SUBMISSION DEADLINE: SEPTEMBER 3, 2019 What: 4th CFPB Research Conference on Consumer Finance When: December 12th-13th, 2019 Where: Catholic University in Washington, DC In December 2019, the Consumer Financial Protection Bureau (CFPB) will host its fourth research conference on consumer finance at Catholic University in Washington, DC. Information on prior conferences can be found here: […]

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A bill shielding what is now Ohio's largest online school and its sponsor from the negative consequences of accepting thousands of former Electronic Classroom of Tomorrow students is headed to Gov. John Kasich for his signature.

'"Safe and well" outlines the actions the Government of South Australia is taking to support families at risk of entering the child protection system, protect children from harm when they come into care, and invest in young people to leave care with opportunities for a bright future.

Weinstein, Harvey, 1952-

Berlin (Louisen-Str. 53) : Published by F. Silber, [between 1800 and 1899]

London (No. 90, Cheapside, & 8, Pall Mall) : Published ... by Hurst, Robinson & Co., March 1st. 1824.

London (No. 90, Cheapside, & 8, Pall Mall) : Published ... by Hurst, Robinson & Co., March 1st. 1824.

[London], [1824]

[London] : [publisher not identified], [2019]

Steven Poser
Jun 1, 2003; 23:4420-4427
Cellular

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

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Mitochondrial fission catalyzed by dynamin-related protein 1 (Drp1) is necessary for mitochondrial biogenesis and maintenance of healthy mitochondria. However, excessive fission has been associated with multiple neurodegenerative disorders, and we recently reported that mice with smaller mitochondria are sensitized to ischemic stroke injury. Although pharmacological Drp1 inhibition has been put forward as neuroprotective, the specificity and mechanism of the inhibitor used is controversial. Here, we provide genetic evidence that Drp1 inhibition is neuroprotective. Drp1 is activated by dephosphorylation of an inhibitory phosphorylation site, Ser637. We identify Bβ2, a mitochondria-localized protein phosphatase 2A (PP2A) regulatory subunit, as a neuron-specific Drp1 activator in vivo. Bβ2 KO mice of both sexes display elongated mitochondria in neurons and are protected from cerebral ischemic injury. Functionally, deletion of Bβ2 and maintained Drp1 Ser637 phosphorylation improved mitochondrial respiratory capacity, Ca²⁺ homeostasis, and attenuated superoxide production in response to ischemia and excitotoxicity in vitro and ex vivo. Last, deletion of Bβ2 rescued excessive stroke damage associated with dephosphorylation of Drp1 S637 and mitochondrial fission. These results indicate that the state of mitochondrial connectivity and PP2A/Bβ2-mediated dephosphorylation of Drp1 play a critical role in determining the severity of cerebral ischemic injury. Therefore, Bβ2 may represent a target for prophylactic neuroprotective therapy in populations at high risk of stroke.

SIGNIFICANCE STATEMENT With recent advances in clinical practice including mechanical thrombectomy up to 24 h after the ischemic event, there is resurgent interest in neuroprotective stroke therapies. In this study, we demonstrate reduced stroke damage in the brain of mice lacking the Bβ2 regulatory subunit of protein phosphatase 2A, which we have shown previously acts as a positive regulator of the mitochondrial fission enzyme dynamin-related protein 1 (Drp1). Importantly, we provide evidence that deletion of Bβ2 can rescue excessive ischemic damage in mice lacking the mitochondrial PKA scaffold AKAP1, apparently via opposing effects on Drp1 S637 phosphorylation. These results highlight reversible phosphorylation in bidirectional regulation of Drp1 activity and identify Bβ2 as a potential pharmacological target to protect the brain from stroke injury.

Prohibitin (PHB) is a critical protein involved in many cellular activities. In brain, PHB resides in mitochondria, where it forms a large protein complex with PHB2 in the inner TFmembrane, which serves as a scaffolding platform for proteins involved in mitochondrial structural and functional integrity. PHB overexpression at moderate levels provides neuroprotection in experimental brain injury models. In addition, PHB expression is involved in ischemic preconditioning, as its expression is enhanced in preconditioning paradigms. However, the mechanisms of PHB functional regulation are still unknown. Observations that nitric oxide (NO) plays a key role in ischemia preconditioning compelled us to postulate that the neuroprotective effect of PHB could be regulated by NO. Here, we test this hypothesis in a neuronal model of ischemia–reperfusion injury and show that NO and PHB are mutually required for neuronal resilience against oxygen and glucose deprivation stress. Further, we demonstrate that NO post-translationally modifies PHB through protein S-nitrosylation and regulates PHB neuroprotective function, in a nitric oxide synthase-dependent manner. These results uncover the mechanisms of a previously unrecognized form of molecular regulation of PHB that underlies its neuroprotective function.

SIGNIFICANCE STATEMENT Prohibitin (PHB) is a critical mitochondrial protein that exerts a potent neuroprotective effect when mildly upregulated in mice. However, how the neuroprotective function of PHB is regulated is still unknown. Here, we demonstrate a novel regulatory mechanism for PHB that involves nitric oxide (NO) and shows that PHB and NO interact directly, resulting in protein S-nitrosylation on residue Cys⁶⁹ of PHB. We further show that nitrosylation of PHB may be essential for its ability to preserve neuronal viability under hypoxic stress. Thus, our study reveals a previously unknown mechanism of functional regulation of PHB that has potential therapeutic implications for neurologic disorders.

What happens when money is given directly to people living in dire conditions? Will children be better nourished? Will families be more productive or will they become dependent? Will economies grow stronger? Today, some 70 percent of the world population, most of which live in rural areas, have no access to adequate social protection measures. For this reason, FAO has [...]

Eradicating world hunger can only be achieved if food is safe, nutritious and of good quality. Eating unsafe food increases the chances of contracting diseases and can be, in some cases, deadly. Unsafe food can also lead to rejections causing food to be wasted, which then impacts on food security. One thing is certain: there can be no food security [...]

Many of us look back on our childhoods with warm feelings. But for more than 150 million girls and boys between the ages of 5 and 17 around the world, childhood means something else: poverty, a lack of education and working long hours in dangerous conditions.  

Illustrators are sharing artwork of Amabie, a spirit first popularized during the Edo period, on social media

Doctors and nurses are attaching smiling photos of themselves to the outside of their protective gear to maintain connections with patients

Speech by Mr Fehmi Mehmeti, Governor of the Central Bank of the Republic of Kosovo, at the press conference where the details of the measures taken by the CBK for maintaining health in the economy were given, Pristina, 3 April 2020.

Jharkhand bans 11 brands of pan masala for one year to protect public health  Zee NewsJharkhand bans 11 pan-masala brands on health concerns  Hindustan TimesJharkhand Bans 11 Pan Masala Brands for One Year to Protect Public Health&n...

A man goes from being sought by gangsters to being sought by God.

EUGENE Cairns (Herald Letters, May 6) feels that a fitting tribute to our NHS heroes would be to name hospitals and wards after those who have died in our service during the pandemic crisis.

Neglect cases in Child Protective Services often receive home-based interventions, but their success in preventing maltreatment recidivism has been elusive. Structured, behavioral skills models, such as SafeCare, are promising but have not been tested in full-scale implementation trials.

This cluster trial experiment demonstrates significant maltreatment recidivism reduction due to implementing the SafeCare model in a fully scaled-up statewide system. The findings support adopting the SafeCare model for these types of services. (Read the full article)

Rotavirus vaccine efficacy is lower in low-income settings with the highest child mortality due to diarrhea. In recently published clinical trials of rotavirus vaccines in Africa, waning of efficacy was also noted among children aged ≥1 year.

These data offer the first evidence of the duration of protection of the pentavalent rotavirus vaccine against severe rotavirus disease after routine use of the vaccine in a developing country setting. (Read the full article)

Clinical trials have demonstrated that prophylactic human papillomavirus (HPV) vaccines are highly effective in preventing HPV infection, but the impact of vaccination on HPV prevalence rates in real-world, community settings is uncertain.

This study provides evidence of a substantial decrease in the prevalence of vaccine-type HPV among young women and evidence of herd protection in a community only 4 years after the quadrivalent HPV vaccine was licensed. (Read the full article)

Infants with hypoxic-ischemic encephalopathy suffer a high rate (>40%) of death or moderate to severe disability, even after therapeutic hypothermia. High-dose erythropoietin (Epo) reduces brain injury and improves neurologic function in animal models of neonatal hypoxic-ischemic brain injury.

Multiple doses of Epo (up to 2500 U/kg intravenously) given in conjunction with hypothermia are well tolerated in newborns with HIE. Epo doses of 1000 U/kg intravenously in cooled infants produce plasma concentrations that are neuroprotective in animal studies. (Read the full article)

Data from several states that have implemented protective eyewear mandates at the scholastic level have shown a substantial reduction in eye injuries. However, there are no studies that critically evaluate the effectiveness of protective eyewear in girls’ field hockey.

Data collected from regional/national high school sports injury surveillance databases by certified athletic trainers has resulted in the largest prospective national study examining the effectiveness of mandated protective eyewear in reducing head, eye/orbital, concussive, and facial injuries performed to date. (Read the full article)

Prenatal cocaine exposure is associated with the trajectories of childhood behavior problems. Exposure effects may also be related to maternal use of other substances during pregnancy, and risk factors other than prenatal exposure may augment the detrimental cocaine effects.

The balance between cumulative risk and protective indexes predicts behavior outcomes, independent of prenatal drug exposure. A high protective index even with a high level of risks can mitigate the detrimental effects of drug exposure on behavior problem trajectory. (Read the full article)

Over the past decade, child welfare has focused on permanency for children through policy changes intended to reduce OOH placements. Yet little is known about recent trends in child maltreatment or children in OOH care.

Despite increased maltreatment investigations from 2000 through 2010, the population of children in OOH placements declined, while experiencing greater prior trauma and current emotional disturbance. These changes may have resulted in a smaller but more complex OOH population. (Read the full article)

Waning effectiveness of 5 doses of acellular pertussis vaccines is well documented after 6 years of age, but data are lacking for fewer doses in younger children.

In 2- to 3-month-old infants, 1 dose of the diphtheria–tetanus–acellular pertussis vaccine gave significant protection against hospitalized pertussis. The effectiveness of 3 doses decreased from 84% between 6 and 11 months to 59% after 3 years. (Read the full article)

Duration of protection among children and adolescents who have received the recombinant hepatitis B (HB) vaccination series is known to be long. Less is known about duration of protection of the vaccination series after being administered during infancy.

A robust response to a challenge dose of HB vaccine among adolescents indicates prolonged duration of protection against disease; the addition of a booster dose of HB vaccine to the routine immunization schedule for adolescents appears unnecessary. (Read the full article)

Prior studies have found a positive relationship between macro-level indicators of home foreclosure and child maltreatment rates. The extent to which home foreclosure may be associated with child protective services involvement at the micro level is largely unknown.

Foreclosure filings are positively associated with child protective services involvement. However, this is true of the periods before and after a filing, which are characterized by economic and other stress, which may drive this association more than the filing itself. (Read the full article)

A previous national study conducted over 2 seasons by this group of authors demonstrated the effectiveness of mandated protective eyewear in reducing eye/orbital, concussive, and head/facial injuries in high school girls' field hockey.

Data collected from regional/national high school sports injury surveillance databases by certified athletic trainers over 4 seasons has shown that nationally mandated protective eyewear results in a greater than 3-fold reduced risk of eye/orbital injuries in girls playing high school field hockey. (Read the full article)

Every time an education institution loses a funding source, rethinks program delivery, revises positions, incorporates technology, or changes curriculum, it is making an investment in change. These are sizable, important investments, so why not protect them?

Equipping teachers to help transgender students feel safe and included requires special training, advocates say.

Highly conserved PenI-type class A β-lactamase in pathogenic members of Burkholderia can evolve to extended-spectrum β-lactamase (ESBL), which exhibits hydrolytic activity towards third-generation cephalosporins, while losing its activity towards the original penicillin substrates. We describe three single-amino-acid-substitution mutations in the ArgS arginine-tRNA synthetase that confer extra antibiotic tolerance protection to ESBL-producing Burkholderia thailandensis. This pathway can be exploited to evade antibiotic tolerance induction in developing therapeutic measures against Burkholderia species, targeting their essential aminoacyl-tRNA synthetases.

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.

Google has made it easier to join the company's Advanced Protection Program, which is designed to stop the most sophisticated hackers from breaking into your Gmail account. Before you needed two security keys to enroll. Now you just need a smartphone.

Windows Defender is improving, but you still shouldn't rely on Windows 10's security tools as your sole means of protection. Many free third-party security apps are more effective at keeping you safe. We've tested 17 no-cost services to help you find the best free antivirus for protecting your PC.

SIM-swap fraud complaints seem to be on the rise with a growing number of victims coming forward to share their dreadful experiences. Vodacom offers some helpful tips.

With credit card fraud rising at an alarming rate in the first quarter of the year, the Ombudsman for Banking Services has provided 10 tips to avoid becoming a victim of scammers.

Extremely low or negative yields in global markets make it challenging for investors to generate meaningful returns, says Brian McMillan of Investec Structured Products.

The forthcoming bullying debate will prompt the first votes on lesbian, gay, bisexual, and transgender issues since the U.S. Supreme Court ruling on the right to same-sex marriage.

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