Speech by Mr Agustín Carstens, General Manager of the BIS, at the Eurofi Financial Forum, Helsinki, 12 September 2019.

The cerebellum influences motor control through Purkinje target neurons, which transmit cerebellar output. Such output is required, for instance, for larval zebrafish to learn conditioned fictive swimming. The output cells, called eurydendroid neurons (ENs) in teleost fish, are inhibited by Purkinje cells and excited by parallel fibers. Here, we investigated the electrophysiological properties of glutamatergic ENs labeled by the transcription factor olig2. Action potential firing and synaptic responses were recorded in current clamp and voltage clamp from olig2⁺ neurons in immobilized larval zebrafish (before sexual differentiation) and were correlated with motor behavior by simultaneous recording of fictive swimming. In the absence of swimming, olig2⁺ ENs had basal firing rates near 8 spikes/s, and EPSCs and IPSCs were evident. Comparing Purkinje firing rates and eurydendroid IPSC rates indicated that 1-3 Purkinje cells converge onto each EN. Optogenetically suppressing Purkinje simple spikes, while preserving complex spikes, suggested that eurydendroid IPSC size depended on presynaptic spike duration rather than amplitude. During swimming, EPSC and IPSC rates increased. Total excitatory and inhibitory currents during sensory-evoked swimming were both more than double those during spontaneous swimming. During both spontaneous and sensory-evoked swimming, the total inhibitory current was more than threefold larger than the excitatory current. Firing rates of ENs nevertheless increased, suggesting that the relative timing of IPSCs and EPSCs may permit excitation to drive additional eurydendroid spikes. The data indicate that olig2⁺ cells are ENs whose activity is modulated with locomotion, suiting them to participate in sensorimotor integration associated with cerebellum-dependent learning.

SIGNIFICANCE STATEMENT The cerebellum contributes to movements through signals generated by cerebellar output neurons, called eurydendroid neurons (ENs) in fish (cerebellar nuclei in mammals). ENs receive sensory and motor signals from excitatory parallel fibers and inhibitory Purkinje cells. Here, we report electrophysiological recordings from ENs of larval zebrafish that directly illustrate how synaptic inhibition and excitation are integrated by cerebellar output neurons in association with motor behavior. The results demonstrate that inhibitory and excitatory drive both increase during fictive swimming, but inhibition greatly exceeds excitation. Firing rates nevertheless increase, providing evidence that synaptic integration promotes cerebellar output during locomotion. The data offer a basis for comparing aspects of cerebellar coding that are conserved and that diverge across vertebrates.

Hepatocyte growth factor (HGF) is a multifunctional protein that signals through the MET receptor. HGF stimulates cell proliferation, cell dispersion, neuronal survival, and wound healing. In the inner ear, levels of HGF must be fine-tuned for normal hearing. In mice, a deficiency of HGF expression limited to the auditory system, or an overexpression of HGF, causes neurosensory deafness. In humans, noncoding variants in HGF are associated with nonsyndromic deafness DFNB39. However, the mechanism by which these noncoding variants causes deafness was unknown. Here, we reveal the cause of this deafness using a mouse model engineered with a noncoding intronic 10 bp deletion (del10) in Hgf. Male and female mice homozygous for del10 exhibit moderate-to-profound hearing loss at 4 weeks of age as measured by tone burst auditory brainstem responses. The wild type (WT) 80 mV endocochlear potential was significantly reduced in homozygous del10 mice compared with WT littermates. In normal cochlea, endocochlear potentials are dependent on ion homeostasis mediated by the stria vascularis (SV). Previous studies showed that developmental incorporation of neural crest cells into the SV depends on signaling from HGF/MET. We show by immunohistochemistry that, in del10 homozygotes, neural crest cells fail to infiltrate the developing SV intermediate layer. Phenotyping and RNAseq analyses reveal no other significant abnormalities in other tissues. We conclude that, in the inner ear, the noncoding del10 mutation in Hgf leads to developmental defects of the SV and consequently dysfunctional ion homeostasis and a reduction in the EP, recapitulating human DFNB39 nonsyndromic deafness.

SIGNIFICANCE STATEMENT Hereditary deafness is a common, clinically and genetically heterogeneous neurosensory disorder. Previously, we reported that human deafness DFNB39 is associated with noncoding variants in the 3'UTR of a short isoform of HGF encoding hepatocyte growth factor. For normal hearing, HGF levels must be fine-tuned as an excess or deficiency of HGF cause deafness in mouse. Using a Hgf mutant mouse with a small 10 bp deletion recapitulating a human DFNB39 noncoding variant, we demonstrate that neural crest cells fail to migrate into the stria vascularis intermediate layer, resulting in a significantly reduced endocochlear potential, the driving force for sound transduction by inner ear hair cells. HGF-associated deafness is a neurocristopathy but, unlike many other neurocristopathies, it is not syndromic.

Pattern separation and completion are fundamental hippocampal computations supporting memory encoding and retrieval. However, despite extensive exploration of these processes, it remains unclear whether and how top-down processes adaptively modulate the dynamics between these computations. Here we examine the role of expectation in shifting the hippocampus to perform pattern separation. In a behavioral task, 29 participants (7 males) learned a cue-object category contingency. Then, at encoding, one-third of the cues preceding the to-be-memorized objects, violated the studied rule. At test, participants performed a recognition task with old objects (targets) and a set of parametrically manipulated (very similar to dissimilar) foils for each object. Accuracy was found to be better for foils of high similarity to targets that were contextually unexpected at encoding compared with expected ones. Critically, there were no expectation-driven differences for targets and low similarity foils. To further explore these effects, we implemented a computational model of the hippocampus, performing the same task as the human participants. We used representational similarity analysis to examine how top-down expectation interacts with bottom-up perceptual input, in each layer. All subfields showed more dissimilar representations for unexpected items, with dentate gyrus (DG) and CA3 being more sensitive to expectation violation than CA1. Again, representational differences between expected and unexpected inputs were prominent for moderate to high levels of input similarity. This effect diminished when inputs from DG and CA3 into CA1 were lesioned. Overall, these novel findings strongly suggest that pattern separation in DG/CA3 underlies the effect that violation of expectation exerts on memory.

SIGNIFICANCE STATEMENT What makes some events more memorable than others is a key question in cognitive neuroscience. Violation of expectation often leads to better memory performance, but the neural mechanism underlying this benefit remains elusive. In a behavioral study, we found that memory accuracy is enhanced selectively for unexpected highly similar foils, suggesting expectation violation does not enhance memory indiscriminately, but specifically aids the disambiguation of overlapping inputs. This is further supported by our subsequent investigation using a hippocampal computational model, revealing increased representational dissimilarity for unexpected highly similar foils in DG and CA3. These convergent results provide the first evidence that pattern separation plays an explicit role in supporting memory for unexpected information.

To determine whether Cav1.2 voltage-gated Ca²⁺ channels contribute to astrocyte activation, we generated an inducible conditional knock-out mouse in which the Cav1.2 α subunit was deleted in GFAP-positive astrocytes. This astrocytic Cav1.2 knock-out mouse was tested in the cuprizone model of myelin injury and repair which causes astrocyte and microglia activation in the absence of a lymphocytic response. Deletion of Cav1.2 channels in GFAP-positive astrocytes during cuprizone-induced demyelination leads to a significant reduction in the degree of astrocyte and microglia activation and proliferation in mice of either sex. Concomitantly, the production of proinflammatory factors such as TNFα, IL1β and TGFβ1 was significantly decreased in the corpus callosum and cortex of Cav1.2 knock-out mice through demyelination. Furthermore, this mild inflammatory environment promotes oligodendrocyte progenitor cells maturation and myelin regeneration across the remyelination phase of the cuprizone model. Similar results were found in animals treated with nimodipine, a Cav1.2 Ca²⁺ channel inhibitor with high affinity to the CNS. Mice of either sex injected with nimodipine during the demyelination stage of the cuprizone treatment displayed a reduced number of reactive astrocytes and showed a faster and more efficient brain remyelination. Together, these results indicate that Cav1.2 Ca²⁺ channels play a crucial role in the induction and proliferation of reactive astrocytes during demyelination; and that attenuation of astrocytic voltage-gated Ca²⁺ influx may be an effective therapy to reduce brain inflammation and promote myelin recovery in demyelinating diseases.

SIGNIFICANCE STATEMENT Reducing voltage-gated Ca²⁺ influx in astrocytes during brain demyelination significantly attenuates brain inflammation and astrocyte reactivity. Furthermore, these changes promote myelin restoration and oligodendrocyte maturation throughout remyelination.

Theoretical models and experimental evidence have suggested that connections from the dentate gyrus (DG) to CA3 play important roles in representing orthogonal information (i.e., pattern separation) in the hippocampus. However, the effects of eliminating the DG on neural firing patterns in the CA3 have rarely been tested in a goal-directed memory task that requires both the DG and CA3. In this study, selective lesions in the DG were made using colchicine in male Long–Evans rats, and single units from the CA3 were recorded as the rats performed visual scene memory tasks. The original scenes used in training were altered during testing by blurring to varying degrees or by using visual masks, resulting in maximal recruitment of the DG–CA3 circuits. Compared with controls, the performance of rats with DG lesions was particularly impaired when blurred scenes were used in the task. In addition, the firing rate modulation associated with visual scenes in these rats was significantly reduced in the single units recorded from the CA3 when ambiguous scenes were presented, largely because DG-deprived CA3 cells did not show stepwise, categorical rate changes across varying degrees of scene ambiguity compared with controls. These findings suggest that the DG plays key roles not only during the acquisition of scene memories but also during retrieval when modified visual scenes are processed in conjunction with the CA3 by making the CA3 network respond orthogonally to ambiguous scenes.

SIGNIFICANCE STATEMENT Despite the behavioral evidence supporting the role of the dentate gyrus in pattern separation in the hippocampus, the underlying neural mechanisms are largely unknown. By recording single units from the CA3 in DG-lesioned rats performing a visual scene memory task, we report that the scene-related modulation of neural firing was significantly reduced in the DG-lesion rats compared with controls, especially when the original scene stimuli were ambiguously altered. Our findings suggest that the dentate gyrus plays an essential role during memory retrieval and performs a critical computation to make categorical rate modulation occur in the CA3 between different scenes, especially when ambiguity is present in the environment.

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 [...]

Migration has always existed. It has been a means to reunite with family, to find better jobs, to have a new experience or to start a better life. In 2015, the number of people migrating was up to 1 out of every 7 people in the world.   When it is a choice, migration can be a good way to spread [...]

The 2019 Report of the Technical Cooperation Programme (TCP) examines the role of the TCP to deliver FAO technical assistance for agriculture, food and nutrition in response to countries’ most [...]

Lead decontamination policies enacted in August are now in conflict with measures to prevent spread of COVID-19

A recent excavation located the first physical evidence of the capital of the Maya kingdom of Sak Tz'i', founded in 750 B.C.

A trio of young northern violinists recently joined their contemporaries across Canada for a project that aims to bring people together through music — while being apart.

Canadians helped liberate the Netherlands 75 years ago this week.

This rapid and efficient method to prepare highly purified recombinant adeno-associated viruses (rAAVs) is based on binding of negatively charged rAAV capsids to an anion-exchange resin that is pH dependent.

The Bradford assay is a quick and fairly sensitive method for measuring the concentrations of proteins. It is based on the shift in absorbance maximum of Coomassie Brilliant Blue G-250 dye from 465 to 595 nm following binding to denatured proteins in solution.

Bacterial artificial chromosome (BAC) clones are rendered electrocompetent and transformed with the recombinant shuttle vector, pLD53SCAB/AB-box. Cointegrates are selected by growth on chloramphenicol and ampicillin to ensure recombination of the shuttle vector into the BAC.

Plasmid DNA is prepared from the recombinant shuttle vector pLD53.SCAB/A-B created by cloning of the A and B homology arms for two-step bacterial artificial chromosome (BAC) engineering. To confirm that the A-box and B-box arms have been successfully incorporated into pLD53.SCAB, the pattern of enzyme digestion of the modified plasmid is compared with that of the unmodified pLD53.SCAB. Once the shuttle vector is shown to carry the proper sequences, it is ready for transfer into the BAC host.

The 700-bp A homology arm (A-box) and the 700-bp B homology arm (B-box) are amplified by polymerase chain reaction (PCR) using purified bacterial artificial chromosome (BAC) DNA as template for two-step BAC engineering. The resulting A-box PCR product contains an AscI site at its 5' end (the 5' primer incorporates an AscI site, and the 3' primer does not incorporate any restriction sites). The B-box PCR product contains an XmaI site at its 3' end (the 5' primer does not incorporate any restriction sites, and the 3' primer incorporates an XmaI site). The amplification products are then digested with the appropriate restriction endonucleases to render them suitable for cloning into the shuttle vector.

In two-step bacterial artificial chromosome (BAC) engineering, a single plasmid is introduced into the BAC-carrying cell lines. The shuttle vector pLD53.SCAB (or pLD53.SCAEB) carries the recA gene and the R6K origin, which requires the protein to replicate. PIR2 cells, expressing , are typically used for the amplification of the vector and maintain about 15 copies/cell of the donor vector, which is relatively stable in this host.

FSI Briefs No 2, April 2020. Guidance issued by financial sector authorities in response to the Covid-19 crisis seems to suggest that international efforts to come up with operational resilience standards should take into account at least the following elements: Critical/essential employees: identifying the critical functions and employees that support important business services, as well as ensuring employees' safety and that they can safely resume their duties (remotely, if necessary); IT infrastructure: ensuring that IT infrastructure can support a sharp increase in usage over an extended period and taking steps to safeguard information security; Third-party service providers: ensuring that external service providers and/or critical suppliers are taking adequate measures and are sufficiently prepared for a scenario in which there will be heavy reliance on their services; Cyber resilience: remaining vigilant in order to identify and protect vulnerable systems, and detect, respond and recover from cyber attacks..

Press release: CPMI and IOSCO share authorities´ experiences in cooperation to increase FMI safety and efficiency, 10 December 2019

Press release: CPMI report sets out considerations for developers of wholesale digital tokens, 12 December 2019

The BIS Board of Directors has decided to invite the central banks of Kuwait, Morocco and Vietnam to become members of the BIS. This is the first such expansion since 2011 and will take the number of members to 63.

Press release "Governors and Heads of Supervision announce deferral of Basel III implementation to increase operational capacity of banks and supervisors to respond to Covid-19", 27 March 2020

We need to recognize any signposts leading up and out.

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.

Officials with Maritime Pride Eggs say their Summerside, P.E.I., egg facility will cease processing operations on June 5.

Equities have rallied since 2017 and yet the expected growth in dividends has declined since then. Is the fall in long-term interest rates to be blamed?

Karina LeBlanc was returning home from her second hospital visit after giving birth to her first child, only this time she would have to spend 14 days in self-isolation after doctors feared she contracted COVID-19 during her stay.

Documents created by the top disease investigators in the U.S. meant to give step-by-step advice to local leaders deciding when and how to reopen public places such as mass transit, day care centres and restaurants during the still-raging pandemic have been shelved by the Trump administration.

As British Columbians maintain physical distancing recommendations during the COVID-19 pandemic, this year’s Easter celebrations will have to change. In Kamloops, B.C., organizations are working to make sure Easter is as fun and social as it can be. 

Determining the concentration of protein samples generally is accomplished either by measuring the UV absorbance at 280 nm or by reacting the protein quantitatively with dyes and/or metal ions (Bradford, Lowry, or BCA assays). For purified proteins, UV absorbance remains the most popular method because it is fast, convenient, and reproducible; it does not consume the protein; and it requires no additional reagents, standards, or incubations. No method of protein concentration determination is perfect because each is subject to a different set of constraints such as interference of buffer components and contaminating proteins in direct UV determination (A₂₈₀) or reactivity of individual proteins and buffer components with the detecting reagents in colorimetric assays. In cases in which protein concentration is critical (e.g., determination of catalytic rate constants for an enzyme), it may be advisable to compare the results of several assays.

Equities have rallied since 2017 and yet the expected growth in dividends has declined since then. Is the fall in long-term interest rates to be blamed?

Bank of Italy Working Papers by Eleonora Porreca and Alfonso Rosolia

Central Bank of Chile Working Papers by Benjamín García and Juan Guerra-Salas

Students in Penn State’s Master of Health Administration program are learning first-hand how the skills and competencies they are acquiring in the classroom will be applied in their professional careers. A recent virtual roundtable event provided opportunities for students to learn real-world strategies from health care industry leaders that are being applied in response to the COVID-19 pandemic.

Denver Newsroom, May 7, 2020 / 03:48 pm (CNA).- For the first time in over a century, the annual May 13 celebrations at the Fatima shrine will take place without the physical presence of pilgrims, the bishop of Fatima confirmed this week.

Cardinal Antonio Marto said in a May 3 statement that the celebrations for the Feast of Our Lady of Fatima “will take place as was announced April 6, without the physical presence of pilgrims, in the name of prudence to avoid the risk of spreading the novel coronavirus.”

“As planned in conjunction with the civil authorities, the May 12 and 13 celebrations for this year cannot have the physical presence of the pilgrims and will be transmitted by broadcast and digital media,” he continued.

The cardinal explained that hosting “an unpredictable multitude of people” gathering at a time when the coronavirus pandemic is still a serious threat would go against the efforts of health authorities to gradually lift restrictions imposed to slow the spread of the virus.

“We therefore respect, in an attitude of collaboration with the competent civil authorities, the guidelines for these celebrations to be held with a symbolic presence of participants,” Marto said.

The clarification over the Fatima feast day came as the Portuguese government gradually begins to ease restrictions that had been put in place in response to the pandemic, prompting speculation over whether the May 13 celebrations would be able to take place as normal. The annual event typically draws hundreds of thousands from around the world to the shrine.

The Portuguese Bishops’ Conference had announced earlier this month that public Masses could tentatively resume the weekend of Pentecost, May 30-31, in accordance with guidelines to be established by the country’s health department and the Catholic Church.

Cardinal Marto stressed that the decision to suspend public religious celebrations was based in a sense of responsibility toward the public health, as a way of loving one’s neighbor.

“[A]s much as our hearts would like to be in Fatima celebrating together in the same place, as has been the case since 1917, prudence counsels us not to do so this time,” he said, adding that Catholics can look forward to an end to the pandemic and an opportunity to gather together joyfully in the future.

Fr. Carlos Cabecinhas, rector of the Shrine of Our Lady of Fatima, encouraged pilgrims who are unable to physically attend the events to make an interior pilgrimage, participating in the events of the Solemnity of Our Lady of Fatima through the internet or social media.

“This is a painful time: the shrine exists to welcome the pilgrims and we cannot do so, this is a cause for great sadness; but this decision is also an act of responsibility toward the pilgrims, protecting their health and welfare,” the priest said.

The shrine’s website offers four steps to guide people on this interior pilgrimage.

According to the website, “the celebrations of May 12 and 13 will maintain the usual schedule with recitation of the Rosary at 9:30 p.m. followed by the Candlelight Procession. On the 13th the Rosary will be prayed at 9:00 a.m. followed by the International Mass and the Farewell Procession.”

In March, 24 countries were consecrated to the Sacred Heart of Jesus and the Immaculate Heart of Mary at the Shrine of Our Lady of Fatima.

At that ceremony, Cardinal Marto recalled that Saints Francisco and Jacinto Marto, shepherd children to whom an angel, and then the Blessed Virgin Mary appeared in 1916 and 1917 at Fatima, both died amid the victims of the Spanish flu pandemic.

To date, Johns Hopkins University has reported 26,182 cases of novel coronavirus in Portugal, with 1089 deaths.

 

CNA Staff, May 5, 2020 / 03:01 pm (CNA).- At least 51 workers have been infected with the novel coronavirus at the Grasberg mine in Indonesia, the world’s largest gold mine.

Nine employees of Freeport McMoRan, the organization who operates the mine, have been hospitalized due to COVID-19 and another 42 have been forced into quarantine, UCA News reported May 5.

The mine is located in Papua and is known for its production of gold and copper. The operation includes around 20,000 employees.

Riza Pratama, vice president of Freeport, said the company will fully cooperate with the government's coronavirus task force but will continue mining operations to support the national economy. He said the company will prioritize the health and safety of workers and will conduct regular health screenings, implement social distancing, provide a quarantine area for employees, according to UCA News.

Father Ansel Amo, who heads the Justice, Peace, and Integrity of Creation Commission for the Archdiocese of Merauke, said these measures are not enough to protect workers.

“Freeport management should limit workers’ activities so that they don’t transmit the disease to other people, including local people. They should stop its operations temporarily,” he told UCA News.

Indonesia has seen more than 12,000 cases from the coronavirus, leading to 872 reported deaths as of May 5. Globally, more than 3.7 million cases of the virus have been reported, and a quarter of a million deaths.

Through six camps over the summer, OM Hungary reached over 300 children and youth with the message of the Gospel while teaching English.

Lincoln and Manna from Hong Kong are two of the four candidates to participate in OM EAP’s first Timothy Trek training programme this year.

Name: Sam Castro Home: Pachuca, Mexico Born in: March 1988 Joined OM Ships: September 2013 Previous employment: Veterinarian Current job on board: Shift leader in the book fair

Adolescent use of electronic cigarettes (e-cigarettes) has increased dramatically, with younger and nicotine-naive adolescents starting to use these devices and use them more frequently than combustible cigarettes. In emerging evidence, it is shown that e-cigarettes are not effective in helping adult smokers quit and that youth using e-cigarettes are at risk for becoming nicotine dependent and continuing to use as adults. Important gaps in our knowledge remain regarding the long-term health impact of e-cigarettes, effective strategies to prevent and reduce adolescent e-cigarette use, and the impact of provider screening and counseling to address this new method of nicotine use.

Sunday School isn't just for Sundays anymore - it can be on any given day of the week in Ukraine.

ANDY MURRAY may need to have another operation as he continues his bid to return to top-level tennis.

We see how fair play and the integration of players from different backgrounds is reaping success in Schleswig-Holstein.

American band Iration is not unfazed by the current turmoil across the world brought on by the coronavirus disease (COVID-19) pandemic. Their latest single Right Here Right Now, however, calls for gratitude despite the challenges being faced.

"The messages teens hear are 'Enjoy life: no commitment, keep your choices open and choose comfort'. Is this the consequence of their own choices or of the generation that raised them? Probably both," shares Ewout.