bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of G9a does not phenocopy the requirement for Prdm12 in the development of the nociceptive neuron lineage
Authors: Tsimpos Panagiotis , Desiderio Simon , Cabochette Pauline , Kricha Sadia , Bellefroid Eric J. 
Published: September 2023

ABSTRACTPrdm12 is an epigenetic regulator expressed in developing and mature nociceptive neurons, playing a key role in their specification during neurogenesis and modulating pain sensation at adulthood.In vitrostudies suggested that Prdm12 recruits the methyltransferase G9a through its zinc finger domains to regulate target gene expression, but how Prdm12 interacts with G9a and whether G9a plays a role in Prdm12’s functional properties in sensory ganglia remain unknown. Here we report that the SET domain of G9a is necessary and sufficient for the interaction with Prdm12. We show that Prdm12 is co-expressed with G9a in dorsal root ganglia during early murine development. To address the role of G9a in somatosensory neurogenesis and test the hypothesis that it may function as a mediator of Prdm12’s function during somatosensory neurogenesis, we conditionally inactivated it in neural crest using a Wnt1-Cre transgenic mouse line. We found that G9a ablation in neural crest does not lead to dorsal root ganglia hypoplasia due to the loss of somatic nociceptive neurons nor to the ectopic expression of the visceral determinant Phox2b as observed uponPrdm12ablation. Together, our results confirm Prdm12’s ability to interact with G9a and reveal that this interaction is however not instrumental for its developmental function during nociceptive neuron development.
The internal metabolic state controls behavior inHydrathrough an interplay of enteric and central nervous system-like neuron populations
Authors: Giez Christoph , Noack Christopher , Sakib Ehsan , Bosch Thomas 
Published: September 2023

AbstractHunger and satiety can have an influence on decision making, sensory processing, and motor behavior by altering the internal state of the brain. This process necessitates the integration of peripheral sensory stimuli into the central nervous system. Interestingly, even organisms without a brain, such as the Cnidaria, exhibit feeding dependent behavioral changes. The underlying mechanisms, however, remain unclear. In this study, we demonstrate that neuronal activity in two distinct neuronal populations, the ectodermal N3 neurons and the endodermal N4 neurons inHydra, an ancestral metazoan animal with a diffuse nerve net spread throughout the body with no signs of centralization, are responsible for feeding dependent behavioral changes. Specifically, endodermal N4 neurons are essential for food intake and digestive functions, similar to the enteric nervous system, while the N3 population influences and inhibits other motor related behaviors, comparable to the central nervous system. This fascinating observation provides a new insight into the evolution and the complexity of a simple non-centralized nervous system.
Cardiorespiratory fitness is associated with neuroelectric activity complexity in children with overweight or obesity
Authors: Minguillon Jesus , Perez-Valero Eduardo , Lopez-Gordo Miguel A. , Esteban-Cornejo Irene , Ortega Francisco B. , Mora-Gonzalez Jose 
Published: September 2023

AbstractCardiorespiratory fitness is one of the most important markers of health. Several studies have demonstrated the relationship between cardiorespiratory fitness and brain functioning in healthy children. Some of these works suggested that cardiorespiratory fitness may have a protective role on the executive function, which represents a set of cognitive mechanisms used to control and coordinate other cognitive abilities. This is particularly relevant in children with overweight or obesity. In these studies, neuroelectric activity is recorded using medical imaging techniques or electroencephalography (EEG). Among the EEG studies, analyses based on the P3 event related potential stand out. However, complementary analyses are necessary to understand the neural mechanisms underlying the associations between cardiorespiratory fitness and brain functioning. EEG complexity, a useful feature that measures the regularity of neuroelectric activity, has been previously associated with cardiorespiratory fitness in adolescents. In this work, we evaluate this association in a group of 87 Caucasian children with overweight/obesity. Our results reveal that the children with higher cardiorespiratory fitness present less EEG complexity while performing a cognitive task that challenges the executive function. In addition, they suggest that the line length, the metric that we used to estimate EEG complexity, performs equally well as those metrics based on the P3 and better than other complexity metrics like sample entropy, as an indicator of cardiorespiratory fitness. Finally, the line length has advantages over the P3: more consistency across EEG regions and cognitive loads, lower experimental complexity, lower computational cost, and higher automatization capability.
In-vivo characterization of magnetic inclusions in the subcortex from non-exponential transverse relaxation decay
Authors: Oliveira Rita , Raynaud Quentin , Jelescu Ileana , Kiselev Valerij G. , Kirilina Evgeniya , Lutti Antoine 
Published: September 2023

AbstractAccording to theoretical studies, the MRI signal decay due to transverse relaxation, in brain tissue with magnetic inclusions (e.g. blood vessels, myelin, iron-rich cells), exhibits a transition from a Gaussian behaviour at short echo times to exponential at long echo times. Combined, the Gaussian and exponential decay parameters carry information about the inclusions (e.g., size, volume fraction) and provide a unique insight into brain tissue microstructure. However, gradient echo decays obtained experimentally typically only capture the long-time exponential behaviour. Here, we provide experimental evidence of non-exponential transverse relaxation signal decay at short times in human subcortical grey matter, from MRI data acquired in vivo at 3T. The detection of the non-exponential behaviour of the signal decay allows the subsequent characterization of the magnetic inclusions in the subcortex.The gradient-echo data was collected with short inter-echo spacings, a minimal echo time of 1.25 ms and novel acquisition strategies tailored to mitigate the effect of motion and cardiac pulsation. The data was fitted using both a standard exponential model and non-exponential theoretical models describing the impact of magnetic inclusions on the MRI signal. The non-exponential models provided superior fits to the data, indicative of a better representation of the observed signal. The strongest deviations from exponential behaviour were detected in the substantia nigra and globus pallidus. Numerical simulations of the signal decay, conducted from histological maps of iron concentration in the substantia nigra, closely replicated the experimental data – highlighting that non-heme iron can be at the source of the non-exponential signal decay.To investigate the potential of the non-exponential signal decay as a tool to characterize brain microstructure, we attempted to estimate the properties of the inclusions at the source of this decay behaviour using two available analytical models of transverse relaxation. Under the assumption of the static dephasing regime, the magnetic susceptibility and volume fractions of the inclusions was estimated to range from 1.8 to 4 ppm and from 0.02 to 0.04 respectively. Alternatively, under the assumption of the diffusion narrowing regime, the typical inclusion size was estimated to be ∼2.4μm. Both simulations and experimental data point towards an intermediate regime with a non-negligible effect of water diffusion to signal decay. Non-exponential transverse relaxation decay provides new means to characterize the spatial distribution of magnetic material within subcortical grey matter tissue with increased specificity, with potential applications to Parkinson’s disease and other pathologies.
Erdr1 orchestrates macrophage polarization and determines cell fate via dynamic interplay with YAP1 and Mid1
Authors: Wang Yuhang 
Published: September 2023

AbstractErythroid differentiation regulator 1 (Erdr1) is a stress-induced, widely distributed, extremely conserved secreted factor found in both humans and mice. Erdr1 is highly linked with the Hippo-YAP1 signaling. Initially identified as an inducer of hemoglobin synthesis, it has emerged as a multifunctional protein, especially in immune cells. Although Erdr1 has been implicated in T cells and NK cell function, its role in macrophage remains unclear. This study aims to explore the function and mechanism of Erdr1 in IL-1β production in macrophages. Data manifest Erdr1 could play an inhibition role in IL-1β production, which also has been reported by previous research. What significance is we discovered Erdr1 can promote IL-1β production which is associated with Erdr1 dose and cell density. We observed that Erdr1 was inhibited in pro-inflammatory (M1) macrophages but was upregulated in anti-inflammatory (M2) macrophages compared to naive macrophages. We hypothesized that Erdr1 dual drives and modulates IL-1β production by binding with distinct adaptors via concentration change. Mechanistically, we demonstrated that Erdr1 dual regulates IL-1β production by dynamic interaction with YAP1 and Mid1 by distinct domains. Erdr1-YAP1 interplay mediates macrophage M2 polarization by promoting an anti-inflammatory response, enhancing catabolic metabolism, and leading to sterile cell death. Whereas, Erdr1-Mid1 interplay mediates macrophage M1 polarization by initiating a pro-inflammatory response, facilitating anabolic metabolism, and causing inflammatory cell death. This study highlights Erdr1 orchestrates macrophage polarization and determines cell date by regulating YAP1 through non-classical Hippo pathway.
Measuring and Reducing Racial Bias in a Pediatric Urinary Tract Infection Model
Authors: Anderson Joshua W. , Shaikh Nader , Visweswaran Shyam 
Published: September 2023

AbstractClinical predictive models that include race as a predictor have the potential to exacerbate disparities in healthcare. Such models can be respecified to exclude race or optimized to reduce racial bias. We investigated the impact of such respecifications in a predictive model – UTICalc – which was designed to reduce catheterizations in young children with suspected urinary tract infections. To reduce racial bias, race was removed from the UTICalc logistic regression model and replaced with two new features. We compared the two versions of UTICalc using fairness and predictive performance metrics to understand the effects on racial bias. In addition, we derived three new models for UTICalc to specifically improve racial fairness. Our results show that, as predicted by previously described impossibility results, fairness cannot be simultaneously improved on all fairness metrics, and model respecification may improve racial fairness but decrease overall predictive performance.
Uptake, safety, and effectiveness of inactivated influenza vaccine in patients with inflammatory bowel disease: a nationwide study in the UK using data from the Clinical Practice Research Datalink
Authors: Nakafero Georgina , Grainge Matthew J. , Card Tim , Mallen Christian D. , Nguyen Van-Tam Jonathan S. , Abhishek Abhishek 
Published: September 2023

AbstractObjectiveWe investigated UK wide inactivated influenza vaccine (IIV) uptake in adults with inflammatory bowel disease (IBD), the association between vaccination against influenza and IBD flare, and the effectiveness of IIV in preventing morbidity and mortality.DesignData for adults with IBD prior to 1stSeptember 2018 were extracted from the Clinical Practice Research Datalink (CPRD) Gold, a database of electronic health records originated during routine care of patients in the UK. It is linked to hospitalization and mortality records. We calculated the proportion of patients vaccinated against seasonal influenza in the 2018-2019 influenza cycle. To investigate vaccine effectiveness, we calculated propensity score (PS) for vaccination and undertook Cox proportional hazard regression with inverse-probability treatment weighting on PS. We employed self-controlled case series (SCCS) to investigate the association between vaccination and IBD flare.ResultsData for 13,631 IBD patients (50.4% male, mean age 52.9 years) were included. Fifty percent were vaccinated during the influenza cycle while 32.1% were vaccinated before influenza virus circulated in the community. Vaccination was associated with a non-significant reduction in hospitalisation for pneumonia (aHR (95%CI) 0.52 (0.20-1.37), including in the influenza active period (aHR (95%CI) 0.48 (0.18-1.27)). Administration of the influenza vaccine was not associated with IBD flare.ConclusionThe uptake of influenza vaccine is low in IBD patients and the majority are not vaccinated before influenza virus circulates in the community. Vaccination with the IIV is not associated with IBD flare. These findings add to the evidence to promote vaccination in patients with IBD.Key messagesWhat is already known on the topicInactivated influenza vaccine is recommended in people with IBD treated with immune suppressing drugs.Concerns about influenza vaccine causing IBD flare and lack of data on the effectiveness of influenza vaccine in people with IBD are barriers to seasonal influenza vaccination in this population.What this study addsThe uptake of seasonal influenza vaccination is low in IBD patients.Seasonal influenza vaccination is not associated with IBD flare and is more likely to prevent serious complications of influenza in this population.How this study might affect research, practice, or policyThis study provides new data on the uptake, effectiveness, and safety of influenza vaccine in people with IBD and adds to the accumulating evidence to promote vaccination in this population.
Measuring the influence of expectations, beliefs, and medication side effects on the risk for drug discontinuation among individuals starting new medications
Authors: Blackburn David F , Yao Shenzhen , Taylor Jeffery G. , Alefan Qais , Lix Lisa M. , Eurich Dean T. , Choudhry Niteesh K. 
Published: September 2023

AbstractObjectivesTo measure the impact of beliefs, expectations, side effects, and their combined effects on the risk for medication non-persistence.DesignA population-based questionnaire.Setting and ParticipantsIndividuals from Saskatchewan, Canada who started a new antihypertensive, cholesterol-lowering, or antihyperglycemic medication were surveyed about risk factors for non-persistence including: (a) beliefs measured by a composite score of three questions asking about the threat of the condition, importance of the drug, and harm of the drug; (b) incident side effects attributed to treatment; and (c) expectations for side effects before starting treatment. Descriptive statistics and logistic regression models were used to quantify the influence of these risk factors on the outcome of non-persistence. Odds ratios (OR) and 95% confidence intervals (CI) were estimated.Main Outcome MeasureSelf-reported medication non-persistence.ResultsAmong 3,029 respondents, 5.9% (n=179) reported non-persistence within four months after starting the new drug. After adjustment for numerous covariates representing socio-demographics, healthcare providers, medication experiences and beliefs, both negative beliefs (OR 7.26, 95% CI: 4.98 to 10.59) and incident side effects (OR 8.00, 95% CI 5.49 to 11.68) were associated with the highest odds of non-persistence with no evidence of interaction. In contrast, expectations for side effects before starting treatment exhibited an important interaction with incident side effects following treatment initiation. Among respondents with incident side effects (n=741, 24.5%), the risk for early non-persistence was 11.5% if they indicated an expectation for side effects before starting the medication compared to 23.6% if they did not (adjusted OR 0.38, 95% CI 0.25 to 0.60).ConclusionsExpectations for side effects may be a previously unrecognized but important marker of the probability to persist with treatment. A high percentage of new medication users appeared unprepared for the possibility of side effects from their new medication making them less resilient if side effects occur.What is already known on this topicPrior expectations for side effects are thought to increase the risk for nocebo effects and increase the risk for medication non-persistence.Medication non-persistence remains a major threat to patient outcomes.What this study addsExpectations for side effects from medications may be a previously unrecognizedprotectivefactor against non-persistence.A high percentage of new medication users appear unprepared for the possibility of side effects from their new medication making them less resilient if side effects occur.
Structure of the portal complex fromStaphylococcus aureuspathogenicity island 1 transducing particles in situ and in solution
Authors: Mukherjee Amarshi , Kizziah James L. , Hawkins N’Toia C. , Nasef Mohamed O. , Parker Laura K. , Dokland Terje 
Published: September 2023

ABSTRACTStaphylococcus aureusis an important human pathogen, and the prevalence of antibiotic resistance is a major public health concern. The evolution of pathogenicity and resistance inS. aureusoften involves acquisition of mobile genetic elements (MGEs). Bacteriophages play an especially important role, since transduction represents the main mechanism for horizontal gene transfer.S. aureuspathogenicity islands (SaPIs), including SaPI1, are MGEs that carry genes encoding virulence factors, and are mobilized at high frequency through interactions with specific “helper” bacteriophages, such as 80α, leading to packaging of the SaPI genomes into virions made from structural proteins supplied by the helper. Among these structural proteins is the portal protein, which forms a ring-like portal at a fivefold vertex of the capsid, through which the DNA is packaged during virion assembly and ejected upon infection of the host. We have used high- resolution cryo-electron microscopy to determine structures of theS. aureusbacteriophage 80α portal in solution and in situ in the empty and full SaPI1 virions, and show how the portal interacts with the capsid. These structures provide a basis for understanding portal and capsid assembly and the conformational changes that occur upon DNA packaging and ejection.
Early morning run-training results in enhanced endurance performance adaptations in mice
Authors: Hesketh Stuart J. , Sexton Casey L. , Wolff Christopher A. , Viggars Mark R. , Esser Karyn A. 
Published: September 2023

AbstractTime-of-day differences in acute exercise performance in mice are well established with late active phase (afternoon) runners exhibiting significantly greater endurance performance compared to early active phase (morning) runners. In this study, we asked if performance adaptations would be different when training for 6 weeks at two different times of day, and if this corresponds to steady state changes in the phase of peripheral tissue clocks. To address these questions, we endurance trained female PER2::Luciferase mice, at the same relative workload, either in the morning, at ZT13, or in the afternoon, at ZT22. Then, after training, we recorded luminescence from tissues of PER2::Luciferase mice to report timing of tissue clocks in several peripheral tissues. After 6 weeks, we found that both groups exhibited significant improvements in maximal endurance capacity (total treadmill work)(p< 0.0001), but the morning runners exhibited an enhanced rate of adaptation as there was no detectable difference in maximal endurance capacity(p= 0.2182) between the morning and afternoon runners. In addition, morning and afternoon runners exhibited divergent clock phase shifts with a significant 5-hour phase advance in the EDL (p< 0.0001) and soleus (p< 0.0001) of morning runners, but a phase delay in the EDL (p< 0.0001) and Soleus (p< 0.0001) of afternoon runners. Therefore, our data demonstrate that morning training enhances endurance adaptations compared to afternoon training in mice, and we suggest this is due to phase advancement of muscle clocks to better align metabolism with exercise performance.Key points summaryTime-of-day differences in exercise performance are well established in the literature. We observe that after 6 weeks of endurance exercise training there is no longer a time-of-day specific difference in endurance performance.Consistent endurance training performed in morning (ZT13) results in a greater performance increase compared to exercise training during the afternoon (ZT22).Removal of time-of-day differences in performance through exercise training is strongly associated with significant phase shifts (~5 hour advance) of the muscle clock.
Morphological, molecular, and functional characterization of mouse glutamatergic myenteric neurons
Authors: Liu Jia , Zhang Shaopeng , Emadi Sharareh , Guo Tiantian , Chen Longtu , Feng Bin 
Published: September 2023

AbstractThe enteric nervous system (ENS) functions largely independently of the central nervous system (CNS). Correspondingly, glutamate, the dominant neurotransmitter in the CNS and sensory afferents, is not a primary neurotransmitter in the ENS. Only a fraction (approximately 2%) of myenteric neurons in the mouse distal colon and rectum (colorectum) are positive for vesicular glutamate transporter type 2 (VGLUT2), the structure and function of which remain undetermined. Here, we systematically characterized VGLUT2-positive enteric neurons (VGLUT2-ENs) through sparse labeling with adeno-associated virus, single-cell mRNA sequencing (scRNA-seq), and GCaMP6f calcium imaging. Our results reveal that the majority of VGLUT2-ENs (29 out of 31, 93.5%) exhibited Dogiel type I morphology with a single aborally projecting axon; most axons (26 out of 29, 89.7%) are between 4 and 10 mm long, each traversing 19 to 34 myenteric ganglia. These anatomical features exclude the VGLUT2-ENs from being intrinsic primary afferent or motor neurons. The scRNA-seq conducted on 52 VGLUT2-ENs suggests different expression profiles from conventional descending interneurons. Ex vivo GCaMP6f recordings from flattened colorectum indicate that almost all VGLUT2-EN (181 out of 215, 84.2%) are indirectly activated by colorectal stretch via nicotinic cholinergic neural transmission. In conclusion, VGLUT2-ENs are a functionally unique group of enteric neurons with single aborally projecting long axons that traverse multiple myenteric ganglia and are activated indirectly by colorectal mechanical stretch. This knowledge will provide a solid foundation for subsequent studies on the potential interactions of VGLUT2-EN with extrinsic colorectal afferents via glutamatergic neurotransmission.New & NoteworthyWe reveal that VGLUT2-positive enteric neurons (EN), although constituting a small fraction of total EN, are homogeneously expressed in the myenteric ganglia, with a slight concentration at the intermediate region between the colon and rectum. This concentration coincides with the entry zone of extrinsic afferents into the colorectum. Given that VGLUT2-ENs are indirectly activated by colorectal mechanical stretch, they are likely to participate in visceral nociception through glutamatergic neural transmission with extrinsic afferents.