Manganese (Mn) is an essential micronutrient required for the normal development of many organs, including the brain. Although its roles as a cofactor in several enzymes and in maintaining optimal physiology are well-known, the overall biological functions of Mn are rather poorly understood. Alterations in body Mn status are associated with altered neuronal physiology and cognition in humans, and either overexposure or (more rarely) insufficiency can cause neurological dysfunction. The resultant balancing act can be viewed as a hormetic U-shaped relationship for biological Mn status and optimal brain health, with changes in the brain leading to physiological effects throughout the body and vice versa. This review discusses Mn homeostasis, biomarkers, molecular mechanisms of cellular transport, and neuropathological changes associated with disruptions of Mn homeostasis, especially in its excess, and identifies gaps in our understanding of the molecular and biochemical mechanisms underlying Mn homeostasis and neurotoxicity.

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.

Balamuthia mandrillaris is an under-reported, pathogenic free-living amoeba that causes Balamuthia amoebic encephalitis (BAE) and cutaneous skin infections. Although cutaneous infections are not typically lethal, BAE with or without cutaneous involvement is usually fatal. This is due to the lack of drugs that are both efficacious and can cross the blood-brain barrier. We aimed to discover new leads for drug discovery by screening the open-source Medicines for Malaria Venture (MMV) Malaria Box and MMV Pathogen Box, with 800 compounds total. From an initial single point screen at 1 and 10 μM, we identified 54 hits that significantly inhibited the growth of B. mandrillaris in vitro. Hits were reconfirmed in quantitative dose-response assays and 23 compounds (42.6%) were confirmed with activity greater than miltefosine, the current standard of care.

Background:

Energy balance–related factors, such as body mass index (BMI), diet, and physical activity, may influence colorectal cancer etiology through interconnected metabolic pathways, but their combined influence is less clear.

Your weekly selection of awesome robot videos

A new two-way teleoperation system sends your motions to the robot and the robot's motions to you

This uncanny story of preppy drug dealers has a touch of Heathers and a bit of Bret Easton Ellis, and an intriguing take on what high school is really like

Tayarisha Poe, like her partial namesake, has a gift for the uncanny. She is the photographer and film-maker behind this feature debut, which began as an online multimedia project and was developed as a conventional movie through the Sundance screenwriters and directors labs. What has emerged is an intriguing, opaque, tonally elusive story that seems weirdly unfinished. It is set in a privileged high school – a world of ivy-covered stone buildings and shady quadrangles where rich kids are separated into malign and mutually hostile cliques. It has a touch of Donna Tartt and Bret Easton Ellis, a hint of Heathers and a bit of the elegant, disdainful satire of Dear White People.

Somehow, though, it is odder, more stylised and contrived, always holding out the possibility that it is set in the future, or in an alternative present on some other planet, or inside the head of one of its characters who is having a disturbing dream – the kind that ends just as it is about to give up its meaning. Right until the closing credits, I half-expected the face of each person on screen to flip upwards, revealing a Stepford-like set of dials.

Modern Games is a new studio working to create games that combine physical and digital play. The company was founded by husband-and-wife team Justin and Amanda Kifer — serial entrepreneurs who previously launched companies including Citizen Local (acquired by MyLife in 2011) and Fidgetly, a fidget spinner company that also created a motion controller for […]

Measuring tiny differences in mass between different quantum states provides new insights into heavy atoms.

Balancing home, office work takes toll on mental health  Deccan Chronicle

The retro runner has made (another) comeback

Paul Pogba claims unfinished business lured him back to Manchester United as Real Madrid and Juventus line up to prise him away again this summer.

Chelsea goalkeeper Kepa Arrizabalaga has rejected speculation linking him with a move away from the club, insisting he has a "very good relationship" with coach Frank Lampard.

Liverpool's success combined with the current enforced break from football may have convinced Jurgen Klopp to prolong any future retirement plans, according to football journalist Guillem Balague.

Liverpool's 2005 Champions League winners would have no chance of beating the current Reds crop, according to football journalist Guillem Balague.

What’s needed after Covid-19 is a bigger, smarter state, with more devolved decisions, a greener economy and a stronger safety net

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The words are straining to come out. Boris Johnson hero worships Winston Churchill so it is obvious how the prime minister will pitch this week’s announcement of the plan to get Britain out of lockdown.

In late 1942, victory in the north African desert had suggested that the tide of the war might have turned but Churchill was cautious. “Now this is not the end,” he said in a speech at London’s Mansion House. “It is not even the beginning of the end. But it is, perhaps, the end of the beginning.”

Just say "no" to mom guilt.

Measuring tiny differences in mass between different quantum states provides new insights into heavy atoms.

«Bikini body» versus silhouette bedonnante... Sur les réseaux sociaux, l’affaire est entendue: le confinement se traduira par des kilos en plus.

Huffington Post: Data Exclusivity: Getting the Balance Right      A great article on the downsides of cutting or removing data exclusivity provisions for biologics.  The article points out that data protection is needed to enhance safety and create incentives to research and produce new innovative drugs that cost billions of dollars.  However, the author argues that the period must be […]

This blog was written by Ankit Mahadevia, CEO of Spero Therapeutics, as part of the From The Trenches feature of LifeSciVC.  If CEOs have empowered their teams effectively, they have three roles during times of rapid change: Motivator in chief

The post The Balancing Act: Taking A Systematic Approach To Hard Decisions In Times Of Rapid Change appeared first on LifeSciVC.

Exercise is good for the immune system but, as with anything, balance is key and this is especially the case when it comes to matching the type and level of activity with the right nutrition, as will be expertly explained in NutraIngredients' upcoming webinar.

Moving discoveries from academia to industry requires a delicate balance of risk, reward, skill sets and personalities, according to a translational panel held at BIO-Europe's partnering conference.

NHRC Chairperson, Justice KG Balakrishnan will be our guest at Idea Exchange on October 11. Send us your questions for him.

As Ramadan begins, Pakistan has loosened social distancing restrictions on gatherings in mosques, allowing communal prayers to go forward during the holy month. David Rubenstein Fellow Madiha Afzal explains how Prime Minister Imran Khan's political compromise with the religious right and cash assistance programs for the poor help burnish his populist image, while leaving it…

As Ramadan begins, Pakistan has loosened social distancing restrictions on gatherings in mosques, allowing communal prayers to go forward during the holy month. David Rubenstein Fellow Madiha Afzal explains how Prime Minister Imran Khan's political compromise with the religious right and cash assistance programs for the poor help burnish his populist image, while leaving it…

Bruce Jones explores the prospects for cooperation on global finance and transnational threats, the need for new investments in global economic and energy diplomacy, and the case for new crisis management tools to help de-escalate inevitable tensions among emerging powers across the globe.

Abstract Converting retirement savings balances into a stream of retirement income is one of the most difficult financial decisions that households need to make. New financial products, however, offer people alternative ways to receive retirement income. We propose a default decumulation solution that could be added to retirement plans to simplify decumulation choices in much…

The modern age poses many questions about the nature of privacy and civil liberties. Data flows across borders and through the hands of private companies, governments, and non-state actors. For the U.S. intelligence community, what do civil liberties protections look like in this digital age? These kinds of questions are on top of longstanding ones…

Abstract The objective of this paper is to explore how the external balance of the United States might evolve in future years as the economy emerges from the recession. We examine the issue both from the domestic perspective of the saving and investment balance and from the external side in terms of the basic determinants of…

With the national economy virtually immobilized as a result of the COVID-19 pandemic, it might seem like the crisis is going to mute the issue of regional economic divergence and its pattern of booming superstar cities and depressed, left-behind places. But don’t be so sure about that. In fact, the pandemic might intensify the unevenness…

Almost a year and a half after the Communist Party of China’s 18th Party Congress and one year into the term of the new government, China and the world are waiting for the new leadership’s plans to further transform China’s economy and to improve governance. What new reform measures should be the focus? Why are…

This November, after focusing on foreign policy concerns around the globe and congressional midterm elections at home, President Barack Obama will travel to Beijing to attend the APEC Economic Leaders’ Meeting in hopes of preserving and enhancing one of his key foreign policy achievements—the rebalance to Asia. Obama’s trip to China will be his first…

This November, after focusing on foreign policy concerns around the globe and congressional midterm elections at home, President Barack Obama will travel to Beijing to attend the APEC Economic Leaders’ Meeting in hopes of preserving and enhancing one of his key foreign policy achievements—the rebalance to Asia. Obama’s trip to China will be his first…

When President-elect Barack Obama assumes office in January, he will face a series of critical, complex and interrelated challenges in the Middle East. Each of these issues demands immediate attention: the ongoing war in Iraq; Iran’s regional and nuclear aspirations; the faltering Israeli-Palestinian peace process; and weak governments in Lebanon and Palestine.Recognizing the critical nature…

Walmart has been in the sustainability spotlight over the last few years, both for implementing its own efficiency measures and for raising the bar for industry at large. Some view these initiatives with skepticism because the

This woodland cabin in the Bohemia region of the Czech Repbulic keeps it simple but clever, with one end perched on a large rock.

A wooden kids' bike with a cork seat adapts to the child's necessity as it learns how to cycle. First as a tricycle, then a balance bike and finally as a bike with pedals B'Kid is a longlasting and beautiful object.

More and more people are working remotely. Now, alternative travel companies are offering what they are calling "co-workations" -- a combination of a creative business trip and inspirational adventure holiday for location-independent professionals.

Get your dark chocolate fix with less guilt. Balance Bar introduces a new energy bar featuring sustainably farmed cocoa beans.

Healthcare leaders and the public say how they would balance the NHS’ books

Sri Mulyani Indrawati, COO & Managing Director at the World Bank, says China's attempt to shift its economic model will require many policy adjustments.