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...

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.

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

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: 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

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

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.

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].

Phenotypic plasticity is defined as the property of organisms to produce distinct phenotypes in response to environmental variation. While for more than a century, biologists have proposed this organismal feature to play an important role in evolution and the origin of novelty, the idea has remained contentious. Plasticity is found in all domains of life, but only recently has there been an increase in empirical studies. This contribution is intended as a fresh view and will discuss current and future challenges of plasticity research, and the need to identify associated molecular mechanisms. After a brief summary of conceptual, theoretical, and historical aspects, some of which were responsible for confusion and contention, I will formulate three major research directions and predictions for the role of plasticity as a facilitator of novelty. These predictions result in a four-step model that, when properly filled with molecular mechanisms, will reveal plasticity as a major factor of evolution. Such mechanistic insight must be complemented with comparative investigations to show that plasticity has indeed created novelty and innovation. Together, such studies will help develop a true developmental evolutionary biology.

Key Points

ABSTRACT

By modulating the structure, diversity, and trophic outputs of microbial communities, phages play crucial roles in many biomes. In oligotrophic polar deserts, the effects of katabatic winds, constrained nutrients, and low water availability are known to limit microbial activity. Although phages may substantially govern trophic interactions in cold deserts, relatively little is known regarding the precise ecological mechanisms. Here, we provide the first evidence of widespread antiphage innate immunity in Antarctic environments using metagenomic sequence data from hypolith communities as model systems. In particular, immunity systems such as DISARM and BREX are shown to be dominant systems in these communities. Additionally, we show a direct correlation between the CRISPR-Cas adaptive immunity and the metavirome of hypolith communities, suggesting the existence of dynamic host-phage interactions. In addition to providing the first exploration of immune systems in cold deserts, our results suggest that phages actively challenge niche communities in Antarctic polar deserts. We provide evidence suggesting that the regulatory role played by phages in this system is an important determinant of bacterial host interactions in this environment.

IMPORTANCE In Antarctic environments, the combination of both abiotic and biotic stressors results in simple trophic levels dominated by microbiomes. Although the past two decades have revealed substantial insights regarding the diversity and structure of microbiomes, we lack mechanistic insights regarding community interactions and how phages may affect these. By providing the first evidence of widespread antiphage innate immunity, we shed light on phage-host dynamics in Antarctic niche communities. Our analyses reveal several antiphage defense systems, including DISARM and BREX, which appear to dominate in cold desert niche communities. In contrast, our analyses revealed that genes which encode antiphage adaptive immunity were underrepresented in these communities, suggesting lower infection frequencies in cold edaphic environments. We propose that by actively challenging niche communities, phages play crucial roles in the diversification of Antarctic communities.

C. M. Lind, J. Agugliaro, and T. M. Farrell

Mounting an immune response may be energetically costly and require the diversion of resources away from other physiological processes. Yet, both the metabolic cost of immune responses and the factors that impact investment priorities remain poorly described in many vertebrate groups. For example, although viviparity has evolved many times in vertebrates, the relationship between immune function and pregnancy has been disproportionately studied in placental mammals. To examine the energetic costs of immune activation and the modulation of immune function during pregnancy in a non-mammalian vertebrate, we elicited an immune response in pregnant and non-pregnant pygmy rattlesnakes, Sistrurus miliarius, using lipopolysaccharide (LPS). Resting metabolic rate (RMR) was measured using flow-through respirometry. Immune function was examined using bactericidal assays and leukocyte counts. The RMR of pygmy rattlesnakes increased significantly in response to LPS injection. There was no statistically significant difference in the metabolic response of non-reproductive and pregnant snakes to LPS. Mean metabolic increments for pregnant females, non-reproductive females, and males were 13%, 18%, and 26%, respectively. The ratio of heterophils to lymphocytes was elevated in response to LPS across reproductive categories; however, LPS did not impact plasma bactericidal ability in non-reproductive snakes. Although pregnant females had significantly higher plasma bactericidal ability compared to non-reproductive snakes prior to manipulation, their bactericidal ability declined in response to LPS. LPS administration also significantly reduced several litter characteristics, particularly when administrated relatively early in pregnancy. Our results indicate that immune performance is energetically costly, altered during pregnancy, and that immune activation during pregnancy may result in tradeoffs that affect offspring in a viviparous reptile.

Virus-like-particle (VLP) influenza vaccines can be given intramuscularly (i.m.) or intranasally (i.n.) and may have advantages over split-virion formulations in the elderly. We tested a plant-made VLP vaccine candidate bearing the viral hemagglutinin (HA) delivered either i.m. or i.n. in young and aged mice. Young adult (5- to 8-week-old) and aged (16- to 20-month-old) female BALB/c mice received a single 3-μg dose based on the HA (A/California/07/2009 H1N1) content of a plant-made H1-VLP (i.m. or i.n.) split-virion vaccine (i.m.) or were left naive. After vaccination, humoral and splenocyte responses were assessed, and some mice were challenged. Both VLP and split vaccines given i.m. protected 100% of the young animals, but the VLP group lost the least weight and had stronger humoral and cellular responses. Compared to split-vaccine recipients, aged animals vaccinated i.m. with VLP were more likely to survive challenge (80% versus 60%). The lung viral load postchallenge was lowest in the VLP i.m. groups. Mice vaccinated with VLP i.n. had little detectable immune response, but survival was significantly increased. In both age groups, i.m. administration of the H1-VLP vaccine elicited more balanced humoral and cellular responses and provided better protection from homologous challenge than the split-virion vaccine.

Therapeutic inertia is a prevalent problem in people with type 2 diabetes in primary care and affects clinical outcomes. It arises from a complex interplay of patient-, clinician-, and health system–related factors. Ultimately, clinical practice guidelines have not made an impact on improving glycemic targets over the past decade. A more proactive approach, including focusing on optimal combination agents for early glycemic durability, may reduce therapeutic inertia and improve clinical outcomes.

Despite significant advances in therapies for pediatric type 1 diabetes, achievement of glycemic targets remains elusive, and management remains burdensome for patients and their families. This article identifies common challenges in diabetes management at the patient-provider and health care system levels and proposes practical approaches to overcoming therapeutic inertia to enhance health outcomes for youth with type 1 diabetes.

As COVID-19 continues to surge, cancer scientists engaged in basic research face unique challenges. At centers throughout the United States, investigators are confronting difficult decisions about which experiments to continue, while securing supplies and creating contingency plans for a complete shutdown.

We report the diagnostic challenges and the clinical course of a patient with an extraordinary presentation of B-lymphoblastic leukemia (B-ALL) with eosinophilia. We identified a novel ZBTB20-JAK2 gene fusion as a chimeric RNA transcript using the Archer platform. This gene fusion from the same patient was recently identified by Peterson et al. (2019) at the genomic level using a different sequencing technology platform. The configuration of this gene fusion predicts the production of a kinase-activating JAK2 fusion protein, which would normally lead to a diagnosis of Philadelphia chromosome–like B-ALL (Ph-like B-ALL). However, the unusual presentation of eosinophilia led us to demonstrate the presence of this gene fusion in nonlymphoid hematopoietic cells by fluorescence in situ hybridization (FISH) studies with morphologic correlation. Therefore, we believe this disease, in fact, represents blast crisis arising from an underlying myeloid neoplasm with JAK2 rearrangements. This case illustrates the difficulty in differentiating Ph-like B-ALL and myeloid/lymphoid neoplasm with eosinophilia and gene rearrangements (MLN-EGR) in blast crisis. As currently defined, the diagnosis of MLN-EGR relies on the hematologic presentations and the identification of marker gene fusions (including PCM1-JAK2, ETV6-JAK2, and BCR-JAK2). However, these same gene fusions, when limited to B-lymphoblasts, also define Ph-like B-ALL. Yet, our case does not conform to either condition. Therefore, the assessment for lineage restriction of gene rearrangements to reflect the pathophysiologic difference between B-ALL and MLN-EGR in blast crisis is likely a more robust diagnostic approach and allows the inclusion of MLN-EGR with novel gene fusions.

It all boils down to how resilient the region is, says an urban planner and designer based in Manila.

Tens of thousands of new apartments enter the Ho Chi Minh City market every year, putting pressure on investors who want to reap returns from rental apartments.

If you didn’t feel challenged enough by Indivisible‘s main platforming and punching campaign, here’s some good news for ya. Lab Zero have released a new DLC for their turn-ish-based RPG today that promises the “forty specially crafted levels await to test your platforming and combat skills.” The Razmi’s Challenges DLC is available now, so you […]

Get ready for the first scored event in DARPA's latest Grand Challenge

Roboticists share what they've learned so far from DARPA's Subterranean Challenge, and how they readied their bots for the next event—the Tunnel Circuit

How autonomous robots in the underground scavenger hunt pick up points for their teams

Supporting long-range communications inside of a mine is extremely difficult, so DARPA SubT teams are trying out some creative approaches

It's about more than just first place as teams look toward more competitions in 2020

New Pokemon Go Throwback challenges start today for the Johto region. Here's a recap of all field research tasks and rewards on offer for the next seven days.

Bill Maher said Republicans "don't care" about Tara Reade's sexual assault allegations, saying such claims are simply used as a "unilateral weapon" against Democrats.

The Roses are Red Challenge has caught the internet and has become a fad now as the netizens are coming up with a hilarious line which rhyme with roses are red. It is the netizens who have started this trend amid lockdown and most of them are making their own versions of their poems. Most of them tickle your funny bone with the one-liners which have caught the attention of the Internet users.

Arsenal and England midfielder Jordan Nobbs will be a columnist for 90min & BBC Sport pundit at the Women's World Cup in France this summer, as Phil Neville's Lionesses' look to secure a maiden World Cup triumph. Two wins from our first two games is obviously what we were all hoping for. The first game of a World Cup, or any other major tournament, is never going to be one where you're playing at your absolute best. But the 2-1 win over was Scotland was great given the pre-match hype, the..

Beggs was on a leave of absence from the post when the Challenger space shuttle broke apart 73 seconds after launch on Jan. 28, 1986, killing all seven aboard

The renewable energy source has never quite lived up to its potential, but a new experiment in Nova Scotia could flip the script

Smithsonian Secretary Lonnie G. Bunch III says: ‘It’s time to put our heads down, and work’

A court asked the Indian government on Friday to respond to a challenge against its order for compulsory use of a contact tracing app by public and private sector employees returning to work amid the world's biggest coronavirus lockdown.

Follow our live coronavirus updates here Coronavirus: the symptoms

A group of parents who were challenged by police over a trip to the beach during the coronavirus lockdown claimed their children needed a "change of air".

A pregnant doctor and her husband are bringing a legal challenge against the Government which questions the lawfulness of current guidance and a failure to source PPE.

The nine-year-old was inspired by hero fundraiser Captain Tom Moore's £30 million fundraiser

The Court of Appeal has upheld the conviction of school teacher Gordon Park for the "lady in the lake" murder of his wife following a posthumous challenge.

The Budd family hopes to raise £20,000 for charities including The Felix Project You can donate at virginmoneygiving.com/fund/FoodforLondonNOW

Damien Conrad from The Felix Project shares his story You can donate here virginmoneygiving.com/fund/FoodforLondonNOW

Low staff numbers and a lack of PPE are among the challenges facing schools as they draw together plans to reopen.

The travel industry has sifted through the BBC show’s many sex scenes to showcase shots of Ireland’s landscape

Promoting Ireland as a tourism destination used to be straightforward – just showcase the bucolic landscape and put a slogan on the end – but that was before Normal People turned a chunk of the Atlantic coast into Fifty Shades of Sligo.

The television adaptation of Sally Rooney’s novel features beautiful shots of Sligo’s beaches and mountains, plus Trinity College Dublin, but there is also sex. Lots of sex.

NASA has awarded the University of Washington a $499,864 grant to develop a competition that calls on students to turn a simulated lava tube into a habitat suitable for harboring humans on the moon or Mars. The exploration and habitation skills competition will be funded as part of NASA's Artemis Student Challenges program, which plays off the themes of the Artemis moon program to inspire the next generation of explorers and engineers. The competition will involve navigating a rover through a facsimile lava tube and surface structures, generating maps, identifying valuable resources and deploying an airtight barrier to seal the… Read More

These are trying times, not least because corporate life needs to go on, which for millions of businesses means delivering compute resources…

The health care sector has cut 1.4 million jobs in April. And as COVID-19 has consumed health care resources, other essential routine procedures — like screenings for strokes — have gone down.

He invited Sylvester Stallone and Arnold Schwarzenegger to also take part.

Adam Silver outlined a potentially grim future for the NBA in a call with players, calling the pandemic the "single greatest challenge of all our lives."