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Maharashtra State Road Improvement Project

Approved project 52298-001 in India.




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Maharashtra Rural High Voltage Distribution System Expansion Program

Approved project 50193-003 in India.




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Evolution of ASEAN Financial Integration in the Comparative Perspective

ASEAN could learn from the European Union’s experience, particularly under the current global challenges.




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Evolution of ASEAN Financial Integration in the Comparative Perspective

ASEAN could learn from the European Union’s experience, particularly under the current global challenges.




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Govt mulls single window clearance for SEZs in Madhya Pradesh

INDORE: To ensure hassle-free establishment of special economic zones (SEZs) in Indore, the state government is all set to go for Development Control Regulation (DCR). On the lines of Gujarat, a single window clearance system is being planned for them. A decision to this effect is likely to be taken during the meeting of the state cabinet in Bhopal on Wednesday. Once cleared, the Act will empower the SEZ development commissioner to sort out the issues and give necessary permission to the SEZs that have already been allotted land by the state government and received notifications for the SEZ status. They include TCS, Infosys and Impetus. While TCS and Impetus […]




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HARMAN Partners with A.R. Rahman Foundation and India's Prominent Theatre - Ranga Shankara to Empower Youth through Music and Arts

BENGALURU, INDIA –  HARMAN (NYSE:HAR), the premier connected technologies company for automotive, consumer and enterprise markets, today announced that it has launched its global corporate social responsibility initiative, ‘HARMAN Inspired’, in India....




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HARMAN Welcomes Indie Music Stars Swarathma, Mame Khan and Darshan Doshi as Brand Ambassadors

MUMBAI, INDIA – HARMAN Professional Solutions, the global leader in audio, video, lighting and control systems, including networked AV, today announced popular fusion rock band Swarathma, Rajasthani folk singer Mame Khan and percussionist Darshan Doshi...




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Elevate Your Quarantine Studio: Presented By JBL




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JBL and Garage Italia Bring a New Beat to Custom-Designed Cars

Music and driving are a powerful combination, and JBL automotive sound is designed to connect consumers to their vehicles at an emotional level. From Italy-based creative agency Garage Italia to leading auto manufacturers who leverage JBL’s audio ...




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The paradoxes of Zen Buddhism could help us grasp fundamental physics

If you're struggling to understand the mysteries of quantum physics and relativity, you need all the help you can get – even borrowing Buddhist mysticism, shows a new book




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Time travel without paradoxes is possible with many parallel timelines

Time travel brings up paradoxes that break the laws of physics, but multiple similar timelines running parallel to one another could get around this




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We may have spotted a parallel universe going backwards in time

Strange particles observed by an experiment in Antarctica could be evidence of an alternative reality where everything is upside down




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Millions of hairy tarantula skins could be used to mop up oil spills

The dense, bristly hairs on the skins shed by tarantulas when they moult are naturally efficient sponges and could be used to soak up ocean oil spills




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Every Arabica coffee plant may come from a single common ancestor

Genetic analysis suggests all Arabica coffee plants are descended from a single common ancestor, and this lack of genetic diversity makes them vulnerable to extinction




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Little green invaders: how parakeets conquered the world

Move over Martians, Earth has already been invaded by little green aliens, but how did parakeets become one of the most successful invasive species ever?




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Scaramucci's SkyBridge hit with heavy redemption requests as fund fell: letter

Investors in SkyBridge Capital asked for hundreds of millions of dollars back after the fund suffered a 23% loss in March when investments made by its debt-focused hedge fund managers soured, Anthony...




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Today's global warming is unparalleled in the past 2000 years

We now know that past periods when Earth cooled and warmed were only regional. The finding rebuffs the myth that today's planet-wide warming is a natural blip




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FDA commissioner in self-quarantine after exposure to person with COVID-19

U.S. Food and Drug Administration Commissioner Stephen Hahn is in self-quarantine for a couple of weeks after coming into contact with someone who tested positive for COVID-19, an FDA spokesman told Reuters late on Friday.




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Rights group says Saudi Arabia is holding a senior prince incommunicado since March

Human Rights Watch (HRW) said on Saturday that Saudi Arabian authorities recently detained and are holding incommunicado Prince Faisal bin Abdullah, who had previously been netted in an anti-corruption drive and released in late 2017.




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Ancient humans in the Sahara ate fish before the lakes dried up

As a changing climate dried out the Sahara desert, ancient humans transitioned from eating lots of tilapia and catfish to more mammal-heavy meals




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Dulce de leche: How to turn condensed milk into a tasty caramel sauce

How to use the Maillard reaction to make delicious dulce de leche – the ultimate comfort food when you are stuck indoors, says Sam Wong




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A Minute With: Tim Gunn on pajamas and post-quarantine fashion

Even Tim Gunn, the immaculately dressed fashion mentor from "Project Runway" and Amazon's new competition show "Making the Cut," is finding it hard to get out of his pajamas these days.




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Locked out of galleries, Londoners find Caravaggio street art

Londoners locked out of galleries can find an alternative art fix on a wall under under some railway arches after street artist Lionel Stanhope painted a Caravaggio classic, updated for the coronavirus age.




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We may have spotted a parallel universe going backwards in time

Strange particles observed by an experiment in Antarctica could be evidence of an alternative reality where everything is upside down




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Little green invaders: how parakeets conquered the world

Move over Martians, Earth has already been invaded by little green aliens, but how did parakeets become one of the most successful invasive species ever?




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EU Commission calls for state guarantees for vouchers for cancelled travel

The European Commission will tell countries in the European Union to provide state guarantees for travel vouchers during the coronavirus pandemic, if they prefer people to accept the vouchers instead of cash refunds, according to a strategy document seen by Reuters.




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UPDATE 1-Britain to quarantine travellers for 14 days, UK airlines association says

* Airports say it could be devastating for aviation industry (Adds details, changes sourcing)




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A Minute With: Tim Gunn on pajamas and post-quarantine fashion

Even Tim Gunn, the immaculately dressed fashion mentor from "Project Runway" and Amazon's new competition show "Making the Cut," is finding it hard to get out of his pajamas these days.




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Brain implant lets man with paralysis move and feel with his hand

A brain-computer interface has helped a man with a severe spinal cord injury move and feel using a hand again, letting him carefully lift light objects such as a paper cup




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Routine Ear Wax 'Flush' Leaves Woman's Face Paralyzed

Title: Routine Ear Wax 'Flush' Leaves Woman's Face Paralyzed
Category: Health News
Created: 12/19/2019 12:00:00 AM
Last Editorial Review: 12/20/2019 12:00:00 AM




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Paralyzed Patient Moves Prosthetic Arm With Her Mind

Title: Paralyzed Patient Moves Prosthetic Arm With Her Mind
Category: Health News
Created: 4/30/2013 12:35:00 PM
Last Editorial Review: 5/1/2013 12:00:00 AM




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Malaria Parasite Is Infecting, Killing U.S. Baby Deer

Title: Malaria Parasite Is Infecting, Killing U.S. Baby Deer
Category: Health News
Created: 5/2/2018 12:00:00 AM
Last Editorial Review: 5/3/2018 12:00:00 AM




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Nearly 700 at LA Universities Remain Under Measles Quarantine

Title: Nearly 700 at LA Universities Remain Under Measles Quarantine
Category: Health News
Created: 4/29/2019 12:00:00 AM
Last Editorial Review: 4/29/2019 12:00:00 AM




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Measles Case Leads to Quarantine of Cruise Ship in St. Lucia

Title: Measles Case Leads to Quarantine of Cruise Ship in St. Lucia
Category: Health News
Created: 5/2/2019 12:00:00 AM
Last Editorial Review: 5/2/2019 12:00:00 AM




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What Day Is It? This Is Your Brain on Quarantine

If it feels like all your internal clocks are melting as your stay-at-home days drone on, you are not alone. Researchers say that people in various levels of COVID-19 quarantine around the world are reporting a distorted sense of time.




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What Is Paracentesis?

Title: What Is Paracentesis?
Category: Procedures and Tests
Created: 3/23/2020 12:00:00 AM
Last Editorial Review: 3/23/2020 12:00:00 AM




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Your Sushi May Serve Up Parasitic Worms

Title: Your Sushi May Serve Up Parasitic Worms
Category: Health News
Created: 4/13/2020 12:00:00 AM
Last Editorial Review: 4/14/2020 12:00:00 AM




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Kevzara (sarilumab)

Title: Kevzara (sarilumab)
Category: Medications
Created: 4/21/2020 12:00:00 AM
Last Editorial Review: 4/21/2020 12:00:00 AM




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Vyxeos (daunorubicin and cytarabine)

Title: Vyxeos (daunorubicin and cytarabine)
Category: Medications
Created: 4/24/2020 12:00:00 AM
Last Editorial Review: 4/24/2020 12:00:00 AM




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3D Printed Teeth with Enamel and Dentin Layer for Educating Dental Students in Crown Preparation

Commonly used model teeth are so far uniform in color and hardness. There is no discrimination between enamel and dentin part of a tooth. This condition makes it difficult to train a preparation technique, which is adapted to real tooth substance. The aim of this study was to design and establish a 3D printed tooth with different layers for enamel and dentin for education in crown preparation. A printable tooth with different layers for enamel and dentin was designed, and all 38 fourth-year dental students in the first clinical course in prosthodontics and 30 experienced dentists were trained during a voluntary hands-on course in 2019. Prior to the study, the students had used standard model teeth and real-teeth models in their preclinical education. They had experience in caries removal and preparation on real patients. The perceived benefits of the 3D printed tooth were evaluated by a questionnaire. All individuals in both groups completed the questionnaire, for a 100% response rate. The results showed that the printed tooth was given an overall mean grade of 2.3 (students) and 2.0 (experts) on a scale from 1=excellent to 5=poor. The difference in hardness between the dentin and enamel layer was given a mean of 2.4 (students and experts) and the difference in color a 1.7 (students) and 1.8 (experts). The tooth model with the prepared tooth illustrating an ideal preparation was graded 1.6 (students and experts). In this study, the students had the opportunity to learn a correct crown preparation on a printed tooth with different material properties for enamel and dentin. The learning effect with this tooth model was rated as good on the questionnaire by both students and expert dentists.




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Using Colonization Assays and Comparative Genomics To Discover Symbiosis Behaviors and Factors in Vibrio fischeri

ABSTRACT

The luminous marine Gram-negative bacterium Vibrio (Aliivibrio) fischeri is the natural light organ symbiont of several squid species, including the Hawaiian bobtail squid, Euprymna scolopes, and the Japanese bobtail squid, Euprymna morsei. Work with E. scolopes has shown how the bacteria establish their niche in the light organ of the newly hatched host. Two types of V. fischeri strains have been distinguished based upon their behavior in cocolonization competition assays in juvenile E. scolopes, i.e., (i) niche-sharing or (ii) niche-dominant behavior. This study aimed to determine whether these behaviors are observed with other V. fischeri strains or whether they are specific to those isolated from E. scolopes light organs. Cocolonization competition assays between V. fischeri strains isolated from the congeneric squid E. morsei or from other marine animals revealed the same sharing or dominant behaviors. In addition, whole-genome sequencing of these strains showed that the dominant behavior is polyphyletic and not associated with the presence or absence of a single gene or genes. Comparative genomics of 44 squid light organ isolates from around the globe led to the identification of symbiosis-specific candidates in the genomes of these strains. Colonization assays using genetic derivatives with deletions of these candidates established the importance of two such genes in colonization. This study has allowed us to expand the concept of distinct colonization behaviors to strains isolated from a number of squid and fish hosts.

IMPORTANCE There is an increasing recognition of the importance of strain differences in the ecology of a symbiotic bacterial species and, in particular, how these differences underlie crucial interactions with their host. Nevertheless, little is known about the genetic bases for these differences, how they manifest themselves in specific behaviors, and their distribution among symbionts of different host species. In this study, we sequenced the genomes of Vibrio fischeri isolated from the tissues of squids and fishes and applied comparative genomics approaches to look for patterns between symbiont lineages and host colonization behavior. In addition, we identified the only two genes that were exclusively present in all V. fischeri strains isolated from the light organs of sepiolid squid species. Mutational studies of these genes indicated that they both played a role in colonization of the squid light organ, emphasizing the value of applying a comparative genomics approach in the study of symbioses.




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Parallel Genomics Uncover Novel Enterococcal-Bacteriophage Interactions

ABSTRACT

Bacteriophages (phages) have been proposed as alternative therapeutics for the treatment of multidrug-resistant bacterial infections. However, there are major gaps in our understanding of the molecular events in bacterial cells that control how bacteria respond to phage predation. Using the model organism Enterococcus faecalis, we used two distinct genomic approaches, namely, transposon library screening and RNA sequencing, to investigate the interaction of E. faecalis with a virulent phage. We discovered that a transcription factor encoding a LytR family response regulator controls the expression of enterococcal polysaccharide antigen (epa) genes that are involved in phage infection and bacterial fitness. In addition, we discovered that DNA mismatch repair mutants rapidly evolve phage adsorption deficiencies, underpinning a molecular basis for epa mutation during phage infection. Transcriptomic profiling of phage-infected E. faecalis revealed broad transcriptional changes influencing viral replication and progeny burst size. We also demonstrate that phage infection alters the expression of bacterial genes associated with intra- and interbacterial interactions, including genes involved in quorum sensing and polymicrobial competition. Together, our results suggest that phage predation has the potential to influence complex microbial behavior and may dictate how bacteria respond to external environmental stimuli. These responses could have collateral effects (positive or negative) on microbial communities, such as the host microbiota, during phage therapy.

IMPORTANCE We lack fundamental understanding of how phage infection influences bacterial gene expression and, consequently, how bacterial responses to phage infection affect the assembly of polymicrobial communities. Using parallel genomic approaches, we have discovered novel transcriptional regulators and metabolic genes that influence phage infection. The integration of whole-genome transcriptomic profiling during phage infection has revealed the differential regulation of genes important for group behaviors and polymicrobial interactions. Our work suggests that therapeutic phages could more broadly influence bacterial community composition outside their intended host targets.




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Context Is Key: Comparative Biology Illuminates the Vertebrate Microbiome

ABSTRACT

Microbes affect vertebrates on timescales from daily to evolutionary, and the cumulative effect of these interactions is immense. However, how microbiomes compare across (host) species is poorly understood, as most studies focus on relatively few species. A recent mBio article by S. J. Song, J. G. Sanders, F. Delsuc, J. Metcalf, et al. (mBio 11:e02901-19, 2019, https://doi.org/10.1128/mBio.02901-19) expands our collective understanding of the vertebrate microbiome by analyzing ~900 species. They demonstrate that patterns within mammals contrast with those within birds. Their results suggest many hypotheses about the role of host ecology and evolution on microbiome variation. Bats, the only volant mammals, appear to contradict many of the general mammal microbiome trends, in some ways resembling birds. What role has powered flight, and the evolution thereof, played in microbiome structure and function? Comparative methods, mechanistic hypotheses, and theory will elucidate this exciting question (and others) that we can ask using Song, Sanders et al.’s data and results.




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In Vitro Characterization of Protein Effector Export in the Bradyzoite Stage of Toxoplasma gondii

ABSTRACT

The ubiquitous parasite Toxoplasma gondii exhibits an impressive ability to maintain chronic infection of its host for prolonged periods. Despite this, little is known regarding whether and how T. gondii bradyzoites, a quasi-dormant life stage residing within intracellular cysts, manipulate the host cell to maintain persistent infection. A previous proteomic study of the cyst wall, an amorphous layer of proteins that forms underneath the cyst membrane, identified MYR1 as a putative cyst wall protein in vitro. Because MYR1 is known to be involved in the translocation of parasite-derived effector proteins into the host cell, we sought to determine whether parasites transitioning toward the bradyzoite life stage retain the capacity to translocate proteins via this pathway. By epitope tagging the endogenous loci of four known effectors that translocate from the parasitophorous vacuole into the host cell nucleus, we show, by immunofluorescence assays, that most effectors accumulate in the host nucleus at early but not late time points after infection, during the tachyzoite-to-bradyzoite transition and when parasites further along the bradyzoite differentiation continuum invade a new host cell. We demonstrate that the suppression of interferon gamma signaling, which was previously shown to be mediated by the effector TgIST, also occurs in the context of prolonged infection with bradyzoites and that TgIST export is a process that occurs beyond the early stages of host cell infection. These findings have important implications regarding how this highly successful parasite maintains persistent infection of its host.

IMPORTANCE Toxoplasma bradyzoites persist within tissue cysts and are refractory to current treatments, serving as a reservoir for acute complications in settings of compromised immunity. Much remains to be understood regarding how this life stage successfully establishes and maintains persistent infection. In this study, we investigated whether the export of parasite effector proteins into the host cell occurs during the development of in vitro tissue cysts. We quantified the presence of four previously described effectors in host cell nuclei at different time points after bradyzoite differentiation and found that they accumulated largely during the early stages of infection. Despite a decline in nuclear accumulation, we found that one of these effectors still mediated its function after prolonged infection with bradyzoites, and we provide evidence that this effector is exported beyond early infection stages. These findings suggest that effector export from within developing tissue cysts provides one potential mechanism by which this parasite achieves chronic infection.




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More than Simple Parasites: the Sociobiology of Bacteriophages and Their Bacterial Hosts

ABSTRACT

Bacteria harbor viruses called bacteriophages that, like all viruses, co-opt the host cellular machinery to replicate. Although this relationship is at first glance parasitic, there are social interactions among and between bacteriophages and their bacterial hosts. These social interactions can take on many forms, including cooperation, altruism, and cheating. Such behaviors among individuals in groups of bacteria have been well described. However, the social nature of some interactions between phages or phages and bacteria is only now becoming clear. We are just beginning to understand how bacteriophages affect the sociobiology of bacteria, and we know even less about social interactions within bacteriophage populations. In this review, we discuss recent developments in our understanding of bacteriophage sociobiology, including how selective pressures influence the outcomes of social interactions between populations of bacteria and bacteriophages. We also explore how tripartite social interactions between bacteria, bacteriophages, and an animal host affect host-microbe interactions. Finally, we argue that understanding the sociobiology of bacteriophages will have implications for the therapeutic use of bacteriophages to treat bacterial infections.




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Gamma Interferon Is Required for Chlamydia Clearance but Is Dispensable for T Cell Homing to the Genital Tract

ABSTRACT

While there is no effective vaccine against Chlamydia trachomatis infection, previous work has demonstrated the importance of C. trachomatis-specific CD4+ T cells (NR1 T cells) in pathogen clearance. Specifically, NR1 T cells have been shown to be protective in mice, and this protection depends on the host’s ability to sense the cytokine gamma interferon (IFN-). However, it is unclear what role NR1 production or sensing of IFN- plays in T cell homing to the genital tract or T cell-mediated protection against C. trachomatis. Using two-photon microscopy and flow cytometry, we found that naive wild-type (WT), IFN-–/–, and IFN-R–/– NR1 T cells specifically home to sections in the genital tract that contain C. trachomatis. We also determined that protection against infection requires production of IFN- from either NR1 T cells or endogenous cells, further highlighting the importance of IFN- in clearing C. trachomatis infection.

IMPORTANCE Chlamydia trachomatis is an important mucosal pathogen that is the leading cause of sexually transmitted bacterial infections in the United States. Despite this, there is no vaccine currently available. In order to develop such a vaccine, it is necessary to understand the components of the immune response that can lead to protection against this pathogen. It is well known that antigen-specific CD4+ T cells are critical for Chlamydia clearance, but the contexts in which they are protective or not protective are unknown. Here, we aimed to characterize the importance of gamma interferon production and sensing by T cells and the effects on the immune response to C. trachomatis. Our work here helps to define the contexts in which antigen-specific T cells can be protective, which is critical to our ability to design an effective and protective vaccine against C. trachomatis.




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Evolution of Host Specificity by Malaria Parasites through Altered Mechanisms Controlling Genome Maintenance

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.




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The Hypercomplex Genome of an Insect Reproductive Parasite Highlights the Importance of Lateral Gene Transfer in Symbiont Biology

ABSTRACT

Mobile elements—plasmids and phages—are important components of microbial function and evolution via traits that they encode and their capacity to shuttle genetic material between species. We here report the unusually rich array of mobile elements within the genome of Arsenophonus nasoniae, the son-killer symbiont of the parasitic wasp Nasonia vitripennis. This microbe’s genome has the highest prophage complement reported to date, with over 50 genomic regions that represent either intact or degraded phage material. Moreover, the genome is predicted to include 17 extrachromosomal genetic elements, which carry many genes predicted to be important at the microbe-host interface, derived from a diverse assemblage of insect-associated gammaproteobacteria. In our system, this diversity was previously masked by repetitive mobile elements that broke the assembly derived from short reads. These findings suggest that other complex bacterial genomes will be revealed in the era of long-read sequencing.

IMPORTANCE The biology of many bacteria is critically dependent on genes carried on plasmid and phage mobile elements. These elements shuttle between microbial species, thus providing an important source of biological innovation across taxa. It has recently been recognized that mobile elements are also important in symbiotic bacteria, which form long-lasting interactions with their host. In this study, we report a bacterial symbiont genome that carries a highly complex array of these elements. Arsenophonus nasoniae is the son-killer microbe of the parasitic wasp Nasonia vitripennis and exists with the wasp throughout its life cycle. We completed its genome with the aid of recently developed long-read technology. This assembly contained over 50 chromosomal regions of phage origin and 17 extrachromosomal elements within the genome, encoding many important traits at the host-microbe interface. Thus, the biology of this symbiont is enabled by a complex array of mobile elements.




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Characterization of the Efflux Capability and Substrate Specificity of Aspergillus fumigatus PDR5-like ABC Transporters Expressed in Saccharomyces cerevisiae

ABSTRACT

This research analyzed six Aspergillus fumigatus genes encoding putative efflux proteins for their roles as transporters. The A. fumigatus genes abcA, abcC, abcF, abcG, abcH, and abcI were cloned into plasmids and overexpressed in a Saccharomyces cerevisiae strain in which the highly active endogenous ABC transporter gene PDR5 was deleted. The activity of each transporter was measured by efflux of rhodamine 6G and accumulation of alanine β-naphthylamide. The transporters AbcA, AbcC, and AbcF had the strongest efflux activities of these compounds. All of the strains with plasmid-expressed transporters had more efflux activity than did the PDR5-deleted background strain. We performed broth microdilution drug susceptibility testing and agar spot assays using an array of compounds and antifungal drugs to determine the transporter specificity and drug susceptibility of the strains. The transporters AbcC and AbcF showed the broadest range of substrate specificity, while AbcG and AbcH had the narrowest range of substrates. Strains expressing the AbcA, AbcC, AbcF, or AbcI transporter were more resistant to fluconazole than was the PDR5-deleted background strain. Strains expressing AbcC and AbcF were additionally more resistant to clotrimazole, itraconazole, ketoconazole, and posaconazole than was the background strain. Finally, we analyzed the expression levels of the genes by reverse transcription-quantitative PCR (RT-qPCR) in triazole-susceptible and -resistant A. fumigatus clinical isolates. All of these transporters are expressed at a measurable level, and transporter expression varied significantly between strains, demonstrating the high degree of phenotypic variation, plasticity, and divergence of which this species is capable.

IMPORTANCE One mechanism behind drug resistance is altered export out of the cell. This work is a multifaceted analysis of membrane efflux transporters in the human fungal pathogen A. fumigatus. Bioinformatics evidence infers that there is a relatively large number of genes in A. fumigatus that encode ABC efflux transporters. However, very few of these transporters have been directly characterized and analyzed for their potential role in drug resistance.

Our objective was to determine if these undercharacterized proteins function as efflux transporters and then to better define whether their efflux substrates include antifungal drugs used to treat fungal infections. We chose six A. fumigatus potential plasma membrane ABC transporter genes for analysis and found that all six genes produced functional transporter proteins. We used two fungal systems to look for correlations between transporter function and drug resistance. These transporters have the potential to produce drug-resistant phenotypes in A. fumigatus. Continued characterization of these and other transporters may assist in the development of efflux inhibitor drugs.




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Single-Dose, Intranasal Immunization with Recombinant Parainfluenza Virus 5 Expressing Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Spike Protein Protects Mice from Fatal MERS-CoV Infection

ABSTRACT

Middle East respiratory syndrome coronavirus (MERS-CoV) can cause severe and fatal acute respiratory disease in humans and remains endemic in the Middle East since first being identified in 2012. There are currently no approved vaccines or therapies available for MERS-CoV. In this study, we evaluated parainfluenza virus 5 (PIV5)-based vaccine expressing the MERS-CoV envelope spike protein (PIV5/MERS-S) in a human DPP4 knockin C57BL/6 congenic mouse model (hDPP4 KI). Following a single-dose intranasal immunization, PIV5-MERS-S induced neutralizing antibody and robust T cell responses in hDPP4 KI mice. A single intranasal administration of 104 PFU PIV5-MERS-S provided complete protection against a lethal challenge with mouse-adapted MERS-CoV (MERSMA6.1.2) and improved virus clearance in the lung. In comparison, single-dose intramuscular immunization with 106 PFU UV-inactivated MERSMA6.1.2 mixed with Imject alum provided protection to only 25% of immunized mice. Intriguingly, an influx of eosinophils was observed only in the lungs of mice immunized with inactivated MERS-CoV, suggestive of a hypersensitivity-type response. Overall, our study indicated that PIV5-MERS-S is a promising effective vaccine candidate against MERS-CoV infection.

IMPORTANCE MERS-CoV causes lethal infection in humans, and there is no vaccine. Our work demonstrates that PIV5 is a promising vector for developing a MERS vaccine. Furthermore, success of PIV5-based MERS vaccine can be employed to develop a vaccine for emerging CoVs such as SARS-CoV-2, which causes COVID-19.