine Parvovirus Strain PPV2010, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JN872448","term_id":"374676766","term_text":"JN872448"}}JN872448 [85]
• Common midwife toad megavirus, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JQ231222","term_id":"375281729","term_text":"JQ231222"}}JQ231222 [86]
• Dengue Virus Serotype 4, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JN983813","term_id":"372290533","term_text":"JN983813"}}JN983813 [87]
• Duck Tembusu Virus, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JF270480","term_id":"367465451","term_text":"JF270480"}}JF270480 [88]
• Duck Tembusu Virus, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JQ314464","term_id":"377824036","term_text":"JQ314464"}}JQ314464 [88]
• Duck Tembusu Virus, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JQ314465","term_id":"377824038","term_text":"JQ314465"}}JQ314465 [88]
• Emiliania huxleyi Virus 202, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"HQ634145","term_id":"356927554","term_text":"HQ634145"}}HQ634145 [89]
• Emiliania huxleyi Virus EhV-88, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JF974310","term_id":"347600450","term_text":"JF974310"}}JF974310 [89]
• Emiliania huxleyi EhV-201, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JF974311","term_id":"357972615","term_text":"JF974311"}}JF974311 [89]
• Emiliania huxleyi EhV-207, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JF974317","term_id":"347600924","term_text":"JF974317"}}JF974317 [89]
• Emiliania huxleyi EhV-208, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JF974318","term_id":"347601393","term_text":"JF974318"}}JF974318 [89]
• Glarea lozoyensis, sequence accession GUE00000000 [90]
• Nannochloropis gaditana, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"AGNI00000000","term_id":"366047505","term_text":"AGNI00000000"}}AGNI00000000 [91]
• Oryza sativa cv., sequence accession DRA000499 [92]
• Partetravirus, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JN990269","term_id":"374718987","term_text":"JN990269"}}JN990269 [93]
• Porcine Bocavirus PBoV5, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JN831651","term_id":"371449604","term_text":"JN831651"}}JN831651 [94]
• Porcine epidemic diarrhea virus, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JQ282909","term_id":"377824029","term_text":"JQ282909"}}JQ282909 [95]
• Pseudomonas aeruginosa lytic bacteriophage PA1Ø, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"HM624080","term_id":"315418954","term_text":"HM624080"}}HM624080 [96]
• Pseudomonas fluorescens phage OBP, sequence accesssion {"type":"entrez-nucleotide","attrs":{"text":"JN627160","term_id":"359842892","term_text":"JN627160"}}JN627160 [97]
• RNA Virus from Avocado, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JN880414","term_id":"371444768","term_text":"JN880414"}}JN880414 [98]
• Salmonella enterica Serovar Typhimurium Bacteriophage SPN1S, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JN391180","term_id":"370344404","term_text":"JN391180"}}JN391180 [99]
• Schistosoma haematobium, sequence accession PRJNA78265 [100]
• Schistosoma mansoni, sequence accession {"type":"entrez-protein","attrs":{"text":"ERP00038","term_id":"550209647","term_text":"ERP00038"}}ERP00038 [101]
• Stenopirates sp., sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JN100019","term_id":"340008214","term_text":"JN100019"}}JN100019 [102]
• T7-Like Virus, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JN651747","term_id":"374713556","term_text":"JN651747"}}JN651747 [103]
• Vibrio harveyi siphophage VHS1, sequence accession {"type":"entrez-nucleotide","attrs":{"text":"JF713456","term_id":"334898816","term_text":"JF713456"}}JF713456 [104]
• Tyrolean ice man, sequence accession ERP001144 [105]

     

Safety,Tolerability, Pharmacodynamics and Pharmacokinetics of Umeclidinium and Vilanterol Alone and in Combination: A Randomized Crossover Trial

Umeclidinium bromide (GSK573719; UMEC), a new long-acting muscarinic receptor antagonist (LAMA), is in development with vilanterol ({"type":"entrez-nucleotide","attrs":{"text":"GW642444","term_id":"290522278","term_text":"GW642444"}}GW642444; VI), a selective long-acting β₂ agonist (LABA), as a once-daily inhaled combination therapy for the treatment of chronic obstructive pulmonary disease (COPD). A single dose healthy volunteer study was conducted to assess the safety and tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of inhaled umeclidinium (500 µg) and vilanterol (50 µg) when administered separately and in combination using a novel dry powder inhaler (NDPI). Co-administration of single inhaled doses of umeclidinium and vilanterol to healthy Japanese subjects was well tolerated and not associated with meaningful changes in systemic exposure or PD effects compared with administration of either compound individually. Pharmacokinetic assessments showed rapid absorption for both drugs (Tmax = 5 min for both umeclidinium and vilanterol) followed by rapid elimination with median tlast of 4–5 h for umeclidinium and median tlast of 1.5–2.0 h for vilanterol. Assessments of pharmacokinetic interaction were inconclusive since for umeclidinium, Cmax following combination was higher than umeclidinium alone but not AUC whereas for vilanterol, AUC following combination was higher than vilanterol alone but not Cmax. There were no obvious trends observed between individual maximum supine heart rate and umeclidinium Cmax or vilanterol Cmax when delivered as umeclidinium 500 µg and vilanterol 50 µg combination or when delivered as umeclidinium or vilanterol alone.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00976144","term_id":"NCT00976144"}}NCT00976144     

Streptomyces antibioticalis, a Novel Species from a Sanitary Landfill Soil

A novel isolate belonging to the genus Streptomyces, strain SL-4^T, was isolated from soil sample collected from a sanitary landfill, New Delhi, India. The taxonomic status of this isolate was studied by polyphasic approach including morphological, physiological and chemo-taxonomic characterization. Spore chains of SL-4^T were open loops, hooks or extended spirals of wide diameter (retinaculiperti). The cell wall peptidoglycan of the isolate SL-4^T contained L,L-diaminopimelic acid, suggesting that the strain has a cell wall of chemotype-I. The polar lipid profile of the isolate was of Type II, with phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannosides. The 16SrRNA gene sequence similarity between SL-4^T and its phylogenetic relatives Streptomyces atrovirens NRRLB 16357^T ({"type":"entrez-nucleotide","attrs":{"text":"DQ026672","term_id":"68137786","term_text":"DQ026672"}}DQ026672), S. albogriseolus NRRLB 1305^T ({"type":"entrez-nucleotide","attrs":{"text":"AJ494865","term_id":"21742835","term_text":"AJ494865"}}AJ494865), S viridodiastaticus NBRC 13106^T ({"type":"entrez-nucleotide","attrs":{"text":"AB184317","term_id":"90960133","term_text":"AB184317"}}AB184317), S. caelestis NRRL 2418^T ({"type":"entrez-nucleotide","attrs":{"text":"X80824","term_id":"587528","term_text":"X80824"}}X80824), S. flavoviridis NBRC 12772^T ({"type":"entrez-nucleotide","attrs":{"text":"AB184842","term_id":"90960663","term_text":"AB184842"}}AB184842), S. pilosus NBRC 12807^T ({"type":"entrez-nucleotide","attrs":{"text":"AB184161","term_id":"90959977","term_text":"AB184161"}}AB184161) and S. longispororuber NBRC 13488^T ({"type":"entrez-nucleotide","attrs":{"text":"AB184440","term_id":"90960256","term_text":"AB184440"}}AB184440) was 99.65, 99.65, 99.64, 99.23, 99.15, 99.14 and 99.13 % respectively. Subsequent DNA–DNA hybridization experiments with the test strain and its clade members showed 55.27, 44.27, 36.86, and 15.65 % relatedness between SL-4^T and its relatives S. atrovirens,S. albogriseolus, S. viridodiastaticus and S. longispororuber respectively. The genotypic and phenotypic data was analyzed to verify possibility of the isolate SL-4^T representing novel member of the genus Streptomyces, for which the name S. antibioticalis is being proposed. The type strain is SL-4^T (=CCM 7434^T=MTCC 8588^T).     

Effects of Bone Marrow-Derived Mesenchymal Stem Cells on the Axonal Outgrowth through Activation of PI3K/AKT Signaling in Primary Cortical Neurons Followed Oxygen-Glucose Deprivation Injury

Background

Transplantation with bone marrow-derived mesenchymal stem cells (BMSCs) improves the survival of neurons and axonal outgrowth after stroke remains undetermined. Here, we investigated whether PI3K/AKT signaling pathway is involved in these therapeutic effects of BMSCs.

Methodology/Principal Findings

(1) BMSCs and cortical neurons were derived from Sprague-Dawley rats. The injured neurons were induced by Oxygen–Glucose Deprivation (OGD), and then were respectively co-cultured for 48 hours with BMSCs at different densities (5×10³, 5×10⁵/ml) in transwell co-culture system. The average length of axon and expression of GAP-43 were examined to assess the effect of BMSCs on axonal outgrowth after the damage of neurons induced by OGD. (2) The injured neurons were cultured with a conditioned medium (CM) of BMSCs cultured for 24 hours in neurobasal medium. During the process, we further identified whether PI3K/AKT signaling pathway is involved through the adjunction of {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 (a specific phosphatidylinositide-3-kinase (PI3K) inhibitor). Two hours later, the expression of pAKT (phosphorylated AKT) and AKT were analyzed by Western blotting. The length of axons, the expression of GAP-43 and the survival of neurons were measured at 48 hours.

Results

Both BMSCs and CM from BMSCs inreased the axonal length and GAP-43 expression in OGD-injured cortical neurons. There was no difference between the effects of BMSCs of 5×10⁵/ml and of 5×10³/ml on axonal outgrowth. Expression of pAKT enhanced significantly at 2 hours and the neuron survival increased at 48 hours after the injured neurons cultured with the CM, respectively. These effects of CM were prevented by inhibitor {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002.

Conclusions/Significance

BMSCs promote axonal outgrowth and the survival of neurons against the damage from OGD in vitro by the paracrine effects through PI3K/AKT signaling pathway.     

Targeting Polo-Like Kinases: A Promising Therapeutic Approach for Cancer Treatment

Polo-like kinases (Plks) are a family of serine-threonine kinases that regulate multiple intracellular processes including DNA replication, mitosis, and stress response. Plk1, the most well understood family member, regulates numerous stages of mitosis and is overexpressed in many cancers. Plk inhibitors are currently under clinical investigation, including phase III trials of volasertib, a Plk inhibitor, in acute myeloid leukemia and rigosertib, a dual inhibitor of Plk1/phosphoinositide 3-kinase signaling pathways, in myelodysplastic syndrome. Other Plk inhibitors, including the Plk1 inhibitors GSK461364A, TKM-080301, {"type":"entrez-nucleotide","attrs":{"text":"GW843682","term_id":"295327265","term_text":"GW843682"}}GW843682, purpurogallin, and poloxin and the Plk4 inhibitor CFI-400945 fumarate, are in earlier clinical development. This review discusses the biologic roles of Plks in cell cycle progression and cancer, and the mechanisms of action of Plk inhibitors currently in development as cancer therapies.     

Screening for Novel LRRK2 Inhibitors Using a High-Throughput TR-FRET Cellular Assay for LRRK2 Ser935 Phosphorylation

Background

Mutations in the leucine-rich repeat kinase-2 (LRRK2) have been linked to Parkinson’s disease. Recent studies show that inhibition of LRRK2 kinase activity decreased the level of phosphorylation at its own Ser910 and Ser935, indicating that these sites are prime targets for cellular readouts of LRRK2 inhibition.

Methodology/Principal Findings

Using Time-Resolved Förster Resonance Energy Transfer (TR-FRET) technology, we developed a high-throughput cellular assay for monitoring LRRK2 phosphorylation at Ser935. LRRK2-Green Fluorescence Protein (GFP) fusions were expressed in cells via BacMam. Phosphorylation at Ser935 in these cells is detected using a terbium labeled anti-phospho-Ser935 antibody that generates a TR-FRET signal between terbium and GFP. LRRK2 wild-type and G2019S are constitutively phosphorylated at Ser935 in cells as measured by TR-FRET. The phosphorylation level is reduced for the R1441C mutant and little could be detected for the kinase-dead mutant D1994A. The TR-FRET cellular assay was further validated using reported LRRK2 inhibitors including LRRK2-IN-1 and our results confirmed that inhibition of LRRK2 can reduce the phosphorylation level at Ser935. To demonstrate the utility of this assay for screening, we profiled a small library of 1120 compounds. Three known LRRK2 inhibitors were identified and 16 hits were followed up in the TR-FRET and a cytotoxicity assay. Interestingly, out of the top 16 hits, five are known inhibitors of IκB phosphorylation, two CHK1 and two CDC25 inhibitors. Thirteen hits were further tested in a biochemical LRRK2 kinase activity assay and Western blot analysis for their effects on the phosphorylation of Ser910, Ser935, Ser955 and Ser973.

Conclusions/Significance

We developed a TR-FRET cellular assay for LRRK2 Ser935 phosphorylation that can be applied to the screening for LRRK2 inhibitors. We report for the first time that several compounds such as IKK16, CHK1 inhibitors and {"type":"entrez-nucleotide","attrs":{"text":"GW441756","term_id":"315858226","term_text":"GW441756"}}GW441756 can inhibit LRRK2 Ser935 phosphorylation in cells and LRRK2 kinase activity in vitro.     

Hypoxic Conditioned Medium from Rat Cerebral Cortical Cells Enhances the Proliferation and Differentiation of Neural Stem Cells Mainly through PI3-K/Akt Pathways

Purpose

To investigate the effects of hypoxic conditioned media from rat cerebral cortical cells on the proliferation and differentiation of neural stem cells (NSCs) in vitro, and to study the roles of PI3-K/Akt and JNK signal transduction pathways in these processes.

Methods

Cerebral cortical cells from neonatal Sprague–Dawley rat were cultured under hypoxic and normoxic conditions; the supernatant was collected and named ‘hypoxic conditioned medium’ (HCM) and ‘normoxic conditioned medium’ (NCM), respectively. We detected the protein levels (by ELISA) of VEGF and BDNF in the conditioned media and mRNA levels (by RT-PCR) in cerebral cortical cells. The proliferation (number and size of neurospheres) and differentiation (proportion of neurons and astrocytes over total cells) of NSCs was assessed. {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 and SP600125, inhibitors of PI3-K/Akt and JNK, respectively, were applied, and the phosphorylation levels of PI3-K, Akt and JNK were measured by western blot.

Results

The protein levels and mRNA expressions of VEGF and BDNF in 4% HCM and 1% HCM were both higher than that of those in NCM. The efficiency and speed of NSCs proliferation was enhanced in 4% HCM compared with 1% HCM. The highest percentage of neurons and lowest percentage of astrocytes was found in 4% HCM. However, the enhancement of NSCs proliferation and differentiation into neurons accelerated by 4% HCM was inhibited by {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 and SP600125, with {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 having a stronger inhibitory effect. The increased phosphorylation levels of PI3-K, Akt and JNK in 4% HCM were blocked by {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 and SP600125.

Conclusions

4%HCM could promote NSCs proliferation and differentiation into high percentage of neurons, these processes may be mainly through PI3-K/Akt pathways.