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Preclinical imaging studies offer a unique access to the rat brain, allowing investigations that go beyond what is possible in human studies. Unfortunately, these techniques still suffer from a lack of dedicated and standardized neuroimaging tools, namely brain templates and descriptive atlases. Here, we present two rat brain MRI templates and their associated gray matter, white matter and cerebrospinal fluid probability maps, generated from ex vivo T 2 * -weighted images (90 µm isotropic resolution) and in vivo T 2 -weighted images (150 µm isotropic resolution). In association with these templates, we also provide both anatomical and functional 3D brain atlases, respectively derived from the merging of the Waxholm and Tohoku atlases, and analysis of resting-state functional MRI data. Finally, we propose a complete set of preclinical MRI reference resources, compatible with common neuroimaging software, for the investigation of rat brain structures and functions. Magnetic resonance imaging (MRI) is widely used to study the rat brain. Here, the authors provide standardized MRI brain templates and descriptive atlases for the rat, incorporating both structural and functional MRI data, along with associated resources.

Public health preparedness for coronavirus (CoV) disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal CoVs (sCoVs) and other cocirculating viruses in the West of Scotland, United Kingdom. We analyzed routine diagnostic data for >70 000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43, and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently, and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity.

Future fault-tolerant quantum computers will require storing and processing quantum data in logical qubits. Here we realize a suite of logical operations on a distance-2 surface code qubit built from seven physical qubits and stabilized using repeated error-detection cycles. Logical operations include initialization into arbitrary states, measurement in the cardinal bases of the Bloch sphere and a universal set of single-qubit gates. For each type of operation, we observe higher performance for fault-tolerant variants over non-fault-tolerant variants, and quantify the difference. In particular, we demonstrate process tomography of logical gates, using the notion of a logical Pauli transfer matrix. This integration of high-fidelity logical operations with a scalable scheme for repeated stabilization is a milestone on the road to quantum error correction with higher-distance superconducting surface codes. Large-scale quantum computers will manipulate quantum information encoded in error-corrected logical qubits. A complete set of operations has now been realized on a logical qubit with error detection.

Increasing environmental distress is associated with a growing asthma incidence; no treatments are available but montelukast (MTK)—an antagonist of the cysteinyl leukotrienes receptor 1—is widely used in the management of symptoms among adults and children. Recently, new molecular targets have been identified and MTK has been proposed for repurposing in other therapeutic applications, with several ongoing clinical trials. The proposed applications include neuroinflammation control, which could be explored in some neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases (AD and PD). However, this drug has been associated with an increasing number of reported neuropsychiatric adverse drug reactions (ADRs). Besides, and despite being on the market since 1998, MTK metabolism is still poorly understood and the mechanisms underlying neuropsychiatric ADRs remain unknown. We review the role of MTK as a modulator of leukotriene pathways and systematize the current knowledge about MTK metabolism. Known toxic effects of MTK are discussed, and repurposing applications are presented comprehensively, with a focus on AD and PD.

Stress is a well-established trigger for a number of neuropsychiatric disorders, as it alters both structure and function of several brain regions and its networks. Herein, we conduct a longitudinal neuroimaging study to assess how a chronic unpredictable stress protocol impacts the structure of the rat brain and its functional connectome in both high and low responders to stress. Our results reveal the changes that stress triggers in the brain, with structural atrophy affecting key regions such as the prelimbic, cingulate, insular and retrosplenial, somatosensory, motor, auditory and perirhinal/entorhinal cortices, the hippocampus, the dorsomedial striatum, nucleus accumbens, the septum, the bed nucleus of the stria terminalis, the thalamus and several brain stem nuclei. These structural changes are associated with increasing functional connectivity within a network composed by these regions. Moreover, using a clustering based on endocrine and behavioural outcomes, animals were classified as high and low responders to stress. We reveal that susceptible animals (high responders) develop local atrophy of the ventral tegmental area and an increase in functional connectivity between this area and the thalamus, further spreading to other areas that link the cognitive system with the fight-or-flight system. Through a longitudinal approach we were able to establish two distinct patterns, with functional changes occurring during the exposure to stress, but with an inflection point after the first week of stress when more prominent changes were seen. Finally, our study revealed differences in functional connectivity in a brainstem–limbic network that distinguishes resistant and susceptible responders before any exposure to stress, providing the first potential imaging-based predictive biomarkers of an individual’s resilience/vulnerability to stressful conditions.

This research was funded by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) (NORTE-01-0145-FEDER-000023) and by the Portuguese Foundation for Science and Technology ((M-ERA-NET/0022/2016), Transitional Rule DL 57/2016 (CTTI-57/18-I3BS(5)), and (IF/01285/2015)).

The long history of the research concerning the possible existence of bound or resonant states in light multineutron systems, essentially 3 n and 4 n, is reviewed. Both the experimental and the theoretical points of view have been considered, with the aim of showing a clear picture of all the different detection and calculation techniques that have been used, with particular emphasis in the issues that have been found. Finally, some aspects of the present and future research in this field are discussed.

Chronic stress is a major risk factor for several human disorders that affect modern societies. The brain is a key target of chronic stress. In fact, there is growing evidence indicating that exposure to stress affects learning and memory, decision making and emotional responses, and may even predispose for pathological processes, such as Alzheimer’s disease and depression. Lipids are a major constituent of the brain and specifically signaling lipids have been shown to regulate brain function. Here, we used a mass spectrometry-based lipidomic approach to evaluate the impact of a chronic unpredictable stress (CUS) paradigm on the rat brain in a region-specific manner. We found that the prefrontal cortex (PFC) was the area with the highest degree of changes induced by chronic stress. Although the hippocampus presented relevant lipidomic changes, the amygdala and, to a greater extent, the cerebellum presented few lipid changes upon chronic stress exposure. The sphingolipid and phospholipid metabolism were profoundly affected, showing an increase in ceramide (Cer) and a decrease in sphingomyelin (SM) and dihydrosphingomyelin (dhSM) levels, and a decrease in phosphatidylethanolamine (PE) and ether phosphatidylcholine (PCe) and increase in lysophosphatidylethanolamine (LPE) levels, respectively. Furthermore, the fatty-acyl profile of phospholipids and diacylglycerol revealed that chronic stressed rats had higher 38 carbon(38C)-lipid levels in the hippocampus and reduced 36C-lipid levels in the PFC. Finally, lysophosphatidylcholine (LPC) levels in the PFC were found to be correlated with blood corticosterone (CORT) levels. In summary, lipidomic profiling of the effect of chronic stress allowed the identification of dysregulated lipid pathways, revealing putative targets for pharmacological intervention that may potentially be used to modulate stress-induced deficits.

Large-scale flank collapses are one of the main hazards associated with the evolution of volcanic islands. Precisely dating such events is critical to evaluate the frequency of destabilization episodes and further assess the triggering mechanism(s) associated with internal and/or external factors, such as volcano dynamics, regional tectonics, and global paleoclimatic changes. Here, we constrain the age of a pumice-rich pyroclastic deposit exposed on the eastern flank of Flores Island (Azores), which we interpret as a co-blast deposit generated by a major flank collapse that destroyed the whole western flank of the former volcanic edifice. Twelve single-grain 40 Ar/ 39 Ar analyses, performed on 250–500 µm anorthoclase feldspars (mean K/Ca close to 5) with our high-sensitivity multi-collector NGX mass spectrometer, provide a robust weighted mean age of 1.32 ± 0.01 Ma for this eruption. This new age is consistent with previous K/Ar data bracketing the flank collapse between 1.30 ± 0.04 and 1.18 ± 0.09 Ma, and indicates that this event occurred at the end of the main construction phase of the volcano. The explosion produced pumice-rich layers preceded by a lahar as attested by a polygenetic mudflow deposit underlying the dated deposit. From the geochemistry of lavas erupted just before and after the collapse, we speculate upon the possible role of magmatic processes on flank destabilization. We propose a first hypothesis where differentiation in a shallow magma reservoir could have favored edifice inflation, ground shaking, and flank failure, triggering a decompression-induced violent eruption. Overall, our study shows that high-sensitivity mass spectrometers have now reached analytical performances allowing to measure precisely and accurately ages on relatively small and moderately K-rich single feldspars, which is of the utmost importance for dating heterogeneous blasts and tephra deposits that may have been induced by large-scale flank collapses during the late Quaternary.

Analysis of the currently established Bayesian nearest neighbors classification model points to a connection between the computation of its normalizing constant and issues of NP-completeness. An alternative predictive model constructed by aggregating the predictive distributions of simpler nonlocal models is proposed, and analytic expressions for the normalizing constants of these nonlocal models are derived, ensuring polynomial time computation without approximations. Experiments with synthetic and real datasets showcase the predictive performance of the proposed predictive model.