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Abstract Background In dinoflagellates, a unique and extremely divergent genomic and nuclear organization has evolved. The highly unusual features of dinoflagellate nuclei and genomes include permanently condensed liquid crystalline chromosomes, primarily packaged by proteins other than histones, genes organized in very long unidirectional gene arrays, a general absence of transcriptional regulation, high abundance of the otherwise very rare DNA modification 5-hydroxymethyluracil (5-hmU), and many others. While most of these fascinating properties are originally identified in the 1970s and 1980s, they have not yet been investigated using modern genomic tools. Results In this work, we address some of the outstanding questions regarding dinoflagellate genome organization by mapping the genome-wide distribution of 5-hmU (using both immunoprecipitation-based and basepair-resolution chemical mapping approaches) and of chromatin accessibility in the genome of the Symbiodiniaceae dinoflagellate Breviolum minutum. We find that the 5-hmU modification is preferentially enriched over certain classes of repetitive elements, often coincides with the boundaries between gene arrays, and is generally correlated with decreased chromatin accessibility, the latter otherwise being largely uniform along the genome. We discuss the potential roles of 5-hmU in the functional organization of dinoflagellate genomes and its relationship to the transcriptional landscape of gene arrays. Conclusions Our results provide the first window into the 5-hmU and chromatin accessibility landscapes in dinoflagellates.

Dinoflagellates are ecologically important and essential to corals and other cnidarians as phytosymbionts, but their photosystems had been underexplored. Recently, photosystem I (PSI) of dinoflagellate Symbiodinium sp. was structurally characterized using cryo-Electron Microscopy (cryo-EM). These analyses revealed a distinct organization of the PSI supercomplex, including two previously unidentified subunits, PsaT and PsaU, and shed light on interactions between light harvesting antenna proteins and the PSI core. These results have implications with respect to the evolution of dinoflagellates and their association with cnidarians.

Abstract Kaon physics is at a turning point – while the rare-kaon experiments NA62 and KOTO are in full swing, the end of their lifetime is approaching and the future experimental landscape needs to be defined. With HIKE, KOTO-II and LHCb-Phase-II on the table and under scrutiny, it is a very good moment in time to take stock and contemplate about the opportunities these experiments and theoretical developments provide for particle physics in the coming decade and beyond. This paper provides a compact summary of talks and discussions from the Kaons@CERN 2023 workshop, held in September 2023 at CERN.

Digital health technologies (DHTs) can transform neurological assessments, improving quality and continuity of care. In the United States, the Food & Drug Administration (FDA) oversees the safety and efficacy of these technologies, employing a detailed regulatory process that classifies devices based on risk and requires rigorous review and post-market surveillance. Following FDA approval, DHTs enter the Current Procedural Terminology, Relative Value Scale Update Committee, and Centers for Medicare & Medicaid Services coding and valuation processes leading to coverage and payment decisions. DHT adoption is challenged by rapid technologic advancements, an inconsistent evidence base, marketing discrepancies, ambiguous coding guidance, and variable health insurance coverage. Regulators, policymakers, and payers will need to develop better methods to evaluate these promising technologies and guide their deployment. This includes striking a balance between patient safety and clinical effectiveness versus promotion of innovation, especially as DHTs increasingly incorporate artificial intelligence. Data validity, cybersecurity, risk management, societal, and ethical responsibilities should be addressed. Regulatory advances can support adoption of these promising tools by ensuring DHTs are safe, effective, accessible, and equitable.

Abstract Freshwater mussels preserve valuable information about hydrology, climate, and population dynamics, but developing seasonal chronologies can be problematic. Using clumped isotope thermometry, we produced high-resolution reconstructions of modern and historic (~ 1900) temperatures and δ18Owater from mussel shells collected from an impounded river, the Brazos in Texas, before and after damming. We also performed high-resolution growth band analyses to investigate relationships between mussel growth rate, rainfall, and seasonal temperature. Reconstructed δ18Owater and temperature vary little between the modern (3R5) and historic shell (H3R). However, a positive relationship between reconstructed δ18Owater and growth rate in H3R indicates that aside from diminished growth in winter, precipitation and flow rate are the strongest controls on mussel growth in both modern and pre-dam times. Overall, our results demonstrate (1) the impact, both positive and negative, of environmental factors such as flow alteration and temperature on mussel growth and (2) the potential for clumped isotopes in freshwater mussels as a paleohydrology and paleoclimate proxies in terrestrial environments.

Abstract Objective Alzheimer's disease neuropathologic change and alpha‐synucleinopathy commonly co‐exist and contribute to the clinical heterogeneity of dementia. Here, we examined tau epitopes marking various stages of tangle maturation to test the hypotheses that tau maturation is more strongly associated with beta‐amyloid compared to alpha‐synuclein, and within the context of mixed pathology, mature tau is linked to Alzheimer's disease clinical phenotype and negatively associated with Lewy body dementia. Methods We used digital histology to measure percent area‐occupied by pathology in cortical regions among individuals with pure Alzheimer's disease neuropathologic change, pure alpha‐synucleinopathy, and a co‐pathology group with both Alzheimer's and alpha‐synuclein pathologic diagnoses. Multiple tau monoclonal antibodies were used to detect early (AT8, MC1) and mature (TauC3) epitopes of tangle progression. We used linear/logistic regression to compare groups and test the association between pathologies and clinical features. Results There were lower levels of tau pathology (β = 1.86–2.96, p

An international consensus report in 2019 recommended a classification system for limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC). The suggested neuropathologic staging system and nomenclature have proven useful for autopsy practice and dementia research. However, some issues remain unresolved, such as cases with unusual features that do not fit with current diagnostic categories. The goal of this report is to update the neuropathologic criteria for the diagnosis and staging of LATE-NC, based primarily on published data. We provide practical suggestions about how to integrate available genetic information and comorbid pathologies [e.g., Alzheimer's disease neuropathologic changes (ADNC) and Lewy body disease]. We also describe recent research findings that have enabled more precise guidance on how to differentiate LATE-NC from other subtypes of TDP-43 pathology [e.g., frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS)], and how to render diagnoses in unusual situations in which TDP-43 pathology does not follow the staging scheme proposed in 2019. Specific recommendations are also made on when not to apply this diagnostic term based on current knowledge. Neuroanatomical regions of interest in LATE-NC are described in detail and the implications for TDP-43 immunohistochemical results are specified more precisely. We also highlight questions that remain unresolved and areas needing additional study. In summary, the current work lays out a number of recommendations to improve the precision of LATE-NC staging based on published reports and diagnostic experience.

BACKGROUND: Availability of quality-assured medical abortion medicines plays a crucial role in providing comprehensive abortion care. However, access to these medicines is still restricted for many abortion seekers. Increasing availability of affordable, quality-assured mifepristone and misoprostol is important to improve access to safe medical abortion services. Driven by the outcomes of a global consultation hosted by the World Health Organization and the Swedish International Development Cooperation Agency in 2018, we decided to holistically examine access to medical abortion medicines from supply to demand. The overarching principle of the national landscape assessments was to generate evidence to support policy dialog and policymaking that is contextual to the needs of the country. This paper aims to describe the framework and methodological approach used in the World Health Organization landscape assessments of medical abortion medicines at country-level. METHODS: A country assessment protocol was developed to guide the methodology of the World Health Organization landscape assessments. The assessment protocol included adaptation of an existing availability framework, an online desk review and literature review for existing data available for the country of interest, country-level key informant interviews, and analysis of the data to identify barriers and opportunities to improve medical abortion availability. CONCLUSION: The availability framework and methodology will allow the identification of key barriers that limit readiness of medical abortion medicines, and the development of opportunities to overcome those barriers. The national landscape assessments will provide directions for future investments and offer guidance for policy and programming on medical abortion care.

PurposeGliomagenesis and resistance of glioblastoma (GBM) are believed to be mediated by glioma stem cells (GSC). Evidence suggests that SHH signaling promotes GSC proliferation and self-renewal.MethodsABTC-0904 was a two-arm, multicenter phase 0/II study of GDC-0449, an oral inhibitor of Smoothened (SMO) in patients undergoing resection for recurrent GBM. All patients (Arms I and II) had surgery and received drug post-operatively. Only patients in Arm I received drug prior to surgery. The primary objective was to determine 6-month progression free survival (PFS-6). Secondary endpoints include median PFS (mPFS) and overall survival (mOS), response rate, and toxicity. Correlative studies included bioanalysis of GDC-0449, and inhibition of SHH signaling, GSC proliferation and self-renewal.ResultsForty-one patients were enrolled. Pharmacokinetics of GDC-0449 in plasma demonstrated levels within expected therapeutic range in 75% of patients. The proportion of tumorcells producing CD133+ neurospheres, neurosphere proliferation, self-renewal, and expression of the SHh downstream signaling was significantly decreased in Arm I following GDC-0449 treatment (p

BackgroundHealth care providers reporting patients to government authorities is a main way people attempting self-managed abortion (SMA) become exposed to legal risks. Little is known about health care provider decision-making regarding SMA reporting.MethodsWe conducted semi-structured interviews with 37 clinicians who provided care in hospital-based obstetrics or emergency departments (13 obstetricians/gynecologists, two advance practice registered nurses providing obstetrics care, 12 emergency medicine physicians, and 10 family medicine physicians) throughout the United States. The interview guide asked participants to describe one or more cases of caring for a patient who may have attempted SMA and about related reporting decisions. We coded responses to answer two questions: What comes to mind for health care providers when asked to think about experiences caring for a patient who may have attempted SMA? Based on health care provider experiences, how might people who providers suspect may have attempted SMA end up reported?ResultsAbout half of participants had cared for someone who may have attempted SMA for that pregnancy. Only two mentioned SMA with misoprostol. Most participants described cases where they were unsure whether the patient had attempted to end their pregnancy on purpose. In most instances, participants mentioned that that the possibility of reporting never occurred to them nor came up. In some cases, participants described a reporting "adjacent" practice - e.g. beginning processes that could lead to substance use, domestic violence, or self-injury/suicide-related reports - or considered reporting related to a perceived need to report abortion complications. In two cases, hospital staff reported to the police and/or Child Protective Services related to the SMA attempt. These involved passing of a fetus after 20 weeks outside the hospital and a domestic violence incident.ConclusionReporting patients who may have attempted SMA may occur via provider perception of a need to report abortion complications and fetal demises, particularly at later gestations, and other reporting requirements (e.g. substance use, domestic violence, child maltreatment, suicide/self-harm).

Rare meson decays are among the most sensitive probes of both heavy and light new physics. Among them, new physics searches using kaons benefit from their small total decay widths and the availability of very large datasets. On the other hand, useful complementary information is provided by hyperon decay measurements. We summarize the relevant phenomenological models and the status of the searches in a comprehensive list of kaon and hyperon decay channels. We identify new search strategies for under-explored signatures, and demonstrate that the improved sensitivities from current and next-generation experiments could lead to a qualitative leap in the exploration of light dark sectors.

IntroductionFrontotemporal lobar degeneration (FTLD) is associated with FTLD due to tau (FTLD-tau) or TDP (FTLD-TDP) inclusions found at autopsy. Arterial Spin Labeling (ASL) MRI is often acquired in the same session as a structural T1-weighted image (T1w), enabling detection of regional changes in cerebral blood flow (CBF). We hypothesize that ASL-T1w registration with more degrees of freedom using boundary-based registration (BBR) will better align ASL and T1w images and show increased sensitivity to regional hypoperfusion differences compared to manual registration in patient participants. We hypothesize that hypoperfusion will be associated with a clinical measure of disease severity, the FTLD-modified clinical dementia rating scale sum-of-boxes (FTLD-CDR).Materials and methodsPatients with sporadic likely FTLD-tau (sFTLD-tau; N = 21), with sporadic likely FTLD-TDP (sFTLD-TDP; N = 14), and controls (N = 50) were recruited from the Connectomic Imaging in Familial and Sporadic Frontotemporal Degeneration project (FTDHCP). Pearson’s Correlation Coefficients (CC) were calculated on cortical vertex-wise CBF between each participant for each of 3 registration methods: (1) manual registration, (2) BBR initialized with manual registration (manual+BBR), (3) and BBR initialized using FLIRT (FLIRT+BBR). Mean CBF was calculated in the same regions of interest (ROIs) for each registration method after image alignment. Paired t-tests of CC values for each registration method were performed to compare alignment. Mean CBF in each ROI was compared between groups using t-tests. Differences were considered significant at p

IntroductionFather-adolescent talk about sex can protect adolescents from sexual risk behaviors. However, few studies explore how family members view fathers' talk with adolescents about sex and relationships. An understanding of how fathers, mothers, and adolescents view fathers' roles in talk with adolescents about sex and relationships can help to guide fathers' talk with adolescents and inform programs to provide targeted support for father-adolescent communication about sex and relationships.MethodsThis study investigates family perceptions of father-adolescent communication about sex and relationships by triangulating data from fathers, mothers, and adolescents using content analysis to conduct between-family analysis and within-family approaches with 15 families (n = 45 individuals) with high school-aged adolescents from across the U.S.ResultsAnalyses showed agreement on the importance of fathers' roles in family talk about sex. The findings showed shared recognition of the importance of fathers' roles in family talk about sex. Between-group analyses showed that fathers, mothers, and adolescents view fathers' roles as emotional supports and open communicators with their adolescents about sex and relationships and as educators and advisors for their adolescent children. Within-family analysis showed that families often agreed that there were gender differences in how fathers talked with their sons and daughters, but family members expressed different views on how adolescents' gender impacts father-adolescent communication about sexual topics.DiscussionThese findings may encourage fathers who are uncertain about the value of their roles in talking with their adolescent children about sex and relationships. They also highlight the importance of examining how fathers' messages to their adolescents about sex and relationships may continue to follow patterns of gender stereotypes. This is the first study to qualitatively triangulate perspectives of fathers, mothers, and adolescents on father-adolescent communication about sex and relationships. Since fathers are often less involved than mothers in parent-adolescent communication about sex and relationships, an understanding of how mothers and adolescents see fathers' roles and messages can help provide a pathway for fathers' engagement which works within a family system.

Abstract Objectives During the coronavirus disease 2019 (COVID‐19) pandemic surge, alternate care sites (ACS) such as the waiting room or hospital lobby were created amongst hospitals nationwide to help alleviate emergency department (ED) overflow. Despite the end of the pandemic surge, many of these ACS remain functional given the burden of prolonged ED wait times, with providers now utilizing the waiting room or ACS to initiate care. Therefore, the objective of this study is to evaluate if initiating patient care in ACS helps to decrease time to disposition. Methods Retrospective data were collected on 61,869 patient encounters presenting to an academic medical center ED. Patients with an emergency severity index (ESI) of 1 were excluded. The “pre‐ACS” or control data consisted of 38,625 patient encounters from September 30, 2018 to October 1, 2019, prior to the development of ACS, in which the patient was seen by a physician after they were brought to an assigned ED room. The “post‐ACS” study cohort consisted of 23,244 patient encounters from September 30, 2022 to October 1, 2023, after the initiation of ACS, during which patients were initially seen by a provider in an ACS. ACS at this institution included the three following areas: waiting room, ambulance waiting area, and a newly constructed ACS that was built next to the ED entrance on the first floor of the hospital. The newly constructed ACS consisted of 16 care spaces each containing an upright exam chair with dividers between each care space. Door‐to‐disposition time (DTD) was calculated by identifying the time when the patient entered the ED and the time when disposition was decided (admission requested or patient discharged). Using regression analysis, we compared the two data sets to determine significant differences among DTD time. Results The largest proportion of encounters were among ESI 3 patients, that is, 56.1%. There was a significant increase in median DTD for ESI 2 and 3 patients who were seen initially in an ACS compared to those who were not seen until they were in an assigned ER room. Specifically, there was a median increase of 40.9 min for ESI 2 patients and 18.8 min for ESI 3 patients who were seen initially in an ACS (p

Background Acute pain due to rib fractures causes significant in-hospital morbidity and impacts patients’ quality of life after discharge. Intraoperative transthoracic cryoneurolysis of the intercostal nerves can improve postoperative pain; however, non-surgical patients are provided limited analgesia options. Here, we describe our experience with a bedside cryoanalgesia technique for management of acute rib fracture pain.Methods Five patients at a single level I trauma center completed bedside intercostal nerve cryoneurolysis (INC) using a handheld cryotherapy device and ultrasound guidance. Relative pain ratings (scale 0–10/10) and maximal incentive spirometry (ISmax) volumes were taken prior to the procedure as a baseline. Patients were observed for 24 hours after procedure, with relative pain ratings and ISmax recorded at 1, 8, 16, and 24 hours after procedure.Results Our patients were 29–88 years old and had one to five single-sided rib fractures. At baseline, they had high pre-procedure pain ratings (7–10/10) and ISmax volumes of 800–2000 mL. Many had improvements in their pain rating but little change in their ISmax at 1 hour (1–5/10 and 1000–2000 mL, respectively) and 8 hours (1–5/10 and 1250–2400 mL, respectively). ISmax volumes improved by 16 hours (1500–2400 mL) with comparable pain ratings (0–5/10). At 24 hours, pain ratings and ISmax ranged from 0 to 8/10 and from 1500 mL to 2400 mL, respectively. Each patient had improved pain control and ISmax volumes compared with their pre-procedure values. All patients reported the procedure as an asset to their recovery at discharge.Conclusions Our study demonstrates patients with rib fractures may experience improved pain ratings and ISmax values after INC. Percutaneous INC appears to be a viable adjunct to multimodal pain control for patients with rib fractures and should be considered in patients with difficult pain control. Further studies are required to fully assess INC safety, efficacy, post-discharge outcomes, and utility in patients with altered mental status or on mechanical ventilation.Level of evidence Level V, case series.

Abstract Introduction Depression and its components significantly impact dementia prediction and severity, necessitating reliable objective measures for quantification. Methods We investigated associations between emotion‐based speech measures (valence, arousal, and dominance) during picture descriptions and depression dimensions derived from the geriatric depression scale (GDS, dysphoria, withdrawal‐apathy‐vigor (WAV), anxiety, hopelessness, and subjective memory complaint). Results Higher WAV was associated with more negative valence (estimate = ‐0.133, p = 0.030). While interactions of apolipoprotein E (APOE) 4 status with depression dimensions on emotional valence did not reach significance, there was a trend for more negative valence with higher dysphoria in those with at least one APOE4 allele (estimate = –0.404, p = 0.0846). Associations were similar irrespective of dementia severity. Discussion Our study underscores the potential utility of speech biomarkers in characterizing depression dimensions. In future research, using emotionally charged stimuli may enhance emotional measure elicitation. The role of APOE on the interaction of speech markers and depression dimensions warrants further exploration with greater sample sizes. Highlights Participants reporting higher apathy used more negative words to describe a neutral picture. Those with higher dysphoria and at least one APOE4 allele also tended to use more negative words. Our results suggest the potential use of speech biomarkers in characterizing depression dimensions.

In the United States, 19 allergen extracts of different specificities are standardized, which means that their potencies are determined in comparison to a US reference standard. For cat allergen extracts, potency is determined by measuring Fel d 1 content expressed in in Fel d 1 units, and with a unitage that correlates with skin test reactions (bioequivalent allergy units or BAU). Currently, Fel d 1 content is measured with a radial immunodiffusion (RID) assay that uses polyclonal sheep antisera to detect the allergenic protein by producing a white precipitin line in agar gel. However, the RID is considered cumbersome, and the polyclonal sera may qualitatively vary among animals and may recognize epitopes irrelevant to human allergic disease. In this report, we describe a quantitative two-site immunoenzymetric assay (IEMA) for Fel d 1 that uses immobilized capture and soluble biotin-labeled detection Fel d 1-specific human IgE monoclonal antibodies (mAb) that have been class-switched to IgG4. Together, they sandwich Fel d 1 molecules from extracts. Using purified natural Fel d 1 as a calibrator, the historically reported ∼4 micrograms Fel d 1/Fel d 1 unit assignment was directly measured in this mAb-based IEMA at 3.12 ± 0.24 micrograms of Fel d 1 per Fel d 1 unit. This IEMA appears to be equivalent to RID in the measurement of biological potencies of commercial cat hair and cat pelt extracts marketed in the United States.

Basal cell carcinoma (BCC) is classified histologically into subtypes that determine treatment decisions. MicroRNAs (miRs) are short noncoding RNAs that may serve as diagnostic biomarkers. We investigated if particular miRs could distinguish BCC subtypes. We sequenced miRs from 55 archival BCC and 9 control skin specimens and then validated these miRs by qRT-PCR assay on a second BCC cohort (18 superficial, 16 nodular, 15 infiltrative) and control skin (n = 12). Expression values for individual miRs were normalized to miR-16-5p, which was the least variant among the control skin and BCC samples. We found that (i) miR-383-5p and miR-145-5p are downregulated in all BCC subtypes compared with control skin, (ii) miR-181c-5p is downregulated in superficial compared with invasive (nodular/infiltrative) BCC, and (iii) miR-22-5p and miR-708-5p are upregulated in infiltrative compared with superficial/nodular BCC and miR-30c-5p is downregulated in infiltrative compared with nodular BCC. Receiver operating characteristic analysis demonstrated excellent capacity of these miRs to discriminate between BCC and control skin (area under the curve, 0.94–0.98), whereas the capacity to discriminate between superficial and invasive subtypes was less robust (area under the curve, 0.7–0.8). Future prospective studies may determine the utility of these miRs as diagnostic biomarkers to guide biopsy and treatment of BCC.

Alpha oscillations play a vital role in managing the brain's resources, inhibiting neural activity as a function of their phase and amplitude, and are changed in many brain disorders. Developing minimally invasive tools to modulate alpha activity and identifying the parameters that determine its response to exogenous modulators is essential for the implementation of focussed interventions. We introduce Alpha Closed-Loop Auditory Stimulation (αCLAS) as an EEG-based method to modulate and investigate these brain rhythms in humans with specificity and selectivity, using targeted auditory stimulation. Across a series of independent experiments, we demonstrate that αCLAS alters alpha power, frequency, and connectivity in a phase, amplitude, and topography-dependent manner. Using single-pulse-αCLAS, we show that the effects of auditory stimuli on alpha oscillations can be explained within the theoretical framework of oscillator theory and a phase-reset mechanism. Finally, we demonstrate the functional relevance of our approach by showing that αCLAS can interfere with sleep onset dynamics in a phase-dependent manner.

Background: Xylazine is an ⍺2 adrenergic receptor agonist and a veterinary sedative that can cause severe health complications yet interventions to detect and treat human exposure remain underdeveloped. Community-based drug checking services (DCS) involve the testing of small amounts of drugs to increase community knowledge of unregulated supplies and decrease harms. This study characterized xylazine awareness, desire, use and exposure among people who use drugs (PWUD) in Rhode Island, US. Methods: We analyzed data from an ongoing PWUD cohort study. In 2023, 125 PWUD were enrolled and surveyed. Using point-of-care Fourier Transform infrared spectroscopy (FTIR-S), we tested a drug sample from each participant onsite and confirmed the results offsite at a laboratory. Results were conveyed in real-time, along with harm reduction education, referrals to resources and care. Results: Virtually all participants (99.2 %) wanted to avoid xylazine exposure. Half (51.2 %) knew what xylazine was, and a quarter (26.1 %) suspected previous exposure. Xylazine exposure was primarily surmised through sedating (45.2 %) and ulcerative (29.0 %) effects. Only 8.8 % of participants submitted a sample that they expected to contain xylazine. Xylazine was detected in 14.5 % of samples using FTIR-S and in 21.4 % of samples using a dual laboratory approach of gas chromatography mass spectrometry (GC-MS) and liquid chromatography quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS). Participants thought that these xylazine-positive samples were fentanyl (78.3 %), heroin (13.0 %), or Percocet® (8.7 %). Conclusion: Implementing point-of-care DCS at harm reduction organizations could be useful in rapidly increasing xylazine awareness and engaging at-risk individuals in prevention, harm reduction, treatment, and rapid care for xylazine-related wounds.

Summary: A signal mixer facilitates rich computation, which has been the building block of modern telecommunication. This frequency mixing produces new signals at the sum and difference frequencies of input signals, enabling powerful operations such as heterodyning and multiplexing. Here, we report that a neuron is a signal mixer. We found through ex vivo and in vivo whole-cell measurements that neurons mix exogenous (controlled) and endogenous (spontaneous) subthreshold membrane potential oscillations, producing new oscillation frequencies, and that neural mixing originates in voltage-gated ion channels. Furthermore, we demonstrate that mixing is evident in human brain activity and is associated with cognitive functions. We found that the human electroencephalogram displays distinct clusters of local and inter-region mixing and that conversion of the salient posterior alpha-beta oscillations into gamma-band oscillations regulates visual attention. Signal mixing may enable individual neurons to sculpt the spectrum of neural circuit oscillations and utilize them for computational operations.

Summary: Dinoflagellate genomes often are very large and difficult to assemble, which has until recently precluded their analysis with modern functional genomic tools. Here, we present a protocol for mapping three-dimensional (3D) genome organization in dinoflagellates and using it for scaffolding their genome assemblies. We describe steps for crosslinking, nuclear lysis, denaturation, restriction digest, ligation, and DNA shearing and purification. We then detail procedures sequencing library generation and computational analysis, including initial Hi-C read mapping and 3D-DNA scaffolding/assembly correction.For complete details on the use and execution of this protocol, please refer to Marinov et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.