French translation of the BIS press release about the BIS Quarterly Review, March 2018

To view more press releases, please visit http://www.snl.com/irweblinkx/news.aspx?iid=1024452.

The action potential (AP) waveform controls the opening of voltage-gated calcium channels and contributes to the driving force for calcium ion flux that triggers neurotransmission at presynaptic nerve terminals. Although the frog neuromuscular junction (NMJ) has long been a model synapse for the study of neurotransmission, its presynaptic AP waveform has never been directly studied, and thus the AP waveform shape and propagation through this long presynaptic nerve terminal are unknown. Using a fast voltage-sensitive dye, we have imaged the AP waveform from the presynaptic terminal of male and female frog NMJs and shown that the AP is very brief in duration and actively propagated along the entire length of the terminal. Furthermore, based on measured AP waveforms at different regions along the length of the nerve terminal, we show that the terminal is divided into three distinct electrical regions: A beginning region immediately after the last node of Ranvier where the AP is broadest, a middle region with a relatively consistent AP duration, and an end region near the tip of nerve terminal branches where the AP is briefer. We hypothesize that these measured changes in the AP waveform along the length of the motor nerve terminal may explain the proximal-distal gradient in transmitter release previously reported at the frog NMJ.

SIGNIFICANCE STATEMENT The AP waveform plays an essential role in determining the behavior of neurotransmission at the presynaptic terminal. Although the frog NMJ is a model synapse for the study of synaptic transmission, there are many unknowns centered around the shape and propagation of its presynaptic AP waveform. Here, we demonstrate that the presynaptic terminal of the frog NMJ has a very brief AP waveform and that the motor nerve terminal contains three distinct electrical regions. We propose that the changes in the AP waveform as it propagates along the terminal can explain the proximal-distal gradient in transmitter release seen in electrophysiological studies.

As the clock ticks on the Millennium Development Goals (MDGs), the world community is deep in discussion over the successor global framework. Many current practices are damaging the planet’s ecosystems and the biodiversity essential for healthy food production. By 2050 an estimated additional 2 billion people will be living on Earth.  This means food production must rise by 60%. From 8 MDGs [...]

Climate change is what most of us perceive as the top global threat, and the dangers it poses affect present and future generations alike.  How global warming is threatening the planet has been a theme in children’s books for all ages for some time.   How everyone, especially today’s youth, can make a difference to the future of the world [...]

Perhaps from outer space, it is easy to get the perspective that we only have one earth and that it is succumbing to climate change. Seeing the earth from space though is a feat that, unfortunately, most of us will never accomplish. We have to rely on Astronaut Thomas Pesquet and the other brave women and men astronauts to provide [...]

Differential detergent fractionation of cells is a rapid method for extraction of cytoplasmic and nuclear proteins in preparation of an immunoprecipitation. This method can be applied for use of adherent or suspension cells and can significantly reduce nonspecific background in an immunoprecipitation by separation of cellular compartments into individual fractions. The lysis of cells by differential detergents permits the rapid extraction of proteins from the cytoplasm (digitonin), the cytoplasmic membranes, and organelles (Triton X-100), and nucleoplasm (Tween/DOC), facilitated through the use of distinct extraction buffers. Cytoplasmic and nuclear matrix proteins as well as DNA are left behind during the detergent-based extraction.

In this protocol, DNA fragments are separated according to size by electrophoresis through low-melting-temperature agarose, and then recovered by melting the agarose and extracting with phenol:chloroform. The protocol works best for DNA fragments ranging in size from 0.5 to 5.0 kb. Yields of DNA fragments outside this range are usually lower, but often are sufficient for many purposes.

Visit our four downtown locations where you can taste euphoria in our creative and delicious all natural ice-cream, yogurts and sorbets!

Bike the Sites of the Nation's Capital! It's the fun and easy way to get to get up close and personal with Washington's landmarks

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Discover the real George Washington through his restored home and gardens, over 1,000 artifacts, and an immersive Revolutionary War "snow" experience

Voted "Washington's Best Tour" by Washingtonian Magazine. See the best of Washington aboard on our 2 hour tour with live narration

Take a bus tour to the sites of movies and TV shows. Your guide will entertain you as you visit over 30 locations used in West Wing, The Exorcist and more

Get up close to the DC sites on a Segway! Segs in the City offers daily guided 1 hour and 2 hour Segway tours and rentals. Join the fun!

The Best Museum Experience of All Things Washington, D.C. Experience the stories behind the people and events of the Nation's Capital.

Remarks (delivered via videoconference) by Mr John C Williams, President and Chief Executive Officer of the Federal Reserve Bank of New York, at the Economic Club of New York, New York City, 16 April 2020.

A proposed class action lawsuit has been filed in B.C. Supreme Court which, if successful, could mean every ICBC-insured motorist and crash victim will be in line for a share of almost $1 billion. 

Central Bank of Chile Working Papers by Tomás Gómez, Alejandro Jara and David Moreno

CNA Staff, May 5, 2020 / 02:01 pm (CNA).- After complaints that a pro-life event held by the Aberdeen Life Ethics Society violated a 'safe space policy', an investigation has resulted in no action being taken against the pro-life group.

Ales held an event March 12 called “Does Abortion Violate Human Rights?”, about which some students at Aberdeen University complained. Among the complaints were that it included “highly graphic material,” the Gaudie, Aberdeen University's student paper, reported April 30.

Ales told the Gaudie that “In response to these unfounded complaints, we provided [the Aberdeen University Students' Association] with various examples of our efforts to warn attendees about sensitive content. We maintain that these efforts fulfilled our obligation to caution anyone who might be uncomfortable with an honest discussion of abortion (i.e., the intentional killing of antenatal humans by vacuum aspiration, poisoning, and/or dismemberment).”

“Thankfully, AUSA was satisfied with our defence against these vexatious complaints and will take no action against us. We look forward to organising future public events about the ethical importance of human life in the womb, and we pledge to continue to offer clear and explicit content warnings about the grisly reality of abortion,” the pro-life group continued.

Ausa told complainants that “the issues have been raised with ALES and they have provided assurances to AUSA that clearer and more explicit content warnings, and cautions will be issued, prior to showing similar videos in the future,” and that “on this basis we have concluded that no further action will be taken by AUSA against ALES and this matter is now concluded.”

One of those who complained about the event, Martin Le Brech, called Ausa's decision “very disappointing,” adding: I hope AUSA will thoroughly scrutinise ALES' activities and listen to the wider University community that is utterly embarrassed such misinformation and graphic contents are regularly spread on campus. We need to make sure our University is a safe space for everybody, free of bigotry and insidious violence.”

And Leah Robb, president of the Pro-Choice Society, said that if Ales “continue with similar events/demonstrations I am considering launching another complaint to AUSA.”

Ales was granted affiliation by the Aberdeen student association in May 2019, following a protracted disagreement.

In October 2018 Ausa had prevented the affiliation of Ales, citing its own pro-choice policy which it adopted in 2017. The policy says, in part, that “Ausa should oppose the unreasonable display of pro-life material within campus and at Ausa events.”

The move limited Ale's access to funds and venues at the university.

After failing to have the policy changed, Ales filed a lawsuit in April 2019 against Ausa and the university, “alleging unlawful discrimination against the society and the violation of rights protected by UK law.”

In its lawsuit, Ales charged that Ausa's no platform policy violates the Equality Act 2010 and the Human Rights Act 1998 by restricting “the freedoms of association and belief for certain students on the basis of an ideological litmus test.”

According to the Gaudie, Ales received “a financial pay-out” from Ausa over the matter.

After receiving affiliation, Ales stated: “We look forward to actively engaging with the student body and working to foster a civil yet honest conversation about the vitally important ethical issues surrounding human life. While there are some intolerant students who wanted our society to fail … we truly believe that there are many more students on this campus who are willing to take a fair-minded approach to this debate. These are the students we’ve heard from all along the way – they may not agree with our position, but they adamantly believe that we should be free to espouse our beliefs on campus.”

Pro-life groups at other Scottish universities have faced similar problems.

In 2018 the University of Strathclyde (in Glasgow) lifted a ban on pro-life groups following legal pressure. Strathclyde Sudents for Life argued that the student associaton's no platforming policy violated the Equality Act 2010 “by directly discriminating against a group of students based on their beliefs.”

Glasgow Students for Life were barred from affiliation by the Glasgow University's Students' Representative Council in November 2018.

In March 2018 a joint committee on human rights of the UK parliament noted troubling barriers to free speech at the nation's universities, writing: “Whilst the original intention behind safe space policies may have been to ensure that minority or vulnerable groups can feel secure, in practice the concept of safe spaces has proved problematic, often marginalising the views of minority groups.”

Tampico, Mexico :: After a five-week maintenance period, Logos Hope resumes her schedule in a new port, to an enthusiastic reception.

Australia's central bank has predicted that the country is facing its biggest economic contraction on record.

The head of the International Monetary Fund said Friday that previous estimates for the world economy to contract by three percent this year were too optimistic.

Members of OM Costa Rica help a 90-year-old woman get to her doctor appointment at a hospital six hours away from her home.

NICOLA Sturgeon said she does not expect police to be “routinely patrolling office blocks” as sweeping new enforcement powers come into force to include workplaces flouting social distancing rules.

Sunday, April 19, 2020.

A pair of new studies find that, when given a choice, white parents tend to send their children to schools that are predominantly white.

What does it take to get students interested in learning entrepreneurial skills?

Infants and children with diagnosed food allergy are at risk for acute, potentially life-threatening symptoms. Limited data are available on the frequency, severity, and circumstances of reactions and caretaker medical response.

This study describes food allergy reaction frequency, circumstances, and response. Pitfalls that may inform improved anticipatory guidance included lack of vigilance, misreading ingredient labels, allergen cross-contact, nonaccidental allergen feeding, and underutilization of epinephrine for severe reactions. (Read the full article)

Materialism and life satisfaction are known to be associated with each other. Research among adults has shown that materialism and life satisfaction negatively affect each other, leading to a downward spiral.

In contrast to research conducted among adults, no longitudinal effect of materialism on life satisfaction was found for 8- to 11-year-olds. However, life satisfaction did negatively affect materialism, but only for children who were frequently exposed to advertising. (Read the full article)

Antimicrobials are a medication class frequently implicated in pediatric adverse drug reactions (ADRs). Trimethoprim-sulfamethoxazole (TMP-SMX) is long recognized as a contributor to the burden of these undesired and unpredictable events.

TMP-SMX ADRs increased from 2000 to 2009, with the majority of children taking the antibiotic for skin and soft tissue infections. The significant increase in TMP-SMX prescribing for these infections may result in a continued increase of associated ADRs. (Read the full article)

National asthma treatment guidelines include the recommendation that all asthma patients receive a written asthma action plan. No previous study has sought to examine the readability, suitability, and content of asthma action plans within a nationally representative sample.

Although variability was found across written asthma action plans, and improvements in readability, suitability, and content are needed, there were also many common elements that would support a move to a single universal standard action plan. (Read the full article)

Previous evaluations of local reactions after the fifth diphtheria-tetanus-acellular pertussis (DTaP) vaccine in children 4 to 6 years of age have revealed that vaccination in the thigh is associated with a lower risk of local reactions compared with vaccination in the arm.

Among children 12 to 35 months of age, injection of DTaP vaccine in the thigh is associated with a lower risk of local reactions compared with vaccination in the arm. (Read the full article)

Hospitalized pediatric patients are often exposed to many medications during an inpatient admission. Drug–drug interactions may increase the risk of developing medication-related adverse drug events, leading to serious clinical morbidity and mortality.

Exposure to "major" potential drug–drug interactions occurs in 41% of pediatric hospitalizations in children’s hospitals. One-half of all these exposures were due to less common specific drug pairs (≤3% of patients exposed per hospital day) and thus may be less clinically familiar. (Read the full article)

Recent studies highlight the abundance of commensal coagulase-negative staphylococci (CoNS) on healthy skin. Evidence suggests that CoNS actively shape the skin immunological and microbial milieu to resist colonization or infection by opportunistic pathogens, including methicillin resistant Staphylococcus aureus (MRSA), in a variety of mechanisms collectively termed colonization resistance. One potential colonization resistance mechanism is the application of quorum sensing, also called the Accessory Gene Regulator (agr) system, which is ubiquitous among staphylococci. Common and rare CoNS make autoinducing peptides (AIPs) that function as MRSA agr inhibitors, protecting the host from invasive infection. In a screen of CoNS spent media we found that Staphylococcus simulans, a rare human skin colonizer and frequent livestock colonizer, released potent inhibitors of all classes of MRSA agr signaling. We identified three S. simulans agr classes, and have shown intraspecies cross-talk between non-cognate S. simulans agr types for the first time. The S. simulans AIP-I structure was confirmed, and the novel AIP-II and AIP-III structures were solved via mass spectrometry. Synthetic S. simulans AIPs inhibited MRSA agr signaling with nanomolar potency. S. simulans in competition with MRSA reduced dermonecrotic and epicutaneous skin injury in murine models. Addition of synthetic AIP-I also effectively reduced MRSA dermonecrosis and epicutaneous skin injury in murine models. These results demonstrate potent anti-MRSA quorum sensing inhibition by a rare human skin commensal, and suggest that cross-talk between CoNS and MRSA may be important in maintaining healthy skin homeostasis and preventing MRSA skin damage during colonization or acute infection.

Durlobactam (DUR, also known as ETX2514) is a novel β-lactamase inhibitor with broad activity against Ambler class A, C, and D β-lactamases. Addition of DUR to sulbactam (SUL) in vitro restores SUL activity against clinical isolates of Acinetobacter baumannii. The safety and pharmacokinetics (PK) of DUR alone and with SUL and/or imipenem/cilastatin (IMI/CIL) were evaluated in healthy subjects. This was a randomized, placebo-controlled study. In Part A, subjects including an elderly cohort (DUR 1 g) received single ascending doses of DUR 0.25-8 g. In Part B, multiple ascending dose of DUR 0.25-2 g were administered every 6 hours (q6h) for 29 doses. In Parts C and D, the drug-drug interaction (DDI) potential, including safety, of DUR (1 g) with SUL (1 g) and/or IMI/CIL (0.5/0.5 g) was investigated after single and multiple doses. Plasma and urine concentrations of DUR, SUL, and IMI/CIL were determined. Among 124 subjects, DUR was generally safe and well tolerated either alone or in combination with SUL and/or IMI/CIL. After single and multiple doses, DUR demonstrated linear dose proportional exposure across the studied dose ranges. Renal excretion was a predominant clearance mechanism. No drug:drug interaction potential was identified between DUR and SUL and/or IMI/CIL. SUL-DUR, 1 g (of each component) administered q6h with a 3 hour IV infusion, is under development for the treatment of serious infections due to A. baumannii.

Two non-amidated host defence peptides named Pin2[G] and FA1 were evaluated against three types of pathogenic bacteria; two isolated from diabetic foot ulcer patients, Staphylococcus aureus UPD13 and Pseudomonas aeruginosa UPD3, and another from a commercial collection, Salmonella enterica serovar Typhimurium (ATCC 14028). In vitro experiments showed that the antimicrobial performance of the synthetic peptides, Pin2[G] and FA1, was modest, although FA1 was more effective than Pin2[G]. In contrast Pin2[G] had superior in vivo anti-infective activity to FA1 in rabbit wound infections by the diabetic foot ulcer pathogens S. aureus UPD13 and P. aeruginosa UPD3. Indeed, Pin2[G] reduced bacterial colony counts of both S. aureus UPD13 and P. aeruginosa UPD3 by >100,000-fold after 48-72 h on skin wounds of infected rabbits, while in similar infected wounds, FA1 had no major effects at 72-96 h of treatment. Ceftriaxone was equally effective vs. Pseudomonas but less effective vs. S. aureus infections. Additionally, the two peptides were evaluated in mice against intragastrically inoculated S. enterica ser. Typhimurium (ATCC 14028). Only Pin2[G], at 0.56 mg/kg, was effective in reducing systemic (liver) infection by >67-fold, equivalent to the effect of treatment with levofloxacin. Pin2[G] showed superior immunomodulatory activity in increasing chemokine production by a human bronchial cell line and suppressing poly(IC)-induced pro-inflammatory IL6 production. These data showed that the in vitro antimicrobial activity of these peptides was not correlated with their in vivo anti-infective activity, and suggest that other factors such as immunomodulatory activity were more important.

Peroxidases are a group of heterogeneous family of enzyme that plays diverse biological functions. Ascorbate peroxidase is a redox enzyme that is reduced by trypanothione, which plays a central role in the redox defence system of Leishmania. In view of developing new and novel therapeutics, we have performed in silico studies in order to search for ligand library and identification of new drug candidates and its physiological role against promastigotes and intracellular amastigotes of Leishmania donovani. Our results demonstrated that the selected inhibitor ZINC96021026 has significant anti-leishmanial effect and effectively killed both free and intracellular forms of the parasite. ZINC96021026 was found to be identical to ML-240, a selective inhibitor of Valosin-containing protein (VCP) or p97, a member of AAA-ATPase protein family which was derived from the scaffold of DBeQ, targeting the D2-ATPase domain of the enzyme. ZINC96021026 (ML-240) thus have broad range of cellular functions, thought to be derived from its ability to unfold proteins or disassemble protein complexes besides inhibiting the ascorbate peroxidase activity. ML-240 may inhibits the parasite's ascorbate peroxidase leading to extensive apoptosis and inducing generation of reactive oxygen species. Taken together, our results demonstrated that ML-240 could be an attractive therapeutic option for treatment against leishmaniasis.

OBJECTIVES:

Our first aim was to examine baseline differences in body dissatisfaction, depression, and anxiety symptoms by gender, age, and Tanner (ie, pubertal) stage. Our second aim was to test for changes in youth symptoms over the first year of receiving gender-affirming hormone therapy. Our third aim was to examine potential differences in change over time by demographic and treatment characteristics. Youth experiences of suicidal ideation, suicide attempt, and nonsuicidal self-injury (NSSI) are also reported.

Former Hearts chairman Leslie Deans has urged the club to take legal action against the SPFL as well as those who voted to end the season early, effectively relegating the Jambos.

Teachers need coaching from proactive and intentional leaders who see everything in their buildings as their responsibility, writes guest blogger Michael Sonbert. Until then, teachers will bear the brunt of our national criticism.

As the world continues to face the ongoing impacts of the global coronavirus pandemic, Penn State President Eric Barron outlined Friday the University’s actions over the past five months to address the challenges, protect the health and safety of the University community, and prepare for the future.

Four Penn State World Campus energy and sustainability policy majors spent the year working with Pennsylvania boroughs to inventory greenhouse gas emissions, and coming up with climate action plans for reducing them.

Following a March 19 announcement by Pennsylvania Gov. Tom Wolf to end physical operations at many businesses statewide, Penn State Executive Vice President and Provost Nicholas P. Jones shared the following message with the University community.

Penn State Executive Vice President and Provost Nicholas P. Jones has shared a message updating the University community on steps being taken to monitor the evolving worldwide coronavirus outbreak and prepare for the safety and well-being of students, faculty, staff and visitors.

Following UN Special Representative for Libya Bernardino León’s announcement of a new Government of National Accord, Joost Hiltermann, Crisis Group’s Middle East and North Africa Program Director, had the following reaction.

Today, 98% of households with 2- to 8-year-old children include a mobile device, like smartphones, tablets, and iPods or other smart-mobile devices, an increase from 75% in 2013. We are really connected, but not connecting at all.