A cerebellar internal model calibrates a feedback controller involved in sensorimotor control

Animals can adjust their behavior in response to changes in the environment when these changes can be predicted. Here the authors show the role of the cerebellum in zebrafish that change their swimming as they adjust to long-lasting changes in visual feedback Animals must adapt their behavior to survive in a changing environment. Behavioral adaptations can be evoked by two mechanisms: feedback control and internal-model-based control. Feedback controllers can maintain the sensory state of the animal at a desired level under different environmental conditions. In contrast, internal models learn the relationship between the motor output and its sensory consequences and can be used to recalibrate behaviors. Here, we present multiple unpredictable perturbations in visual feedback to larval zebrafish performing the optomotor response and show that they react to these perturbations through a feedback control mechanism. In contrast, if a perturbation is long-lasting, fish adapt their behavior by updating a cerebellum-dependent internal model. We use modelling and functional imaging to show that the neuronal requirements for these mechanisms are met in the larval zebrafish brain. Our results illustrate the role of the cerebellum in encoding internal models and how these can calibrate neuronal circuits involved in reactive behaviors depending on the interactions between animal and environment

Visualizing anatomically registered data with Brainrender

Three-dimensional (3D) digital brain atlases and high-throughput brain wide imaging techniques generate large multidimensional datasets that can be registered to a common reference frame. Generating insights from such datasets depends critically on visualization and interactive data exploration, but this a challenging task. Currently available software is dedicated to single atlases, model species or data types, and generating 3D renderings that merge anatomically registered data from diverse sources requires extensive development and programming skills. Here, we present brainrender: an open-source Python package for interactive visualization of multidimensional datasets registered to brain atlases. Brainrender facilitates the creation of complex renderings with different data types in the same visualization and enables seamless use of different atlas sources. High-quality visualizations can be used interactively and exported as high-resolution figures and animated videos. By facilitating the visualization of anatomically registered data, brainrender should accelerate the analysis, interpretation, and dissemination of brain-wide multidimensional data

BrainGlobe Atlas API: a common interface for neuroanatomical atlases

Summary: Neuroscientists routinely perform experiments aimed at recording or manipulating neural activity, uncovering physiological processes underlying brain function or elucidating aspects of brain anatomy. Understanding how the brain generates behaviour ultimately depends on merging the results of these experiments into a unified picture of brain anatomy and function. Brain atlases are crucial in this endeavour: by outlining the organization of brain regions they provide a reference upon which our understanding of brain function can be anchored. More recently, digital high-resolution 3d atlases have been produced for several model organisms providing an invaluable resource for the research community. Effective use of these atlases depends on the availability of an application programming interface (API) that enables researchers to develop software to access and query atlas data. However, while some atlases come with an API, these are generally specific for individual atlases, and this hinders the development and adoption of open-source neuroanatomy software. The BrainGlobe atlas API (BG-Atlas API) overcomes this problem by providing a common interface for programmers to download and process data across a variety of model organisms. By adopting the BG-Atlas API, software can then be developed agnostic to the atlas, increasing adoption and interoperability of packages in neuroscience and enabling direct integration of different experimental modalities and even comparisons across model organisms

Exploiting the flexibility of the pyrochlore composition for acid-resilient Iridium oxide electrocatalysts in proton exchange membranes

Iridate pyrochlore oxides (Na,Ca)2-x(Ir2-yMy)O6·nH2O (M = Sb, Zr, Ru, Rh) are studied as resilient electrocatalysts for the oxygen evolution reaction under acid conditions. The materials crystallise from aqueous solution under alkali hydrothermal conditions with 10-40 nm crystallite size. Refinement of their crystal structures using both powder neutron and X-ray diffraction determined the composition of the materials, and Ir LIII-edge XANES spectroscopy shows the average Ir oxidation state to be close to 4.5 in all materials, consistent with bond valence sums. All materials show high electrocatalytic activity for the oxygen evolution reaction and the electrocatalyst which best maintains activity on cycling is the sodium-free Ca2-xIr2O6·nH2O, while the (Na,Ca)2-xIr2O6·nH2O material shows highest activity when normalised for surface area. In membrane electrode assemblies, carbon corrosion is minimised, making the materials suitable for use in catalyst layers in proton exchange membrane devices, such as electrolysers and fuel cells. Under strongly acidic conditions it is proved that while A-site Ca and Na are readily leached, the average pyrochlore structure is maintained, as is electrocatalytic activity, with charge balance achieved by inclusion of protons in the pyrochlore structure in the form of bridging hydroxyls, as seen using inelastic neutron scattering spectroscopy

(M,Ru)O2 (M = Mg, Zn, Cu, Ni, Co) rutiles and their use as oxygen evolution electrocatalysts in membrane electrode assemblies under acidic conditions

The rutiles (M,Ru)O2 (M = Mg, Zn, Co, Ni, Cu) are formed directly under hydrothermal conditions at 240 °C from potassium perruthenate and either peroxides of zinc or magnesium, or poorly crystalline oxides of cobalt, nickel or copper. The polycrystalline powders consist of lath-shaped crystallites, tens of nanometres in maximum dimension. Powder neutron diffraction shows that the materials have expanded a axis and contracted c axis compared to the parent RuO2, but there is no evidence of lowering of symmetry to other AO2-type structures, supported by Raman spectroscopy. Rietveld refinement shows no evidence for oxide non-stoichiometry and provides a formula (MxRu1-x)O2 with 0.14 < x < 0.2, depending on the substituent metal. This is supported by energy-dispersive X-ray analysis on the transmission electron microscope, while Ru K-edge XANES spectroscopy shows that upon inclusion of the substituent the average Ru oxidation state is increased to balance charge. Variable temperature magnetic measurements provide evidence for atomic homogeneity of the mixed metal materials, with suppression of the high temperature antiferromagnetism of RuO2 and increased magnetic moment. The new rutiles all show enhanced electrocatalysis compared to reference RuO2 materials for oxygen evolution in 1 M H2SO4 electrolyte at 60 °C, with higher specific and mass activity (per Ru) than a low surface area crystalline RuO2, and with less Ru dissolution over 1000 cycles compared to an RuO2 with a similar surface area. Magnesium substitution provides the optimum balance between stability and activity, despite leaching of the Mg2+ into solution, and this was proved in membrane electrode assemblies

Targeting poly(ADP-ribose) polymerase activity for cancer therapy

Poly(ADP-ribosyl)ation is a ubiquitous protein modification found in mammalian cells that modulates many cellular responses, including DNA repair. The poly(ADP-ribose) polymerase (PARP) family catalyze the formation and addition onto proteins of negatively charged ADP-ribose polymers synthesized from NAD+. The absence of PARP-1 and PARP-2, both of which are activated by DNA damage, results in hypersensitivity to ionizing radiation and alkylating agents. PARP inhibitors that compete with NAD+ at the enzyme’s activity site are effective chemo- and radiopotentiation agents and, in BRCA-deficient tumors, can be used as single-agent therapies acting through the principle of synthetic lethality. Through extensive drug-development programs, third-generation inhibitors have now entered clinical trials and are showing great promise. However, both PARP-1 and PARP-2 are not only involved in DNA repair but also in transcription regulation, chromatin modification, and cellular homeostasis. The impact on these processes of PARP inhibition on long-term therapeutic responses needs to be investigated

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR &lt; 60 mL/min/1.73 m2) or eGFR reduction &gt; 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR &lt; 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR &gt; 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Using Digital Storytelling to communicate chemical risks in food to high school students.

The research project, \u201c Chemical risk in food: comparing web- and paper-based communication tools \u201d , funded by the Italian Ministry of Health, intended to make a comparative assessment of the most effective tools to use in communication campaigns on chemical risks associated with food. The aim of the project was to raise awareness among adolescents about the problem of food safety and, as a result, to reduce the risk of exposure to chemical contaminants contained in food The objective of the project was to build a message and to disseminate it to a sample of young people aged between 16 and 18 in North East Italy, by means of two tools: one web- and the other paper-based. The choice of storytelling, as a method to develop the message on both the web- and the paper- based tools, is one of the more innovative aspects of the project pilot. Storytelling was identified as a technique able to facilitate understanding of scientific notions and to foster learning by emotionally involving the target. The use of this technique can be considered absolutely original in the communication of risk for consumer safety. Evaluation showed that the use of the storytelling technique had a positive impact on the target involved. From the data collected through the evaluation questionnaires, it was found that most of the young people (83%) considered the technique to be an effective means of communication able to attract the curiosity of their peers. Besides being an important innovation in the field of food risk communications, the direct involvement of the students in designing the communication tools in the early stages of the project and their participation in building the Digital Storytelling product proved to be a means of arousing the curiosity not only of the spectators but also of the students involved in the participatory process. Implementation of the storytelling technique actually required the young people to reflect on their own experience and daily life and to build a narrative related to the subject in question. In particular, the results of the analyses showed that, of the various elements used to build the tool, the students who saw the Digital Storytelling product reported appreciating that the actors were people of their own age, indicating this as an effective way of conveying the communication message to the identified targe

Hypotension during sham apheresis in a patient taking ACE inhibitors

JAM