Calcium scoring on coronary computed angiography tomography with photon-counting detector technology: Predictors of performance.

INTRODUCTION: Obtaining accurate coronary artery calcium (CAC) score measurements from CCTA datasets with virtual non-iodine (VNI) algorithms would reduce acquisition time and radiation dose. We aimed to assess the agreement of VNI-derived and conventional true non-contrast (TNC)-based CAC scores and to identify the predictors of accuracy. METHODS: CCTA datasets were acquired with either 120 or 140 â€‹kVp. CAC scores and volumes were calculated from TNC and VNI images in 197 consecutive patients undergoing CCTA. CAC density score, mean volume/lesion, aortic Hounsfield units and standard deviations were then measured. Finally, percentage deviation (VNI - TNC/TNC∗100) of CTA-derived CAC scores from non-enhanced scans was calculated for each patient. Predictors (including anthropometric and acquisition parameters, as well as CAC characteristics) of the degree of discrepancy were evaluated using linear regression analysis. RESULTS: While the agreement between TNC and VNI was substantial (mean bias, 6.6; limits of agreement, 178.5/145.3), a non-negligible proportion of patients (36/197, 18.3%) were falsely reclassified as CAC score â€‹= â€‹0 on VNI. The use of higher tube voltage significantly decreased the percentage deviation relative to TNC-based values (ߠ​= â€‹-0.21 [95%CI: 0.38 to -0.03], p â€‹= â€‹0.020) and a higher CAC density score also proved to be an independent predictor of a smaller difference (ߠ​= â€‹-0.22 [95%CI: 0.37 to -0.07], p â€‹= â€‹0.006). CONCLUSION: The performance of VNI-based calcium scoring may be improved by increased tube voltage protocols, while the accuracy may be compromised for calcified lesions of lower density. The implementation of VNI in clinical routine, however, needs to be preceded by a solution for detecting smaller lesions as well.

Mastitis in a flock of milking sheep.

INTRODUCTION: Determination of somatic cell counts (SCC) becomes more and more important also for ewe's milk. SCC can be a useful indicator of milk quality for milk processors while it can be a mastitis indicator for sheep keepers and an important selection criterion for breeders. The objective of our study was to acquire basic information about factors influencing SCC variability in lambing ewes of the Tsigai (T) and Improved Valachian (IV) breeds. Somatic cell counts (SCC) were determined in 866 milk samples in 2017 and 2018, during lamb sucking and during milking period. An instrument Fossomatic 90 (Foss Electric, Hillerød, Denmark) was used for analysis. Average SCC varied from 270 to 1897 × 103 cells/ml during lamb sucking and from 268 to 2139 × 103 cells/ml during milking period. Differences between the sampling periods were statistically significant in 2017. An increase in SCC was observed at the end of both sucking and milking periods. An overall evaluation of lactation brought about the average SCC at 364 × 103 cells/ml in 2017 (log(10) SCC - 2,25) and at 1,091 × 103 cells/ml in 2018 (log(10) SCC - 2,68). The indicator log(10) was significantly influenced by breed in 2017 (T - 2,61; IV - 2,75). The effect of lactation number and number of sucking lambs did not have any significant influence on SCC.

INTRODUCTION: La détermination du nombre de cellules somatiques (CCS) devient de plus en plus importante, y compris pour le lait de brebis. Le CCS peut être un indicateur utile de la qualité du lait pour les transformateurs tandis qu'il peut être un indicateur de mammites pour les éleveurs de brebis et un critère de sélection important pour les sélectionneurs. L'objectif de notre étude était d'acquérir des informations de base sur les facteurs influençant la variabilité de la CCS chez les brebis agnelées des races Tsigai (T) et Valachian améliorée (IV). Le nombre de cellules somatiques (CCS) a été déterminé dans 866 échantillons de lait en 2017 et 2018, pendant la tétée des agneaux et pendant la période de traite. Un instrument Fossomatic 90 (Foss Electric, Hillerød, Danemark) a été utilisé pour l'analyse. Le CCS moyen a varié de 270 à 1897 × 103 cellules/ml pendant la tétée des agneaux et de 268 à 2139 × 103 cellules/ml pendant la période de traite. Les différences entre les périodes d'échantillonnage étaient statistiquement significatives en 2017. Une augmentation du CCS a été observée à la fin des périodes de tétée et de traite. Une évaluation globale de la lactation a permis d'obtenir un CCS moyen de 364 × 103 cellules/ml en 2017 (log(10) CCS ­ 2,25) et de 1 091 × 103 cellules/ml en 2018 (log(10) CCS ­ 2,68). L'indicateur log(10) a été significativement influencé par la race en 2017 (T ­ 2,61 ; IV ­ 2,75). L'effet du nombre de lactations et du nombre d'agneaux de lait n'a pas eu d'influence significative sur le CCS.

A NPAS4-NuA4 complex couples synaptic activity to DNA repair.

Neuronal activity is crucial for adaptive circuit remodelling but poses an inherent risk to the stability of the genome across the long lifespan of postmitotic neurons1-5. Whether neurons have acquired specialized genome protection mechanisms that enable them to withstand decades of potentially damaging stimuli during periods of heightened activity is unknown. Here we identify an activity-dependent DNA repair mechanism in which a new form of the NuA4-TIP60 chromatin modifier assembles in activated neurons around the inducible, neuronal-specific transcription factor NPAS4. We purify this complex from the brain and demonstrate its functions in eliciting activity-dependent changes to neuronal transcriptomes and circuitry. By characterizing the landscape of activity-induced DNA double-strand breaks in the brain, we show that NPAS4-NuA4 binds to recurrently damaged regulatory elements and recruits additional DNA repair machinery to stimulate their repair. Gene regulatory elements bound by NPAS4-NuA4 are partially protected against age-dependent accumulation of somatic mutations. Impaired NPAS4-NuA4 signalling leads to a cascade of cellular defects, including dysregulated activity-dependent transcriptional responses, loss of control over neuronal inhibition and genome instability, which all culminate to reduce organismal lifespan. In addition, mutations in several components of the NuA4 complex are reported to lead to neurodevelopmental and autism spectrum disorders. Together, these findings identify a neuronal-specific complex that couples neuronal activity directly to genome preservation, the disruption of which may contribute to developmental disorders, neurodegeneration and ageing.

Translational insights into mechanisms underlying residual venous obstruction and the role of factor XI, P-selectin and GPVI in recurrent venous thromboembolism.

BACKGROUND: Residual venous obstruction (RVO) after deep vein thrombosis (DVT) is considered a risk factor of recurrent venous thromboembolism (VTE), arterial events and post-thrombotic syndrome (PTS). We hypothesized thrombo-inflammatory markers might be associated with RVO and clinical outcomes. MATERIALS AND METHODS: In a DVT cohort with routine RVO-assessment and 5-year follow-up, patients were invited for blood withdrawal after stopping anticoagulants. Thrombin generation potential, coagulation enzyme:inhibitor complexes, soluble platelet markers and clinical markers were measured in platelet-poor plasma. Associations were represented as odds ratio (OR) or hazard ratio (HR) per standard deviation. RESULTS: Patients with RVO (102/306, 33 %) had higher rates of PTS (24 vs. 12 %, p = 0.008), but similar rates of recurrence (16 vs. 15 %, p = 0.91) and arterial events (7 vs. 4 %, p = 0.26). RVO was associated with thrombin peak height (OR 1.40 [1.04-1.88]), endogenous thrombin potential (ETP, OR 1.35 [1.02-1.79]), and CRP (OR 1.74 [1.10-2.75]). Recurrent VTE was associated with ETP (HR 1.36 [1.03-1.81]), FXIa:C1-inhibitor (HR 1.34 [1.04-1.72]), thrombin:antithrombin (HR 1.36 [1.16-1.59]), soluble P-selectin (HR 2.30 [1.69-3.11]), soluble glycoprotein VI (sGPVI, HR 1.30 [1.01-1.69]), D-dimer (HR 1.56 [1.31-1.86]), and factor VIII (HR 1.44 [1.15-1.82]). Arterial events were associated with sGPVI (HR 1.80 [1.25-2.59]). PTS was not associated with any marker. CONCLUSIONS: Our findings indicate RVO was associated with thrombo-inflammation, but this did not predict clinical outcomes in this setting. Importantly, we found recurrent VTE was associated with ongoing coagulation and platelet activation in patients well beyond the acute phase of DVT. Furthermore, sGPVI indicated an increased risk of arterial events, highlighting the role of platelets in arterial thrombosis following DVT.

Unusual early peaks of airborne ragweed (Ambrosia L.) pollen in the Pannonian Biogeographical Region.

Early peaks of airborne ragweed (Ambrosia L.) pollen concentrations were observed at several monitoring stations in Hungary in June 2017 and 2018, one month before the usual start of the pollen season at the end of July. Backward trajectories were calculated to simulate potential sources of pollen collected at different locations in the Pannonian Biogeographical Region. In a collaboration between aerobiological and phenological networks, a nationwide campaign was conducted to collect field data of ragweed blooming. During field surveys, ragweed plants having extremely early blooming were found most abundantly in a rural site near Vaja (North-East Hungary) and other locations in Hungary. Field observations matched with source areas identified by trajectory analyses; i.e., early-flowering ragweed plants were found at some of these locations. Although similar peaks of airborne pollen concentrations were not detected in other years (e.g., 2016, 2019-2021), alarming results suggest the possibility of expanding seasons of ragweed allergy.

Expected Bayesian estimation for exponential model based on simple step stress with Type-I hybrid censored data.

The procedure of selecting the values of hyper-parameters for prior distributions in Bayesian estimate has produced many problems and has drawn the attention of many authors, therefore the expected Bayesian (E-Bayesian) estimation method to overcome these problems. These approaches are used based on the step-stress acceleration model under the Exponential Type-I hybrid censored data in this study. The values of the distribution parameters are derived. To compare the E-Bayesian estimates to the other estimates, a comparative study was conducted using the simulation research. Four different loss functions are used to generate the Bayesian and E-Bayesian estimators. In addition, three alternative hyper-parameter distributions were used in E-Bayesian estimation. Finally, a real-world data example is examined for demonstration and comparative purposes.

Classical and Bayesian Inference Using Type-II Unified Progressive Hybrid Censored Samples for Pareto Model.

In the lifetime and reliability experiments, the censored samples play a fundamental and important role in order to control time and cost. The researchers developed the censored sample schemes to solve the problems that arise by applying the previous methods. Recently, Górny and Cramer (2018) proposed a new general type of censored sample called Type-II unified progressive hybrid censored sample. In this paper, we present an overview of the Type-II unified progressive hybrid censored sample. We used this censored sample to compute the maximum likelihood estimates of unknown parameters from the Pareto distribution, as well as Bayesian estimates for unknown parameters under three different error loss functions. The point and interval Bayesian predictions one- and two-sample Bayesian predictions from the Pareto distribution are shown. Simulation studies are carried out to compare the efficacy of the various inference approaches. Finally, real data sets are examined to determine the applicability of the proposed model and various estimating approaches.

Estimations of Generalized Exponential Distribution Parameters Based on Type I Generalized Progressive Hybrid Censored Data.

Type I generalized progressive hybrid censoring scheme is a combination of Type I and Type II progressive hybrid censoring schemes, and it is one of the most recent advancements in data censoring. In this article, based on Type I generalized progressive hybrid censoring data from generalized exponential distribution, the maximum likelihood and Bayesian estimators of distribution's parameters as well as the reliability and hazard functions are approximately calculated. Also, the credible interval estimators of these quantities are obtained. Since these quantities cannot be obtained in closed form, so simulation and analysis using a Monte Carlo simulation study with Gibbs sampling are taken. Finally, an illustrative example using real data set is presented to compare the proposed procedures presented and developed here.

The lifetime analysis of the Weibull model based on Generalized Type-I progressive hybrid censoring schemes.

In this study, we estimate the unknown parameters, reliability, and hazard functions using a generalized Type-I progressive hybrid censoring sample from a Weibull distribution. Maximum likelihood (ML) and Bayesian estimates are calculated using a choice of prior distributions and loss functions, including squared error, general entropy, and LINEX. Unobserved failure point and interval Bayesian predictions, as well as a future progressive censored sample, are also developed. Finally, we run some simulation tests for the Bayesian approach and numerical example on real data sets using the MCMC algorithm.

Hemolytic Uremic Syndrome in Egyptian Children: A Single Center Experience across 10 Years.

Hemolytic uremic syndrome (HUS) is a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI) and is the most common cause of AKI in children. We aimed to demonstrate the clinical patterns, laboratory findings, management, and outcomes of HUS in Egyptian children. This was a retrospective cohort study carried out in the Nephrology Unit of the Pediatric Department at Tanta University Hospitals. Hospital-based records of HUS cases between January 2009 and January 2019 were used to obtain the disease history, clinical manifestations, investigations, treatment, and outcomes. Sixty-eight children were included in the study: 63 (96.56%) with Shiga-toxin-producing Escherichia coli (STEC) HUS and five (7.53%) with atypical HUS. The boy-to-girl ratio was 1.19:1. The age at the onset of the disease ranged from 0.5 to 13 years, with a median of 2.25 years. The main presenting manifestations were pallor (80.88%), diarrhea (67.65%), oliguria (54.41%), and convulsions (19.21%). The survival rate was 85.29%, whereas the mortality rate was 14.71%. Thirty-seven patients (54.41%) recovered completely, 17 (25%) patients survived but with chronic kidney disease, and four patients (5.88%) progressed to end-stage renal disease and are currently maintained on dialysis. The risk factors for mortality were female gender, age <5 years, anuria, and an affected central nervous system (CNS). STEC-HUS had a higher incidence than atypical HUS with better outcomes. Early dialysis improved the outcome in terms of mortality in young patients, females, and those with an affected CNS.

Sustained inflammation, coagulation activation and elevated endothelin-1 levels without macrovascular dysfunction at 3 months after COVID-19.

INTRODUCTION: Endothelial damage and thrombosis caused by COVID-19 may imperil cardiovascular health. More than a year since the WHO declared COVID-19 pandemic, information on its effects beyond the acute phase is lacking. We investigate endothelial dysfunction, coagulation and inflammation, 3 months post-COVID-19. MATERIALS AND METHODS: A cohort study was conducted including 203 patients with prior COVID-19. Macrovascular dysfunction was assessed by measuring the carotid artery diameter in response to hand immersion in ice-water. A historic cohort of 312 subjects served as controls. Propensity score matching corrected for baseline differences. Plasma concentrations of endothelin-1 were measured in patients post-COVID-19, during the acute phase, and in matched controls. Coagulation enzyme:inhibitor complexes and inflammatory cytokines were studied. RESULTS AND CONCLUSIONS: The prevalence of macrovascular dysfunction did not differ between the COVID-19 (18.6%) and the historic cohort (22.5%, RD -4%, 95%CI: -15-7, p = 0.49). Endothelin-1 levels were significantly higher in acute COVID-19 (1.67 ± 0.64 pg/mL) as compared to controls (1.24 ± 0.37, p < 0.001), and further elevated 3 months post-COVID-19 (2.74 ± 1.81, p < 0.001). Thrombin:antithrombin(AT) was high in 48.3%. Markers of contact activation were increased in 16-30%. FVIIa:AT (35%) and Von Willebrand Factor:antigen (80.8%) were elevated. Inflammatory cytokine levels were high in a majority: interleukin(IL)-18 (73.9%), IL-6 (47.7%), and IL-1ra (48.9%). At 3 months after acute COVID-19 there was no indication of macrovascular dysfunction; there was evidence, however, of sustained endothelial cell involvement, coagulation activity and inflammation. Our data highlight the importance of further studies on SARS-CoV-2 related vascular inflammation and thrombosis, as well as longer follow-up in recovered patients.

Transcriptional profiling of sequentially generated septal neuron fates.

The septum is a ventral forebrain structure known to regulate innate behaviors. During embryonic development, septal neurons are produced in multiple proliferative areas from neural progenitors following transcriptional programs that are still largely unknown. Here, we use a combination of single-cell RNA sequencing, histology, and genetic models to address how septal neuron diversity is established during neurogenesis. We find that the transcriptional profiles of septal progenitors change along neurogenesis, coinciding with the generation of distinct neuron types. We characterize the septal eminence, an anatomically distinct and transient proliferative zone composed of progenitors with distinctive molecular profiles, proliferative capacity, and fate potential compared to the rostral septal progenitor zone. We show that Nkx2.1-expressing septal eminence progenitors give rise to neurons belonging to at least three morphological classes, born in temporal cohorts that are distributed across different septal nuclei in a sequential fountain-like pattern. Our study provides insight into the molecular programs that control the sequential production of different neuronal types in the septum, a structure with important roles in regulating mood and motivation.

Modelling the COVID-19 Mortality Rate with a New Versatile Modification of the Log-Logistic Distribution.

The goal of this paper is to develop an optimal statistical model to analyze COVID-19 data in order to model and analyze the COVID-19 mortality rates in Somalia. Combining the log-logistic distribution and the tangent function yields the flexible extension log-logistic tangent (LLT) distribution, a new two-parameter distribution. This new distribution has a number of excellent statistical and mathematical properties, including a simple failure rate function, reliability function, and cumulative distribution function. Maximum likelihood estimation (MLE) is used to estimate the unknown parameters of the proposed distribution. A numerical and visual result of the Monte Carlo simulation is obtained to evaluate the use of the MLE method. In addition, the LLT model is compared to the well-known two-parameter, three-parameter, and four-parameter competitors. Gompertz, log-logistic, kappa, exponentiated log-logistic, Marshall-Olkin log-logistic, Kumaraswamy log-logistic, and beta log-logistic are among the competing models. Different goodness-of-fit measures are used to determine whether the LLT distribution is more useful than the competing models in COVID-19 data of mortality rate analysis.

Rewiring of human neurodevelopmental gene regulatory programs by human accelerated regions.

Human accelerated regions (HARs) are the fastest-evolving regions of the human genome, and many are hypothesized to function as regulatory elements that drive human-specific gene regulatory programs. We interrogate the in vitro enhancer activity and in vivo epigenetic landscape of more than 3,100 HARs during human neurodevelopment, demonstrating that many HARs appear to act as neurodevelopmental enhancers and that sequence divergence at HARs has largely augmented their neuronal enhancer activity. Furthermore, we demonstrate PPP1R17 to be a putative HAR-regulated gene that has undergone remarkable rewiring of its cell type and developmental expression patterns between non-primates and primates and between non-human primates and humans. Finally, we show that PPP1R17 slows neural progenitor cell cycle progression, paralleling the cell cycle length increase seen predominantly in primate and especially human neurodevelopment. Our findings establish HARs as key components in rewiring human-specific neurodevelopmental gene regulatory programs and provide an integrated resource to study enhancer activity of specific HARs.

Calibrated automated thrombogram II: removing barriers for thrombin generation measurements.

BACKGROUND: Thrombin generation (TG) assessed by Calibrated Automated Thrombogram (CAT-I) reflects the overall capacity of plasma to generate thrombin, thus evaluating the balance between the anti- and procoagulant processes. However, with this method the calibrator curve is usually not measured until completion which has a severe impact on the calculation of the TG parameters, especially under conditions where almost all substrate is consumed. In addition, direct thrombin inhibitor (DTI) cannot be present in the calibration sample due to inhibition of the calibrator. We have developed a modified TG assay (CAT-II) and performed head-to-head comparison with the CAT-I method using the same fluorometer. Furthermore, we have compared our CAT-II method to a new automated TG instrument (ST®-Genesia) using the same calibration method. METHODS: TG was assessed with CAT-I and CAT-II using the same fulorometer and with ST®-Genesia in control plasma and plasma containing different anticoagulants (dabigatran, rivaroxaban, apixaban) and plasmas to which common interfering substances, bilirubin, hemoglobin and lipids were added. In CAT-I, calibration was against the same plasma containing calibrator in the presence of fluorogenic substrate (Z-GGR-AMC). In contrast, CAT-II method and ST®-Genesia used a standard concentration of thrombin in buffer and 7-amino-4-methylcoumarin (AMC) in a separate plasma sample for calibration. RESULTS: TG obtained from CAT-I using anticoagulant-free plasmas was lower compared with TG from CAT-II but both methods demonstrated an intra-assay variation less than 5% on all measured parameters. When comparing the two different calibration methods in the presence of different anticoagulants, a high correlation was seen in the presence of rivaroxaban and apixaban (R2 > 0.97), but not with dabigatran, a direct thrombin inhibitor. CAT-II method showed dose-dependent inhibition of TG in the presence of dabigatran, while CAT-I was not able to detect it. Both methods were able to correct for the interfering substances. CONCLUSIONS: Our results showed high similarity between the results of CAT-I and CAT-II method when it is applied in control plasmas and plasmas not inhibited with a direct thrombin inhibitor. Furthermore, both the CAT-II method and ST-Genesia using the same calibration method were able to detect the effect of all oral anticoagulants. Taken together, applying a new calibration method is a significant improvement for monitoring patients on direct thrombin inhibitors while not introducing any bias to results obtained on other types of samples.

In vitro elution characteristics of gentamicin- and teicoplanin-loaded CMW1 and Palacos R bone cement.

PURPOSE: To compare the in vitro elution characteristics of CMW1 and Palacos R bone cement loaded with gentamicin, teicoplanin, or in combination. METHODS: Four bone cement discs were prepared for each cement type. Disc 1 contained no antibiotics; disc 2 contained 0.5 g gentamicin; disc 3 contained 2 g teicoplanin; disc 4 contained 0.5 g gentamicin and 2 g teicoplanin. Elution studies were conducted using a fluorescence polarisation immunoassay technique and performed at intervals of 6 weeks. RESULTS: For CMW1, gentamicin and teicoplanin elution levels in combination discs were higher than those in the single antibiotic discs (p < 0.001 & p < 0.06). For Palacos R, gentamicin elution levels in combination discs were higher than those in the single antibiotic discs (p < 0.001), but teicoplanin elution levels in combination discs were lesser than that from the single antibiotic discs (p < 0.02). In single and combination discs, gentamicin elution levels in Palacos R were higher than those in CMW1 (p < 0.001 & p < 0.001). Palacos R eluted more teicoplanin than CMW1, except in combined disc with gentamicin, when less teicoplanin was eluted. CONCLUSION: Antibiotic elution is higher in Palacos R than CMW1. Antibiotic combination in both cement types has the synergistic effect of increasing antibiotic elution, except for teicoplanin from Palacos R. When high elution of gentamicin is required, Palacos R is preferable. When high elution of teicoplanin is required, Palacos R with only teicoplanin is superior to CMW1.

Evaluation of Insecticidal Effects of Plants Essential Oils Extracted from Basil, Black Seeds and Lavender against Sitophilus oryzae.

The risk of using synthetic insecticides to the environment, human health, and the emergence of new genera of pests resistant to that kind of drugs, have led to attention in natural compounds. The present study aimed at evaluating the insecticidal activity of 0.25-6 mg/cm2 of basil (Ocimum basilicum), black seeds (Nigella sativa), and lavender (Lavandula angustifolia) essential oils (EOs) against one of the major stored product pests, Sitophilus oryzae (L.). This was done by assessing mortality and repellent percentage assay in the adult stage, as well as analysing up and down-regulated genes associated with toxicity effect of selected EOs. The three studied EOs showed a toxic effect on S. oryzae; where O. basilicum and L. angustifolia EOs explicated 100% mortality at 6 mg/cm2 after 48 and 24 h, respectively. The highest repellence activity was recorded for O. basilicum EO at 0.75 mg/cm2 with value 82.3% after exposure time 5 h. In the highest dose (6 mg/cm2), the maximum up-regulated expression level of detoxification DEGs genes (CL1294 and CL 8) and cytochrome p45o gene (CYP4Q4) in Lavandula angustifolia EOs exhibited 8.32, 6.08, and 3.75 fold changes, respectively, as compared with 4.76 fold at 10 ppm malathion and 1.02 fold change in acetone control.

Dominant Fifth-Order Correlations in Doped Quantum Antiferromagnets.

Traditionally, one- and two-point correlation functions are used to characterize many-body systems. In strongly correlated quantum materials, such as the doped 2D Fermi-Hubbard system, these may no longer be sufficient, because higher-order correlations are crucial to understanding the character of the many-body system and can be numerically dominant. Experimentally, such higher-order correlations have recently become accessible in ultracold atom systems. Here, we reveal strong non-Gaussian correlations in doped quantum antiferromagnets and show that higher-order correlations dominate over lower-order terms. We study a single mobile hole in the t-J model using the density matrix renormalization group and reveal genuine fifth-order correlations which are directly related to the mobility of the dopant. We contrast our results to predictions using models based on doped quantum spin liquids which feature significantly reduced higher-order correlations. Our predictions can be tested at the lowest currently accessible temperatures in quantum simulators of the 2D Fermi-Hubbard model. Finally, we propose to experimentally study the same fifth-order spin-charge correlations as a function of doping. This will help to reveal the microscopic nature of charge carriers in the most debated regime of the Hubbard model, relevant for understanding high-T_{c} superconductivity.

Bidirectional perisomatic inhibitory plasticity of a Fos neuronal network.

Behavioural experiences activate the FOS transcription factor in sparse populations of neurons that are critical for encoding and recalling specific events1-3. However, there is limited understanding of the mechanisms by which experience drives circuit reorganization to establish a network of Fos-activated cells. It is also not known whether FOS is required in this process beyond serving as a marker of recent neural activity and, if so, which of its many gene targets underlie circuit reorganization. Here we demonstrate that when mice engage in spatial exploration of novel environments, perisomatic inhibition of Fos-activated hippocampal CA1 pyramidal neurons by parvalbumin-expressing interneurons is enhanced, whereas perisomatic inhibition by cholecystokinin-expressing interneurons is weakened. This bidirectional modulation of inhibition is abolished when the function of the FOS transcription factor complex is disrupted. Single-cell RNA-sequencing, ribosome-associated mRNA profiling and chromatin analyses, combined with electrophysiology, reveal that FOS activates the transcription of Scg2, a gene that encodes multiple distinct neuropeptides, to coordinate these changes in inhibition. As parvalbumin- and cholecystokinin-expressing interneurons mediate distinct features of pyramidal cell activity4-6, the SCG2-dependent reorganization of inhibitory synaptic input might be predicted to affect network function in vivo. Consistent with this prediction, hippocampal gamma rhythms and pyramidal cell coupling to theta phase are significantly altered in the absence of Scg2. These findings reveal an instructive role for FOS and SCG2 in establishing a network of Fos-activated neurons via the rewiring of local inhibition to form a selectively modulated state. The opposing plasticity mechanisms acting on distinct inhibitory pathways may support the consolidation of memories over time.