Exiting low inflation traps by "consensus": nominal wages and price stability - Speech by Luiz A Pereira da Silva and Benoît Mojon, based on the keynote speech at the Eighth High-level Policy Dialogue between the Eurosystem and Latin American Central Banks, Cartagena de Indias, Colombia, 28-29 November 2019.

Op-ed by Agustín Carstens published in the Financial Times on 29 March 2020.

Synaptic dysfunction provoking dysregulated cortical neural circuits is currently hypothesized as a key pathophysiological process underlying clinical manifestations in Alzheimer's disease and related neurodegenerative tauopathies. Here, we conducted PET along with postmortem assays to investigate time course changes of excitatory and inhibitory synaptic constituents in an rTg4510 mouse model of tauopathy, which develops tau pathologies leading to noticeable brain atrophy at 5-6 months of age. Both male and female mice were analyzed in this study. We observed that radiosignals derived from [¹¹C]flumazenil, a tracer for benzodiazepine receptor, in rTg4510 mice were significantly lower than the levels in nontransgenic littermates at 2-3 months of age. In contrast, retentions of (E)-[¹¹C]ABP688, a tracer for mGluR5, were unaltered relative to controls at 2 months of age but then gradually declined with aging in parallel with progressive brain atrophy. Biochemical and immunohistochemical assessment of postmortem brain tissues demonstrated that inhibitory, but not excitatory, synaptic constituents selectively diminished without overt loss of somas of GABAergic interneurons in the neocortex and hippocampus of rTg4510 mice at 2 months of age, which was concurrent with enhanced immunoreactivity of cFos, a well-characterized immediate early gene, suggesting that impaired inhibitory neurotransmission may cause hyperexcitability of cortical circuits. Our findings indicate that tau-induced disruption of the inhibitory synapse may be a critical trigger of progressive neurodegeneration, resulting in massive neuronal loss, and PET assessments of inhibitory versus excitatory synapses potentially offer in vivo indices for hyperexcitability and excitotoxicity early in the etiologic pathway of neurodegenerative tauopathies.

SIGNIFICANCE STATEMENT In this study, we examined the in vivo status of excitatory and inhibitory synapses in the brain of the rTg4510 tauopathy mouse model by PET imaging with (E)-[¹¹C]ABP688 and [¹¹C]flumazenil, respectively. We identified inhibitory synapse as being significantly dysregulated before brain atrophy at 2 months of age, while excitatory synapse stayed relatively intact at this stage. In line with this observation, postmortem assessment of brain tissues demonstrated selective attenuation of inhibitory synaptic constituents accompanied by the upregulation of cFos before the formation of tau pathology in the forebrain at young ages. Our findings indicate that selective degeneration of inhibitory synapse with hyperexcitability in the cortical circuit constitutes the critical early pathophysiology of tauopathy.

Nitric oxide (NO) is an important signaling molecule that fulfills diverse functional roles as a neurotransmitter or diffusible second messenger in the developing and adult CNS. Although the impact of NO on different behaviors such as movement, sleep, learning, and memory has been well documented, the identity of its molecular and cellular targets is still an area of ongoing investigation. Here, we identify a novel role for NO in strengthening inhibitory GABA_A receptor-mediated transmission in molecular layer interneurons of the mouse cerebellum. NO levels are elevated by the activity of neuronal NO synthase (nNOS) following Ca²⁺ entry through extrasynaptic NMDA-type ionotropic glutamate receptors (NMDARs). NO activates protein kinase G with the subsequent production of cGMP, which prompts the stimulation of NADPH oxidase and protein kinase C (PKC). The activation of PKC promotes the selective strengthening of α3-containing GABA_ARs synapses through a GABA receptor-associated protein-dependent mechanism. Given the widespread but cell type-specific expression of the NMDAR/nNOS complex in the mammalian brain, our data suggest that NMDARs may uniquely strengthen inhibitory GABAergic transmission in these cells through a novel NO-mediated pathway.

SIGNIFICANCE STATEMENT Long-term changes in the efficacy of GABAergic transmission is mediated by multiple presynaptic and postsynaptic mechanisms. A prominent pathway involves crosstalk between excitatory and inhibitory synapses whereby Ca²⁺-entering through postsynaptic NMDARs promotes the recruitment and strengthening of GABA_A receptor synapses via Ca²⁺/calmodulin-dependent protein kinase II. Although Ca²⁺ transport by NMDARs is also tightly coupled to nNOS activity and NO production, it has yet to be determined whether this pathway affects inhibitory synapses. Here, we show that activation of NMDARs trigger a NO-dependent pathway that strengthens inhibitory GABAergic synapses of cerebellar molecular layer interneurons. Given the widespread expression of NMDARs and nNOS in the mammalian brain, we speculate that NO control of GABAergic synapse efficacy may be more widespread than has been appreciated.

Hydrocephalus is a pathologic condition associated with various brain diseases, including Alzheimer's disease (AD). Dysfunctional ependymal cells (EpCs) are believed to contribute to the development of hydrocephalus. It is thus of interest to investigate EpCs' development and function. Here, we report that vacuolar protein sorting-associated protein 35 (VPS35) is critical for EpC differentiation, ciliogenesis, and survival, and thus preventing neonatal hydrocephalus. VPS35 is abundantly expressed in EpCs. Mice with conditional knock-out (cKO) of Vps35 in embryonic (Vps35^GFAP-Cre and Vps35^Emx1-Cre) or postnatal (Vps35^Foxj1-CreER) EpC progenitors exhibit enlarged lateral ventricles (LVs) and hydrocephalus-like pathology. Further studies reveal marked reductions in EpCs and their cilia in both Vps35^GFAP-Cre and Vps35^Foxj1-CreER mutant mice. The reduced EpCs appear to be due to impairments in EpC differentiation and survival. Additionally, both Vps35^GFAP-Cre and Vps35^Foxj1-CreER neonatal pups exhibit increased cell proliferation and death largely in a region close to LV-EpCs. Many microglia close to the mutant LV-EpC region become activated. Depletion of the microglia by PLX3397, an antagonist of colony-stimulating factor 1 receptor (CSF1R), restores LV-EpCs and diminishes the pathology of neonatal hydrocephalus in Vps35^Foxj1-CreER mice. Taken together, these observations suggest unrecognized functions of Vps35 in EpC differentiation, ciliogenesis, and survival in neonatal LV, and reveal pathologic roles of locally activated microglia in EpC homeostasis and hydrocephalus development.

SIGNIFICANCE STATEMENT This study reports critical functions of vacuolar protein sorting-associated protein 35 (VPS35) not only in promoting ependymal cell (EpC) differentiation, ciliogenesis, and survival, but also in preventing local microglial activation. The dysfunctional EpCs and activated microglia are likely to induce hydrocephalus.

Enjoy a low-cost, healthy diet from your very own vegetable garden and get the chance to make money by selling your own products. Start your own vegetable garden to grow, prepare and eat your own delicious fruits and vegetables with these tips: Do your research: When you begin your own vegetable garden you should understand the type of soil you work [...]

At the beginning of the year we took a tour of 6 incredible plants you might not have heard of. Diets worldwide – from forest roots and leaves such as the moringa in Africa and parts of Asia to cardoon, the close relative of the artichoke in Europe – are varied, suited to local environment and can counter malnutrition and [...]

Illegal, Unreported and Unregulated fishing, also known as IUU, robs the world’s oceans of 26 million tonnes of seafood annually, bringing financial losses to a staggering US$ 23 billion a year. Illegal fishing severely affects the livelihoods of fishers and other fisher-sector stakeholders and exacerbates poverty and food insecurity. It undermines the accuracy of fisheries’ stock assessments and threatens the [...]

Smallholders and people living in rural areas in Africa grow a huge variety of edible plants other than rice, wheat or maize. These crops, including the African yam bean, have long been neglected although they represent an excellent alternative food supplement to most diets. Grown in pockets of tropical Central, West and East Africa, the African yam bean (Sphenostylis stenocarpa) [...]

Food waste has become a dangerous habit: buying more than we need at supermarkets, letting fruits and vegetables spoil at home or ordering more than we can eat at restaurants.  Each year, about 1/3 of the food we produce globally is lost or wasted. In developing countries, a large part of this food (40%) is lost at the harvest or processing [...]

FAO plays an important and unique role as a neutral forum, offering unbiased, high-quality information across all areas related to food, agriculture and sustainable natural resources management. With over 500 new publications a year, FAO provides robust technical knowledge and global statistics. By broadly disseminating timely, accurate and compelling information, FAO informs the work of practitioners, researchers and policy-makers, while raising [...]

Disasters, like an earthquake or a violent coup d’état, can strike suddenly, or like droughts and floods, develop slowly. Emergencies are devastating for people everywhere, but for those whose livelihoods or food needs depend entirely on agriculture and natural resources, these disasters can often be overwhelming. FAO addresses emergencies in a variety of ways from early warning and preparedness to [...]

The British Navy knew it couldn't completely disguise a ship to protect it from attack during WWI. So they turned to 'Dazzle Painting'

The snails are an invasive crop pest that are known to eat more than just coffee rust

After abdicating the British throne, Edward was appointed governor of the Bahamas, where he temporarily lived in a lavish home in Nassau

The cats also cross the road an average of 4.5 times in six days, putting themselves in danger

But will that keep susceptible populations safe?

The vineyard deploys a daily bird-based battalion to pluck snails and insects off their plants

With many zoos and aquariums closed to the public, keepers let animals roam empty hallways to meet their neighbors

Blending marshmallows with scientific rigor, the contest offers levity during a difficult time

The story behind the image, and its removal, led to mixed reactions from the public, including native communities

The rankings stay much the same from year to year, but in 2019, Pembroke Welsh corgis broke the top ten for the first time

This jumping spider was personable and very easy to photograph as it was willing to sit still, facing me.

Highway 8, otherwise known as the Dempster Highway, will be closed to all traffic at 5 p.m. on Friday, according to the government of the Northwest Territories.

Staff halted $100 service over pandemic concerns, forcing homeowners to private plumbers much more, and Danny Breen is urging them to contact the city.

A new book explores the evolution of cartography throughout more than a century of commercial air travel

Some school travel groups in Cape Breton that had trips cancelled in March due to COVID-19 are still waiting to get their money back.

Tampa Bay Rays' Blake Snell claimed champion status after defeating Lucas Giolito of the Chicago White Sox in the inaugural MLB The Show player league on Sunday.

As a result of the pandemic, USPS, which has run at a loss for years, is even more cash-strapped. It expects to lose $2 billion each month during the pandemic. That prompted Postmaster General Megan Brennan to ask Congress for $50 billion in funds -- $25 billion to offset lost revenue from declining mail volume due to the pandemic, and another $25 billion for modernization.

Salesforce has announced a new version of Work.com designed to help businesses function safely during the COVID-19 pandemic. "Work.com is a completely new initiative using an existing domain name that we previously owned," said Salesforce spokesperson Joel Steinfeld. "Our focus is on speed and moving as quickly as possible to help our customers, and Work.com is an optimal way to do that.

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.

Seventy-three homeless shelters and other community organizations are getting extra funding to help pay for basics like extra food, cleaning and staff during the COVID-19 pandemic.

The National Capital Commission (NCC) says tulip admirers can "feel free" to take photos of the colourful flowers while visiting the Canadian Tulip Festival after placing signs saying photography wasn't allowed in tulip beds earlier this week.

For Canadian champion Roman Sadovsky and former Canadian champions Nam Nguyen and Keegan Messing, the Four Continents results will determine who takes the one spot available in the men's event at the worlds.

Canada's Joseph Phan was eighth after a highly competitive men's short program Wednesday at the world junior figure skating championships.

Quebec Health Minister Danielle McCann says the government is evaluating whether to allow the world figure skating championships to go ahead next week in Montreal.

The world figure skating championships, scheduled for March 18-22 in Montreal, have been cancelled because of the spread of COVID-19.

11 startups to pitch at NEXT Canada's virtual Venture Reveal  BetaKit

Govt hikes borrowing limit by over 50% to Rs 12 trn as virus grips economy  Business StandardRaghuram Rajan says monetisation neither a game changer nor catastrophe  LivemintBank credit up 6.74% to Rs 102.69 lakh crore; deposits ris...

Players from La Liga side Eibar have issued a joint statement expressing their concerns about returning to training and matches while the new coronavirus remains a threat.

The Vancouver Whitecaps said it has ordered two player to self-quarantine for 14 days after they violated club and league orders to abide by physical distancing guidelines in B.C.

Since early 2019, the Russell 2000, the primary index for small cap stocks, has lagged mid and large cap benchmarks....

The post Why Small Caps Lag In This Economic Downturn appeared first on OpenMarkets.

The number of cases of COVID-19 in First Nations reserves continues to rise this week, with 161 confirmed positive cases reported as of May 5.

It's not often people want to hang onto winter, but a Summerside, P.E.I. woman has kept a piece of it in her freezer for over a decade: a snowball in a ziplock bag.

The mullahs are cold calculators.

Leonard Rodriquez's grieving loved ones say he was a man who would drop everything to help those in need. But they say his death could have been prevented if he'd had the personal protective gear he needed to do his job.