Lipid II is an essential precursor of the bacterial cell wall biosynthesis and thereby an important target for various antibiotics. Several lanthionine-containing peptide antibiotics target lipid II with lanthionine-stabilized lipid II-binding motifs. Here, we used the biosynthesis system of the lantibiotic nisin to synthesize a two lipid II binding motifs-containing lantibiotic, termed TL19, which contains the N-terminal lipid II binding motif of nisin and the distinct C-terminal lipid II binding motif of one peptide of the two-component haloduracin (i.e. HalA1). Further characterization demonstrated that (i) TL19 exerts 64-fold stronger antimicrobial activity against E. faecium than nisin (1-22), which has only one lipid II binding site, and (ii) both the N- and C-terminal domains are essential for the potent antimicrobial activity of TL19, as evidenced by mutagenesis of each single and double domains. These results show the feasibility of a new approach to synthesize potent lantibiotics with two different lipid II binding motifs to treat specific antibiotic-resistant pathogens.

Multi-drug resistance among Gram-negative bacteria is a major global public health threat. Metallo-β-lactamases (MBLs) target the most widely-used antibiotic class, the β-lactams, including the most recent-generation carbapenems. Interspecies spread renders these enzymes a serious clinical threat and there are no clinically-available inhibitors. We present crystal structures of IMP-13, a structurally-uncharacterized MBL from Gram-negative Pseudomonas aerugionasa found in clinical outbreaks globally, and characterize the binding using solution NMR-spectroscopy and molecular-dynamics simulations. Crystal structures of apo IMP-13 and bound to four clinically-relevant carbapenem antibiotics (doripenem, ertapenem, imipenem and meropenem) are presented. Active site plasticity and the active-site loop, where a tryptophan residue stabilizes the antibiotic core scaffold, are essential to the substrate-binding mechanism. The conserved carbapenem scaffold plays the most significant role in IMP-13 binding, explaining the broad substrate specificity. The observed plasticity and substrate-locking mechanism provide opportunities for rational drug design of novel metallo-β-lactamase inhibitors, essential in the fight against antibiotic resistance.

Carbapenem pharmacokinetic profiles are significantly changed in critically ill patients because of the drastic variability of the patients' physiological parameters. Published population PK studies have mainly focused on specific diseases and the majority of these studies had small sample sizes. The aim of this study was to develop a population PK model of imipenem in critically ill patients that estimated the influence of various clinical and biological covariates and the use of Extracorporeal Membrane Oxygenation (ECMO) and Continuous Renal Replacement Therapy (CRRT). A two-compartment population PK model with Creatinine clearance (CrCL), body weight (WT), and ECMO as fixed effects was developed using the non-linear mixed effect model (NONMEM). A Monte Carlo simulation was performed to evaluate various dosing schemes and different levels of covariates based on the pharmacokinetic/pharmacodynamic index (f%T>MIC) for the range of clinically relevant minimum inhibitory concentrations(MICs). The results showed that there may be insufficient drug use in the clinical routine drug dose regimen, and 750mg Q6h could achieve a higher treatment success rate. The blood concentrations of imipenem in ECMO patients were lower than that of non-ECMO patients, therefore dosage may need to be increased. The dosage may need adjustment for patients with CrCL ≤ 70ml/min, but dose should be lowered carefully to avoid the insufficient drug exposure. Dose adjustment is not necessary for patients within the WT ranging from 50-80 kg. Due to the large variation in PK profile of imipenem in critically ill patients, TDM should be carried out to optimize drug regimens.

Despite the worldwide re-emergence of the chikungunya virus (CHIKV) and the high morbidity associated with CHIKV infections, there is no approved vaccine or antiviral treatment available. We here aim to identify the target of a novel class of CHIKV inhibitors i.e. CHVB series. CHVB compounds inhibit the in vitro replication of CHIKV isolates with 50% effective concentrations in the low micromolar range. A CHVB-resistant variant (CHVB^res) was selected that carried two mutations in the gene encoding nsP1 (responsible for viral RNA capping), one mutation in nsP2 and one mutation in nsP3. Reverse genetics studies demonstrated that both nsP1 mutations were necessary and sufficient to achieve ~18-fold resistance, suggesting that CHVB targets viral mRNA capping. Interestingly, CHVB^res was cross-resistant to the previously described CHIKV capping inhibitors from the MADTP series, suggesting they share a similar mechanism of action. In enzymatic assays, CHVB inhibited the methyltransferase and guanylyltransferase activities of alphavirus nsP1 proteins. To conclude, we identified a class of CHIKV inhibitors that targets the viral capping machinery. The potent anti-CHIKV activity makes this chemical scaffold a potential candidate for CHIKV drug development.

Trivantis Lectora Inspire is more expensive than fellow Editors' Choice pick Articulate Storyline 2. With that said, it's still worth checking out as it is a very powerful eLearning authoring tool.

Emilee Yaeger, an undergraduate student in the Science BS/MBA accelerated joint degree program, has been selected as the recipient of the 2019 Eberly College of Science Cooperative Education Student of the Year Award. The award recognizes the student’s academic achievements and contributions to the participating employer, the University, the community, and the field of cooperative education.

Penn State Health has appointed Don McKenna as president of Penn State Health Hampden Medical Center.

Beth E. Michalec, lecturer of corporate communication at Penn State Lehigh Valley, earned a doctorate in rhetoric from Duquesne University. Michalec was selected as a Fulbright specialist in June 2019 by the U.S. Department of State.

Many teachers scrapped their lesson plans on Monday and gave their students space to talk about Kobe Bryant.

Online learners at Penn State have elected 10 leaders to the World Campus Student Government Association to serve in the 2020-21 school year.

If your battery capacity ever drops below 80 percent when you have AppleCare+, you're in luck!

Six trustees were elected or appointed to serve on the Penn State Board of Trustees today (May 8).

All Classroom Q&A posts offering advice on Science Instruction (from the past eight years!) are described and linked to in this compilation post.

The College of Earth and Mineral Sciences’ Graduate Fellows for Science Advocacy and Diversity (EMS-GFSAD) program is wrapping up its inaugural year and has already had an impact in promoting a diverse and inclusive scientific community.

Michael Mann, distinguished professor of atmospheric sciences and director of Penn State's Earth System Science Center at Penn State, has been elected to the National Academy of Sciences, recognizing distinguished and continuing achievements in original research. Membership in the NAS is one of the highest honors given to a scientist or engineer in the United States.

Former Vice President Joe Biden has approved a series of new hires that will significantly expand his campaign ahead of the general election fight with President Trump.

Bernadette Lear, Penn State University Libraries behavioral sciences and education librarian and coordinator of library instruction at the Penn State Harrisburg Library, has been elected vice chair/chair elect of the Library History Round Table, a membership group of the American Library Association.

Rebecca Mattson, head of faculty and research services for the H. Laddie Montague Jr. Law Library, Penn State University Libraries, and professor of legal research at Penn State Law at University Park, has been elected vice chair/chair elect of the Research Instruction and Patron Services Special Interest Section of the American Association of Law Libraries.

Selected poems of Rachelle Bowser, Rachel Mennies, Erin Murphy and Eleanor Stanford have been chosen to represent the Pennsylvania Center for the Book’s 2020 Public Poetry Project, with poetry interpreted into art posters for the annual event.

Segway-Ninebot hopes the new vehicles will appeal to urban dwellers. Pricing and launch dates have yet to be announced, but expect more details at CES next month.

From the ashes of the failed Fisker Karma sports car, automotive designer Henrik Fisker has designed a futuristic battery-powered luxury SUV that won't break the bank.

By providing instant torque to all four wheels you can drive as normal in all conditions according to Nissan, while also feeling like you're in a sports car.

Students report that schools' filters, firewalls, and blockage of social media sites are obstacles to their use of educational technology.

Lewis Macdonald MSP has been elected as a temporary Deputy Presiding Officer (DPO) of the Scottish Parliament. The election was held as part of the Parliament's response to the coronavirus pandemic.

Don't rely on Facebook's self-regulation to save us from election interference in this year's critical elections. In fact, despite a PR push to the contrary, the company is doubling down on the access it sells to would-be meddlers.

To view more press releases, please visit http://ir.wintrust.com/news.aspx?iid=1024452.

While there's a chance for SA to be downgraded to non-investment grade in November, rating firms may wait for the outcome of the ANC elective conference, says economist Kim Silberman.

Amsterdam and Groningen will stage the expanded 16-team finals from 19 January to 6 February 2022.

States don't routinely collect information on districts' materials purchases. If they plan to use curriculum as a lever to improve student learning, they should, a new brief argues.

Lebanon’s Ministry of Telecommunications has been authorized by the Cabinet to temporarily operate the country’s two cellular networks until a new tender is launched, Minister of Telecommunications Talal Hawat said Tuesday.

Dec. 9, 2017 program cancelled and incorporated into March 24, 2018 program.

Lecture by Theo Braunskill, Lenapé citizen and Elders Council member, and Nena Todd, manager of the Delaware Division of Historical and Cultural Affairs’ downtown Dover museums.

Election Day is still a few days away, but Delaware students tallied their votes for statewide offices today in Dover at the 2018 Student Mock Election Convention. In what’s become a bellwether for elections in Delaware, students picked incumbents Sen. Tom Carper and Congresswoman Lisa Blunt Rochester to continue representing the First State in Washington.

Fun and thought-provoking Constitutional programs to take place on April 4, 11, 18 and 25, 2019.

Secretary of State Jeffrey Bullock has suspended the Delaware electrician license of Andrew S. Atkins for engaging in unlawful sexual conduct with a minor.

Series features Bill Manthorpe, retired U.S. Navy captain and author.

The Skoda Enyaq will be offered in both rear-wheel drive and all-wheel drive variants with three different battery capacities and five performance specs.

The Delaware Division of Libraries and Delaware Department of Labor (DOL) rolled out the partnership in February 2019 to be able to reach out to more residents who may be in need of services but can’t travel to Department of Labor locations. With the many computers available at libraries, a staff member can offer residents […]

Review of: Multi-Agent-Based Simulation XIX. 19th International Workshop, MABS 2018, Stockholm, Sweden, July 14, 2018, Revised Selected Papers by Davidsson, Paul, Verhagen, Harko (Eds.), reviewed by Patrycja Antosz

Participants in Delaware's Women, Infants and Children (WIC) program can now use special coupons to purchase fresh fruits and vegetables at 11 Delaware farmers' markets under a pilot program beginning this week.

As the 2018 growing season officially comes to an end, the U.S. Department of Agriculture’s National Agricultural Statistics Service (NASS) will contact producers in Delaware to gather final year-end crop production numbers and the amount of grain and oilseeds they store on their farms. At the same time, NASS will survey grain facility operators to determine year-end grain and oilseed stocks.

The Delaware Department of Agriculture has partnered with the Delaware Electric Cooperative to launch a new irrigation grant program to help Delaware farmers install environmentally friendly irrigation systems.

Delaware selected as one of only two states in the nation to participate  New Castle, Del. – On Tuesday, Lt. Governor Hall-Long joined members of Delaware’s Behavioral Health Consortium and members of The Pew Charitable Trusts to announce a newly formed partnership that will work to reshape Delaware’s behavioral health treatment system for those struggling […]

NEW CASTLE (Oct. 15, 2018) – Department of Health and Social Services (DHSS) Secretary Dr. Kara Odom Walker, a board-certified family physician, has been elected as a member of the prestigious National Academy of Medicine (NAM), Academy President Victor Dzau announced today during the organization’s annual meeting in Washington. Secretary Walker is one of 75 […]

The Governor’s Advisory Council for Exceptional Citizens (GACEC) and its community partners, are pleased to report that the Heart 2 Heart Hugs campaign has now begun. Heart 2 Heart Hugs is focused on providing warmth, comfort, hugs and smiles for kids and young adults in Delaware who are homeless or in foster care. Donations of […]

DOVER (May 15, 2019) – During the 18th Prescription Drug Take-Back Day event on April 27, 2019, Delaware collected 5,385 pounds of unwanted or expired medicine, according to the U.S. Drug Enforcement Administration (DEA) and the Division of Public Health (DPH). That amount is approximately 1,600 pounds more than the 3,739 pounds collected in October. […]

NEW CASTLE (June 26, 2019) – Governor John Carney has signed into law House Bill 81, which mandates that employers with 50 or more employees remit child support payments to the Department of Health and Social Services’ Division of Child Support Services (DCSS) by electronic funds transfer (EFT) or electronic data interchange (EDI). The law […]

The State Office of Volunteerism (SOV) and the Delaware Department of Health and Social Services (DHSS) are partnering with Stockings for Soldiers on a public donation campaign to collect items during October and November to send to members of the military serving overseas during the holidays.

Industry executives say the slump in electronics could only deepen in the first quarter of this fiscal, mainly due to the lockdown, and further accelerate a slide in the overall merchandise exports.