Brain state dynamics differ between eyes open and eyes closed rest.

The human brain exhibits spatio-temporally complex activity even in the absence of external stimuli, cycling through recurring patterns of activity known as brain states. Thus far, brain state analysis has primarily been restricted to unimodal neuroimaging data sets, resulting in a limited definition of state and a poor understanding of the spatial and temporal relationships between states identified from different modalities. Here, we applied hidden Markov model (HMM) to concurrent electroencephalography-functional magnetic resonance imaging (EEG-fMRI) eyes open (EO) and eyes closed (EC) resting-state data, training models on the EEG and fMRI data separately, and evaluated the models' ability to distinguish dynamics between the two rest conditions. Additionally, we employed a general linear model approach to identify the BOLD correlates of the EEG-defined states to investigate whether the fMRI data could be used to improve the spatial definition of the EEG states. Finally, we performed a sliding window-based analysis on the state time courses to identify slower changes in the temporal dynamics, and then correlated these time courses across modalities. We found that both models could identify expected changes during EC rest compared to EO rest, with the fMRI model identifying changes in the activity and functional connectivity of visual and attention resting-state networks, while the EEG model correctly identified the canonical increase in alpha upon eye closure. In addition, by using the fMRI data, it was possible to infer the spatial properties of the EEG states, resulting in BOLD correlation maps resembling canonical alpha-BOLD correlations. Finally, the sliding window analysis revealed unique fractional occupancy dynamics for states from both models, with a selection of states showing strong temporal correlations across modalities. Overall, this study highlights the efficacy of using HMMs for brain state analysis, confirms that multimodal data can be used to provide more in-depth definitions of state and demonstrates that states defined across different modalities show similar temporal dynamics.

Blood flow restriction as a post-exercise recovery strategy: A systematic review of the current status of the literature.

The aim of this study was to systematically review the current literature on blood flow restriction (BFR) as a post-exercise recovery strategy. Experimental studies investigating the effect of BFR on recovery after exercise were included. Only studies meeting the following inclusion criteria were selected: (a) studies investigating about BFR as a post-exercise recovery strategy in athletes and healthy individuals; (b) the full text being available in English; (c) experimental research study design. Studies that exclusively analyzed BFR as a recovery strategy during the exercise (e.g., recovery strategy between bouts of exercise) were excluded. A literature review was conducted on the PubMed, Cochrane, and Web of Science electronic databases up until May 7th, 2023. The main findings were that (i) 9 studies investigated passive BFR as a post-exercise recovery strategy, which shows a significant lack of research in both team and individual sports (especially in female populations), and only 2 studies used active BFR protocols; (ii) although a high quality range of studies was observed, there were methodological limitations such as BFR interventions that were usually conducted after fatiguing protocols or fitness tests, which may not represent the real exercise (e.g., a sprint session of 6 sets of 50 m may induce muscle damage but it does not represent the demands of a team sport like rugby or soccer); (iii) there is a lack of consistency in BFR protocols (e.g., number of cycles or duration of the occlusion-reperfusion periods) for recovery; (iv) some studies showed beneficial effects while others found no positive or detrimental effects of BFR as a post-exercise recovery strategy in comparison with the control/SHAM group. In conclusion, only 11 studies investigated BFR as a post-exercise recovery strategy and there is not any significant amount of evidence in team or individual sports (especially in female populations). BFR could be a potential post-exercise recovery strategy, but practitioners should use caution when applying this method of recovery for their athletes and clients. In addition, it would be of interest for high performance-related practitioners to have a better understanding of the benefits of BFR interventions combined with either active or passive forms of exercise as a post-exercise recovery strategy.

Light-induced insulator-metal transition in Sr2IrO4 reveals the nature of the insulating ground state.

Sr2IrO4 has attracted considerable attention due to its structural and electronic similarities to La2CuO4, the parent compound of high-Tc superconducting cuprates. It was proposed as a strong spin-orbit-coupled Jeff = 1/2 Mott insulator, but the Mott nature of its insulating ground state has not been conclusively established. Here, we use ultrafast laser pulses to realize an insulator-metal transition in Sr2IrO4 and probe the resulting dynamics using time- and angle-resolved photoemission spectroscopy. We observe a gap closure and the formation of weakly renormalized electronic bands in the gap region. Comparing these observations to the expected temperature and doping evolution of Mott gaps and Hubbard bands provides clear evidence that the insulating state does not originate from Mott correlations. We instead propose a correlated band insulator picture, where antiferromagnetic correlations play a key role in the gap opening. More broadly, our results demonstrate that energy-momentum-resolved nonequilibrium dynamics can be used to clarify the nature of equilibrium states in correlated materials.

A widespread electrical brain network encodes anxiety in health and depressive states.

In rodents, anxiety is charactered by heightened vigilance during low-threat and uncertain situations. Though activity in the frontal cortex and limbic system are fundamental to supporting this internal state, the underlying network architecture that integrates activity across brain regions to encode anxiety across animals and paradigms remains unclear. Here, we utilize parallel electrical recordings in freely behaving mice, translational paradigms known to induce anxiety, and machine learning to discover a multi-region network that encodes the anxious brain-state. The network is composed of circuits widely implicated in anxiety behavior, it generalizes across many behavioral contexts that induce anxiety, and it fails to encode multiple behavioral contexts that do not. Strikingly, the activity of this network is also principally altered in two mouse models of depression. Thus, we establish a network-level process whereby the brain encodes anxiety in health and disease.

Continent-wide genomic analysis of the African buffalo (Syncerus caffer).

The African buffalo (Syncerus caffer) is a wild bovid with a historical distribution across much of sub-Saharan Africa. Genomic analysis can provide insights into the evolutionary history of the species, and the key selective pressures shaping populations, including assessment of population level differentiation, population fragmentation, and population genetic structure. In this study we generated the highest quality de novo genome assembly (2.65 Gb, scaffold N50 69.17 Mb) of African buffalo to date, and sequenced a further 195 genomes from across the species distribution. Principal component and admixture analyses provided little support for the currently described four subspecies. Estimating Effective Migration Surfaces analysis suggested that geographical barriers have played a significant role in shaping gene flow and the population structure. Estimated effective population sizes indicated a substantial drop occurring in all populations 5-10,000 years ago, coinciding with the increase in human populations. Finally, signatures of selection were enriched for key genes associated with the immune response, suggesting infectious disease exert a substantial selective pressure upon the African buffalo. These findings have important implications for understanding bovid evolution, buffalo conservation and population management.

Changes in cannabis involvement in emergency department visits for anxiety disorders after cannabis legalization: a repeated cross-sectional study.

Background: An increasing number of countries have or are considering legalizing cannabis. One concern is that legalization of cannabis will result in increased cannabis use and in turn a higher prevalence of anxiety disorders. We examined changes in emergency department (ED) visits for anxiety disorders with cannabis involvement in Ontario, over a period that involved medical and non-medical cannabis legalization. Methods: This repeated cross-sectional population-based study identified all ED visits for anxiety disorders from residents of Ontario, Canada aged 10-105 between 2008 and 2022 (n = 15.7 million individuals). We used interrupted time series analyses to examine immediate and gradual changes in cannabis-involvement and alcohol-involvement (control condition) over four policy periods: medical cannabis legalization (January 2008-November 2015), expanded medical access (December 2015-September 2018), non-medical cannabis legalization with restrictions (October 2018-February 2020), and commercialization which overlapped with the COVID-19 pandemic (March 2020-December 2022). Poisson models were used to generate incidence rate ratios with 95% confidence intervals. Findings: Over the 14-year study, there were 438,700 individuals with one or more ED visits for anxiety disorders of which 3880 (0.89%) individuals had cannabis involvement and 6329 (1.45%) individuals had alcohol involvement. During the commercialization/COVID-19 period monthly rates of anxiety disorders with cannabis-involvement were 156% higher (0.11 vs 0.29 per 100,000 individuals) relative to the pre-legalization period, compared to a 27% increase for alcohol-involvement (0.27 vs 0.35 per 1100,000 individuals). Rates of anxiety ED visits with cannabis involvement per 100,000 individuals increased gradually over the study period with no immediate or gradual changes after expanded medical access, legalization with restrictions or commercialization/COVID-19. However, during the commercialization/COVID-19 period there were large declines in total anxiety disorder ED visits and anxiety disorder ED visits with alcohol-involvement. Consequently, during this period there was an immediate 31.4% relative increase in the proportion of anxiety visits with cannabis-involvement (incidence rate ratio [IRR], 1.31; 95% CI 1.05-1.65). Interpretation: We found large relative increases in anxiety disorder ED visits with cannabis involvement over a 14-year period involving medical and non-medical cannabis legalization. These findings may reflect increasing anxiety disorder problems from cannabis use, increasing self-medication of anxiety disorders with cannabis use, or both. The proportion of anxiety ED visits with cannabis involvement increased during the final period of the study but could have been the results of the market commercialization, COVID-19 or both and ongoing monitoring is indicated. Funding: Canadian Institutes of Health Research (grant #452360).

Geographical migration and fitness dynamics of Streptococcus pneumoniae.

Streptococcus pneumoniae is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location1,2. The extent and mechanisms of spread and vaccine-driven changes in fitness and antimicrobial resistance remain largely unquantified. Here using geolocated genome sequences from South Africa (n = 6,910, collected from 2000 to 2014), we developed models to reconstruct spread, pairing detailed human mobility data and genomic data. Separately, we estimated the population-level changes in fitness of strains that are included (vaccine type (VT)) and not included (non-vaccine type (NVT)) in pneumococcal conjugate vaccines, first implemented in South Africa in 2009. Differences in strain fitness between those that are and are not resistant to penicillin were also evaluated. We found that pneumococci only become homogenously mixed across South Africa after 50 years of transmission, with the slow spread driven by the focal nature of human mobility. Furthermore, in the years following vaccine implementation, the relative fitness of NVT compared with VT strains increased (relative risk of 1.68; 95% confidence interval of 1.59-1.77), with an increasing proportion of these NVT strains becoming resistant to penicillin. Our findings point to highly entrenched, slow transmission and indicate that initial vaccine-linked decreases in antimicrobial resistance may be transient.

Non-pharmaceutical interventions for COVID-19 transiently reduced pneumococcal and Haemophilus influenzae carriage in a cross-sectional pediatric cohort in Southampton, UK.

The Southampton pneumococcal carriage study of children under 5 years old continued during the coronavirus disease 2019 (COVID-19) pandemic. Here, we present data from October 2018 to March 2023 describing prevalence of pneumococci and other pathobionts during the winter seasons before, during, and after the introduction of non-pharmaceutical interventions (NPIs) to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Nasopharyngeal swabs were collected from children attending outpatient clinics at a secondary care hospital and community healthcare sites. Pre-NPIs, in 2019/2020, the carriage prevalence of pneumococci at the hospital site was 32% (n = 161 positive/499 participants). During NPIs, this fell to 19% (n = 12/64), although based on fewer participants compared to previous years due to COVID-19 restrictions on health-care attendance. In 2021/2022, after NPIs had eased, prevalence rebounded to 33% (n = 15/46) [compared to NPIs period, χ2 (1, N = 110) =2.78, P = 0.09]. Carriage prevalence at community healthcare sites fell significantly from 27% (n = 127/470) in 2019/2020 to 19% during the NPI period (n = 44/228) in 2020/2021 [χ2 (1, N = 698) =4.95, P = 0.026]. No rebound was observed in 2021/2022 [19% (n = 56/288)]. However, in a multivariate logistic regression model, neither site had a significantly lower carriage prevalence during the NPI period compared to the post NPI period. A reduction in serotype diversity was observed in 2020/2021. Carriage of Haemophilus influenzae was particularly affected by NPIs with a significant reduction observed. In conclusion, among children under 5 years of age, transient, modest, and statistically non-significant alterations in carriage of both Streptococcus pneumoniae and H. influenzae were associated with SARS-CoV-2 NPIs.IMPORTANCEStreptococcus pneumoniae (the pneumococcus) continues to be a major contributor to global morbidity and mortality. Using our long-running pediatric study, we examined changes in pneumococcal carriage prevalence in nearly 3,000 children under the age of 5 years between the winters of 2018/2019 and 2022/2023. This period coincided with the severe acute respiratory syndrome coronavirus 2 pandemic and, in particular, the implementation of national strategies to limit disease transmission in the UK. We observed a transient reduction of both Streptococcus pneumoniae and Haemophilus influenzae in these populations during this period of non-pharmaceutical interventions. This aligned with the reduction in invasive pneumococcal disease seen in the UK and is therefore a likely contributor to this phenomenon.

Epidemiology of Travel-Associated Dengue from 2007 to 2022: A GeoSentinel Analysis.

BACKGROUND: Dengue is a leading cause of febrile illness among international travellers. We aimed to describe the epidemiology and clinical characteristics of imported dengue in returning travellers evaluated at GeoSentinel sites from 2007-2022. METHODS: We retrieved GeoSentinel records of dengue among travellers residing in non-endemic countries. We considered dengue confirmed when diagnosed by a positive DENV-specific RT-PCR, positive NS-1 antigen, and/or anti-DENV IgG seroconversion, and probable when diagnosed by single anti-DENV IgM or high titre anti-DENV IgG detection. Severe dengue was defined as evidence of clinically significant plasma leakage or bleeding, organ failure, or shock, according to the 2009 WHO guidance. Complicated dengue was defined as either severe dengue or dengue with presence of any warning sign. Analyses were descriptive. RESULTS: This analysis included 5958 travellers with confirmed (n = 4859; 81.6%) or probable (n = 1099; 18.4%) dengue. The median age was 33 years (range: < 1-91); 3007 (50.5%) travellers were female. The median travel duration was 21 days (interquartile range [IQR]: 15-32). The median time between illness onset and GeoSentinel site visit was 7 days (IQR: 4-15). The most frequent reasons for travel were tourism (67.3%), visiting friends or relatives (12.2%), and business (11.0%). The most frequent regions of acquisition were Southeast Asia (50.4%), South-Central Asia (14.9%), the Caribbean (10.9%), and South America (9.2%). Ninety-five (1.6%) travellers had complicated dengue, of whom 27 (0.5%) had severe dengue, and one died. Of 2710 travellers with data available, 724 (26.7%) were hospitalized. The largest number of cases (n = 835) was reported in 2019. CONCLUSIONS: A broad range of international travellers should be aware of the risk of acquiring dengue and receive appropriate pretravel counselling regarding preventive measures. Prospective cohort studies are needed to further elucidate dengue risk by destination and over time, as well as severe outcomes and prolonged morbidity (long-dengue) due to travel-related dengue.

Functional stress responses in Glaucophyta: Evidence of ethylene and abscisic acid functions in Cyanophora paradoxa.

Glaucophytes, an enigmatic group of freshwater algae, occupy a pivotal position within the Archaeplastida, providing insights into the early evolutionary history of plastids and their host cells. These algae possess unique plastids, known as cyanelles that retain certain ancestral features, enabling a better understanding of the plastid transition from cyanobacteria. In this study, we investigated the role of ethylene, a potent hormone used by land plants to coordinate stress responses, in the glaucophyte alga Cyanophora paradoxa. We demonstrate that C. paradoxa produces gaseous ethylene when supplied with exogenous 1-aminocyclopropane-1-carboxylic acid (ACC), the ethylene precursor in land plants. In addition, we show that cells produce ethylene natively in response to abiotic stress, and that another plant hormone, abscisic acid (ABA), interferes with ethylene synthesis from exogenously supplied ACC, while positively regulating reactive oxygen species (ROS) accumulation. ROS synthesis also occurred following abiotic stress and ACC treatment, possibly acting as a second messenger in stress responses. A physiological response of C. paradoxa to ACC treatment is growth inhibition. Using transcriptomics, we reveal that ACC treatment induces the upregulation of senescence-associated proteases, consistent with the observation of growth inhibition. This is the first report of hormone usage in a glaucophyte alga, extending our understanding of hormone-mediated stress response coordination into the Glaucophyta, with implications for the evolution of signaling modalities across Archaeplastida.

Feasibility of the flipped classroom approach for health education in a clinical weight loss program.

Aim: To assess the feasibility of the flipped classroom pedagogy in a clinical weight loss program and its impact on 6-month weight change. Methods: Adults with overweight/obesity enrolled in a 6-month program with a structured diet (portion-controlled meals and fruits/vegetables) and exercise plan (≥150mins/week), plus weekly, 1-h group education sessions. Sessions used a flipped classroom approach: educational content was delivered beforehand via podcast/video and book readings and session time involved application-based activities (e.g., case studies, games). Satisfaction surveys were completed at 3 months. Weight change was assessed using paired t-tests (SAS 9.4, significance 0.05). Results: Eighteen participants completed 6 months (retention 94%). Participants maintained diet adherence and exercise at 3 months (∼84% diet adherence, ∼153mins exercise/week) and 6 months (∼83% diet adherence, ∼158mins exercise/week), as well as attendance to behavioral sessions (3 months: 77%; 6mo: 71%). Satisfaction surveys showed high program enjoyment (∼8.1/10). Mean weight change at 3 and 6 months was -6.5 ± 4.2% and - 9.3 ± 5.0% (both p < 0.01), respectively. Conclusion: The flipped classroom pedagogy was feasible for delivery in a clinical weight loss program and supported significant 6-month weight loss. Innovation: This is the first evaluation of the flipped classroom in a clinical setting and supports the investigation of this pedagogy in weight management.

Sustained benefits of onabotulinumtoxinA treatment in chronic migraine: An analysis of the pooled Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) randomized controlled trials.

OBJECTIVE: To characterize the long-term (56-week) benefits of continuous onabotulinumtoxinA treatment response in individuals with chronic migraine (CM) who achieved reduction to <15 headache days/month with treatment. BACKGROUND: There are limited data exploring reductions in monthly headache days to levels consistent with episodic migraine among those experiencing CM. Understanding the impact of sustained preventive treatment response in CM can provide important information about the impact of successful therapy. METHODS: The two Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy trials of onabotulinumtoxinA in adults included a 24-week, randomized, double-blind, placebo-controlled phase and a 32-week open-label phase. Data were pooled to determine proportions of individuals with <15 headache days/month while on treatment during several time periods in the double-blind phase (Weeks 21-24; any 12 consecutive weeks; Weeks 13-24) and the entire study (Weeks 53-56; any 12 consecutive weeks; any 4-week period). We assessed the long-term impact on mean monthly headache days and changes from baseline on the six-item Headache Impact Test (HIT-6) and Migraine-Specific Quality of Life questionnaire version 2.1 (MSQv2.1). RESULTS: We analyzed 1384 participants with chronic migraine (double-blind: onabotulinumtoxinA, n = 688; placebo, n = 696; open-label: n = 688 [onabotulinumtoxinA]). The discontinuation rates prior to the completion of the full 56-week treatment period for onabotulinumtoxinA and placebo were 25.4% (n = 175) and 29.3% (n = 204), respectively. During Weeks 13-24 of the double-blind phase, significantly more onabotulinumtoxinA-treated (386/688 [56.1%]) than placebo-treated (342/696 [49.1%]) individuals had <15 headache days/month (p = 0.010), with fewer monthly headache days for onabotulinumtoxinA versus placebo responders. The proportions of participants achieving <15 monthly headache days with onabotulinumtoxinA were 60.9% (419/688) at Weeks 25-56, 81.1% (558/688) at Weeks 53-56, and 79.4% (546/688) during any consecutive 12-week period. Mean changes from baseline on the HIT-6 and MSQv2.1 questionnaire surpassed within-group minimal important difference thresholds in all periods. At Week 24, onabotulinumtoxinA-treated participants who achieved <15 monthly headache days during Weeks 21-24 had a greater mean HIT-6 score reduction (-6.5 vs. -1.4) and greater mean MSQv2.1 Role-Function Restrictive score improvements (21.3 vs. 6.4) than those who did not achieve <15 monthly headache days during the same period. CONCLUSIONS: Participants who achieved <15 monthly headache days with onabotulinumtoxinA treatment achieved meaningful benefits in headache-related disability and migraine-specific quality of life compared with those who remained at or above the 15-monthly headache days threshold. Sustained benefits observed over 56 weeks support long-term onabotulinumtoxinA use for the prevention of CM.

Kinetically Controlled and Nonequilibrium Assembly of Block Copolymers in Solution.

Covalent polymers are versatile macromolecules that have found widespread use in society. Contemporary methods of polymerization have made it possible to construct sequence polymers, including block copolymers, with high precision. Such copolymers assemble in solution when the blocks have differing solubilities. This produces nano- and microparticles of various shapes and sizes. While it is straightforward to draw an analogy between such amphiphilic block copolymers and phospholipids, these two classes of molecules show quite different assembly characteristics. In particular, block copolymers often assemble under kinetic control, thus producing nonequilibrium structures. This leads to a rich variety of behaviors being observed in block copolymer assembly, such as pathway dependence (e.g., thermal history), nonergodicity and responsiveness. The dynamics of polymer assemblies can be readily controlled using changes in environmental conditions and/or integrating functional groups situated on polymers with external chemical reactions. This perspective highlights that kinetic control is both pervasive and a useful attribute in the mechanics of block copolymer assembly. Recent examples are highlighted in order to show that toggling between static and dynamic behavior can be used to generate, manipulate and dismantle nonequilibrium states. New methods to control the kinetics of block copolymer assembly will provide endless unanticipated applications in materials science, biomimicry and medicine.

Climate change introduces threatened killer whale populations and conservation challenges to the Arctic.

The Arctic is the fastest-warming region on the planet, and the lengthening ice-free season is opening Arctic waters to sub-Arctic species such as the killer whale (Orcinus orca). As apex predators, killer whales can cause significant ecosystem-scale changes. Setting conservation priorities for killer whales and their Arctic prey species requires knowledge of their evolutionary history and demographic trajectory. Using whole-genome resequencing of 24 killer whales sampled in the northwest Atlantic, we first explored the population structure and demographic history of Arctic killer whales. To better understand the broader geographic relationship of these Arctic killer whales to other populations, we compared them to a globally sampled dataset. Finally, we assessed threats to Arctic killer whales due to anthropogenic harvest by reviewing the peer-reviewed and gray literature. We found that there are two highly genetically distinct, non-interbreeding populations of killer whales using the eastern Canadian Arctic. These populations appear to be as genetically different from each other as are ecotypes described elsewhere in the killer whale range; however, our data cannot speak to ecological differences between these populations. One population is newly identified as globally genetically distinct, and the second is genetically similar to individuals sampled from Greenland. The effective sizes of both populations recently declined, and both appear vulnerable to inbreeding and reduced adaptive potential. Our survey of human-caused mortalities suggests that harvest poses an ongoing threat to both populations. The dynamic Arctic environment complicates conservation and management efforts, with killer whales adding top-down pressure on Arctic food webs crucial to northern communities' social and economic well-being. While killer whales represent a conservation priority, they also complicate decisions surrounding wildlife conservation and resource management in the Arctic amid the effects of climate change.

Krause corpuscles are genital vibrotactile sensors for sexual behaviours.

Krause corpuscles, which were discovered in the 1850s, are specialized sensory structures found within the genitalia and other mucocutaneous tissues1-4. The physiological properties and functions of Krause corpuscles have remained unclear since their discovery. Here we report the anatomical and physiological properties of Krause corpuscles of the mouse clitoris and penis and their roles in sexual behaviour. We observed a high density of Krause corpuscles in the clitoris compared with the penis. Using mouse genetic tools, we identified two distinct somatosensory neuron subtypes that innervate Krause corpuscles of both the clitoris and penis and project to a unique sensory terminal region of the spinal cord. In vivo electrophysiology and calcium imaging experiments showed that both Krause corpuscle afferent types are A-fibre rapid-adapting low-threshold mechanoreceptors, optimally tuned to dynamic, light-touch and mechanical vibrations (40-80 Hz) applied to the clitoris or penis. Functionally, selective optogenetic activation of Krause corpuscle afferent terminals evoked penile erection in male mice and vaginal contraction in female mice, while genetic ablation of Krause corpuscles impaired intromission and ejaculation of males and reduced sexual receptivity of females. Thus, Krause corpuscles of the clitoris and penis are highly sensitive mechanical vibration detectors that mediate sexually dimorphic mating behaviours.

Optical manipulation of the charge-density-wave state in RbV3Sb5.

Broken time-reversal symmetry in the absence of spin order indicates the presence of unusual phases such as orbital magnetism and loop currents1-4. The recently discovered kagome superconductors AV3Sb5 (where A is K, Rb or Cs)5,6 display an exotic charge-density-wave (CDW) state and have emerged as a strong candidate for materials hosting a loop current phase. The idea that the CDW breaks time-reversal symmetry7-14 is, however, being intensely debated due to conflicting experimental data15-17. Here we use laser-coupled scanning tunnelling microscopy to study RbV3Sb5. By applying linearly polarized light along high-symmetry directions, we show that the relative intensities of the CDW peaks can be reversibly switched, implying a substantial electro-striction response, indicative of strong nonlinear electron-phonon coupling. A similar CDW intensity switching is observed with perpendicular magnetic fields, which implies an unusual piezo-magnetic response that, in turn, requires time-reversal symmetry breaking. We show that the simplest CDW that satisfies these constraints is an out-of-phase combination of bond charge order and loop currents that we dub a congruent CDW flux phase. Our laser scanning tunnelling microscopy data open the door to the possibility of dynamic optical control of complex quantum phenomenon in correlated materials.

Estimating geographical spread of Streptococcus pneumoniae within Israel using genomic data.

Understanding how pathogens spread across geographical space is fundamental for control measures such as vaccination. Streptococcus pneumoniae (the pneumococcus) is a respiratory bacterium responsible for a large proportion of infectious disease morbidity and mortality globally. Even in the post-vaccination era, the rates of invasive pneumococcal disease (IPD) remain stable in most countries, including Israel. To understand the geographical spread of the pneumococcus in Israel, we analysed 1174 pneumococcal genomes from patients with IPD across multiple regions. We included the evolutionary distance between pairs of isolates inferred using whole-genome data within a relative risk (RR) ratio framework to capture the geographical structure of S. pneumoniae. While we could not find geographical structure at the overall lineage level, the extra granularity provided by whole-genome sequence data showed that it takes approximately 5 years for invasive pneumococcal isolates to become fully mixed across the country.This article contains data hosted by Microreact.

Longitudinal changes in iron homeostasis in human experimental and clinical malaria.

BACKGROUND: The interaction between iron status and malaria is incompletely understood. We evaluated longitudinal changes in iron homeostasis in volunteers enrolled in malaria volunteer infection studies (VIS) and in Malaysian patients with falciparum and vivax malaria. METHODS: We retrieved data and samples from 55 participants (19 female) enrolled in malaria VIS, and 171 patients (45 female) with malaria and 30 healthy controls (13 female) enrolled in clinical studies in Malaysia. Ferritin, hepcidin, erythropoietin, and soluble transferrin receptor (sTfR) were measured by ELISA. FINDINGS: In the VIS, participants' parasitaemia was correlated with baseline mean corpuscular volume (MCV), but not iron status (ferritin, hepcidin or sTfR). Ferritin, hepcidin and sTfR all increased during the VIS. Ferritin and hepcidin normalised by day 28, while sTfR remained elevated. In VIS participants, baseline ferritin was associated with post-treatment increases in liver transaminase levels. In Malaysian patients with malaria, hepcidin and ferritin were elevated on admission compared to healthy controls, while sTfR increased following admission. By day 28, hepcidin had normalised; however, ferritin and sTfR both remained elevated. INTERPRETATION: Our findings demonstrate that parasitaemia is associated with an individual's MCV rather than iron status. The persistent elevation in sTfR 4 weeks post-infection in both malaria VIS and clinical malaria may reflect a causal link between malaria and iron deficiency. FUNDING: National Health and Medical Research Council (Program Grant 1037304, Project Grants 1045156 and 1156809; Investigator Grants 2016792 to BEB, 2016396 to JCM, 2017436 to MJG); US National Institute of Health (R01-AI116472-03); Malaysian Ministry of Health (BP00500420).

Choline supplementation in early life improves and low levels of choline can impair outcomes in a mouse model of Alzheimer's disease.

Maternal choline supplementation (MCS) improves cognition in Alzheimer's disease (AD) models. However, the effects of MCS on neuronal hyperexcitability in AD are unknown. We investigated the effects of MCS in a well-established mouse model of AD with hyperexcitability, the Tg2576 mouse. The most common type of hyperexcitability in Tg2576 mice are generalized EEG spikes (interictal spikes [IIS]). IIS also are common in other mouse models and occur in AD patients. In mouse models, hyperexcitability is also reflected by elevated expression of the transcription factor ∆FosB in the granule cells (GCs) of the dentate gyrus (DG), which are the principal cell type. Therefore, we studied ΔFosB expression in GCs. We also studied the neuronal marker NeuN within hilar neurons of the DG because reduced NeuN protein expression is a sign of oxidative stress or other pathology. This is potentially important because hilar neurons regulate GC excitability. Tg2576 breeding pairs received a diet with a relatively low, intermediate, or high concentration of choline. After weaning, all mice received the intermediate diet. In offspring of mice fed the high choline diet, IIS frequency declined, GC ∆FosB expression was reduced, and hilar NeuN expression was restored. Using the novel object location task, spatial memory improved. In contrast, offspring exposed to the relatively low choline diet had several adverse effects, such as increased mortality. They had the weakest hilar NeuN immunoreactivity and greatest GC ΔFosB protein expression. However, their IIS frequency was low, which was surprising. The results provide new evidence that a diet high in choline in early life can improve outcomes in a mouse model of AD, and relatively low choline can have mixed effects. This is the first study showing that dietary choline can regulate hyperexcitability, hilar neurons, ΔFosB, and spatial memory in an animal model of AD.