Bovine Leukemia Virus Infection in Dairy Cattle: Effect on Serological Response to Immunization against J5 Escherichia coli Bacterin

Thirteen bovine leukemia virus- (BLV-) negative and 22 BLV-positive Holstein cows were immunized with J5 Escherichia coli bacterin at dry off, three weeks before calving, during the second week after calving, and three weeks after the third immunization. Serum was collected before the initial immunization, immediately before the third and fourth immunizations, and 21 days after the fourth immunization. Anti-J5 E. coli IgM, IgG1, and IgG2 titers were determined by ELISA. Anti-J5 E. coli IgM titers did not differ significantly (P = .98) between groups. Increases in anti-J5 E. coli IgG1 titers were higher in the BLV-negative cows (P = .057). Geometric mean anti-J5 E. coli IgG2 titers increased fourfold in the BLV-negative cows, which was significantly higher (P = .007) than the twofold increase in the BLV-positive cows. Cattle infected with BLV may have impaired serologic responses following immunization with J5 bacterin, and response may differ according to antibody isotype

Nanofibrillated Cellulose from Appalachian Hardwoods Logging Residues as Template for Antimicrobial Copper

TEMPO nanofibrillated cellulose (TNFC) from two underutilized Appalachian hardwoods, Northern red oak (Quercus rubra) and yellow poplar (Liriodendron tulipifera), was prepared to determine its feasibility to be used as template for antimicrobial metallic copper particles. In addition, a comparison of the TNFC from the two species in terms of their morphological, chemical, thermal, and mechanical properties was also performed. The woody biomass was provided in the form of logging residue from Preston County, West Virginia. A traditional kraft process was used to produce the pulp followed by a five-stage bleaching. Bleached pulps were then subjected to a TEMPO oxidation process using the TEMPO/NaBr/NaClO system to facilitate the final mechanical fibrillation process and surface incorporation of metallic copper. The final TNFC diameters for red oak and yellow poplar presented similar dimensions, 3.8±0.74 nm and 3.6±0.85 nm, respectively. The TNFC films fabricated from both species exhibited no statistical differences in both Young’s modulus and the final strength properties. Likely, after the TEMPO oxidation process both species exhibited similar carboxyl group content, of approximately 0.8 mmol/g, and both species demonstrated excellent capability to incorporate antimicrobial copper on their surfaces

Towards the scalable isolation of cellulose nanocrystals from tunicates

ABSTRACT: In order for sustainable nanomaterials such as cellulose nanocrystals (CNCs) to be utilized in industrial applications, a large-scale production capacity for CNCs must exist. Currently the only CNCs available commercially in kilogram scale are obtained from wood pulp (W-CNCs). Scaling the production capacity of W-CNCs isolation has led to their use in broader applications and captured the interest of researchers, industries and governments alike. Another source of CNCs with potential for commercial scale production are tunicates, a species of marine animal. Tunicate derived CNCs (T-CNCs) are a high aspect ratio CNC, which can complement commercially available W-CNCs in the growing global CNC market. Herein we report the isolation and characterization of T-CNCs from the tunicate Styela clava, an invasive species currently causing significant harm to local aquaculture communities. The reported procedure utilizes scalable CNC processing techniques and is based on our experiences from laboratory scale T-CNC isolation and pilot scale W-CNC isolation. To our best knowledge, this study represents the largest scale where T-CNCs have been isolated from any tunicate species, under any reaction conditions. Demonstrating a significant step towards commercial scale isolation of T-CNCs, and offering a potential solution to the numerous challenges which invasive tunicates pose to global aquaculture communities

Identification of PKD1L1 Gene Variants in Children with the Biliary Atresia Splenic Malformation Syndrome

Biliary atresia (BA) is the most common cause of end‐stage liver disease in children and the primary indication for pediatric liver transplantation, yet underlying etiologies remain unknown. Approximately 10% of infants affected by BA exhibit various laterality defects (heterotaxy) including splenic abnormalities and complex cardiac malformations — a distinctive subgroup commonly referred to as the biliary atresia splenic malformation (BASM) syndrome. We hypothesized that genetic factors linking laterality features with the etiopathogenesis of BA in BASM patients could be identified through whole exome sequencing (WES) of an affected cohort. DNA specimens from 67 BASM subjects, including 58 patient‐parent trios, from the NIDDK‐supported Childhood Liver Disease Research Network (ChiLDReN) underwent WES. Candidate gene variants derived from a pre‐specified set of 2,016 genes associated with ciliary dysgenesis and/or dysfunction or cholestasis were prioritized according to pathogenicity, population frequency, and mode of inheritance. Five BASM subjects harbored rare and potentially deleterious bi‐allelic variants in polycystin 1‐like 1, PKD1L1, a gene associated with ciliary calcium signaling and embryonic laterality determination in fish, mice and humans. Heterozygous PKD1L1 variants were found in 3 additional subjects. Immunohistochemical analysis of liver from the one BASM subject available revealed decreased PKD1L1 expression in bile duct epithelium when compared to normal livers and livers affected by other non‐cholestatic diseases. Conclusion WES identified bi‐allelic and heterozygous PKD1L1 variants of interest in 8 BASM subjects from the ChiLDReN dataset. The dual roles for PKD1L1 in laterality determination and ciliary function suggest that PKD1L1 is a new, biologically plausible, cholangiocyte‐expressed candidate gene for the BASM syndrome

Cardiac safety of indacaterol in healthy subjects: a randomized, multidose, placebo- and positive-controlled, parallel-group thorough QT study

<p>Abstract</p> <p>Background</p> <p>Indacaterol is a novel once-daily ultra long-acting β₂-agonist for the treatment of chronic obstructive pulmonary disease. It is known that β₂-agonists, like other adrenergic compounds, can prolong the QT-interval. This thorough QT/QTc study (as per ICH E14 guideline) evaluated the effect of indacaterol on the QT interval in healthy subjects.</p> <p>Methods</p> <p>In this randomized, double-blind, parallel-group, placebo- and positive-controlled (open-label moxifloxacin) study, non-smoking healthy subjects (18-55 years, body mass index: 18.5-32.0 kg/m²) were randomized (4:4:2:4:1) to 14-day treatment with once-daily indacaterol (150 μg, 300 μg, or 600 μg), placebo, or placebo/moxifloxacin (double-blind 14-day treatment with placebo and a single open-label dose of 400 mg moxifloxacin on Day 14). The primary endpoint was the change from baseline on Day 14 in QTcF (QT interval corrected for heart rate using Fridericia's formula).</p> <p>Results</p> <p>In total, 404 subjects were randomized to receive indacaterol (150 [n = 108], 300 [n = 108], 600 μg [n = 54]), placebo (n = 107), or placebo/moxifloxacin (n = 27); 388 subjects completed the study. Maximal time-matched mean (90% confidence intervals) treatment differences from placebo in QTcF change from baseline on Day 14 were 2.66 (0.55, 4.77), 2.98 (1.02, 4.93) and 3.34 (0.86, 5.82) ms for indacaterol 150 μg, 300 μg and 600 μg, respectively. Study sensitivity was confirmed with moxifloxacin demonstrating a significant maximal time-matched QTcF prolongation of 13.90 (10.58, 17.22) ms compared to placebo. All indacaterol doses were well tolerated.</p> <p>Conclusion</p> <p>Indacaterol, at doses up to 600 μg once daily (2-4 times the therapeutic dose) does not have any clinically relevant effect on the QT interval.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01263808">NCT01263808</a></p

HIGH-PERFORMANCE CELLULOSE NANOFIBRIL COMPOSITE FILMS

Cellulose nanofibril/phenol formaldehyde (CNF/PF) composite films with high work of fracture were prepared by filtering a mixture of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) oxidized wood nanofibers and water-soluble phenol formaldehyde with resin contents ranging from 5 to 20 wt%, followed by hot pressing. The composites were characterized by tensile testing, dynamic mechanical analysis, scanning electron microscopy, atomic force microscopy, thermo-gravimetric analysis, and moisture/water absorption. Neat CNF films had tensile stress and Young’s modulus of 232 MPa and 4.79 GPa, respectively. PF resin was found to be well dispersed in the composites, although the resin increased the roughness of the film surfaces. Hygroscopic capacities of the composites were dramatically reduced, as compared to neat films, in both high humidity environments and when soaked in water. The composites exhibited slightly reduced tensile strength with modestly increased storage modulus compared to neat CNF films. Remarkably, the work of fracture ranged from 20 to 27 MJ/m3, making these films among the toughest reported for cellulose nanocomposites