For 2020 "Sports Mom of the Year," Kyle Neddenriep received heartfelt nominations from fathers, mothers, husbands, sons, daughters and friends.

The past several weeks have brought a whirlwind of emotions for the Loggan family as beloved North Central AD Paul Loggan died from COVID-19.

Dani Bereznay, one of the fastest esports Formula 1 drivers in the world, talks about taking on real-life F1 drivers.

In 1961, F1 driver Sir Stirling Moss won the hearts of the nation to be crowned Sportsview Personality winner.

With latest scores and headlines sent straight to your device, personalisation and much more, ensure you have a great sporting life with BBC Sport.

Formula E's new esports competition will be streamed live across BBC platforms.

In one weekend Stoffel Vandoorne manages to qualify on pole position in two races and crash out of both of them.

Formula 1 chairman Chase Carey has admitted that the sport's owners are preparing for "the remote possibility of no racing in 2020".

You might never think of Germany as a cricket nation, but there has been a huge transformation over the past five years.

Sporting events in the Netherlands will have to take place without fans until there is a coronavirus vaccine, Dutch Health Minister Hugo de Jonge says.

Public transport usage won't recover to pre-Covid19 levels once the lockdown ends, a survey suggests.

"Extreme caution" will be needed when the UK eases lockdown, Grant Shapps says as he announces transport measures.

On 4 May, 2020 Minister Nathi Mthethwa hosted a briefing, updating the public on the Department of Sports, Arts and Cultures Corona relief funds, and the received applications.

Arsene Wenger says Liverpool will be regarded as 2019/20 Premier League winners even if the season is abandoned because of the coronavirus.

Rafael Nadal insists all players, including Novak Djokovic, will need to take a coronavirus vaccine should one become available.

Andy Robertson admits he would "love" the chance to play for Scottish giants Celtic one day.

The Vuelta a Espana organisers have confirmed that a race already rescheduled and shortened would also now cut its foray into neighbouring Portugal from the 2020 itinerary.

Former England opener Alex Hales is confident he has matured as a player and believes he is ready to make a return to international cricket.

It isn’t surprising that former Springbok tighthead Richard Bands is remembered mainly for one bullocking run for the Springboks in Dunedin in 2003.

India top-order batsman Rohit Sharma is hopeful their tour to Australia at the end of 2020 is allowed to proceed.

France defender Samuel Umtiti has picked up a calf injury in just the second session since Barcelona returned to training from the cornonavirus quarantine.

Salomon Rondon says he was on his way to joining Manchester United in January only for Dalian Professional to block the move.

Danny Jordaan says it would be massively complicated to ensure the safety of supporters should the PSL return while Covid-19 is still prevalent in South Africa.

Police in Haiti are investigating allegations that the president of the national football federation raped teenage girls.

Australia's Super Rugby competition is planning for an early July return, a spokesman has said.

Six-time world champion Lewis Hamilton has said he feels "fresher than ever" following an unexpected break from Formula One.

The South African Football Association has confirmed the appointment of advocate Tebogo Motlanthe as new acting CEO.

Philadelphia Phillies star Bryce Harper believes Major League Baseball should relax its "dumb" rule preventing top players from competing in the Olympics.

AC Milan have revealed that none of their first-team footballers or staff were positive for coronavirus.

The genial young administrator with a burgeoning reputation chuckles when it's pointed out to him that he can't seem to shake off 'working' for some of South Africa's biggest businessmen.

Including a shoulder-brush with a livid Steve Waugh, Rob Houwing remembers witnessing SA's heroic finish to an otherwise stormy 2001/02 Australian tour.

Former Proteas head coach Ray Jennings is adamant Aiden Markram should be chosen as Faf du Plessis' replacement as captain of the Test team.

Sundowns coach Pitso Mosimane says the premature return of football, even behind closed doors, poses a number of potential problems.

NZ Rugby CEO Mark Robinson says there is still no clarity on the prospects for Test rugby in 2020, but said they will explore every avenue.

Passport renewal isn't quite simple, but it is straightforward. You just need to prepare with the right forms, supporting documentation, and some patience.

The post Passport Renewal: Everything American Travelers Need to Know appeared first on Vagabondish.

Part of the Sport Relief promo for the BBC UK Homepage

Part of the Sport Relief promo for the BBC UK Homepage

Part of the Sport Relief promo for the BBC UK Homepage

Sport Relief is back and you can get involved right now by signing up and getting sponsored for the Mile on March 16.

Sulfur is essential for biological processes such as amino acid biogenesis, iron–sulfur cluster formation, and redox homeostasis. To acquire sulfur-containing compounds from the environment, bacteria have evolved high-affinity uptake systems, predominant among which is the ABC transporter family. Theses membrane-embedded enzymes use the energy of ATP hydrolysis for transmembrane transport of a wide range of biomolecules against concentration gradients. Three distinct bacterial ABC import systems of sulfur-containing compounds have been identified, but the molecular details of their transport mechanism remain poorly characterized. Here we provide results from a biochemical analysis of the purified Escherichia coli YecSC-FliY cysteine/cystine import system. We found that the substrate-binding protein FliY binds l-cystine, l-cysteine, and d-cysteine with micromolar affinities. However, binding of the l- and d-enantiomers induced different conformational changes of FliY, where the l- enantiomer–substrate-binding protein complex interacted more efficiently with the YecSC transporter. YecSC had low basal ATPase activity that was moderately stimulated by apo FliY, more strongly by d-cysteine–bound FliY, and maximally by l-cysteine– or l-cystine–bound FliY. However, at high FliY concentrations, YecSC reached maximal ATPase rates independent of the presence or nature of the substrate. These results suggest that FliY exists in a conformational equilibrium between an open, unliganded form that does not bind to the YecSC transporter and closed, unliganded and closed, liganded forms that bind this transporter with variable affinities but equally stimulate its ATPase activity. These findings differ from previous observations for similar ABC transporters, highlighting the extent of mechanistic diversity in this large protein family.

Purinergic signaling by extracellular ATP regulates a variety of cellular events and is implicated in both normal physiology and pathophysiology. Several molecules have been associated with the release of ATP and other small molecules, but their precise contributions have been difficult to assess because of their complexity and heterogeneity. Here, we report on the results of a gain-of-function screen for modulators of hypotonicity-induced ATP release using HEK-293 cells and murine cerebellar granule neurons, along with bioluminescence, calcium FLIPR, and short hairpin RNA–based gene-silencing assays. This screen utilized the most extensive genome-wide ORF collection to date, covering 90% of human, nonredundant, protein-encoding genes. We identified two ABCG1 (ABC subfamily G member 1) variants, which regulate cellular cholesterol, as modulators of hypotonicity-induced ATP release. We found that cholesterol levels control volume-regulated anion channel–dependent ATP release. These findings reveal novel mechanisms for the regulation of ATP release and volume-regulated anion channel activity and provide critical links among cellular status, cholesterol, and purinergic signaling.

Numerous zinc ectoenzymes are metalated by zinc and activated in the compartments of the early secretory pathway before reaching their destination. Zn transporter (ZNT) proteins located in these compartments are essential for ectoenzyme activation. We have previously reported that ZNT proteins, specifically ZNT5–ZNT6 heterodimers and ZNT7 homodimers, play critical roles in the activation of zinc ectoenzymes, such as alkaline phosphatases (ALPs), by mobilizing cytosolic zinc into these compartments. However, this process remains incompletely understood. Here, using genetically-engineered chicken DT40 cells, we first determined that Zrt/Irt-like protein (ZIP) transporters that are localized to the compartments of the early secretory pathway play only a minor role in the ALP activation process. These transporters included ZIP7, ZIP9, and ZIP13, performing pivotal functions in maintaining cellular homeostasis by effluxing zinc out of the compartments. Next, using purified ALP proteins, we showed that zinc metalation on ALP produced in DT40 cells lacking ZNT5–ZNT6 heterodimers and ZNT7 homodimers is impaired. Finally, by genetically disrupting both ZNT5 and ZNT7 in human HAP1 cells, we directly demonstrated that the tissue-nonspecific ALP-activating functions of both ZNT complexes are conserved in human cells. Furthermore, using mutant HAP1 cells, we uncovered a previously-unrecognized and unique spatial regulation of ZNT5–ZNT6 heterodimer formation, wherein ZNT5 recruits ZNT6 to the Golgi apparatus to form the heterodimeric complex. These findings fill in major gaps in our understanding of the molecular mechanisms underlying zinc ectoenzyme activation in the compartments of the early secretory pathway.

CJ Fielding
Aug 1, 1997; 38:1503-1521
Reviews

Michael Dean
Jul 1, 2001; 42:1007-1017
Thematic Reviews

CJ Fielding
Feb 1, 1995; 36:211-228
Reviews

Following its evoked release, dopamine (DA) signaling is rapidly terminated by presynaptic reuptake, mediated by the cocaine-sensitive DA transporter (DAT). DAT surface availability is dynamically regulated by endocytic trafficking, and direct protein kinase C (PKC) activation acutely diminishes DAT surface expression by accelerating DAT internalization. Previous cell line studies demonstrated that PKC-stimulated DAT endocytosis requires both Ack1 inactivation, which releases a DAT-specific endocytic brake, and the neuronal GTPase, Rit2, which binds DAT. However, it is unknown whether Rit2 is required for PKC-stimulated DAT endocytosis in DAergic terminals or whether there are region- and/or sex-dependent differences in PKC-stimulated DAT trafficking. Moreover, the mechanisms by which Rit2 controls PKC-stimulated DAT endocytosis are unknown. Here, we directly examined these important questions. Ex vivo studies revealed that PKC activation acutely decreased DAT surface expression selectively in ventral, but not dorsal, striatum. AAV-mediated, conditional Rit2 knockdown in DAergic neurons impacted baseline DAT surface:intracellular distribution in DAergic terminals from female ventral, but not dorsal, striatum. Further, Rit2 was required for PKC-stimulated DAT internalization in both male and female ventral striatum. FRET and surface pulldown studies in cell lines revealed that PKC activation drives DAT-Rit2 surface dissociation and that the DAT N terminus is required for both PKC-mediated DAT-Rit2 dissociation and DAT internalization. Finally, we found that Rit2 and Ack1 independently converge on DAT to facilitate PKC-stimulated DAT endocytosis. Together, our data provide greater insight into mechanisms that mediate PKC-regulated DAT internalization and reveal unexpected region-specific differences in PKC-stimulated DAT trafficking in bona fide DAergic terminals.

Purinergic signaling by extracellular ATP regulates a variety of cellular events and is implicated in both normal physiology and pathophysiology. Several molecules have been associated with the release of ATP and other small molecules, but their precise contributions have been difficult to assess because of their complexity and heterogeneity. Here, we report on the results of a gain-of-function screen for modulators of hypotonicity-induced ATP release using HEK-293 cells and murine cerebellar granule neurons, along with bioluminescence, calcium FLIPR, and short hairpin RNA–based gene-silencing assays. This screen utilized the most extensive genome-wide ORF collection to date, covering 90% of human, nonredundant, protein-encoding genes. We identified two ABCG1 (ABC subfamily G member 1) variants, which regulate cellular cholesterol, as modulators of hypotonicity-induced ATP release. We found that cholesterol levels control volume-regulated anion channel–dependent ATP release. These findings reveal novel mechanisms for the regulation of ATP release and volume-regulated anion channel activity and provide critical links among cellular status, cholesterol, and purinergic signaling.

Membrane-bound proteins have been proposed to mediate the transport of long-chain FA (LCFA) transport through the plasma membrane (PM). These proposals are based largely on reports that PM transport of LCFAs can be blocked by a number of enzymes and purported inhibitors of LCFA transport. Here, using the ratiometric pH indicator (2',7'-bis-(2-carboxyethyl)-5-(and-6-)-carboxyfluorescein and acrylodated intestinal FA-binding protein-based dual fluorescence assays, we investigated the effects of nine inhibitors of the putative FA transporter protein CD36 on the binding and transmembrane movement of LCFAs. We particularly focused on sulfosuccinimidyl oleate (SSO), reported to be a competitive inhibitor of CD36-mediated LCFA transport. Using these assays in adipocytes and inhibitor-treated protein-free lipid vesicles, we demonstrate that rapid LCFA transport across model and biological membranes remains unchanged in the presence of these purported inhibitors. We have previously shown in live cells that CD36 does not accelerate the transport of unesterified LCFAs across the PM. Our present experiments indicated disruption of LCFA metabolism inside the cell within minutes upon treatment with many of the "inhibitors" previously assumed to inhibit LCFA transport across the PM. Furthermore, using confocal microscopy and a specific anti-SSO antibody, we found that numerous intracellular and PM-bound proteins are SSO-modified in addition to CD36. Our results support the hypothesis that LCFAs diffuse rapidly across biological membranes and do not require an active protein transporter for their transmembrane movement.