ADB has provided several targeted interventions to support its developing member countries in combating the effects of the COVID-19 pandemic from its early stages. In support of ADB’s effort, the Government of Japan is...

After a lacklustre first half, home sales across the top six cities in the country are expected to rise 26 per cent in the second half of 2014 compared to a year ago, according to a research report by property advisory firm Knight Frank. A negative sentiment among home buyers due to the slow economy, high interest rates, inflation and also political uncertainty had tempered home sales in the first half of the year. While new launches in the period dropped 32 per cent, sales volume was down 27 per cent. But now, with a positive election result, a stable government at the centre and sops for the housing sector […]

Nepal has 2.7% of the earth’s freshwater, yet the people of Kathmandu, Nepal’s most developed region, struggle with scarce water supply.

ADB is formulating an aggressive set of actions to protect the poor, the vulnerable, and wider populations across Asia and the Pacific. And to ensure economies will rebound as swiftly as possible.

Thanks to investment from Australia and ADB, a new clean water plant in Ebeye, in the north-west corner of the Marshall Islands, is changing lives.

Google engineers have spoken out about their claims of quantum supremacy, questioning IBM’s challenges and revealing some of their big plans for coming years

A new book from Jim Al-Khalili makes cutting-edge physics easily understandable and makes it clear why he fell in love with the subject as a teenager

Welsh mezzo-soprano Katherine Jenkins will stream a concert from an empty Royal Albert Hall on Friday evening, as locked-down Britain marks the 75th anniversary of "Victory in Europe" Day.

With the help of their webs, spiders are capable of foresight, planning, learning and other smarts that indicate they may possess consciousness

Healthy grey whales are four times more likely to become stranded when solar activity produces lots of radio noise, suggesting solar storms may be blinding their ability to sense magnetic fields

The fossilised remains of the food found in one of the few remaining coastal Neanderthal sites in Europe show they ate plenty of seafood, fish and nuts

The age of a whale shark can be determined by dating the rings of growth in their cartilage, a method that has confirmed that these animals can live for at least 50 years

The weird ‘Ediacaran’ fossils have stumped scientists for decades - now fatty molecules found inside some of them confirm they are the most ancient animals we know

A tsunami kept pinging back and forth for three days after being triggered by the 8 September 2017 Mexico earthquake, posing even more risk to human life

A dead whale found in the Philippines with 40 kilograms of plastic inside its body is the latest example of the problem of plastic pollution

Taal volcano, situated on an island in a lake, began erupting dramatically on Sunday, prompting an evacuation order for 450,000 people in the surrounding area

An 18-year-old who was born without the left half of her brain scores well on IQ tests and plans to attend university, revealing our brain's incredible adaptability

A Neanderthal skeleton unearthed in a cave in Iraq shows signs of having been deliberately buried – more evidence our cousin species behaved a little like we do

A prehistoric human species that lived in Europe 1.2 million to 800,000 years ago is emerging as a contender to be our last common ancestor with Neanderthals

A piece of string found in a cave in France is the oldest ever discovered and shows that Neanderthals knew how to twist fibres together to make cords

After being sidelined as a non-essential business, some self-driving car companies can put their vehicles back on the roads to make food and other deliveries - a win-win scenario that allows them to continue testing their nascent technology.

When it comes to electric vehicles, there’s no denying the multitude of benefits for manufacturers, consumers, and the environment – from reduced emissions to lower fuel costs, increased efficiency, and lower noise pollution. These benefits continue to...

With the help of their webs, spiders are capable of foresight, planning, learning and other smarts that indicate they may possess consciousness

Title: Type 2 Diabetes in Kids a Challenge to Control
Category: Health News
Created: 5/1/2012 11:01:00 AM
Last Editorial Review: 5/1/2012 12:00:00 AM

Title: Seniors Undertreated for Asthma, and Many Skip Inhalers: Study
Category: Health News
Created: 5/1/2012 2:05:00 PM
Last Editorial Review: 5/2/2012 12:00:00 AM

Title: White House to Challenge Ruling on Unlimited Access to 'Morning-After' Pill
Category: Health News
Created: 5/2/2013 10:35:00 AM
Last Editorial Review: 5/2/2013 12:00:00 AM

Title: Study Challenges Salt Guidelines for Kids
Category: Health News
Created: 4/27/2015 12:00:00 AM
Last Editorial Review: 4/28/2015 12:00:00 AM

Title: Half of U.S. Hospitals Could Do More to Prevent Serious Infections, Study Finds
Category: Health News
Created: 4/29/2015 12:00:00 AM
Last Editorial Review: 4/30/2015 12:00:00 AM

Title: Half of U.S. Docs Get Payments From Drug, Device Industries: Study
Category: Health News
Created: 5/2/2017 12:00:00 AM
Last Editorial Review: 5/3/2017 12:00:00 AM

Title: Asthma Inhalers Incorrectly Used by Most Kids in Study
Category: Health News
Created: 4/30/2019 12:00:00 AM
Last Editorial Review: 4/30/2019 12:00:00 AM

Title: In COVID Crisis, Nearly Half of People in Some U.S. States Are Going Hungry
Category: Health News
Created: 4/28/2020 12:00:00 AM
Last Editorial Review: 4/28/2020 12:00:00 AM

Title: Production of Two Excedrin Painkillers Halted
Category: Health News
Created: 1/22/2020 12:00:00 AM
Last Editorial Review: 1/22/2020 12:00:00 AM

Between the first seven days of January 2020 and the last seven days of March, mean daily controller inhaler use rose 14.5%.

A child psychologist advises parents to address the threat of internet challenges with continual, preemptive conversations with kids -- and with special phone settings.

Title: Keflex (cephalexin)
Category: Medications
Created: 12/31/1997 12:00:00 AM
Last Editorial Review: 2/12/2020 12:00:00 AM

Title: Haldol (haloperidol) vs. Abilify (aripiprazole)
Category: Medications
Created: 7/30/2019 12:00:00 AM
Last Editorial Review: 4/10/2020 12:00:00 AM

ABSTRACT

Hantaviruses are the etiological agent of hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). The latter is associated with case fatality rates ranging from 30% to 50%. HCPS cases are rare, with approximately 300 recorded annually in the Americas. Recently, an HCPS outbreak of unprecedented size has been occurring in and around Epuyén, in the southwestern Argentinian state of Chubut. Since November of 2018, at least 29 cases have been laboratory confirmed, and human-to-human transmission is suspected. Despite posing a significant threat to public health, no treatment or vaccine is available for hantaviral disease. Here, we describe an effort to identify, characterize, and develop neutralizing and protective antibodies against the glycoprotein complex (Gn and Gc) of Andes virus (ANDV), the causative agent of the Epuyén outbreak. Using murine hybridoma technology, we generated 19 distinct monoclonal antibodies (MAbs) against ANDV GnGc. When tested for neutralization against a recombinant vesicular stomatitis virus expressing the Andes glycoprotein (GP) (VSV-ANDV), 12 MAbs showed potent neutralization and 8 showed activity in an antibody-dependent cellular cytotoxicity reporter assay. Escape mutant analysis revealed that neutralizing MAbs targeted both the Gn and the Gc. Four MAbs that bound different epitopes were selected for preclinical studies and were found to be 100% protective against lethality in a Syrian hamster model of ANDV infection. These data suggest the existence of a wide array of neutralizing antibody epitopes on hantavirus GnGc with unique properties and mechanisms of action.

IMPORTANCE Infections with New World hantaviruses are associated with high case fatality rates, and no specific vaccine or treatment options exist. Furthermore, the biology of the hantaviral GnGc complex, its antigenicity, and its fusion machinery are poorly understood. Protective monoclonal antibodies against GnGc have the potential to be developed into therapeutics against hantaviral disease and are also great tools to elucidate the biology of the glycoprotein complex.

ABSTRACT

The archaeal cytoplasmic membrane provides an anchor for many surface proteins. Recently, a novel membrane anchoring mechanism involving a peptidase, archaeosortase A (ArtA), and C-terminal lipid attachment of surface proteins was identified in the model archaeon Haloferax volcanii. ArtA is required for optimal cell growth and morphogenesis, and the S-layer glycoprotein (SLG), the sole component of the H. volcanii cell wall, is one of the targets for this anchoring mechanism. However, how exactly ArtA function and regulation control cell growth and morphogenesis is still elusive. Here, we report that archaeal homologs to the bacterial phosphatidylserine synthase (PssA) and phosphatidylserine decarboxylase (PssD) are involved in ArtA-dependent protein maturation. Haloferax volcanii strains lacking either HvPssA or HvPssD exhibited motility, growth, and morphological phenotypes similar to those of an artA mutant. Moreover, we showed a loss of covalent lipid attachment to SLG in the hvpssA mutant and that proteolytic cleavage of the ArtA substrate HVO_0405 was blocked in the hvpssA and hvpssD mutant strains. Strikingly, ArtA, HvPssA, and HvPssD green fluorescent protein (GFP) fusions colocalized to the midcell position of H. volcanii cells, strongly supporting that they are involved in the same pathway. Finally, we have shown that the SLG is also recruited to the midcell before being secreted and lipid anchored at the cell outer surface. Collectively, our data suggest that haloarchaea use the midcell as the main surface processing hot spot for cell elongation, division, and shape determination.

IMPORTANCE The subcellular organization of biochemical processes in space and time is still one of the most mysterious topics in archaeal cell biology. Despite the fact that haloarchaea largely rely on covalent lipid anchoring to coat the cell envelope, little is known about how cells coordinate de novo synthesis and about the insertion of this proteinaceous layer throughout the cell cycle. Here, we report the identification of two novel contributors to ArtA-dependent lipid-mediated protein anchoring to the cell surface, HvPssA and HvPssD. ArtA, HvPssA, and HvPssD, as well as SLG, showed midcell localization during growth and cytokinesis, indicating that haloarchaeal cells confine phospholipid processing in order to promote midcell elongation. Our findings have important implications for the biogenesis of the cell surface.

ABSTRACT

Recent outbreaks of yellow fever virus (YFV) in West Africa and Brazil resulted in rapid depletion of global vaccine emergency stockpiles and raised concerns about being unprepared against future YFV epidemics. Here we report that a live attenuated virus similar to the Japanese encephalitis virus (JEV) vaccine JE-CVax/Imojev that consists of YFV-17D vaccine from which the structural (prM/E) genes have been replaced with those of the JEV SA14-14-2 vaccine strain confers full protection in mice against lethal YFV challenge. In contrast to the YFV-17D-mediated protection against YFV, this protection is not mediated by neutralizing antibodies but correlates with YFV-specific nonneutralizing antibodies and T cell responses against cell-associated YFV NS1 and other YFV nonstructural (NS) proteins. Our findings reveal the potential of YFV NS proteins to mediate protection and demonstrate that chimeric flavivirus vaccines, such as Imojev, could confer protection against two flaviviruses. This dual protection may have implications for the possible off-label use of JE-CVax in case of emergency and vaccine shortage during YFV outbreaks. In addition, populations in Asia that have been vaccinated with Imojev may already be protected against YFV should outbreaks ever occur on that continent, as several countries/regions in the Asia-Pacific are vulnerable to international spread of the YFV.

IMPORTANCE Efficient and safe vaccines against yellow fever (e.g., YFV-17D) that provide long-lasting protection by rapidly inducing neutralizing antibody responses exist. However, the vaccine supply cannot cope with an increasing demand posed by urban outbreaks in recent years. Here we report that JE-CVax/Imojev, a YFV-17D-based chimeric Japanese encephalitis vaccine, also efficiently protects against YFV infection in mice. In case of shortage of the YFV vaccine during yellow fever outbreaks, (off-label) use of JE-CVax/Imojev may be considered. Moreover, wider use of JE-CVax/Imojev in Asia may lower the risk of the much-feared YFV spillover to the continent. More generally, chimeric vaccines that combine surface antigens and replication machineries of two distinct flaviviruses may be considered dual vaccines for the latter pathogen without induction of surface-specific antibodies. Following this rationale, novel flavivirus vaccines that do not hold a risk for antibody-dependent enhancement (ADE) of infection (inherent to current dengue vaccines and dengue vaccine candidates) could be designed.

ABSTRACT

Lipopolysaccharide (LPS) is an essential glycolipid present in the outer membrane (OM) of many Gram-negative bacteria. Balanced biosynthesis of LPS is critical for cell viability; too little LPS weakens the OM, while too much LPS is lethal. In Escherichia coli, this balance is maintained by the YciM/FtsH protease complex, which adjusts LPS levels by degrading the LPS biosynthesis enzyme LpxC. Here, we provide evidence that activity of the YciM/FtsH protease complex is inhibited by the essential protein YejM. Using strains in which LpxC activity is reduced, we show that yciM is epistatic to yejM, demonstrating that YejM acts upstream of YciM to prevent toxic overproduction of LPS. Previous studies have shown that this toxicity can be suppressed by deleting lpp, which codes for a highly abundant OM lipoprotein. It was assumed that deletion of lpp restores lipid balance by increasing the number of acyl chains available for glycerophospholipid biosynthesis. We show that this is not the case. Rather, our data suggest that preventing attachment of lpp to the peptidoglycan sacculus allows excess LPS to be shed in vesicles. We propose that this loss of OM material allows continued transport of LPS to the OM, thus preventing lethal accumulation of LPS within the inner membrane. Overall, our data justify the commitment of three essential inner membrane proteins to avoid toxic over- or underproduction of LPS.

IMPORTANCE Gram-negative bacteria are encapsulated by an outer membrane (OM) that is impermeable to large and hydrophobic molecules. As such, these bacteria are intrinsically resistant to several clinically relevant antibiotics. To better understand how the OM is established or maintained, we sought to clarify the function of the essential protein YejM in Escherichia coli. Here, we show that YejM inhibits activity of the YciM/FtsH protease complex, which regulates synthesis of the essential OM glycolipid lipopolysaccharide (LPS). Our data suggest that disrupting proper communication between LPS synthesis and transport to the OM leads to accumulation of LPS within the inner membrane (IM). The lethality associated with this event can be suppressed by increasing OM vesiculation. Our research has identified a completely novel signaling pathway that we propose coordinates LPS synthesis and transport.

This season’s flu vaccine was 45% effective overall and 55% effective among children and teens, the Centers for Disease Control and Prevention reported in February.

Objective

De novo missense mutations in the RHOBTB2 gene have been described as causative for developmental and epileptic encephalopathy.

Despite the ecological relevance of diatoms, many aspects of their photosynthetic machinery remain poorly understood. Diatoms differ from the green lineage of oxygenic organisms by their photosynthetic pigments and light-harvesting complex (Lhc) proteins, the latter of which are also called fucoxanthin-chlorophyll proteins (FCP). These are composed of three groups of proteins: Lhcf as the main group, Lhcr that are PSI associated, and Lhcx that are involved in photoprotection. The FCP complexes are assembled in trimers and higher oligomers. Several studies have investigated the biochemical properties of purified FCP complexes, but limited knowledge is available about their interaction with the photosystem cores. In this study, isolation of stable supercomplexes from the centric diatom Thalassiosira pseudonana was achieved. To preserve in vivo structure, the separation of thylakoid complexes was performed by native PAGE and sucrose density centrifugation. Different subpopulations of PSI and PSII supercomplexes were isolated and their subunits identified. Analysis of Lhc antenna composition identified Lhc(s) specific for either PSI (Lhcr 1, 3, 4, 7, 10–14, and Lhcf10) or PSII (Lhcf 1–7, 11, and Lhcr2). Lhcx6_1 was reproducibly found in PSII supercomplexes, whereas its association with PSI was unclear. No evidence was found for the interaction between photosystems and higher oligomeric FCPs, comprising Lhcf8 as the main component. Although the subunit composition of the PSII supercomplexes in comparison with that of the trimeric FCP complexes indicated a close mutual association, the higher oligomeric pool is only weakly associated with the photosystems, albeit its abundance in the thylakoid membrane.

The current coronavirus 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, raises important questions as to whether pre-morbid use or continued administration of inhaled corticosteroids (ICS) affects the outcomes of acute respiratory infections due to coronavirus. Many physicians are concerned about whether individuals positive for SARS-CoV-2 and taking ICS should continue them or stop them, given that ICS are often regarded as immunosuppressive. A number of key questions arise. Are people with asthma or COPD at increased risk of developing COVID-19? Do ICS modify this risk, either increasing or decreasing it? Do ICS influence the clinical course of COVID-19? (figure 1). Whether ICS modify the risk of developing COVID-19 or the clinical course of COVID-19 in people who do not have lung disease should also be considered (figure 1).

For decades inhaled corticosteroids have been central to the management of asthma and are proven to be effective in maintaining symptom control, reducing exacerbations and preserving quality of life through mediation of airway inflammation. However, a small minority of patients have disease which is refractory to high dose inhaled corticosteroid (ICS) therapy and require additional oral corticosteroids to achieve acceptable control of symptoms and exacerbations. Severe asthma represents less than 10% of the total asthma population [1] but is the most serious, life-affecting and costly form of the condition [2].

We wish to thank J. Britton and co-workers for responding to our editorial and giving us an opportunity to clarify our position as well as correct a few misunderstandings. We definitely share the same goal, which is to relieve Europe and the rest of the world from the terrible results of the tobacco epidemic. We also do not "blankly oppose e-cigarettes"; however, we strongly advocate against a harm reduction strategy including e-cigarettes as well as heated tobacco products [1]. As clinicians we all see reluctant smokers where e-cigarettes can be tried as a last resort for getting off cigarette smoking, but that is of little relevance for a general harm reduction strategy. We also agree that the UK has achieved a lot in the area of smoking cessation but would argue that this has been achieved by impressive tobacco control, not by the use of e-cigarettes, and that a country such as Australia, which has banned nicotine-containing e-cigarettes, has achieved similar results.

The respiratory community is united in its desire to reduce and eliminate the harm caused by tobacco smoking, which is at present on course to kill one billion people in the 21st century. The stated policy of the European Respiratory Society is to strive "constantly to promote strong and evidence-based policies to reduce the burden of tobacco related diseases". In our view, the recent ERS Tobacco Control Committee statement on tobacco harm reduction [1], though well-intentioned, appears to be based on a number of false premises and draws its conclusions from a partial account of available data. It also presents a false dichotomy between the provision of "conventional" tobacco control and harm reduction approaches. We therefore respond, in turn, to the seven arguments presented against the adoption of harm reduction in the Committee's statement.

The World Health Organization (WHO) has listed moxifloxacin and linezolid among the preferred "group A" drugs in the treatment of multidrug-resistant (MDR)-tuberculosis (TB) [1]. Therapeutic drug monitoring (TDM) could potentially optimise MDR-TB therapy, since moxifloxacin and linezolid show large pharmacokinetic variability [1–4]. TDM of moxifloxacin focuses on identifying patients with low drug exposure who are at risk of treatment failure and acquired fluoroquinolone resistance [5, 6]. Alternatively, TDM of linezolid strives to reduce toxicity while ensuring an adequate drug exposure because of its narrow therapeutic index [1, 3, 7].