Allele-Specific Inhibition of Histone Demethylases

Histone demethylases play a critical role in mammalian gene expression by removing methyl groups from lysine residues in degree- and site-specific manner. To specifically interrogate members and isoforms of this class of enzymes, we have developed demethylase variants with an expanded active site. The mutant enzymes are capable of performing lysine demethylation with wild-type proficiency, but are sensitive to inhibition by cofactor-competitive molecules embellished with a complementary steric “bump”. The selected inhibitors show more than 20-fold selectivity over the wild-type demethylase, thus overcoming issues typical to pharmacological and genetic approaches. The mutant–inhibitor pairs are shown to act on a physiologically relevant full-length substrate. By engineering a conserved amino acid to achieve member-specific perturbation, this study provides a general approach for studying histone demethylases in diverse cellular processes.     

Role network measures to assess healthcare team adaptation to complex situations: the case of venous thromboembolism prophylaxis

Hospitals are complex environments that rely on clinicians working together to provide appropriate care to patients. These clinical teams adapt their interactions to meet changing situational needs. Venous thromboembolism (VTE) prophylaxis is a complex process that occurs throughout a patient’s hospitalisation, presenting five stages with different levels of complexity: admission, interruption, re-initiation, initiation, and transfer. The objective of our study is to understand how the VTE prophylaxis team adapts as the complexity in the process changes; we do this by using social network analysis (SNA) measures. We interviewed 45 clinicians representing 9 different cases, creating 43 role networks. The role networks were analysed using SNA measures to understand team changes between low and high complexity stages. When comparing low and high complexity stages, we found two team adaptation mechanisms: (1) relative increase in the number of people, team activities, and interactions within the team, or (2) relative increase in discussion among the team, reflected by an increase in reciprocity.

 

Practitioner Summary: The reason for this study was to quantify team adaptation to complexity in a process using social network analysis (SNA). The VTE prophylaxis team adapted to complexity by two different mechanisms, by increasing the roles, activities, and interactions among the team or by increasing the two-way communication and discussion throughout the team. We demonstrated the ability for SNA to identify adaptation within a team.     

Virtual fencing technology to intensively graze lactating dairy cattle. II: Effects on cow welfare and behavior

Virtual fencing technology uses a neckband-mounted device to deliver an audio cue when an animal nears a virtual boundary that is set via a global positioning system, followed by an electrical stimulus if it crosses the boundary. The flexibility offered by this technology could revolutionize grazing management on dairy farms, but its application and effects on lactating dairy cattle have not been assessed. This experiment reports on the effects of an electric or a virtual front-fence on dairy cow behavior and welfare. Two temporally separated treatments were applied to a herd of 30 multiparous cows. Cows were provided an estimated 14 to 15 kg of dry matter/cow of fresh pasture in a new paddock every 24 h. From d 1 to 10 cows were grazed using a conventional electric front-fence (control treatment) and from d 14 to 23 they were grazed using a virtual front-fence (eShepherd, Agersens Pty Ltd.). Cows were trained to the technology from d 11 to 13. The milk production and live weight of individual cows were recorded daily. Cortisol concentrations were obtained from milk samples collected from individual cows on 3 d during each of the control and the virtual fence grazing periods, plus the first day of training. From d 6 of the experiment, 6 focal cows were fitted with a RumiWatch (Itin + Hoch GmbH) noseband sensor to monitor grazing and ruminating time, and 8 focal cows were fitted with an IceTag (IceRobotics Ltd.) sensors to monitor activity. Milk production, live weight, and the time cows spent standing and lying did not differ between the electric and virtual fence periods. Milk cortisol concentrations, activity, and the times spent ruminating and grazing were comparable between the electric and early virtual fence periods (i.e., d 1–3 with a virtual fence). However, at d 4 to 6 with a virtual fence, activity (steps taken and motion index) and time spent grazing were lower, and time spent ruminating was greater, compared with an electric fence. Further, least significant difference tests suggest milk cortisol concentrations were higher at d 5 with a virtual fence than at d 8 with an electric fence and d 1 with a virtual fence. We conclude there is no evidence of behavioral and welfare effects of virtual fencing on dairy cows in the days immediately following implementation of the technology in a simple intensive grazing regimen, but a longer study is required to fully elucidate effects beyond this period.     

Quantification and source characterization of volatile organic compounds from exercising and application of chlorine-based cleaning products in a university athletic center

Humans spend approximately 90% of their time indoors, impacting their own air quality through occupancy and activities. Human VOC emissions indoors from exercise are still relatively uncertain, and questions remain about emissions from chlorine-based cleaners. To investigate these and other issues, the ATHLETic center study of Indoor Chemistry (ATHLETIC) campaign was conducted in the weight room of the Dal Ward Athletic Center at the University of Colorado Boulder. Using a Vocus Proton-Transfer-Reaction Time-of-Flight Mass Spectrometer (Vocus PTR-TOF), an Aerodyne Gas Chromatograph (GC), an Iodide-Chemical Ionization Time-of-Flight Mass Spectrometer (I-CIMS), and Picarro cavity ringdown spectrometers, we alternated measurements between the weight room and supply air, allowing for determination of VOC, NH₃, H₂O, and CO₂ emission rates per person (emission factors). Human-derived emission factors were higher than previous studies of measuring indoor air quality in rooms with individuals at rest and correlated with increased CO₂ emission factors. Emission factors from personal care products (PCPs) were consistent with previous studies and typically decreased throughout the day. In addition, N-chloraldimines were observed in the gas phase after the exercise equipment was cleaned with a dichlor solution. The chloraldimines likely originated from reactions of free amino acids with HOCl on gym surfaces.     

Evaluating the impacts of membrane type, coating, fouling, chemical properties and water chemistry on reverse osmosis rejection of seven nitrosoalklyamines, including NDMA

Reverse osmosis (RO) treatment has been found to be effective for a wide range of organics but generally small, polar, uncharged molecules such as N-nitrosodimethylamine (NDMA) can be poorly rejected. The rejection of seven N-nitrosoalkylamines with molecular masses in the range of 78-158Da, including NDMA, N-nitrosodiethylamine (NDEA), N-nitrosomethylethylamine (NMEA), N-nitrosodipropylamine (NDPA), N-nitrosodibutylamine (NDBA), N-nitrosopyrrolidine (NPyr), N-nitrosopiperidine (NPip) by three commercial brackish-water reverse osmosis membranes was studied in flat-sheet cells under cross-flow conditions. The membranes used were ESPA3 (Hydranautics), LFC3 (Hydranautics) and BW-30 (Dow/Filmtec), commonly used in water reuse applications. The effects of varying ionic strength and pH, dip-coating membranes with PEBAX 1657, a hydrophilic polymer, and artificial fouling with alginate on nitrosamine rejection were quantified. Rejection in deionized (DI) water increased with molecular mass from 56 to 70% for NDMA, to 80-91% for NMEA, 89-97% for NPyr, 92-98% for NDEA, and to beyond the detection limits for NPip, NDPA and NDBA. For the nitrosamines with quantifiable transmission, linear correlations (r(2)>0.97) were found between the number of methyl groups and the log(transmission), with factor 0.35 to 0.55 decreases in transmission per added methyl group. A PEBAX coating lowered the ESPA3 rejection of NDMA by 11% but increased the LFC3 and BW30 rejection by 6% and 15%, respectively. Artificially fouling ESPA3 membrane coupons with 170g/m(2) alginate decreased the rejection of NDMA by 18%. A feed concentration of 100mM NaCl decreased rejection of NDMA by 15% and acidifying the DI water feed to pH=3 decreased the rejection by 5%, whereas increasing the pH to 10 did not have a significant (p<0.05) effect.     

Biofilm‐Eradicating Properties of Quaternary Ammonium Amphiphiles: Simple Mimics of Antimicrobial Peptides

Bacterial biofilms are difficult to eradicate because of reduced antibiotic sensitivity and altered metabolic processes; thus, the development of new approaches to biofilm eradication is urgently needed. Antimicrobial peptides (AMPs) and quaternary ammonium cations (QACs) are distinct, yet well‐known, classes of antibacterial compounds. By mapping the general regions of charge and hydrophobicity of QACs onto AMP structures, we designed a small library of QACs to serve as simple AMP mimics. In order to explore the role that cationic charge plays in biofilm eradication, structures were varied with respect to cationic character, distribution of charge, and alkyl side chain. The reported compounds possess minimum biofilm eradication concentrations (MBEC) as low as 25 μM against Gram‐positive biofilms, making them the most active anti‐biofilm structures reported to date. These potent AMP mimics were synthesized in 1–2 steps and hint at the minimal structural requirements for biofilm destruction.     

Reframing Pinterest: Information Literacy for Interior Design Students

This article discusses providing information literacy to interior design students, specifically how over a few years, and several assignment iterations, we moved from a more traditional one-shot library instruction session to a creative Association of College and Research Libraries Framework-inspired assignment using Pinterest as the medium for the students' professionally relevant research project. The outcome of our instruction relied on flexible assignment planning, collaboration as faculty and librarians changed roles, and a focus on information literacy skills needed by professional designers.