David E. Cade, J. Jacob Levenson, Robert Cooper, Rafael de la Parra, D. Harry Webb, and Alistair D. M. Dove

Whale sharks (Rhincodon typus Smith 1828) – the largest extant fish species – reside in tropical environments, making them an exception to the general rule that animal size increases with latitude. How this largest fish thrives in tropical environments that promote high metabolism but support less robust zooplankton communities has not been sufficiently explained. We used open-source inertial measurement units (IMU) to log 397 hours of whale shark behavior in Yucatan, Mexico, at a site of both active feeding and intense wildlife tourism. Here we show that the strategies employed by whale sharks to compensate for the increased drag of an open mouth are similar to ram-feeders five orders of magnitude smaller and one order of magnitude larger. Presumed feeding constituted 20% of the total time budget of four sharks, with individual feeding bouts lasting up to 11 consecutive hrs. Compared to normal, sub-surface swimming, three sharks increased their stroke rate and amplitude while surface feeding, while one shark that fed at depth did not demonstrate a greatly increased energetic cost. Additionally, based on time-depth budgets, we estimate that aerial surveys of shark populations should consider including a correction factor of 3 to account for the proportion of daylight hours that sharks are not visible at the surface. With foraging bouts generally lasting several hours, interruptions to foraging during critical feeding periods may represent substantial energetic costs to these endangered species, and this study presents baseline data from which management decisions affecting tourist interactions with whale sharks may be made.

Maria Stager, Nathan R. Senner, Bret W. Tobalske, and Zachary A. Cheviron

Flexibility in heat generation and dissipation mechanisms provides endotherms the ability to match their thermoregulatory strategy with external demands. However, the degree to which these two mechanisms account for seasonal changes in body temperature regulation is little explored. Here we present novel data on the regulation of avian body temperature to investigate how birds alter mechanisms of heat production and heat conservation to deal with variation in ambient conditions. We subjected Dark-eyed Juncos (Junco hyemalis) to chronic cold acclimations of varying duration and subsequently quantified their metabolic rates, thermal conductance, and ability to maintain normothermia. Cold-acclimated birds adjusted traits related to both heat generation (increased summit metabolic rate) and heat conservation (decreased conductance) to improve their body temperature regulation. Increases in summit metabolic rate occurred rapidly, but plateaued after one week of cold exposure. In contrast, changes to conductance occurred only after nine weeks of cold exposure. Thus, the ability to maintain body temperature continued to improve throughout the experiment, but the mechanisms underlying this improvement changed through time. Our results demonstrate the ability of birds to adjust thermoregulatory strategies in response to thermal cues and reveal that birds may combine multiple responses to meet the specific demands of their environments.

Background

Studies have linked mutations in genes encoding the eight-protein exocyst protein complex to kidney disease, but the underlying mechanism is unclear. Because Drosophila nephrocytes share molecular and structural features with mammalian podocytes, they provide an efficient model for studying this issue.

Background

Previous studies showed that Cdc42, a member of the prototypical Rho family of small GTPases and a regulator of the actin cytoskeleton, is critical for the normal development and health of podocytes. However, upstream regulatory mechanisms for Cdc42 activity in podocytes are largely unknown.

The cell surfaces of many bacteria carry filamentous polypeptides termed adhesins that enable binding to both biotic and abiotic surfaces. Surface adherence is facilitated by the exquisite selectivity of the adhesins for their cognate ligands or receptors and is a key step in niche or host colonization and pathogenicity. Streptococcus gordonii is a primary colonizer of the human oral cavity and an opportunistic pathogen, as well as a leading cause of infective endocarditis in humans. The fibrillar adhesin CshA is an important determinant of S. gordonii adherence, forming peritrichous fibrils on its surface that bind host cells and other microorganisms. CshA possesses a distinctive multidomain architecture comprising an N-terminal target-binding region fused to 17 repeat domains (RDs) that are each ∼100 amino acids long. Here, using structural and biophysical methods, we demonstrate that the intact CshA repeat region (CshA_RD1–17, domains 1–17) forms an extended polymeric monomer in solution. We recombinantly produced a subset of CshA RDs and found that they differ in stability and unfolding behavior. The NMR structure of CshA_RD13 revealed a hitherto unreported all β-fold, flanked by disordered interdomain linkers. These findings, in tandem with complementary hydrodynamic studies of CshA_RD1–17, indicate that this polypeptide possesses a highly unusual dynamic transitory structure characterized by alternating regions of order and disorder. This architecture provides flexibility for the adhesive tip of the CshA fibril to maintain bacterial attachment that withstands shear forces within the human host. It may also help mitigate deleterious folding events between neighboring RDs that share significant structural identity without compromising mechanical stability.

We previously produced a heavy-chain-only antibody (Ab) VH domain (V_HH)-displayed phage library from two alpacas that had been immunized with ricin toxoid and nontoxic mixtures of the enzymatic ricin toxin A subunit (RTA) and binding ricin toxin B subunit (RTB) (D. J. Vance, J. M. Tremblay, N. J. Mantis, and C. B. Shoemaker, J Biol Chem 288:36538–36547, 2013, https://doi.org/10.1074/jbc.M113.519207). Initial and subsequent screens of that library by direct enzyme-linked immunosorbent assay (ELISA) yielded more than two dozen unique RTA- and RTB-specific V_HHs, including 10 whose structures were subsequently solved in complex with RTA. To generate a more complete antigenic map of ricin toxin and to define the epitopes associated with toxin-neutralizing activity, we subjected the V_HH-displayed phage library to additional "pannings" on both receptor-bound ricin and antibody-captured ricin. We now report the full-length DNA sequences, binding affinities, and neutralizing activities of 68 unique V_HHs: 31 against RTA, 33 against RTB, and 4 against ricin holotoxin. Epitope positioning was achieved through cross-competition ELISAs performed with a panel of monoclonal antibodies (MAbs) and verified, in some instances, with hydrogen-deuterium exchange mass spectrometry. The 68 V_HHs grouped into more than 20 different competition bins. The RTA-specific V_HHs with strong toxin-neutralizing activities were confined to bins that overlapped two previously identified neutralizing hot spots, termed clusters I and II. The four RTB-specific V_HHs with potent toxin-neutralizing activity grouped within three adjacent bins situated at the RTA-RTB interface near cluster II. These results provide important insights into epitope interrelationships on the surface of ricin and delineate regions of vulnerability that can be exploited for the purpose of vaccine and therapeutic development.

Telomeres consist of TTAGGG repeats bound by protein complexes that serve to protect the natural end of linear chromosomes. Most cells maintain telomere repeat lengths by using the enzyme telomerase, although there are some cancer cells that use a telomerase-independent mechanism of telomere extension, termed alternative lengthening of telomeres (ALT). Cells that use ALT are characterized, in part, by the presence of specialized PML nuclear bodies called ALT-associated PML bodies (APBs). APBs localize to and cluster telomeric ends together with telomeric and DNA damage factors, which led to the proposal that these bodies act as a platform on which ALT can occur. However, the necessity of APBs and their function in the ALT pathway has remained unclear. Here, we used CRISPR/Cas9 to delete PML and APB components from ALT-positive cells to cleanly define the function of APBs in ALT. We found that PML is required for the ALT mechanism, and that this necessity stems from APBs’ role in localizing the BLM–TOP3A–RMI (BTR) complex to ALT telomere ends. Strikingly, recruitment of the BTR complex to telomeres in a PML-independent manner bypasses the need for PML in the ALT pathway, suggesting that BTR localization to telomeres is sufficient to sustain ALT activity.

In the past few decades, enterovirus A71 (EVA71) has caused devastating outbreaks in the Asia-Pacific region, resulting in serious sequelae in infected young children. No preventive or therapeutic interventions are currently available for curing EVA71 infection, highlighting a great unmet medical need for this disease. Here, we showed that one novel single-domain antibody (sdAb), F1, isolated from an immunized llama, could alleviate EVA71 infection both in vitro and in vivo. We also confirmed that the sdAb clone F1 recognizes EVA71 through a novel conformational epitope comprising the highly conserved region of VP3 capsid protein by using competitive-binding and overlapping-peptide enzyme-linked immunosorbent assays (ELISAs). Because of the virion’s icosahedral structure, we reasoned that adjacent epitopes must be clustered within molecular ranges that may be simultaneously bound by an engineered antibody with multiple valency. Therefore, two single-domain binding modules (F1) were fused to generate an sdAb-in-tandem design so that the capture of viral antigens could be further increased by valency effects. We showed that the tetravalent construct F1xF1-hFc, containing two sdAb-in-tandem on a fragment crystallizable (Fc) scaffold, exhibits more potent neutralization activity against EVA71 than does the bivalent sdAb F1-hFc by at least 5.8-fold. We also demonstrated that, using a human scavenger receptor class B member 2 (hSCARB2) transgenic mouse model, a half dose of the F1xF1-hFc provided better protection against EVA71 infection than did the F1-hFc. Thus, our study furnishes important insights into multivalent sdAb engineering against viral infection and provides a novel strategic deployment approach for preparedness of emerging infectious diseases such as EVA71.

Inhibition of BET protein bromodomains BD1 and BD2 produces unique phenotypes in disease models.

In the third quarter (Q3) of this year, Ho Chi Minh City (HCMC) saw no new supply of affordable housing entering the market. Low profit margin has made this segment unattractive to housing developers.

Publisher Wired Productions and developer Camel 101 have delayed psychological horror game, Those Who Remain, from May 15 to May 28 for the PlayStation 4, Xbox One and Windows PC via Steam. 

View the official release date trailer below:

Here is an overview of the game:

As the lights go out, the embers of darkness are stoked in the sleepy town of Dormont.

Whispers of disappearances carry through the town as a burgeoning, uneasy and irrational fear begins to spread and darkness comes to be an unwelcome reflection to Those Who Remain.

Some mistakes should never happen, not when your life is complete – and yet they do. Edward had the good life, a beautiful wife and the perfect little girl, yet finds himself several whiskeys down and driving through the night of Dormont to end his secret affair – in a bid to fix his mistakes.

As Edward pulls into the Golden Oak Motel, he is unaware just how much this night will change his life…

Key Features:

The horrors and darkness that thrive in the corner of every eye are torn loose…

Those Who Remain places you in an up-close, psychological horror story set in the sleepy town of Dormont – a town in a spiralling split from the fabric of reality, warped by darkness and the deeds of the Citizens who reside.

Confront the uncomfortable horrors reflected by the darkness and survive the night of Dormont as Edward is confronted with a test of his sanity, morality and the shadows of evil that lurks below.

• Darkness Has Eyes -Navigate and survive the encroaching darkness and stay in the protection of the light by any means[br]
• Worlds Torn Asunder – Pave your way ahead by moving between Dormont and its dark otherworldly counterpart to further solve the mysteries held within the dark
• Conscience of Choice – Choose to help any surviving citizens of Dormont you encounter or leave them to the darkness. Innocence cannot always be assumed, and the township of Dormont hides a cursed trove of secrets
• Savor your Sanity – Keep your sanity in check as you delve deeper into the darkness of Dormont – expected rules of the real world have been torn apart
• Follow your Path – Your decisions and choices will determine the fate of Edward, through multiple different branching outcomes

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443413/those-who-remain-delayed-to-may-28-for-ps4-xbox-one-and-steam/

Flying car hopefuls were meant to take off at a competition on a NASA airbase, but no team claimed the prize after a string of crashes and no-shows

In their search for killer apps, robotics companies should look at the amazing evolution of computers

A team of researchers from the University of Exeter has studied potential drivers of ‘rock juggling’ in two species of otters in zoo environments. Although elusive in the wild, otters are noted to be very playful and inquisitive animals based on observations in captivity. The animals are often seen lying on their backs and batting [...]

Touch is key to social relationships, and while coronavirus social distancing measures may limit physical interactions, there are still many ways to connect from afar, says evolutionary psychologist Robin Dunbar

Sierra Leone's president Julius Maada Bio has accused the main opposition party of orchestrating a spate of violent incidents, deepening a political standoff that risks undermining the country's efforts to contain a coronavirus outbreak.

Lyst has released Lyst Index for Q1 2020. Off-White has...

The post Off-White Remains World’s Hottest Brand In Lyst Index Q1 2020 appeared first on Man's World India.

Read our live coronavirus updates HERE Coronavirus: The symptoms

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Follow our live Covid-19 updates HERE Coronavirus: The symptoms

Barclays donates £250,000 to help our appeal to tackle hunger in virus crisis But demand grows amid growing reports one in five at risk of food poverty You can donate here virginmoneygiving.com/fund/FoodforLondonNOW

The global death toll from the coronavirus pandemic has surpassed 200,000, researchers have said.

Road traffic levels have increased despite the coronavirus lockdown remaining in place, new figures show.

Experts have said it is too early to reopen schools in the UK as it is still unclear how coronavirus spreads among children.

Social distancing will be expected "in every single work area" when the UK comes out of lockdown, according to Priti Patel.

Coronavirus lockdown measures could remain in place "for a very period of time", Downing Street has suggested.

Some social distancing measures will remain in place until a coronavirus vaccine has been developed, Michael Gove has said.

Nearly 100 children who were being targeted online by child abusers were saved by police in London during the first four weeks of the lockdown, Scotland Yard revealed today.

There is now an outbreak of COVID-19 linked to Canada Post's main plant in Calgary, according to Alberta Health Services.

Starring Rosamund Pike , Anya Taylor Joy , Aneurin Barnard and Sam Riley. It’s released in March.

The post RADIOACTIVE – Main Trailer appeared first on UKFilmNews.com.

8 May marks the 75th anniversary of the end of the second world war in Europe. Parts of the destruction that resulted from the fight for Berlin are still visible decades later

"Where there is life, there is hope," Garraway wrote in her emotional post

A string of other stars, like Emma's friends Octavia Spencer and Jonah Hill, have also contributed to the #WeThriveInside campaign

Liverpool legend Sir Kenny Dalglish has tested positive for Covid-19 but does not currently have any symptoms of the virus.

Leeds United great Norman Hunter remains "severely unwell" in hospital almost a week after being admitted with coronavirus.

Crystal Palace winger Andros Townsend says the Premier League season must finish in order to maintain the integrity of the competition.

National League clubs have voted in favour of ending the 2019-20 season at its current point.

Belgian top-flight clubs have postponed a vote to ratify the cancellation of the 2019-20 season, meaning a resumption remains possible.

Ed Woodward has indicated Manchester United fans will not be left paying the price for the coronavirus pandemic.

London Mayor Sadiq Khan is confident the NFL remains committed to London despite puling its planned matches from the capital in 2020.

The Premier League, the FA, the government and Sport England have pledged £9.56million to support grassroots football during the pandemic.

CORONAVIRUS can linger in the eyes for weeks and cause a host of problems especially for those who wear contact lenses. How can you protect your eyes during this difficult time and what are the symptoms to spot?

Chris Waller continues his big race domination, taking out The Everest at Randwick with Yes Yes Yes, on a day marked by protests and calls for change after an investigation revealed widespread slaughter and abuse of former racehorses in Australian abattoirs.

Churches and mosques are find ways to stay active.

The NBA has told teams it's moving forward in its plan to allow for practice facilities to reopen Friday in states where stay-at-home measures have been removed or relaxed.

LA84 Foundation has teamed with LAUSD to distribute soccer balls, basketballs, jump ropes and more to help students to stay active while school is closed.