Bright light increases blood pressure and rate-pressure product after a single session of aerobic exercise in men.

This study aimed to test whether bright light (BL) exposure attenuates the reduction in blood pressure (BP) postexercise compared to dim light (DL). Twenty healthy men (27 ± 5 years) randomly underwent two experimental sessions: one under BL (5000 lux) and another under dim light (DL <8lux). In each session, subjects executed a bout of aerobic exercise (cycle ergometer, 30 min, moderate intensity). BP (oscillometric) and heart rate (HR monitor) were measured, and rate-pressure-product (RPP) was calculated. Additionally, a 24-h ambulatory blood pressure monitoring (ABPM) was conducted after the sessions. Systolic BP decreased while HR increased significantly and similarly after the exercise in both sessions. Additionally, systolic BP levels were higher in BL than DL throughout the experimental session (Psession = 0.04). Diastolic (Pinteraction = 0.02) and mean (Pinteraction = 0.03) BPs decreased after exercise in DL (at 30 min), and increased in BL (at 60 and 90 min). RPP increased in both sessions postexercise, but with a main effect revealing higher levels throughout the experimental session in BL than DL (Psession = 0.04) and during the first 3 h of ABPM (p = 0.05). In healthy men, BL exposure increased systolic BP and cardiac work, and abolished the postexercise decreases of diastolic and mean BPs.

Colony context and size-dependent compensation mechanisms give rise to variations in nuclear growth trajectories.

To investigate the fundamental question of how cellular variations arise across spatiotemporal scales in a population of identical healthy cells, we focused on nuclear growth in hiPS cell colonies as a model system. We generated a 3D timelapse dataset of thousands of nuclei over multiple days, and developed open-source tools for image and data analysis and an interactive timelapse viewer for exploring quantitative features of nuclear size and shape. We performed a data-driven analysis of nuclear growth variations across timescales. We found that individual nuclear volume growth trajectories arise from short timescale variations attributable to their spatiotemporal context within the colony. We identified a strikingly time-invariant volume compensation relationship between nuclear growth duration and starting volume across the population. Notably, we discovered that inheritance plays a crucial role in determining these two key nuclear growth features while other growth features are determined by their spatiotemporal context and are not inherited.

Why Are Some Pnictogen(III) Pincer Complexes Planar and Others Pyramidal?

Geometrically-constrained pnictogen pincer complexes have emerged in recent years as platforms for unique stoichiometric and catalytic chemical transformations. These complexes feature dynamic conformations ranging from fully planar at the pnictogen centre to distorted-pyramidal geometries, as well as variation between phases. Although the valued reactivity of pnictogen pincer complexes is ascribed to their geometries, there is no unified model to explain the observed conformational outcomes across different ligands and pnictogen centres. Here we propose such a model through computational analysis of more than 1300 structures across 64 complexes (16 ligands and 4 heavy pnictogens), explaining the experimental observations and making new predictions. By looking at signatures of bond stability (bond lengths, Wiberg bond indices) and delocalization (NPA charges, Hirshfeld charges), our framework posits a pnictogen-based σ-bonding effect that favours pyramidalization and exists in competition with a ligand-based π-bonding effect that favours planarity. Variations in structure as a function of pnictogen identity, ligand tethering, electronics, and aromaticity can be reconciled with reference to a balance between these two opposing forces. Careful consideration of the σ/π-bonding effects may aid in the rational design of future pnictogen pincer complexes with predictable geometries and reactivities.

A Comparative Study of Functional Outcomes in Unstable Pelvic Ring Fractures Treated With Internal Fixator (INFIX) With and Without Sacroiliac Joint Screw Fixation.

Introduction Despite constituting only 3-8% of orthopedic trauma cases, pelvic injuries are associated with high mortality rates, emphasizing the critical need for stable fixation rather than merely anatomical alignment. The use of an anterior, subcutaneous, internal pelvic fixator (INFIX), a novel technique, has shown promise in treating these injuries. Posterior pelvic ring injuries are challenging because they require a significant level of surgical training and technical expertise, and each treatment method has disadvantages. The aim of this study is to compare the clinical and biomechanical outcomes of INFIX with and without sacroiliac screw fixation for unstable pelvic fractures. Methods and methodology Retrospectively, we selected 20 patients with unstable pelvic ring injuries who had come to a high-volume tertiary care hospital and medical college in the state of Maharashtra, India. All the patients were operated on with INFIX; 10 with a sacroiliac joint screw and 10 without a sacroiliac joint screw. We followed up with the patients for six months and evaluated them according to the Majeed score. Results Functional outcomes differed little between INFIX patients operated on with and without a sacroiliac joint screw. However, morbidity, hospital stay, the need for ICU, radiation exposure, and technical ease of surgery were improved in INFIX patients without the sacroiliac screw procedure. We noted an average Majeed score of 78 in the INFIX-alone group and 77.2 in the group that received INFIX with a sacroiliac joint screw. Six months after the surgery, the patients showed signs of a stable bony union, had achieved a full range of motion, and reported no problems in their day-to-day work. Conclusion Although this was a short-term study, we conclude that INFIX without a sacroiliac joint screw showed a comparable functional outcome compared to INFIX with a sacroiliac joint screw. Patients with INFIX alone showed better results; they had reduced surgical time, reduced radiation exposure, and less evidence of neurological harm to the L5-S1 nerve root. The procedure was less complicated and easier for surgeons to learn. Its simplicity and speed were especially beneficial for obese patients.

Synergistic Enhancement of Water-Splitting Performance Using MOF-Derived Ceria-Modified g-C3N4 Nanocomposites: Synthesis, Performance Evaluation, and Stability Prediction with Machine Learning.

Diminishing the charge recombination rate by improving the photoelectrochemical (PEC) performance of graphitic carbon nitride (g-C3N4) is essential for better water oxidation. In this concern, this research explores the competent approach to enhance the PEC performance of g-C3N4 nanosheets (NSs), creating their nanocomposites (NCs) with metal-organic framework (MOF)-derived porous CeO2 nanobars (NBs) along with ZnO nanorods (NRs) and TiO2 nanoparticles (NPs). The synthesis involved preparing CeO2 NBs and g-C3N4 NSs through the calcination of respective precursors, while the sol-gel method is employed for ZnO NRs and TiO2 NPs. Following the subsequent analysis of the physicochemical properties of the materials, the binder-free brush-coating method is deployed to fabricate NC-based photoanodes, followed by an evaluation of the PEC performance through various electrochemical techniques. Remarkably, the binary g-C3N4/CeO2 NCs with 20 wt % CeO2 NBs (gC20 NCs) exhibited a significantly enhanced current density of 0.460 mA/cm2 at 1.23 V vs reversible hydrogen electrode, which is 2.3 times greater than that of bare g-C3N4 NSs (0.195 mA/cm2). Further improvements are observed with ternary gC20/TiO2 (gCT50) and gC20/ZnO (gCZ50) NCs, achieving current densities of 1.810 and 1.440 mA/cm2, respectively. These enhanced current densities are attributed to increased donor densities, reduced charge transfer resistances, and efficient charge transport within the NCs. In addition, higher surface areas with beneficial instinctive defects are perceived for gCT50 and gCZ50 NCs, as revealed by Brunauer-Emmett-Teller and electron spin resonance analysis. Finally, the stability of gCZ50 and gCT50 NC-based photoanodes is predicted and forecasted with the help of the recurrent neural network-based long short-term memory technique. Overall, this study demonstrates the efficacy of organic-inorganic hybrids for efficient photoanodes, facilitating advancements in water-splitting studies.

Cardiovascular disease risk: it is complicated, but race and ethnicity are key, a Bayesian network analysis.

Background: Cardiovascular diseases are the leading cause of morbidity and mortality in the United States. Despite the complexity of cardiovascular disease etiology, we do not fully comprehend the interactions between non-modifiable factors (e.g., age, sex, and race) and modifiable risk factors (e.g., health behaviors and occupational exposures). Objective: We examined proximal and distal drivers of cardiovascular disease and elucidated the interactions between modifiable and non-modifiable risk factors. Methods: We used a machine learning approach on four cohorts (2005-2012) of the National Health and Nutrition Examination Survey data to examine the effects of risk factors on cardiovascular risk quantified by the Framingham Risk Score (FRS) and the Pooled Cohort Equations (PCE). We estimated a network of risk factors, computed their strength centrality, closeness, and betweenness centrality, and computed a Bayesian network embodied in a directed acyclic graph. Results: In addition to traditional factors such as body mass index and physical activity, race and ethnicity and exposure to heavy metals are the most adjacent drivers of PCE. In addition to the factors directly affecting PCE, sleep complaints had an immediate adverse effect on FRS. Exposure to heavy metals is the link between race and ethnicity and FRS. Conclusion: Heavy metal exposures and race/ethnicity have similar proximal effects on cardiovascular disease risk as traditional clinical and lifestyle risk factors, such as physical activity and body mass. Our findings support the inclusion of diverse racial and ethnic groups in all cardiovascular research and the consideration of the social environment in clinical decision-making.

Identifying an acceptable number of ambulatory blood pressure measurements for accuracy of average blood pressure and nocturnal dipping status.

We aimed to identify the minimum number of ambulatory blood pressure (ABP) measures to accurately determine daytime and nighttime systolic blood pressure (BP) averages and nocturnal dipping status (i.e., relative daytime:nighttime change). A total of 43 midlife participants wore an ABP monitor for 24 h with measurements every 20/30 min during the daytime/nighttime, as identified by a sleep diary. We calculated daytime/nighttime systolic BP average and dipping status from all available measurements per participant (i.e., normative data). We then calculated daytime and nighttime BP per participant based on a random selection of 8-20 and 4-10 measurements and replicated random selections 1,000 times. We calculated accuracy by checking the proportion from 1,000 different randomly selected samples for a particular number of measurements that systolic BP was ±5 mmHg of normative data, and dipping status remained unchanged for each participant compared with the normative value. The best fit for the regression model estimated the minimal number of measurements for an accuracy of 95% in BP averages. For a 95% accuracy in estimating daytime and nighttime systolic BP, 11 daytime and 8 nighttime measurements were required. The highest accuracy for dipping status was 91.6 ± 13.4% using 20 daytime and 10 nighttime measures, while the lowest was (83.4 ± 15.1%) using 8 daytime and 4 nighttime measures. In midlife adults, 11 daytime and 8 nighttime measurements are likely enough to calculate average systolic BPs accurately. However, no minimum number is suggested to accurately calculate dipping status.NEW & NOTEWORTHY We found that a minimum of 11 blood pressure (BP) measures are necessary to calculate an accurate average daytime BP, and 8 nighttime measures are necessary to calculate an accurate nighttime average if 95% accuracy is acceptable. Regarding BP dipping status, the current recommendations (20 daytime/7 nighttime) inaccurately classified the dipping status 10.5% of the time, suggesting that guidelines may need to be updated to classify patients as nocturnal dippers or nondippers correctly.

Capacitance of Flexible Polymer/Graphene Microstructures with High Mechanical Strength.

Carbon-modified fibrous structures with high biocompatibility have attracted much attention due to their low cost, sustainability, abundance, and excellent electrical properties. However, some carbon-based materials possess low specific capacitance and electrochemical performance, which pose significant challenges in developing electronic microdevices. In this study, we report a microfluidic-based technique of manufacturing alginate hollow microfibers incorporated by water dispersed modified graphene (bovine serum albumin-graphene). These architectures successfully exhibited enhanced conductivity ∼20 times higher than alginate hollow microfibers without any significant change in the inner dimension of the hollow region (220.0 ± 10.0 µm) compared with pure alginate hollow microfibers. In the presence of graphene, higher specific surface permeability, active ion adsorption sites, and shorter pathways were created. These continuous ion transport networks resulted in improved electrochemical performance. The desired electrochemical properties of the microfibers make alginate/graphene hollow fibers an excellent choice for further use in the development of flexible capacitors with the potential to be used in smart health electronics.

Rigid PN cages as 3-dimensional building blocks for crystalline or amorphous networked materials.

Three-dimensional covalent connectors are valuable synthons for accessing crystalline or amorphous networks. Currently, fused polycyclic alkanes are employed as connectors in this context. We debut phosphorus-nitrogen (PN) cages as new 3-dimensional (3-D) inorganic connectors that yield crystalline and amorphous networks, including examples with gas porosity. We show that the high tunability of PN cages accelerates network diversification and the presence of a responsive 31P NMR spectroscopic handle provides structural insight. Collectively, this work unlocks a new and convenient 3-D synthon for reticular chemistry.

High-throughput screening assay for PARP-HPF1 interaction inhibitors to affect DNA damage repair.

ADP-ribosyltransferases PARP1 and PARP2 play a major role in DNA repair mechanism by detecting the DNA damage and inducing poly-ADP-ribosylation dependent chromatin relaxation and recruitment of repair proteins. Catalytic PARP inhibitors are used as anticancer drugs especially in the case of tumors arising from sensitizing mutations. Recently, a study showed that Histone PARylation Factor (HPF1) forms a joint active site with PARP1/2. The interaction of HPF1 with PARP1/2 alters the modification site from Aspartate/Glutamate to Serine, which has been shown to be a key ADP-ribosylation event in the context of DNA damage. Therefore, disruption of PARP1/2-HPF1 interaction could be an alternative strategy for drug development to block the PARP1/2 activity. In this study, we describe a FRET based high-throughput screening assay to screen inhibitor libraries against PARP-HPF1 interaction. We optimized the conditions for FRET signal and verified the interaction by competing the FRET pair in multiple ways. The assay is robust and easy to automate. Validatory screening showed the robust performance of the assay, and we discovered two compounds Dimethylacrylshikonin and Alkannin, with µM inhibition potency against PARP1/2-HPF1 interaction. The assay will facilitate the discovery of inhibitors against HPF1-PARP1/2 complex and to develop potentially new effective anticancer agents.

H2O/HF Scavenging Mechanism in Cellulose-Based Separators for Lithium-Ion Batteries with Enhanced Cycle Life.

Lithium-ion batteries (LIBs) are increasingly being integrated into the transportation industry due to their high energy density, durability, and low cost. With the growing demand for transportation and other emerging applications, there is a concurrent rise in concern over LIB material sourcing and recycling. This urges the development of LIBs with extended cycle lifespans. One mechanism of capacity fading in LIBs is the dissolution of transition metals into the electrolyte after the cathode is etched with hydrofluoric acid (HF). HF is readily generated by the hydrolysis of the LIB electrolyte salt, lithium hexafluorophosphate (LiPF6), which makes minimizing moisture in the electrolyte a priority in manufacturing. In this study, a nonwoven, cellulose-based separator (CBS) is introduced as an alternative separator for battery technologies to scavenge residual water and HF from the electrolyte. The CBS is shown to be capable of scavenging varying amounts of water from the electrolyte based on different drying processes of the CBS, and a mechanism for this water scavenging is identified based on the materials present in the CBS. In addition, the chemical and electrochemical performance of the CBS in real battery conditions is investigated. Results suggest an effective H2O/HF scavenging capability in the CBS that allows LIB coin cells to have over 17% higher capacity retention than those with conventional separators. Furthermore, studies of the industrially manufactured, commercially relevant cylindrical and pouch cells show remarkable 761 and 103% improvements in the 60% capacity lifetime, respectively. The environmental friendliness, low cost, and easy application empowered by the cycle life improvements shown in this work make this nonwoven CBS a promising candidate for improving industry-level LIB performance.

Potential Neurologic Manifestations of COVID-19 Infection in Neonates.

In contrast to adults, neonates and infants with coronavirus disease 2019 (COVID-19) infection have milder symptoms and are less likely to require hospitalization. However, some neonates with COVID-19 can present with significant symptoms. Recent evidence suggests that neurologic manifestations of neonatal COVID-19 infection may be higher than initially thought. In this comprehensive review of the current literature, we summarize the clinical, laboratory, and radiologic findings, as well as potential management strategies for COVID-19-related neurologic illness in neonates. Although the growing brain may be affected by neurologic disease associated with COVID-19 infection, the few published studies on the long-term outcomes after COVID-19 infection in neonates and infants provide conflicting results. Larger collaborative clinical studies are needed to determine whether COVID-19 infection in neonates has long-term neurodevelopmental outcomes.

UCLMuevete: Increasing the amount of physical activity, work-ability, and cardiorespiratory fitness capacity in university workers through active breaks.

BACKGROUND: Active break programs at the workplace are a promising initiative for increasing workers' physical activity (PA) levels, health, work-ability (WA), and social relationship. OBJECTIVE: To determine the impact of an Active Breaks workplace program based on Bandura's Social Cognitive Theory (SCT) aligned with Behavior Change Techniques (BCT) on PA levels, cardiorespiratory fitness (CRF), WA, and social relationships among university workers. METHODS: #UCLMuévete is a quasi-experimental, 12-week intervention designed according to the TREND and TIDieR-PHP checklists. Sixty-nine university workers were recruited and placed into 17 teams of 3 to 5 people. Participants were instructed to take a 20-min active break every working day (walking, cycling, and functional training). The following variables were measured before and after the 12-week intervention: (1) Amount of PA with accelerometers, (2) CRF through the 6 Min-Walking Test (m), (3) Body composition (fat mass (gr), muscle mass (gr), and bone mineral content (g/cm3) through densitometry), (4) Stress with the BodyGuard2 device, (5) WA through Work Ability Index (WAI), and (6) Social relationships through an ad-hoc questionnaire. Part-time workers, pregnant women, and workers with physical disability were excluded. RESULTS: Significant improvements were observed in the amount of daily moderate-to-vigorous PA (Difference (Dif)., women +8.05 and men +12.31 minutes; p < 0.05; ES = 0.224; 0.379), CRF (Dif., women +52.98 and men +25.53 meters; p < 0.05; ES = 0.578; 0.209), and (Dif., women +2.16 and men +2.39; p < 0.05; ES = 0.150; 0.177). No significant changes were observed in body composition and stress. CONCLUSION: 20 min/day of aerobic and strength active breaks, based on SCT aligned to BCTs, improves university workers' amount of PA, CRF, WAI, and social relationships.

Random Forest Modeling of Acute Toxicity in Anal Cancer: Effects of Peritoneal Cavity Contouring Approaches on Model Performance.

PURPOSE: Our purpose was to analyze the effect on gastrointestinal (GI) toxicity models when their dose-volume metrics predictors are derived from segmentations of the peritoneal cavity after different contouring approaches. METHODS AND MATERIALS: A random forest machine learning approach was used to predict acute grade ≥3 GI toxicity from dose-volume metrics and clinicopathologic factors for 246 patients (toxicity incidence = 9.5%) treated with definitive chemoradiation for squamous cell carcinoma of the anus. Three types of random forest models were constructed based on different bowel bag segmentation approaches: (1) physician-delineated after Radiation Therapy Oncology Group (RTOG) guidelines, (2) autosegmented by a deep learning model (nnU-Net) following RTOG guidelines, and (3) autosegmented but spanning the entire bowel space. Each model type was evaluated using repeated cross-validation (100 iterations; 50%/50% training/test split). The performance of the models was assessed using area under the precision-recall curve (AUPRC) and the receiver operating characteristic curve (AUROCC), as well as optimal F1 score. RESULTS: When following RTOG guidelines, the models based on the nnU-Net auto segmentations (mean values: AUROCC, 0.71 ± 0.07; AUPRC, 0.42 ± 0.09; F1 score, 0.46 ± 0.08) significantly outperformed (P < .001) those based on the physician-delineated contours (mean values: AUROCC, 0.67 ± 0.07; AUPRC, 0.34 ± 0.08; F1 score, 0.36 ± 0.07). When spanning the entire bowel space, the performance of the autosegmentation models improved considerably (mean values: AUROCC, 0.87 ± 0.05; AUPRC, 0.70 ± 0.09; F1 score, 0.68 ± 0.09). CONCLUSIONS: Random forest models were superior at predicting acute grade ≥3 GI toxicity when based on RTOG-defined bowel bag autosegmentations rather than physician-delineated contours. Models based on autosegmentations spanning the entire bowel space show further considerable improvement in model performance. The results of this study should be further validated using an external data set.

Obesity alters the circadian profiles of energy metabolism and glucose regulation in humans.

OBJECTIVE: Given the complex interaction among the circadian system, energy metabolism, and obesity, the authors tested whether having obesity impacts the circadian variation in energy and glucose metabolism in humans. METHODS: Participants with BMI either in the healthy weight or obesity ranges were studied in a 5-day, in-laboratory protocol that equally distributed behaviors (i.e., sleep, eating, exercise) across 24 h. Energy metabolism was measured at rest and during a standardized exercise bout and blood was sampled before and after each identical study meal to assess glucose and insulin levels. RESULTS: In those with a healthy weight, the circadian nadir of energy expenditure, during both rest and exercise, occurred when participants would normally be asleep. However, in those with obesity, this nadir appears to occur during the habitual wake period. Differences in glucose regulation also depended on the circadian phase, such that individuals with obesity appeared to have relatively greater glucose intolerance during the circadian day and produced less insulin during the circadian night. CONCLUSIONS: Obesity is associated with altered circadian energy and glucose metabolism. Understanding and addressing these associations could lead to strategies that improve body weight and metabolic health in people with obesity.

Ligand-enforced geometric constraints and associated reactivity in p-block compounds.

The geometry at an element centre can generally be predicted based on the number of electron pairs around it using valence shell electron pair repulsion (VSEPR) theory. Strategies to distort p-block compounds away from these predicted geometries have gained considerable interest due to the unique structural outcomes, spectroscopic properties or reactivity patterns engendered by such distortion. This review presents an up-to-date group-wise summary of this exciting and rapidly growing field with a focus on understanding how the ligand employed unlocks structural features, which in turn influences the associated reactivity. Relevant geometrically constrained compounds from groups 13-16 are discussed, along with selected stoichiometric and catalytic reactions. Several areas for advancement in this field are also discussed. Collectively, this review advances the notion of geometric tuning as an important lever, alongside electronic and steric tuning, in controlling bonding and reactivity at p-block centres.

Chronological distribution of readings in ambulatory blood pressure monitoring exams affects the nighttime average and the magnitude of blood pressure dipping.

STUDY OBJECTIVES: Averaged nighttime blood pressure (BP) is superior to daytime BP for cardiovascular risk stratification, and the relative change between daytime/nighttime BP (dipping%) significantly predicts cardiovascular risk. Newer reports suggest that 4 measurements at night may be enough for cardiovascular risk stratification. Since BP oscillates across the night, the temporal distribution of measurements across the night may impact nighttime BP and dipping%. Therefore, we compared average nighttime BP and dipping% when using measurements in the first half (1st-half), second (2nd-half), and a combination of both (combined). METHODS: Forty-three (17 females and twenty-six males) midlife adults aged 50±10 years old wore an ambulatory BP monitor for 24 hours at home, programmed to measure BP every 20 minutes when scheduled for daytime and every 30 minutes during a self-selected 8-hour nighttime for time-in-bed. We compared the nighttime BP averages and dipping% when using either the first four measurements from the 1st-half or 2nd-half of the nighttime and combined. RESULTS: Nighttime Systolic BP was significantly different across 1st-half, 2nd-half, and combined (111±9 vs.107±11 vs. 109±9 mmHg, p<0.01), respectively, with significant pairwise differences across all categories (p<0.01 for each). Systolic BP dipping% was significantly different across 1st-half, 2nd-half, and combined (9.9±5.5 vs.13.5±6.4 vs. 11.7±5.0 %, p<0.01), respectively, with significant pairwise differences across all categories (p<0.01 for each. Diastolic BP and diastolic dipping% were similar across the three different bins. CONCLUSION: In midlife adults, systolic nighttime BP and dipping% may depend upon when BP measurements are taken during the night.

Interactions between estradiol and ERK, but not mTOR, signaling is necessary for enhanced cocaine-induced conditioned place preference in female rats.

Women rapidly progress from recreational cocaine use to dependence, consume greater quantities of cocaine, experience more positive subjective effects of cocaine and have higher incidences of relapse during abstinence. These effects have been replicated in animal models of cocaine addiction and indicate an enhanced sensitivity and therefore, vulnerability of females to cocaine addiction. Furthermore, it has been demonstrated that estradiol (E2) is a key mediator of the aforementioned effects of cocaine in women and female animals. However, studies identifying the influence of E2 on cocaine-associated reward and its underlying neurobiological mechanisms are lacking. Here, we further explored the influence of E2 on cocaine conditioned place preference in female rats. We show that E2 mediates cocaine-conditioned reward by potentiating cocaine-context associations. In addition, the E2-mediated increases in cocaine-induced CPP are associated with increased activation of ERK1/2 and mTOR proteins in the nucleus accumbens, dorsal striatum, and ventral tegmental area. To assess the involvement of ERK1/2 and mTOR in E2-mediated enhanced cocaine-CPP, we inhibited ERK1/2 and/or mTOR activity during cocaine-conditioning and before CPP-test. Inhibition of ERK1/2 during conditioning blocked cocaine-CPP in females, inhibition mTOR was without effect, and inhibiting ERK1/2 and mTOR before CPP-test blocked cocaine-CPP. In conclusion, we have established that E2 enhances cocaine-conditioned reward by potentiating cocaine-context associations formed during conditioning. Additionally, activation of ERK1/2 during cocaine-conditioning is necessary for the potentiation of cocaine-conditioned reward by E2. SIGNIFICANCE STATEMENT: Studies characterizing the molecular substrates underlying the effects of E2 during the formation of cocaine-context associations are virtually unknown. In this study, we established the influence of E2 during the formation of cocaine-CPP and characterized the role of ERK1/2 and mTOR activity on this effect within significant nodes of the reward pathway. The elucidation of the role of E2 in cocaine-induced intracellular signaling fills a significant gap in our knowledge regarding the mechanisms by which E2 affects intracellular signaling pathways to indicate the motivational salience of a stimulus. These data are crucial to our understanding of how fluctuating hormone levels can render females increasing sensitive to the rewarding effects of cocaine.

Mechanisms of cilia regeneration in Xenopus multiciliated epithelium in vivo.

Cilia regeneration is a physiological event, and while studied extensively in unicellular organisms, it remains poorly understood in vertebrates. In this study, using Xenopus multiciliated cells (MCCs) as a model, we demonstrate that, unlike unicellular organisms, deciliation removes the transition zone (TZ) along with the ciliary axoneme. While MCCs immediately begin the regeneration of the ciliary axoneme, surprisingly, the assembly of TZ was delayed. Instead, ciliary tip proteins, Sentan and Clamp, were the first to localize to regenerating cilia. Using cycloheximide (CHX) to block new protein synthesis, we show that the TZ protein B9d1 is not a component of the cilia precursor pool and requires new transcription/translation providing insights into the delayed repair of TZ. Moreover, CHX treatment led MCCs to assemble fewer (~ ten compared to ~150 in controls) but about wild-type length (78% of WT) cilia by gradually concentrating ciliogenesis proteins like IFT43 at a select few basal bodies, highlighting the exciting possibility of protein transport between basal bodies to facilitate faster regeneration in cells with multiple cilia. In summary, we demonstrate that MCCs begin regeneration with the assembly of ciliary tip and axoneme followed by TZ, questioning the importance of TZ in motile ciliogenesis.

CREID - A ChemoReceptor-Effector Interaction Database.

The ChemoReceptor-Effector Interaction Database (CREID) is a collection of bacterial chemoreceptor and effector protein and interaction data to understand the process that chemoreceptors and effectors play in various environments. Our website includes terms associated with chemosensory pathways to educate users and those involved in collaborative research to help them understand this complex biological network. It includes 2,440 proteins involved in chemoreceptor and effector systems from 7 different bacterial families with 1,996 chemoeffector interactions. It is available at https://reactcreid.bicbioeng.org.