Mechanoenzymatic reactions with whole cell transaminases: shaken, not stirred

Mechanochemical reactions have emerged in recent years as a green synthetic method because reactions can be performed more rapidly and using less solvent than traditional synthetic approaches. To date, very few mechanoenzymatic reactions have been described. For the first time, transaminases, which are widely used for the amination of aldehydes and ketones, have been used here under mechanoenzymatic conditions to produce amines using significantly less aqueous medium than conventional biocatalytic reactions. The direct use of whole cells was also possible and shorter reaction times could be used to provide amines efficiently with high yields and stereoselectivities

Nucleotide sequence analyses of the MRP1 gene in four populations suggest negative selection on its coding region

BACKGROUND: The MRP1 gene encodes the 190 kDa multidrug resistance-associated protein 1 (MRP1/ABCC1) and effluxes diverse drugs and xenobiotics. Sequence variations within this gene might account for differences in drug response in different individuals. To facilitate association studies of this gene with diseases and/or drug response, exons and flanking introns of MRP1 were screened for polymorphisms in 142 DNA samples from four different populations. RESULTS: Seventy-one polymorphisms, including 60 biallelic single nucleotide polymorphisms (SNPs), ten insertions/deletions (indel) and one short tandem repeat (STR) were identified. Thirty-four of these polymorphisms have not been previously reported. Interestingly, the STR polymorphism at the 5' untranslated region (5'UTR) occurs at high but different frequencies in the different populations. Frequencies of common polymorphisms in our populations were comparable to those of similar populations in HAPMAP or Perlegen. Nucleotide diversity indices indicated that the coding region of MRP1 may have undergone negative selection or recent population expansion. SNPs E10/1299 G>T (R433S) and E16/2012 G>T (G671V) which occur at low frequency in only one or two of four populations examined were predicted to be functionally deleterious and hence are likely to be under negative selection. CONCLUSION: Through in silico approaches, we identified two rare SNPs that are potentially negatively selected. These SNPs may be useful for studies associating this gene with rare events including adverse drug reactions

To what extent has COVID-19 impacted hard-to-reach energy audiences?

Energy users who don’t participate in efficiency and conservation programmes despite ongoing outreach are often referred to as ‘Hard-to-Reach’ (HTR). These individuals or organisations can include, e.g., low income or vulnerable households; renters; and small businesses. More effectively engaging HTR audiences is key to ensuring everyone benefits equitably from low-carbon energy transitions and related (policy) interventions. This is even more so the case in light of the COVID-19 pandemic, and the ongoing implications for energy use and affordability for the most vulnerable (and newly-vulnerable) members of our society.Within this context, the main purpose of this paper is to explore the extent to which HTR energy audiences have been impacted by COVID-19. Our primary method for this work was a comprehensive, critical literature review and a compilation of official statistics. We also collected survey, interview and focus group data during 2020 COVID-19 pandemic responses in the U.S., UK, NZ and Sweden. The geographical scope is determined by a 3-year project focusing on HTR energy users and implemented in partnership with the User-Centred Energy Systems Technology Collaboration Programme (Users TCP) by the International Energy Agency (IEA). Key findings we highlight and discuss in this paper:● Sweden has taken a different approach to manage COVID-19, yet when it comes to mobility, declines in demand (~25%) have shown relatively similar patterns to countries with stricter measures. ● In the UK, energy debt is growing due to higher domestic consumption arising from lockdown measures and the reduced income of many households. Most households (72%) have increased their energy (monthly gas and electricity bills are up £32) use. In response, 36% are turning thermostats down and 27% limiting lighting.● In the U.S., a survey of 1,000 energy customers found that more than 50% are using more energy, and monitoring their energy use less; 15% reported postponing a utility bill. ● NZ’s model COVID-19 “elimination” response has included housing, financial support, and specific energy payments to date, though unhealthy and unaffordable housing remains a major issue.Whereas the pandemic has exacerbated several elements of the HTR policy discourse (e.g. impacts on vulnerable and/or low-income households), our findings also reveal several opportunities and critical aspects for policy makers, researchers and utilities to identify and engage HTR energy users

Mechanoenzymatic reactions for the hydrolysis of PET

Recent advances in the enzymatic degradation of poly(ethylene terphthalate) (PET) have led to a number of PET hydrolytic enzymes and mutants being developed. With the amount of PET building up in the natural world, there is a pressing need to develop scalable methods of breaking down the polymer into its monomers for recycling or other uses. Mechanoenzymatic reactions have gained traction recently as a green and efficient alternative to traditional biocatalytic reactions. For the first time we report increased yields of PET degradation by whole cell PETase enzymes by up to 27-fold by utilising ball milling cycles of reactive aging, when compared with typical solution-based reactions. This methodology leads to up to a 2600-fold decrease in the solvent required when compared with other leading degradation reactions in the field and a 30-fold decrease in comparison to reported industrial scale PET hydrolysis reactions

The Iowa Homemaker vol.19, no.8

Writing, page 1 Speak Softly, page 2 Application Letters – Precursors to your Job, page 3 Cutting Gay Capers in Sally’s Styles, page 4 Homemaker Success Stories, page 6 Women on the Air, page 7 What’s New in Home Economics, page 8 Books from Crib to College, page 10 Jumps in Journalism, page 12 Iowa State Women Gain Recognition, page 13 Fresh Air in the Mechanical Age, page 14 Fashion Writing Challenges the College Journalist, page 15 Behind Bright Jackets, page 16 Land Yourself a Scholarship, page 17 Alums in the News, page 18 Coed Trickery, page 19 Biography of a Home Economist, page 20 From Journalistic Spindles, page 2

Aflatoxin Contamination of Commercial Maize Products during an Outbreak of Acute Aflatoxicosis in Eastern and Central Kenya

In April 2004, one of the largest aflatoxicosis outbreaks occurred in rural Kenya, resulting in 317 cases and 125 deaths. Aflatoxin-contaminated homegrown maize was the source of the outbreak, but the extent of regional contamination and status of maize in commercial markets (market maize) were unknown. We conducted a cross-sectional survey to assess the extent of market maize contamination and evaluate the relationship between market maize aflatoxin and the aflatoxicosis outbreak. We surveyed 65 markets and 243 maize vendors and collected 350 maize products in the most affected districts. Fifty-five percent of maize products had aflatoxin levels greater than the Kenyan regulatory limit of 20 ppb, 35% had levels > 100 ppb, and 7% had levels > 1,000 ppb. Makueni, the district with the most aflatoxicosis case-patients, had significantly higher market maize aflatoxin than did Thika, the study district with fewest case-patients (geometric mean aflatoxin = 52.91 ppb vs. 7.52 ppb, p = 0.0004). Maize obtained from local farms in the affected area was significantly more likely to have aflatoxin levels > 20 ppb compared with maize bought from other regions of Kenya or other countries (odds ratio = 2.71; 95% confidence interval, 1.12–6.59). Contaminated homegrown maize bought from local farms in the affected area entered the distribution system, resulting in widespread aflatoxin contamination of market maize. Contaminated market maize, purchased by farmers after their homegrown supplies are exhausted, may represent a source of continued exposure to aflatoxin. Efforts to successfully interrupt exposure to aflatoxin during an outbreak must consider the potential role of the market system in sustaining exposure

Prevalence of disease related prion protein in anonymous tonsil specimens in Britain: cross sectional opportunistic survey

Objective To establish with improved accuracy the prevalence of disease related prion protein (PrPCJD) in the population of Britain and thereby guide a proportionate public health response to limit the threat of healthcare associated transmission of variant Creutzfeldt-Jakob disease (vCJD)

Case–Control Study of an Acute Aflatoxicosis Outbreak, Kenya, 2004

Objectives: During January–June 2004, an aflatoxicosis outbreak in eastern Kenya resulted in 317 cases and 125 deaths. We conducted a case–control study to identify risk factors for contamination of implicated maize and, for the first time, quantitated biomarkers associated with acute aflatoxicosis. Design: We administered questionnaires regarding maize storage and consumption and obtained maize and blood samples from participants. Participants: We recruited 40 case-patients with aflatoxicosis and 80 randomly selected controls to participate in this study. Evaluations/Measurements: We analyzed maize for total aflatoxins and serum for aflatoxin B(1)–lysine albumin adducts and hepatitis B surface antigen. We used regression and survival analyses to explore the relationship between aflatoxins, maize consumption, hepatitis B surface antigen, and case status. Results: Homegrown (not commercial) maize kernels from case households had higher concentrations of aflatoxins than did kernels from control households [geometric mean (GM) = 354.53 ppb vs. 44.14 ppb; p = 0.04]. Serum adduct concentrations were associated with time from jaundice to death [adjusted hazard ratio = 1.3; 95% confidence interval (CI), 1.04–1.6]. Case patients had positive hepatitis B titers [odds ratio (OR) = 9.8; 95% CI, 1.5–63.1] more often than controls. Case patients stored wet maize (OR = 3.5; 95% CI, 1.2–10.3) inside their homes (OR = 12.0; 95% CI, 1.5–95.7) rather than in granaries more often than did controls. Conclusion: Aflatoxin concentrations in maize, serum aflatoxin B(1)–lysine adduct concentrations, and positive hepatitis B surface antigen titers were all associated with case status. Relevance: The novel methods and risk factors described may help health officials prevent future outbreaks of aflatoxicosis

Biomarker-Directed Targeted Therapy Plus Durvalumab in Advanced Non-Small-Cell Lung Cancer: A Phase 2 Umbrella Trial

For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance—which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment—and developing effective therapies to overcome them, remains an unmet need. Here the phase 2 umbrella HUDSON study evaluated rational combination regimens for advanced NSCLC following failure of anti-PD-(L)1-containing immunotherapy and platinum-doublet therapy. A total of 268 patients received durvalumab (anti-PD-L1 monoclonal antibody)–ceralasertib (ATR kinase inhibitor), durvalumab–olaparib (PARP inhibitor), durvalumab–danvatirsen (STAT3 antisense oligonucleotide) or durvalumab–oleclumab (anti-CD73 monoclonal antibody). Greatest clinical benefit was observed with durvalumab–ceralasertib; objective response rate (primary outcome) was 13.9% (11/79) versus 2.6% (5/189) with other regimens, pooled, median progression-free survival (secondary outcome) was 5.8 (80% confidence interval 4.6–7.4) versus 2.7 (1.8–2.8) months, and median overall survival (secondary outcome) was 17.4 (14.1–20.3) versus 9.4 (7.5–10.6) months. Benefit with durvalumab–ceralasertib was consistent across known immunotherapy-refractory subgroups. In ATM-altered patients hypothesized to harbor vulnerability to ATR inhibition, objective response rate was 26.1% (6/23) and median progression-free survival/median overall survival were 8.4/22.8 months. Durvalumab–ceralasertib safety/tolerability profile was manageable. Biomarker analyses suggested that anti-PD-L1/ATR inhibition induced immune changes that reinvigorated antitumor immunity. Durvalumab–ceralasertib is under further investigation in immunotherapy-refractory NSCLC