Bunyaviruses are significant human pathogens, causing diseases ranging from hemorrhagic fevers to encephalitis. Among these viruses, La Crosse virus (LACV), a member of the California serogroup, circulates in the eastern and midwestern United States. While LACV infection is often asymptomatic, dozens of cases of encephalitis are reported yearly. Unfortunately, no antivirals have been approved to treat LACV infection. Here, we developed a method to rapidly test potential antivirals against LACV infection. From this screen, we identified several potential antiviral molecules, including known antivirals. Additionally, we identified many novel antivirals that exhibited antiviral activity without affecting cellular viability. Valinomycin, a potassium ionophore, was among our top targets. We found that valinomycin exhibited potent anti-LACV activity in multiple cell types in a dose-dependent manner. Valinomycin did not affect particle stability or infectivity, suggesting that it may preclude virus replication by altering cellular potassium ions, a known determinant of LACV entry. We extended these results to other ionophores and found that the antiviral activity of valinomycin extended to other viral families including bunyaviruses (Rift Valley fever virus, Keystone virus), enteroviruses (Coxsackievirus, rhinovirus), flavirivuses (Zika), and coronaviruses (HCoV-229E and MERS-CoV). In all viral infections, we observed significant reductions in virus titer in valinomycin-treated cells. In sum, we demonstrate the importance of potassium ions to virus infection, suggesting a potential therapeutic target to disrupt virus replication.

Importance No antivirals are approved for the treatment of bunyavirus infection. The ability to rapidly screen compounds and identify novel antivirals is one means to accelerate drug discovery for viruses with no approved treatments. We used this approach to screen hundreds of compounds against La Crosse virus, an emerging bunyavirus that causes significant disease, including encephalitis. We identified several known and previously unidentified antivirals. We focused on a potassium ionophore, valinomycin, due to its promising in vitro antiviral activity. We demonstrate that valinomycin, as well as a selection of other ionophores, exhibits activity against La Crosse virus as well as several other distantly related bunyaviruses. We finally observe that valinomycin has activity against a wide array of human viral pathogens, suggesting that disrupting potassium ion homeostasis with valinomycin may be a potent host pathway to target to quell virus infection.

Peroxidases are a group of heterogeneous family of enzyme that plays diverse biological functions. Ascorbate peroxidase is a redox enzyme that is reduced by trypanothione, which plays a central role in the redox defence system of Leishmania. In view of developing new and novel therapeutics, we have performed in silico studies in order to search for ligand library and identification of new drug candidates and its physiological role against promastigotes and intracellular amastigotes of Leishmania donovani. Our results demonstrated that the selected inhibitor ZINC96021026 has significant anti-leishmanial effect and effectively killed both free and intracellular forms of the parasite. ZINC96021026 was found to be identical to ML-240, a selective inhibitor of Valosin-containing protein (VCP) or p97, a member of AAA-ATPase protein family which was derived from the scaffold of DBeQ, targeting the D2-ATPase domain of the enzyme. ZINC96021026 (ML-240) thus have broad range of cellular functions, thought to be derived from its ability to unfold proteins or disassemble protein complexes besides inhibiting the ascorbate peroxidase activity. ML-240 may inhibits the parasite's ascorbate peroxidase leading to extensive apoptosis and inducing generation of reactive oxygen species. Taken together, our results demonstrated that ML-240 could be an attractive therapeutic option for treatment against leishmaniasis.

Malware on an air-gapped computer can transmit data like Morse code by changing screen brightness in a way that's invisible to the naked eye but easily recorded with a camera.

BACKGROUND:

Current guidelines from the American Academy of Pediatrics recommend screening children for developmental problems by using a standardized screening tool and referring at-risk patients to early intervention (EI) or subspecialists. Adoption of guidelines has been gradual, with research showing many children still not being screened and referred.

While we wait for Apple Arcade to launch for iOS devices, Google is preparing its own app/game subscription service for Android called Play Pass.

Don't settle for the default settings on your Android device. With the right launcher, you can customize the screens and layouts of your phone.

Comixology Unlimited lets you dive into more than 20,000 digital comics for just $5.99 per month. Make the most of your subscription by starting with these 10 titles.

At CES, LG Display is showing off a 65-inch concept TV that can bend at the edges, allowing it to switch from a flat-screen display to a curved one in about five seconds. The company also put a bendable OLED on a foldable tablet/laptop.

Philip M. Farrell
Jan 1, 2001; 107:1-13
ARTICLES

The Presiding Officer has today written to all Members to set out new business plans this week. The first ever Members’ Virtual Question Time will be held this Friday, 17 April at 2:30pm.

Plans for further virtual scrutiny at the Scottish Parliament have today been announced by the Scottish Parliament’s Presiding Officer.

The Leonardo opened its doors on Tuesday 3 March. Developers of the 234-metre tall building said the 240-suite hotel and residences were ready for occupation and some residents were already in the process of moving in.

Eight senior Penn State Scranton accounting and finance students participated in the United Way of Lackawanna and Wayne Counties’ annual Volunteer Income Tax Assistance (VITA) program, preparing about 2,250 free tax returns for low-income families and individuals throughout the region.

Penn State Scranton recently donated personal protective equipment (PPE) to two local hospitals, Geisinger Community Medical Center and Commonwealth Health Moses Taylor Hospital, to help them during the growing coronavirus pandemic.

For Penn State Scranton students, the first couple of weeks of remote learning have proven to be a big adjustment — academically and socially. Several campus students shared their initial thoughts regarding the virtual learning experience and being away from the physical campus.

In keeping with Penn State Scranton's current continuing adjustment to an all-virtual environment, the annual Student Recognition Dinner will be held virtually at 6 p.m. on Wednesday, April 22.

On Wednesday, May 13, Penn State Scranton will hold a Virtual Open House for students considering applying to Penn State Scranton from 5 to 6 p.m.

Graduating members of Penn State Scranton’s Lambda Pi Eta Alpha Epsilon Pi chapter received their honor cords recently during a virtual celebration. Lambda Pi Eta is the official honor society of the National Communication Association and currently, the only academic honor society at Penn State Scranton.

Books played an important role in Aslan's salvation. Now he provides literature to other Central Asians.

The federal government’s newly-revamped tool can lead to increased costs. Commissioner Trinidad Navarro has released a rare consumer alert regarding Medicare’s newly-updated Prescription Plan Finder. Throughout this year’s open enrollment period, which ends on December 7, the Department of Insurance has received numerous complaints about the tool and anticipated prescription drug costs. The Prescription Plan […]

Statistics from the Division of Professional Regulation, which licenses controlled substance prescribers, show a 12-percent drop in opioid prescriptions statewide compared to the first quarter of 2017. The number of Delaware patients being treated with opioid medications has also declined by 8 percent over the same time period, the division reports.

Regulations promulgated by the Secretary of State and slated to take effect Jan. 1 will require that new business entities formed in Delaware be screened against lists of persons and groups that have been prohibited from doing business in the United States.

Free outdoor, family-fun event also includes activities and food.

Union Minister Nitin Gadkari on Thursday said Indias own vehicle scrappage policy is likely to be finalised soon. According to the report from PTI, India will soon bring in its vehicle scrappage...

Post the NTO implementation, the dynamics have tilted in favour of the broadcasters.

People are seen going about their lives while a doctor is able to monitor them remotely. Although the ad evokes curiosity, it does not address people’s fear of inserting a device into the body or reveal how the ‘breakthrough’ technology works.

OTT platforms are sexing up their original content library with bigger budgets, foreign locales and slick production values

Ashnoor Kaur is an Indian child actress associated with Hindi television and films. She is known for portraying Naira Singhania in Yeh Rishta Kya Kehlata Hai on Star Plus and Mini Khuranna on Patiala Babes that airs on Sony Entertainment Television

An Indian-origin psychiatrist in the US has to pay USD 1,45,000 as settlement to resolve allegations that he overprescribed opioids to his patients outside the usual course of his professional...

Volker Grimm, Steven F. Railsback, Christian E. Vincenot, Uta Berger, Cara Gallagher, Donald L. DeAngelis, Bruce Edmonds, Jiaqi Ge, Jarl Giske, Jürgen Groeneveld, Alice S.A. Johnston, Alexander Milles, Jacob Nabe-Nielsen, J. Gareth Polhill, Viktoriia Radchuk, Marie-Sophie Rohwäder, Richard A. Stillman, Jan C. Thiele and Daniel Ayllón: The Overview, Design concepts and Details (ODD) protocol for describing Individual- and Agent-Based Models (ABMs) is now widely accepted and used to document such models in journal articles. As a standardized document for providing a consistent, logical and readable account of the structure and dynamics of ABMs, some research groups also find it useful as a workflow for model design. Even so, there are still limitations to ODD that obstruct its more widespread adoption. Such limitations are discussed and addressed in this paper: the limited availability of guidance on how to use ODD; the length of ODD documents; limitations of ODD for highly complex models; lack of sufficient details of many ODDs to enable reimplementation without access to the model code; and the lack of provision for sections in the document structure covering model design rationale, the model’s underlying narrative, and the means by which the model’s fitness for purpose is evaluated. We document the steps we have taken to provide better guidance on: structuring complex ODDs and an ODD summary for inclusion in a journal article (with full details in supplementary material; Table 1); using ODD to point readers to relevant sections of the model code; update the document structure to include sections on model rationale and evaluation. We also further advocate the need for standard descriptions of simulation experiments and argue that ODD can in principle be used for any type of simulation model. Thereby ODD would provide a lingua franca for simulation modelling.

Policy will allow state to consistently address discrimination in the workplace WILMINGTON, Del. – Governor Carney on Monday released a uniform, anti-discrimination policy that will allow state agencies to consistently respond to reports of discrimination, harassment and retaliation in the workplace – and clearly outlines a consistent policy for state employees to report and resolve […]

Relaxation in adherence to prescribed timelines issued by SEBI due to COVID 19

Governor Jack Markell, DNREC Secretary Collin O’Mara and Delaware Department of Agriculture Secretary Ed Kee joined Delmarva Wellnet Foundation-EDEN Delmarva members to celebrate the success of the foundation’s food recycling project REPLENISH.

Agency: GSS Closing Date: 6/2/2020

The number of prescriptions for opioid medications in Delaware, as well as the total quantity of opioids dispensed, have dropped significantly in the 12 months since the Department of State enacted stricter prescribing regulations to help combat the opioid crisis statewide.

Free HIV testing will be offered through the Division of Public Health (DPH) at two Delaware state service centers on Wednesday, June 27, 2018, in observance of National HIV Testing Day. The Centers for Disease Control and Prevention (CDC) recommends that everyone between the ages of 13 and 64 get tested for HIV at least once as part of routine health care.

April Designated as Lung Cancer Screening Awareness Month DOVER – Dramatic “before-and-after-smoking” inflatable lungs shared center stage with Governor John Carney as he urged Delawareans at high risk of lung cancer to get life-saving screenings. Governor Carney proclaimed April as Lung Cancer Screening Awareness Month in Delaware at the Delaware Cancer Consortium’s (DCC) annual retreat […]

To encourage Delawareans to support fall prevention strategies, Governor John Carney and Lieutenant Governor Bethany Hall-Long proclaimed the week of September 22-28, 2019 as Falls Prevention Awareness Week in Delaware. The National Council on Aging (NCOA) designates the first day of the fall season as National Falls Prevention Awareness Day, which is September 23 this year.

Sat., Oct. 26, 2019: Delaware residents can safely dispose of their unused or expired prescription medications at designated sites throughout the state as part of the 18th National Prescription Drug Take-Back Day.

The partnership between Reliance Retail Whatsapp - inked on Wednesda -and could mean more competition for the likes of BigBasket and Grofers and others like Amazon and Flipkart looking to get a share of the food and groceries pie.

The detailed list of equipment that the 2020 Datsun Redi-Go will offer once it is launched has been leaked online which has revealed that the Redi-Go will feature a new dash that offers an 8-inch touchscreen infotainment system.

Touchscreen infotainment systems have become one of the defining characteristics of modern SUVs. Here are five of the largest touchscreens that are available under the Rs 25 lakh bracket.

The upcoming Datsun Redi-Go has been teased, but the styling of the little city hatchback has been leaked online. And now we also know what new features it will offer and with which variant it will be offered in.

Anticipating a huge surge in demand, it came out with a new software for online receipt and settlement of claims and deployed the software on March 29.

Encouraging data sharing can sometimes feel like refereeing kids on Christmas morning. “Mom said you have to SHARE!” my sister bawled, grabbing at the Game Boy in my hand as I held the toy just out of her reach. I had just gotten it as a Christmas present and had [...]

The post With government data sharing, don’t be a data scrooge appeared first on Government Data Connection.

House Intelligence Committee chair Adam Schiff has published all the transcripts of ‘Russiagate’ interviews he had kept secret, blaming President Donald Trump for the delay, but their content belied his conspiracy narrative.
Read Full Article at RT.com

The White House’s persistent claim that Covid-19 is a Chinese lab creation is nothing but a calculated move meant to divert Americans’ anger away from how Trump handles the crisis, German spies reportedly believe.  
Read Full Article at RT.com

  Yes, we are well aware that scrobbling has been around for the past decade. No, we aren’t just reminiscing. Scrobbling has re-entered our radar with Last.fm’s newest project – Buggle...