An OMer encounters a French woman who converted to Islam but misunderstands both Islam and the Christian faith.

There will be two all-European quarter-finals at the FIFA Futsal World Cup with Spain meeting Russia, and Portugal up against Italy following the conclusion of the round of 16 in Thailand.

Lets hope it’s for the right reasons.

Accreditation is the highest recognition afforded to museums in the United States.

Facebook.com gets more streamlined when it comes to navigation, enabling easier discovery of videos, games, and even Groups.

The Delaware Department of Agriculture, DNREC’s Mosquito Control Section and the Delaware Beekeepers Association urge anyone who keeps bees in Delaware to register their bee hives and sign up for all the apps that are available that can help protect the state’s valuable pollinators.

A controlled burn on a 43-acre former farm field along U.S. Route 301 will provide fertile ground for "Delaware's first pollinator mitigation site" - where state officials hope native wildflowers will flourish to restore lost habitat for pollinators such as bees and birds. The Delaware Forest Service  conducted the successful firing operation on March 20 in cooperation DelDOT and DNREC's Division of Fish and Wildlife, which supplied valuable personnel, logistical support, and equipment. Thanks to favorable weather conditions and DelDOT lane adjustments on U.S. 301 North, the four-hour burn caused minimal disruptions to traffic and virtually no smoke effects on the adjacent Spring Mill housing development.

DOVER, Del. – The Delaware Aglands Foundation Board announced that they will institute a rolling application process for their Young Farmer Loan Program to offer young farmers more flexibility in acquiring a farm. Delaware farmers, between 18 and 40 years old have the opportunity to apply for the Young Farmers Loan Program. The program provides […]

Historic-site interpreter served for 25 years.

The post Jackie Collins to retire from downtown Dover museums appeared first on Division of Historical and Cultural Affairs - State of Delaware.

Sony's Xperia 10 and 10 Plus were the midrange counterparts to last year's flagship Xperia 1. Sony did promise an update to Android 10 in "early 2020" but the two midrangers had to wait a bit longer to finally get the latest Google firmware update. With the COVID-19 outbreak disrupting most companies' regular operations the delay is understandable and the good thing is the latest Android version is finally hitting the duo. For the time being, the rollout is limited to select regions and carriers. It bears the 53.1.A.2.2 build number and also adds the March security...

Social media giant Facebook is now rolling out its biggest update for desktop users, after first announcing it at its F8 developer conference last year.

1. Dark mode on Facebook starts rolling out with brand new desktop site  Livemint
2. Facebook for desktop gets dark mode for all: Here's how to get it  India TV News
3. Facebook redesign is finally rolling out for everyone | BGR India  BGR India
4. Facebook rolls out Dark Mode for desktop, other features for all users  India Today
5. You Can Now Activate The New Facebook Website on Your Computer  The Quint
6. View Full coverage on Google News

Alabama landed ESPN 300 wide receiver Jacorey Brooks, the Tide's fourth commit in the 2021 class.

Presentation by George Milad of Uyemura International Corporation

The N2 was closed at the Mtunzini toll plaza after two people died when a fuel tanker and another truck collided and burst into flame, paramedics said.

The 39 year old man was taken to hospital, where he was certified as suffering from grievous injuries 

At HARMAN, it’s our mission to develop state-of-the-art audio solutions that provide enhanced listening experiences for music lovers at home, on the road, and on-stage. In recognition of Make Music Day 2018, we spoke with William “Bootsy” Collins,...

Little Richard, the self-proclaimed "architect of rock 'n' roll" who built his ground-breaking sound with a boiling blend of boogie-woogie, rhythm and blues and gospel, died on Saturday at the age of 87, Rolling Stone magazine reported.

Little Richard, the self-proclaimed "architect of rock 'n' roll" who built his ground-breaking sound with a boiling blend of boogie-woogie, rhythm and blues and gospel, died on Saturday at the age of 87, Rolling Stone magazine reported.

ABSTRACT

The protozoan parasites that cause malaria infect a wide variety of vertebrate hosts, including birds, reptiles, and mammals, and the evolutionary pressures inherent to the host-parasite relationship have profoundly shaped the genomes of both host and parasite. Here, we report that these selective pressures have resulted in unexpected alterations to one of the most basic aspects of eukaryotic biology, the maintenance of genome integrity through DNA repair. Malaria parasites that infect humans continuously generate genetic diversity within their antigen-encoding gene families through frequent ectopic recombination between gene family members, a process that is a crucial feature of the persistence of malaria globally. The continuous generation of antigen diversity ensures that different parasite isolates are antigenically distinct, thus preventing extensive cross-reactive immunity and enabling parasites to maintain stable transmission within human populations. However, the molecular basis of the recombination between gene family members is not well understood. Through computational analyses of the antigen-encoding, multicopy gene families of different Plasmodium species, we report the unexpected observation that malaria parasites that infect rodents do not display the same degree of antigen diversity as observed in Plasmodium falciparum and appear to undergo significantly less ectopic recombination. Using comparative genomics, we also identify key molecular components of the diversification process, thus shedding new light on how malaria parasites balance the maintenance of genome integrity with the requirement for continuous genetic diversification.

IMPORTANCE Malaria remains one of the most prevalent and deadly infectious diseases of the developing world, causing approximately 228 million clinical cases and nearly half a million deaths annually. The disease is caused by protozoan parasites of the genus Plasmodium, and of the five species capable of infecting humans, infections with P. falciparum are the most severe. In addition to the parasites that infect people, there are hundreds of additional species that infect birds, reptiles, and other mammals, each exquisitely evolved to meet the specific challenges inherent to survival within their respective hosts. By comparing the unique strategies that each species has evolved, key insights into host-parasite interactions can be gained, including discoveries regarding the pathogenesis of human disease. Here, we describe the surprising observation that closely related parasites with different hosts have evolved remarkably different methods for repairing their genomes. This observation has important implications for the ability of parasites to maintain chronic infections and for the development of host immunity.

ABSTRACT

Production of metallo-β-lactamases (MBLs), which hydrolyze carbapenems, is a cause of carbapenem resistance in Enterobacteriaceae. Development of effective inhibitors for MBLs is one approach to restore carbapenem efficacy in carbapenem-resistant Enterobacteriaceae (CRE). We report here that sulfamoyl heteroarylcarboxylic acids (SHCs) can competitively inhibit the globally spreading and clinically relevant MBLs (i.e., IMP-, NDM-, and VIM-type MBLs) at nanomolar to micromolar orders of magnitude. Addition of SHCs restored meropenem efficacy against 17/19 IMP-type and 7/14 NDM-type MBL-producing Enterobacteriaceae to satisfactory clinical levels. SHCs were also effective against IMP-type MBL-producing Acinetobacter spp. and engineered Escherichia coli strains overproducing individual minor MBLs (i.e., TMB-2, SPM-1, DIM-1, SIM-1, and KHM-1). However, SHCs were less effective against MBL-producing Pseudomonas aeruginosa. Combination therapy with meropenem and SHCs successfully cured mice infected with IMP-1-producing E. coli and dually NDM-1/VIM-1-producing Klebsiella pneumoniae clinical isolates. X-ray crystallographic analyses revealed the inhibition mode of SHCs against MBLs; the sulfamoyl group of SHCs coordinated to two zinc ions, and the carboxylate group coordinated to one zinc ion and bound to positively charged amino acids Lys224/Arg228 conserved in MBLs. Preclinical testing revealed that the SHCs showed low toxicity in cell lines and mice and high stability in human liver microsomes. Our results indicate that SHCs are promising lead compounds for inhibitors of MBLs to combat MBL-producing CRE.

IMPORTANCE Carbapenem antibiotics are the last resort for control of severe infectious diseases, bloodstream infections, and pneumonia caused by Gram-negative bacteria, including Enterobacteriaceae. However, carbapenem-resistant Enterobacteriaceae (CRE) strains have spread globally and are a critical concern in clinical settings because CRE infections are recognized as a leading cause of increased mortality among hospitalized patients. Most CRE produce certain kinds of serine carbapenemases (e.g., KPC- and GES-type β-lactamases) or metallo-β-lactamases (MBLs), which can hydrolyze carbapenems. Although effective MBL inhibitors are expected to restore carbapenem efficacy against MBL-producing CRE, no MBL inhibitor is currently clinically available. Here, we synthesized 2,5-diethyl-1-methyl-4-sulfamoylpyrrole-3-carboxylic acid (SPC), which is a potent inhibitor of MBLs. SPC is a remarkable lead compound for clinically useful MBL inhibitors and can potentially provide a considerable benefit to patients receiving treatment for lethal infectious diseases caused by MBL-producing CRE.

Early recognition of longus colli calcific tendinitis can prevent unnecessary interventions including antibiotics and surgical procedures.

Key Points

The major obstacle to a cure for HIV infection is the persistence of replication-competent viral reservoirs during antiretroviral therapy. HIV-specific chimeric antigen receptor (CAR) T cells have been developed to target latently infected CD4⁺ T cells that express virus either spontaneously or after intentional latency reversal. Whether HIV-specific CAR-T cells can recognize and eliminate the follicular dendritic cell (FDC) reservoir of HIV-bound immune complexes (ICs) is unknown. We created HIV-specific CAR-T cells using human peripheral blood mononuclear cells (PBMCs) and a CAR construct that enables the expression of CD4 (domains 1 and 2) and the carbohydrate recognition domain of mannose binding lectin (MBL) to target native HIV Env (CD4-MBL CAR). We assessed CAR-T cell cytotoxicity using a carboxyfluorescein succinimidyl ester (CFSE) release assay and evaluated CAR-T cell activation through interferon gamma (IFN-) production and CD107a membrane accumulation by flow cytometry. CD4-MBL CAR-T cells displayed potent lytic and functional responses to Env-expressing cell lines and HIV-infected CD4⁺ T cells but were ineffective at targeting FDC bearing HIV-ICs. CD4-MBL CAR-T cells were unresponsive to cell-free HIV or concentrated, immobilized HIV-ICs in cell-free experiments. Blocking intercellular adhesion molecule-1 (ICAM-1) inhibited the cytolytic response of CD4-MBL CAR-T cells to Env-expressing cell lines and HIV-infected CD4⁺ T cells, suggesting that factors such as adhesion molecules are necessary for the stabilization of the CAR-Env interaction to elicit a cytotoxic response. Thus, CD4-MBL CAR-T cells are unable to eliminate the FDC-associated HIV reservoir, and alternative strategies to eradicate this reservoir must be sought.

IMPORTANCE Efforts to cure HIV infection have focused primarily on the elimination of latently infected CD4⁺ T cells. Few studies have addressed the unique reservoir of infectious HIV that exists on follicular dendritic cells (FDCs), persists in vivo during antiretroviral therapy, and likely contributes to viral rebound upon cessation of antiretroviral therapy. We assessed the efficacy of a novel HIV-specific chimeric antigen receptor (CAR) T cell to target both HIV-infected CD4⁺ T cells and the FDC reservoir in vitro. Although CAR-T cells eliminated CD4⁺ T cells that express HIV, they did not respond to or eliminate FDC bound to HIV. These findings reveal a fundamental limitation to CAR-T cell therapy to eradicate HIV.

The apparent detection of an exoplanet orbiting Fomalhaut was announced in 2008. However, subsequent observations of Fomalhaut b raised questions about its status: Unlike other exoplanets, it is bright in the optical and nondetected in the infrared, and its orbit appears to cross the debris ring around the star without...

David J. Pritchard and Mario Vallejo-Marin

Vibrations play an important role in insect behaviour. In bees, vibrations are used in a variety of contexts including communication, as a warning signal to deter predators and during pollen foraging. However, little is known about how the biomechanical properties of bee vibrations vary across multiple behaviours within a species. In this study, we compared the properties of vibrations produced by Bombus terrestris audax (Hymenoptera: Apidae) workers in three contexts: during flight, during defensive buzzing, and in floral vibrations produced during pollen foraging on two buzz-pollinated plants (Solanum, Solanaceae). Using laser vibrometry, we were able to obtain contactless measures of both the frequency and amplitude of the thoracic vibrations of bees across the three behaviours. Despite all three types of vibrations being produced by the same power flight muscles, we found clear differences in the mechanical properties of the vibrations produced in different contexts. Both floral and defensive buzzes had higher frequency and amplitude velocity, acceleration, and displacement than the vibrations produced during flight. Floral vibrations had the highest frequency, amplitude velocity and acceleration of all the behaviours studied. Vibration amplitude, and in particular acceleration, of floral vibrations has been suggested as the key property for removing pollen from buzz-pollinated anthers. By increasing frequency and amplitude velocity and acceleration of their vibrations during vibratory pollen collection, foraging bees may be able to maximise pollen removal from flowers, although their foraging decisions are likely to be influenced by the presumably high cost of producing floral vibrations.

An aberrant bi-apical Follicucullus specimen (Albaillellaria, Radiolaria) has been discovered from an upper Guadalupian (Middle Permian) chert block of the Kamiaso Unit of the Mino terrane, central Japan. If this specimen was formed with double malformation, it would be the oldest record of this phenomenon in radiolarians and the first record of its kind in Albaillellaria.

Although treatment with the glucocorticoid-induced tumor necrosis factor receptor–related protein (GITR) agonistic antibody (DTA-1) has shown antitumor activity in various tumor models, the underlying mechanism is not fully understood. Here, we demonstrate that interleukin (IL)-21–producing follicular helper T (Tfh) cells play a crucial role in DTA-1–induced tumor inhibition. The administration of DTA-1 increased IL21 expression by Tfh cells in an antigen-specific manner, and this activation led to enhanced antitumor cytotoxic T lymphocyte (CTL) activity. Mice treated with an antibody that neutralizes the IL21 receptor exhibited decreased antitumor activity when treated with DTA-1. Tumor growth inhibition by DTA-1 was abrogated in Bcl6^fl/flCd4^Cre mice, which are genetically deficient in Tfh cells. IL4 was required for optimal induction of IL21-expressing Tfh cells by GITR costimulation, and c-Maf mediated this pathway. Thus, our findings identify GITR costimulation as an inducer of IL21-expressing Tfh cells and provide a mechanism for the antitumor activity of GITR agonism.

Fnr is a transcriptional regulator that controls the expression of a variety of genes in response to oxygen limitation in bacteria. Genome sequencing revealed four genes (fnr1, fnr3, fnr5, and fnr7) coding for Fnr proteins in Paenibacillus polymyxa WLY78. Fnr1 and Fnr3 showed more similarity to each other than to Fnr5 and Fnr7. Also, Fnr1 and Fnr3 exhibited high similarity with Bacillus cereus Fnr and Bacillus subtilis Fnr in sequence and structures. Both the aerobically purified His-tagged Fnr1 and His-tagged Fnr3 in Escherichia coli could bind to the specific DNA promoter. Deletion analysis showed that the four fnr genes, especially fnr1 and fnr3, have significant impacts on growth and nitrogenase activity. Single deletion of fnr1 or fnr3 led to a 50% reduction in nitrogenase activity, and double deletion of fnr1 and fnr3 resulted to a 90% reduction in activity. Genome-wide transcription analysis showed that Fnr1 and Fnr3 indirectly activated expression of nif (nitrogen fixation) genes and Fe transport genes under anaerobic conditions. Fnr1 and Fnr3 inhibited expression of the genes involved in the aerobic respiratory chain and activated expression of genes responsible for anaerobic electron acceptor genes.

IMPORTANCE The members of the nitrogen-fixing Paenibacillus spp. have great potential to be used as a bacterial fertilizer in agriculture. However, the functions of the fnr gene(s) in nitrogen fixation and other metabolisms in Paenibacillus spp. are not known. Here, we found that in P. polymyxa WLY78, Fnr1 and Fnr3 were responsible for regulation of numerous genes in response to changes in oxygen levels, but Fnr5 and Fnr7 exhibited little effect. Fnr1 and Fnr3 indirectly or directly regulated many types of important metabolism, such as nitrogen fixation, Fe uptake, respiration, and electron transport. This study not only reveals the function of the fnr genes of P. polymyxa WLY78 in nitrogen fixation and other metabolisms but also will provide insight into the evolution and regulatory mechanisms of fnr in Paenibacillus.

Two stars in the constellation Sagitta are predicted to smash together in the year 2083, producing an explosion that will outshine every star in the sky

A leading theory for the formation of the moon is that a planet called Theia smashed into the early Earth, but doubts remain. Now a new analysis of lunar rock supports this idea

Little Richard, the self-proclaimed "architect of rock 'n' roll" who built his ground-breaking sound with a boiling blend of boogie-woogie, rhythm and blues and gospel, died on Saturday at the age of 87, Rolling Stone magazine reported.

A recent study has described new states that can be found in super-cold atom experiments, which could have applications for quantum technology.

Boston Dynamics robot dog, known as Spot, is patroling Bishan-Ang Mo Kio Park in Singapore to help with social distancing practices during the coronavirus pandemic, the Singapore government announced.

Little Richard, the self-proclaimed "architect of rock 'n' roll" who built his ground-breaking sound with a boiling blend of boogie-woogie, rhythm and blues and gospel, died on Saturday at the age of 87, Rolling Stone magazine reported.

Read our live coronavirus updates HERE Coronavirus: The symptoms

A cyclist has died after being involved in a collision with a van.

A motorcyclist has died after colliding with a lamppost in east London.

A police motorcyclist has died after a collision with a car while responding to an incident in Sheffield, South Yorkshire Police said.

The US military base near to where the crash which claimed Harry Dunn's life is "looking into" claims a staff member also drove on the wrong side of the road before hitting into a stone wall.

A man has died after his motorbike crashed into the central reservation of a major London road.

Tesco has been slammed after putting clothing on a half price sale in stores despite lockdown rules banning non-essential shopping.