Trueperella pyogenes is an opportunistic pathogen that causes diverse pyogenic infections in livestock. The genes that encode the exotoxin pyolysin (plo) and other putative factors that promote ...adhesion of pathogen to host cells (fimbriae fimA, fimC, fimE, fimG, neuraminidases nanH, nanP, and collagen‐binding protein cbpA) have been associated with virulence, particularly in mastitis and uterus infections of dairy cows. However, the role of these virulence markers in the pathogenicity of the agent in domestic animals infections still is incompletely understood. The genes plo, fimA, fimC, fimE, fimG, nanH, nanP, and cbpA were investigated in 71 T. pyogenes strains recovered from cattle, sheep, goats, dogs, equines, and a pig, recovered from mastitis (n = 35), and non‐mastitis (n = 36) cases (abscesses, reproductive tract diseases, pneumonia, lymphadenitis, encephalitis). The most common genes harboured by the isolates were: plo (71/71 = 100·0%), fimA (70/71 = 98·6%), nanP (56/71 = 78·9%), fimE (53/71 = 74·6%), fimC (46/71 = 64·8%) and nanH (45/71 = 63·4%), whereas cbpA (6/71 = 8·4%) and fimG (4/71 = 5·6%) were uncommon. The most frequent genotypes were plo/fimA/fimE/fimC/nanH/nanP (17/71 = 23·9%), plo/fimA/fimE/nanH/nanP (13/71 = 18·3%), and plo/fimA/fimE/fimC/nanP (11/71 = 15·5%). No association was observed between the presence of genes vs clinical signs or host species. To the best of our knowledge, this is the first report on aforementioned virulence factors of pathogen detected in diseased horses and dogs.
Significance and Impact of the Study
The role of particular virulence factors of Trueperella pyogenes that determine different pyogenic infections among domestic animals is poorly understood. Eight putative virulence genes and genotype profiles of 71 isolates were investigated among different clinical manifestations in domestic animals. The most common genes were plo (71/71 = 100·0%), fimA (70/71 = 98·6%), nanP (56/71 = 78·9%), fimE (53/71 = 74·6%), fimC (46/71 = 64·8%) and nanH (45/71 = 63·4%), whereas plo/fimA/fimE/fimC/nanH/nanP (17/71 = 23·9%), plo/fimA/fimE/nanH/nanP (13/71 = 18·3%), and plo/fimA/fimE/fimC/nanP (11/71 = 15·5%) were the most frequent genotypes. Studies involving virulence factors are critical in the investigation of molecular epidemiology, pathogenicity, and hypothetical differences in the virulence among T. pyogenes strains from different geographical areas.
Significance and Impact of the Study: The role of particular virulence factors of Trueperella pyogenes that determine different pyogenic infections among domestic animals is poorly understood. Eight putative virulence genes and genotype profiles of 71 isolates were investigated among different clinical manifestations in domestic animals. The most common genes were plo (71/71 = 100·0%), fimA (70/71 = 98·6%), nanP (56/71 = 78·9%), fimE (53/71 = 74·6%), fimC (46/71 = 64·8%) and nanH (45/71 = 63·4%), whereas plo/fimA/fimE/fimC/nanH/nanP (17/71 = 23·9%), plo/fimA/fimE/nanH/nanP (13/71 = 18·3%), and plo/fimA/fimE/fimC/nanP (11/71 = 15·5%) were the most frequent genotypes. Studies involving virulence factors are critical in the investigation of molecular epidemiology, pathogenicity, and hypothetical differences in the virulence among T. pyogenes strains from different geographical areas.
IMPORTANCE: Type 2 diabetes is associated with increased cardiovascular (CV) risk. Prior trials have demonstrated CV safety of 3 dipeptidyl peptidase 4 (DPP-4) inhibitors but have included limited ...numbers of patients with high CV risk and chronic kidney disease. OBJECTIVE: To evaluate the effect of linagliptin, a selective DPP-4 inhibitor, on CV outcomes and kidney outcomes in patients with type 2 diabetes at high risk of CV and kidney events. DESIGN, SETTING, AND PARTICIPANTS: Randomized, placebo-controlled, multicenter noninferiority trial conducted from August 2013 to August 2016 at 605 clinic sites in 27 countries among adults with type 2 diabetes, hemoglobin A1c of 6.5% to 10.0%, high CV risk (history of vascular disease and urine-albumin creatinine ratio UACR >200 mg/g), and high renal risk (reduced eGFR and micro- or macroalbuminuria). Participants with end-stage renal disease (ESRD) were excluded. Final follow-up occurred on January 18, 2018. INTERVENTIONS: Patients were randomized to receive linagliptin, 5 mg once daily (n = 3494), or placebo once daily (n = 3485) added to usual care. Other glucose-lowering medications or insulin could be added based on clinical need and local clinical guidelines. MAIN OUTCOMES AND MEASURES: Primary outcome was time to first occurrence of the composite of CV death, nonfatal myocardial infarction, or nonfatal stroke. Criteria for noninferiority of linagliptin vs placebo was defined by the upper limit of the 2-sided 95% CI for the hazard ratio (HR) of linagliptin relative to placebo being less than 1.3. Secondary outcome was time to first occurrence of adjudicated death due to renal failure, ESRD, or sustained 40% or higher decrease in eGFR from baseline. RESULTS: Of 6991 enrollees, 6979 (mean age, 65.9 years; eGFR, 54.6 mL/min/1.73 m2; 80.1% with UACR >30 mg/g) received at least 1 dose of study medication and 98.7% completed the study. During a median follow-up of 2.2 years, the primary outcome occurred in 434 of 3494 (12.4%) and 420 of 3485 (12.1%) in the linagliptin and placebo groups, respectively, (absolute incidence rate difference, 0.13 95% CI, −0.63 to 0.90 per 100 person-years) (HR, 1.02; 95% CI, 0.89-1.17; P < .001 for noninferiority). The kidney outcome occurred in 327 of 3494 (9.4%) and 306 of 3485 (8.8%), respectively (absolute incidence rate difference, 0.22 95% CI, −0.52 to 0.97 per 100 person-years) (HR, 1.04; 95% CI, 0.89-1.22; P = .62). Adverse events occurred in 2697 (77.2%) and 2723 (78.1%) patients in the linagliptin and placebo groups; 1036 (29.7%) and 1024 (29.4%) had 1 or more episodes of hypoglycemia; and there were 9 (0.3%) vs 5 (0.1%) events of adjudication-confirmed acute pancreatitis. CONCLUSIONS AND RELEVANCE: Among adults with type 2 diabetes and high CV and renal risk, linagliptin added to usual care compared with placebo added to usual care resulted in a noninferior risk of a composite CV outcome over a median 2.2 years. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01897532
Macrophages are central cells in mediating the inflammatory response.
We evaluated the effect of high glucose conditions on the inflammatory profile and the autophagy pathway in Bone-Marrow Derived ...Macrophages (BMDM) from diabetic (D-BMDM) (alloxan: 60mg/kg, i.v.) and non-diabetic (ND-BMDM) C57BL/6 mice. BMDM were cultured in medium with normal glucose (5.5 mM), or high glucose (25 mM) concentration and were primed with Nigericin (20µM) stimulated with LPS (100 ng/mL) at times of 30 minutes; 2; 4; 6 and 24 hours, with the measurement of IL-6, IL-1β and TNF-α cytokines.
We have further identified changes in the secretion of pro-inflammatory cytokines IL-6, IL-1β and TNF-α, where BMDM showed increased secretion of these cytokines after LPS + Nigericin stimulation. In addition, changes were observed in the autophagy pathway, where the increase in the autophagic protein LC3b and Beclin-1 occurred by macrophages of non-diabetic animals in hyperglycemic medium, without LPS stimulation. D-BMDM showed a reduction on the expression of LC3b and Beclin-1, suggesting an impaired autophagic process in these cells.
The results suggest that hyperglycemia alters the inflammatory pathways in macrophages stimulated by LPS, playing an important role in the inflammatory response of diabetic individuals.
Prototheca species have increasingly been reported to be opportunistic pathogens that cause mastitis in dairy herds, and it poses an emergent problem because at present, there are no effective ...therapies for the treatment of protothecal mastitis. This study investigated the in vitro algicidal effect of guanidine on 75 Prototheca zopfii genotype 2 strains isolated from 75 cases of clinical and subclinical bovine mastitis. All strains were susceptible to guanidine in vitro with minimal algaecide concentrations ranging from 0·001 to 0·035%. Guanidine is known to have a high microbicidal effect and is considered to be a new generation microbicidal compound. It is not toxic to human mucous membranes and conjunctivas at low concentrations and has been used as a disinfectant in swimming pools and as an antiseptic for human wounds. The algicidal action of guanidine at low concentrations indicates that it could be an alternative disinfectant or antiseptic for cleaning of the dairy environment and milking equipment, in pre‐ and postdipping solutions, in the chemical dry therapy of bovine teats and even in the intramammary therapy of P. zopfii infections. This is the first report of the in vitro algicidal effect of guanidine on P. zopfii strains of animal origin.
Significance and Impact of the Study
Prototheca zopfii genotype 2 is an opportunistic pathogen of bovine mastitis. To date, no effective therapies against protothecal mastitis have been developed. The in vitro algicidal effect of guanidine on 75 P. zopfii genotype 2 strains isolated from cows revealed that all of the isolates were susceptible to the compound at low concentrations, which indicates that guanidine may be used as an antiseptic/disinfectant for dairy milking equipment, in pre‐ and postdipping solutions, and as a chemical dry therapy or an intramammary therapy. This study describes the in vitro algicidal effect of guanidine on P. zopfii for the first time.
Significance and Impact of the Study: Prototheca zopfii genotype 2 is an opportunistic pathogen of bovine mastitis. To date, no effective therapies against protothecal mastitis have been developed. The in vitro algicidal effect of guanidine on 75 P. zopfii genotype 2 strains isolated from cows revealed that all of the isolates were susceptible to the compound at low concentrations, which indicates that guanidine may be used as an antiseptic/disinfectant for dairy milking equipment, in pre‐ and postdipping solutions, and as a chemical dry therapy or an intramammary therapy. This study describes the in vitro algicidal effect of guanidine on P. zopfii for the first time.
The recently initiated Arecibo Legacy Fast ALFA (ALFALFA) survey aims to map ~7000 deg2 of the high Galactic latitude sky visible from Arecibo, providing a H I line spectral database covering the ...redshift range between -1600 and 18,000 km s-1 with ~5 km s-1 resolution. Exploiting Arecibo's large collecting area and small beam size, ALFALFA is specifically designed to probe the faint end of the H I mass function in the local universe and will provide a census of H I in the surveyed sky area to faint flux limits, making it especially useful in synergy with wide-area surveys conducted at other wavelengths. ALFALFA will also provide the basis for studies of the dynamics of galaxies within the Local Supercluster and nearby superclusters, allow measurement of the H I diameter function, and enable a first wide-area blind search for local H I tidal features, H I absorbers at z < 0.06, and OH megamasers in the redshift range 0.16 < z < 0.25. Although completion of the survey will require some 5 years, public access to the ALFALFA data and data products will be provided in a timely manner, thus allowing its application for studies beyond those targeted by the ALFALFA collaboration. ALFALFA adopts a two-pass, minimum intrusion, drift scan observing technique that samples the same region of sky at two separate epochs to aid in the discrimination of cosmic signals from noise and terrestrial interference. Survey simulations, which take into account large-scale structure in the mass distribution and incorporate experience with the ALFA system gained from tests conducted during its commissioning phase, suggest that ALFALFA will detect on the order of 20,000 extragalactic H I line sources out to z ~ 0.06, including several hundred with H I masses M < 107.5 M.
Signaling through the thrombospondin-1 receptor CD47 broadly limits cell and tissue survival of stress, but the molecular mechanisms are incompletely understood. We now show that loss of CD47 permits ...sustained proliferation of primary murine endothelial cells, increases asymmetric division, and enables these cells to spontaneously reprogram to form multipotent embryoid body-like clusters. c-Myc, Klf4, Oct4, and Sox2 expression is elevated in CD47-null endothelial cells, in several tissues of CD47- and thrombospondin-1-null mice, and in a human T cell line lacking CD47. CD47 knockdown acutely increases mRNA levels of c-Myc and other stem cell transcription factors in cells and in vivo, whereas CD47 ligation by thrombospondin-1 suppresses c-Myc expression. The inhibitory effects of increasing CD47 levels can be overcome by maintaining c-Myc expression and are absent in cells with dysregulated c-Myc. Thus, CD47 antagonists enable cell self-renewal and reprogramming by overcoming negative regulation of c-Myc and other stem cell transcription factors.
This work introduces a new equivalent circuit generation method which can compute an accurate equivalent circuit representation for the known/measured impedance characteristics of antennas, which may ...assist in matching circuit design, non-Foster matching network design, and deep-learning antenna design. The method utilizes a modified Drude-Lorentz resonator representation inspired by optical material dispersion modeling to create multiple sub-circuits based on determined resonances in the impedance spectrum. Each computed sub-circuit is necessarily composed of physically realizable resistors, capacitors, and inductors, and they are connected in series to accurately reconstruct the device's corresponding impedance characteristics over a specified region of interest. The process is automated and applicable to a wide range of antennas and electromagnetic devices with multiple resonance phenomena. Current equivalent circuit design methods are limited by a lack of generalization and can require complex, active, or non-realizable circuit topologies. The proposed Drude-Lorentz-based approach can provide valuable insight into an antenna's resonant behavior while remaining general-purpose and only requiring passive components which are physically realizable. This improved generality is achieved by not requiring physical insights, but rather only utilizing the impedance data alone. Additionally, the method creates simpler circuits than other general methods, requiring less components and component types. This method is employed to create equivalent circuits of four different exemplary types of antennas, a patch antenna, a loop antenna, a spherical helix antenna, and a metantenna unit cell. The impedances generated from these circuit examples are compared with results of their full-wave simulation counterparts and found to be in excellent agreement.
The Amazon has the largest watershed in the world, with abundant fresh water reserves. Such abundance contrasts with the quality of the water consumed in the riverine communities. This work ...highlights the importance of assessing the quality of water of the Solimões River in the stretch situated opposite the Community Nossa Senhora das Graças-Costa do Pesqueiro, in front of the town of Manacapuru-Amazonas-Brazil. The research aimed to evaluate environmental indicators for the quality of the river water as well as in households in this community, according to the regional seasonality. The monitored parameters such as conductivity, dissolved oxygen, turbidity, color, pH, nitrate, nitrite, and sulfate were compared with the water quality standards in force in Brazil. Values well above the maximum level allowed (MLA) for color and turbidity parameters were found in some households, indicating that the water collected from the river is not getting appropriate treatment. The analysis of the correlation matrix of the parameters in the flood period of the river evidenced high correlation among dissolved oxygen (D.O), NO
3
−
, Cl
−
, SO
4
2−
, and color. In this study, by principal component analysis (PCA), it was observed that the characteristics of the water, obtained from the river to be consumed in the households, in the flood period showed similarities with the river water samples, indicating absence of efficient treatment for human consumption.
We compare the output of an 18-box geochemical model of the ocean with measurements to investigate the controls on both the mean values and variation of nitrate δ
15N and δ
18O in the ocean interior. ...The δ
18O of nitrate is our focus because it has been explored less in previous work. Denitrification raises the δ
15N and δ
18O of mean ocean nitrate by equal amounts above their input values for N
2 fixation (for δ
15N) and nitrification (for δ
18O), generating parallel gradients in the δ
15N and δ
18O of deep ocean nitrate. Partial nitrate assimilation in the photic zone also causes equivalent increases in the δ
15N and δ
18O of the residual nitrate that can be transported into the interior. However, the regeneration and nitrification of sinking N can be said to decouple the N and O isotopes of deep ocean nitrate, especially when the sinking N is produced in a low latitude region, where nitrate consumption is effectively complete. The δ
15N of the regenerated nitrate is equivalent to that originally consumed, whereas the regeneration replaces nitrate previously elevated in δ
18O due to denitrification or nitrate assimilation with nitrate having the δ
18O of nitrification. This lowers the δ
18O of mean ocean nitrate and weakens nitrate δ
18O gradients in the interior relative to those in δ
15N. This decoupling is characterized and quantified in the box model, and agreement with data shows its clear importance in the real ocean. At the same time, the model appears to generate overly strong gradients in both δ
18O and δ
15N within the ocean interior and a mean ocean nitrate δ
18O that is higher than measured. This may be due to, in the model, too strong an impact of partial nitrate assimilation in the Southern Ocean on the δ
15N and δ
18O of preformed nitrate and/or too little cycling of intermediate-depth nitrate through the low latitude photic zone.
Hypostominae is a subfamily of the family Loricariidae that has a great diversity of species. Accordingly, testicular studies in fish can contribute to the phylogeny and taxonomy of species and to ...the comparison of reproductive aspects between species. Thus, this work aimed to characterize the testicular morphology and spermatogenesis of the Hypostominae species Baryancistrus xanthellus, Peckoltia oligospila and Hypancistrus zebra.
B. xanthellus, P. oligospila and H. zebra had an anastomosed tubular type of testis. The germinal epithelium was continuous with unrestricted spermatogonia, and the proliferative, meiotic and spermiogenic phases were defined in all species. In the spermiogenic phase, spermatids were classified as initial, intermediate and final. Only in B. xanthellus in the final phase was there nuclear rotation. The sperm for the three species had a head with an oval shape and a single flagellum composed of the short midpiece, principal piece and end piece. B. xanthellus and P. oligospila showed a cylindrical flagellum and H. zebra showed projections that produced a flattened appearance.
On the basis testicular structure and ultrastructural characteristics of the germ cells, there was a greater relationship between B. xanthelus and P. oligospila, while H. zebra had particular characteristics. These aspects show that despite belonging to the same subfamily, the species have distinct biological characteristics.
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