Transient Increase Research Articles

Analysis of the dynamic impact behavior and fracture mechanism of coal samples at various temperatures

A thorough understanding of the mechanical properties and fracture mechanisms of coal under high-temperature conditions is crucial for preventing deep coal and rock dynamic disasters. Utilizing the Hopkinson pressure bar experimental system, this study conducts an in-depth analysis of the strength characteristics, failure modes, microscopic properties, and energy consumption effects of coal between 0 and 250℃. The findings reveal that during the heating process, coal’s mass loss increases with temperature, but at a decreasing rate. Significant changes in the coal samples’ dynamic strength, fragmentation, microscopic features, energy evolution, and fracture mechanisms occur at 100℃, marking a turning point in their dynamic behavior. Both dynamic strength and elastic modulus experience a transient increase at 100℃, while the fractal dimension experiences a brief decrease. At 100℃, the thermal expansion of coal particles predominates over the thermal damage from high temperatures, resulting in an increase in the coal samples’ dynamic strength. As the temperature further rises, thermal damage to the coal samples intensifies, leading to a decrease in dynamic strength. Similarly, the absorption and dissipation energy index K of the coal samples experiences a brief increase at 100℃, signifying a sudden change in the energy evolution pattern. Observations of the coal samples’ failure modes upon impact reveal a transition from tensile failure to a combined shear-tensile failure with increasing temperature.

Exploring the relationship between child temperament, maternal psychiatric symptoms, family environment and infant feeding.

Infant temperament is assumed to be primarily innate. However, newer research suggests that maternal affection impacts ratings of temperament and environmental factors, including feeding method, can also influence infant temperament. This study investigates child temperament and its relationships with maternal psychiatric symptoms, environmental variables and feeding method longitudinally in a cohort of children followed from 6 to 72 months. Differences in temperament by feeding group are also investigated. We hypothesized that maternal psychiatric symptoms, environmental stressors, and impaired family dynamics would have negative impact on child temperament, whereas breastfeeding would have a positive impact on child temperament. Mothers' ratings of child's temperament, own psychiatric symptomatology, environmental stresses and family cohesion were obtained in 504 mother-infant dyads via rating scales completed by mothers. Infants were breastfeed (BF), fed soy-based infant formula (SF) or dairy-based infant formula (MF). Linear mixed effect models investigated the relationship of variables on child's temperament while controlling for significant covariates and repeated measurements. Mothers in this study did not endorse clinical-level psychiatric symptomatology; however, when adjusted for significant covariates, higher psychiatric symptomatology significantly correlated with environmental stressors, impaired family dynamics and elevations in temperament ratings of infants' adaptability and mood. There were no lasting differences for temperament between feeding groups. However, some significant transient increases in rhythmicity and adaptability were found between SF and BF children. Positive relationships between family environment stressors and maternal psychiatric ratings were found. Transient differences were found in child temperament based upon feeding method.

Transient Increases in Neural Oscillations and Motor Deficits in a Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor symptoms like tremors and bradykinesia. PD's pathology involves the aggregation of α-synuclein and loss of dopaminergic neurons, leading to altered neural oscillations in the cortico-basal ganglia-thalamic network. Despite extensive research, the relationship between the motor symptoms of PD and transient changes in brain oscillations before and after motor tasks in different brain regions remain unclear. This study aimed to investigate neural oscillations in both healthy and PD model mice using local field potential (LFP) recordings from multiple brain regions during rest and locomotion. The histological evaluation confirmed the significant dopaminergic neuron loss in the injection side in 6-OHDA lesioned mice. Behavioral tests showed motor deficits in these mice, including impaired coordination and increased forelimb asymmetry. The LFP analysis revealed increased delta, theta, alpha, beta, and gamma band activity in 6-OHDA lesioned mice during movement, with significant increases in multiple brain regions, including the primary motor cortex (M1), caudate-putamen (CPu), subthalamic nucleus (STN), substantia nigra pars compacta (SNc), and pedunculopontine nucleus (PPN). Taken together, these results show that the motor symptoms of PD are accompanied by significant transient increases in brain oscillations, especially in the gamma band. This study provides potential biomarkers for early diagnosis and therapeutic evaluation by elucidating the relationship between specific neural oscillations and motor deficits in PD.

Abstract 21: The Detrimental Effects of a Comorbidity of Increased Blood Pressure Variability and High Salt Diet on Cardiovascular and Neurovascular Outcomes

Recent studies have identified increased blood pressure variability (BPV) as a novel risk factor for cognitive decline, independently from absolute BP values. However, the underlying mechanisms are poorly defined. In addition, whether a high salt diet (HSD) contributes to BPV and exacerbates cognitive decline is not known. We tested the hypothesis that vascular damage resulting from blood pressure fluctuations in BPV disrupts critical mechanisms regulating cerebral blood flow (CBF), impairing perfusion and leading to neurovascular dysfunction and cognitive decline. We established a murine BPV model and evaluated the impact of BPV on systemic BP (baroreceptor reflex) and CBF regulation (myogenic and functional hyperemia (FH) responses). Mice were implanted with a cranial window for in-vivo two-photon (2P) imaging. A programmable pump infused 6-8 pulses/day of angiotensin II ((Ang II 18 µg/day) (BPV) or saline (Control) for 25 days, and cardiovascular variables were measured via DSI telemetry. Ang II pulse infusions evoked transient BP increases (Δ43±4 mmHg, MAP; P<0.01,n=8); however, did not induce hypertension in the BPV group. BPV mice displayed increased BPV index (P=0.04,n=12) and cognitive decline (novel object recognition test (P=0.01,n=10)). Telemetry data showed a decrease in bradycardic responses following chronic BPV (P=0.03, n=8). Data from 2P studies showed enhanced myogenic response in parenchymal arterioles of BPV vs Controls (P<0.01,n=9-15 runs) when BP transitions from low to high BP. We observed a blunted FH in BPV vs Control during low BP (P<0.01,n=6-7). During high BP, FH was pronounced in Controls (P<0.01,n=6-7); however, pressure-induced vascular responses were abolished in BPV mice (P<0.01,n=6-7). In separate groups of mice, the Control and BPV protocol was repeated with all mice receiving a high-salt diet (HS; 4% NaCl chow+1% NaCl drinking water: Control+HS or BPV+HS). There were no changes in 24-hr MAP in Control+HS (P>0.85, n=5). Whereas BPV+HS mice developed sustained hypertension (increased 24-hr MAP; P<0.01, n=4). These data demonstrate that BPV alters mechanisms regulating CBF and BP, contributing to cognitive decline and that HSD may exacerbate the detrimental effects of BPV on BP regulating mechanisms. Ongoing studies are examining the comorbid effects of BPV+HS on the cerebrovasculature and direct CBF changes in BPV and BPV+HS mice.

O57 NOCTURNAL BLOOD PRESSURE FLUCTUATION AND DIPPING PATTERNS IN PATIENTS WITH SEVERE OBSTRUCTIVE SLEEP APNOEA

Background and Objective: Nighttime blood pressure (BP) is important for diagnosis of hypertension and for cardiovascular risk stratification. Remarkably, a reverse dipping pattern is a strong and independent predictor of overall mortality and major adverse cardiovascular events. Therefore, the further clarification of the underlying mechanisms of non- and reverse dipping is crucial to improve the treatment of patients with nighttime hypertension. Methods: We investigated 97 patients with suspected obstructive sleep apnoea (OSA, AHI >30) using standard polysomnography and continuous BP measurement based on the pulse-transit-time method (SOMNOscreen Plus®, SOMNOmedics). Frequency and amplitude of fluctuations in systolic BP following sleep disturbances (OSA) were investigated. Results: Apnoeic events went along with transient increases of BP. In some cases, systolic BP did not reach the value before the apnoea but increased over time. We defined elevations of the systolic BP baseline by >10 mmHg with a duration of >10 min as BP superpositions. The superposition periods were also characterized by increased BP amplitudes with peak values of BP up to 220 mmHg. Superposition occurred in 48 patients. Further, 65% of the OSA patients were identified as non-dippers. However, nearly all the patients with superposition (98%) were identified to have non-dipper or reverse dipper patterns. Conclusions: Our study strongly suggests that non-dipping and reverse dipping in patients with severe OSA are causally linked to OSA related BP fluctuations. Further, continuous elevations in SBP baseline (superpositions) result in extreme BP values. This behaviour with high BP peaks may be contributing to the increased mortality in patients with reverse dipping. Therefore, identification and adequate treatment of patients with reverse dipping reduces the cardiovascular risk and may prolong their life.

UNVEILING VISUAL ACUITY AND INTRAOCULAR PRESSURE SHIFTS AFTER Nd:YAG LASER CAPSULOTOMY FOR POSTERIOR CAPSULE OPACIFICATION

Introduction: Posterior capsule opacification (PCO) of the lensis a frequent complication following cataract surgerywith intraocular lens implantation, leading to visual decline and symptoms like blurred vision, glare and halos around lights [1]. Nd:YAG laser capsulotomy is a common treatment for PCO, using a laser to create an opening in the opacified lens capsule to restore vision. Although effective, the procedure can cause a transient increase in intraocular pressure (IOP) [3]. Aim: To evaluate visual acuity outcomes and IOP changes following Nd:YAG laser capsulotomy for PCO. Material and Methods: A prospective cohort study was carried out from December 2022 to June 2024 with 61 eyes of 61 patients posted for Nd:YAG laser capsulotomy, after receiving permission from the Institutional Ethics Committee (IEC) and taking informed written consent from the participating patients. The procedure was performed with standard techniques using Appa YAG Laser Machine Model 307, and patients were followed up at 1 hour, 4 hours, 7 days, 14 days, and 28 days after the procedure. Visual acuity and IOP were monitored, and statistical comparisons were made. Statistical analysis used: Statistical tests to compare pre-procedure and post-procedure outcomesusing paired t-tests and p-value. Results: Visual acuity improved significantly (p-value<0.05) from the pre-procedure mean value of 6/60 to 6/9 one month after the procedure. IOP increased transiently, peaking at 20 mmHg in 4 hours post-procedure but returning to baseline levels (15 mmHg) by 28 days. This pattern of transient IOP elevation is consistent with the inflammatory response following the procedure. Conclusions: Nd:YAG laser capsulotomy improves visual acuity significantly with manageable transient IOP elevations. The procedurehas a favorable safety profile, withIOP levels returning to baseline within a month. Ongoing monitoring is crucial to managing any potential complication, and further research with longer follow-up is recommended for a comprehensive understanding of long-term outcomes.

Regulation of Hippocamposeptal Synaptic Transmission by GABABRs Is Altered in 5XFAD Mice in a Sex- and Age-Dependent Manner

Hippocamposeptal (HS) neurons send GABAergic projections from the hippocampus to the medial septum/diagonal band of Broca (MS/DBB) as part of a reciprocal loop that is critical for memory. HS neurons are proposed to be particularly sensitive to the deleterious effects of pathological exposure to amyloid-β (Aβ), as would occur during Alzheimer’s disease (AD). However, it is not known how HS GABA release in the MS/DBB is altered during the progression of AD. To target HS neurons in a mouse model of AD, we crossed SST-Cre mice to 5XFAD mice and performed stereotaxic injections of Cre-dependent AAV containing mCherry/channelrhodopsin-2 (ChR2) into the hippocampus of offspring at 4, 6, 9, and 12 months. We used optogenetics to selectively stimulate HS terminals while performing whole-cell patch-clamp recordings from MS/DBB neurons in slices. There was a transient reduction in HS-inhibitory postsynaptic current (IPSC) amplitude in female 5XFAD mice at 6 months, but no difference in males at any age, and no difference in paired-pulse ratio in either sex at any age. When bath applying the GABABR agonist, baclofen, we found a larger decrease in HS-IPSC amplitude in 5XFAD females at 9 months and 5XFAD males at 12 months. In 12-month-old 5XFAD females, response to baclofen was significantly reduced. These data suggest that there is a transient increase in responsiveness to GABABR activation in 5XFAD mice that occurs earlier in females than in males. These sex-specific changes to HS function are likely to impact the relay of information between the hippocampus and MS/DBB.

Effects of High Dose Bolus Cholecalciferol on Free Vitamin D Metabolites, Bone Turnover Markers and Physical Function.

High dose bolus cholecalciferol supplementation has been associated with falls and fracture, and this does not appear to be due to hypercalcaemia. The primary aim of this study was to determine the change in free vitamin D and metabolites after high dose bolus supplementation. This was a single centre, double-blinded, randomised, controlled trial of three different oral bolus doses of vitamin D3 (50,000 IU, 150,000 IU, and 500,000 IU) in otherwise healthy, vitamin D deficient (total 25-hydroxylated vitamin 25(OH)D < 30 nmol/L) postmenopausal women. Thirty-three women were randomized to one of the three treatment groups. Twenty-seven vitamin D sufficient (25(OH)D > 50 nmol/L) postmenopausal women were recruited as a concurrent control group. Participants attended five study visits over three months. We measured total 25(OH)D3 and free 25(OH)D, total and free 1,25(OH)2D, parathyroid hormone, fibroblast-growth factor-23, serum calcium, ionised calcium, urinary calcium excretion, and bone turnover markers (procollagen I N-propeptide (PINP), serum C-telopeptides of type I collagen (CTX-I) and Osteocalcin (OC)). We assessed muscle strength and function with grip strength and a short physical performance battery. Postural blood pressure and aldosterone:renin ratio (ARR) was also measured. Total 25(OH)D3 and free 25(OH)D increased in response to dose, and there were proportionate increases in total and free metabolites. Treatment did not affect serum calcium, postural blood pressure, ARR, or physical function. Bone turnover markers increased transiently one week after administration of 500,000 IU. High dose bolus cholecalciferol supplementation does not cause disproportionate increases in free vitamin D or metabolites. We did not identify any effect on blood pressure regulation or physical function that would explain increased falls after high dose treatment. A transient increase in bone turnover markers one week after a 500,000 IU bolus suggests that very high doses can have acute effects on bone metabolism, but the clinical significance of this transient increase is uncertain.

Comparison of Systemic Exposure Between Epinephrine Delivered via Metered-Dose Inhalation and Intramuscular Injection.

Background: Primatene® MIST, an epinephrine metered-dose inhaler (MDI), has long been questioned by some medical professionals for asthma treatment despite having been approved by the Food and Drug Administration. One of the primary reasons for their concerns stemmed from potential cardiovascular complications following epinephrine administration. However, the majority of documented cardiovascular complications seemed to occur following the injection route of the epinephrine. The aim of this study was to evaluate the systemic exposure of epinephrine delivered through different administration routes and to understand its relationship with cardiovascular effects. Since albuterol inhalers are commonly recommended for asthma, albuterol was also studied as a comparator drug. Method: A randomized, evaluator-blinded, three-arm crossover study was conducted in 28 healthy adult subjects to compare the profiles of systemic exposure for epinephrine delivered by MDI versus epinephrine intramuscular (IM) injection and albuterol MDI. Serially sampled plasma epinephrine and albuterol levels were measured and compared between treatment groups. Safety was assessed by adverse events, serial vital signs, electrocardiograms (ECGs), and clinical laboratory tests obtained at each crossover dosing visit. Results: Systemic exogenous drug exposure for inhaled epinephrine MDI (39 pg/mL × hour) was ∼9 times lower than that of epinephrine IM (435 pg/mL × hour) and 122 times lower than that of albuterol MDI (3453 pg/mL × hour) after dose normalization. The Cmax in epinephrine MDI (345 pg/mL) was approximately half of that of epinephrine IM (816 pg/mL) and that of albuterol MDI (681 pg/mL). Plasma drug concentrations for epinephrine MDI dropped rapidly to baseline (∼0.6 hour), while epinephrine IM took ∼8 hours, and albuterol MDI required more than 24 hours. Epinephrine MDI and albuterol MDI resulted in minimal, clinically insignificant changes in vital signs and ECGs, whereas epinephrine IM led to mild transient increases in systolic blood pressure, heart rate, and corrected QT interval. Conclusion: Epinephrine MDI (Primatene MIST) had ∼9 times lower systemic drug exposure (SDE) than that of epinephrine IM and ∼122 times lower than that of albuterol MDI. The lower SDE of inhaled epinephrine also correlated with reassuring safety findings, with no significant cardiovascular adverse effects found, compared with transient effects seen after IM epinephrine. Clinical trial registration number: NCT04207840.

Populus trichocarpa EXPA6 Facilitates Radial and Longitudinal Transport of Na+ under Salt Stress.

Expansins are cell wall (CW) proteins that mediate the CW loosening and regulate salt tolerance in a positive or negative way. However, the role of Populus trichocarpa expansin A6 (PtEXPA6) in salt tolerance and the relevance to cell wall loosening is still unclear in poplars. PtEXPA6 gene was transferred into the hybrid species, Populus alba × P. tremula var. glandulosa (84K) and Populus tremula × P. alba INRA '717-1B4' (717-1B4). Under salt stress, the stem growth, gas exchange, chlorophyll fluorescence, activity and transcription of antioxidant enzymes, Na+ content, and Na+ flux of root xylem and petiole vascular bundle were investigated in wild-type and transgenic poplars. The correlation analysis and principal component analysis (PCA) were used to analyze the correlations among the characteristics and principal components. Our results show that the transcription of PtEXPA6 was downregulated upon a prolonged duration of salt stress (48 h) after a transient increase induced by NaCl (100 mM). The PtEXPA6-transgenic poplars of 84K and 717-1B4 showed a greater reduction (42-65%) in stem height and diameter growth after 15 days of NaCl treatment compared with wild-type (WT) poplars (11-41%). The Na+ accumulation in roots, stems, and leaves was 14-83% higher in the transgenic lines than in the WT. The Na+ buildup in the transgenic poplars affects photosynthesis; the activity of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT); and the transcription of PODa2, SOD [Cu-Zn], and CAT1. Transient flux kinetics showed that the Na+ efflux of root xylem and leaf petiole vascular bundle were 1.9-3.5-fold greater in the PtEXPA6-transgenic poplars than in the WT poplars. PtEXPA6 overexpression increased root contractility and extensibility by 33% and 32%, indicating that PtEXPA6 increased the CW loosening in the transgenic poplars of 84K and 717-1B4. Noteworthily, the PtEXPA6-promoted CW loosening was shown to facilitate Na+ efflux of root xylem and petiole vascular bundle in the transgenic poplars. We conclude that the overexpression of PtEXPA6 leads to CW loosening that facilitates the radial translocation of Na+ into the root xylem and the subsequent Na+ translocation from roots to leaves, resulting in an excessive Na+ accumulation and consequently, reducing salt tolerance in transgenic poplars. Therefore, the downregulation of PtEXPA6 in NaCl-treated Populus trichocarpa favors the maintenance of ionic and reactive oxygen species (ROS) homeostasis under long-term salt stress.

Chemokine-mediated F-actin dynamics, polarity, and migration in B lymphocytes depend on WNK1 signaling.

Ligand-engaged chemokine receptors trigger nucleotide exchange in heterotrimeric Gαi proteins, which stimulates cytoskeletal reorganization and cell polarity changes. To better understand the signaling events responsible for these cellular changes, we focused on early changes in F-actin dynamics after engagement of the chemokine receptor CXCR5 in murine splenic B cells. Within 10 seconds of exposure to the CXCR5 ligand CXCL13, three-dimensional lamellar-like pseudopods and F-actin-rich ridges appeared. The transient F-actin increase depended on Gαi2/3 signaling, the PI3K/AKT pathway, ERK activation, phospholipase C activity, and Rac1/2 activation mediated by Dock2 (dedicator of cytokinesis 2). Immunoblot analyses identified the kinase WNK1 (with no lysine kinase 1) as a potential early AKT effector. Treating B cells with specific WNK inhibitors disrupted F-actin dynamics and impaired B cell polarity, motility, and chemotaxis. These changes were mimicked in a murine B cell line by CRISPR-Cas9 gene editing of Wnk1, which also suggested that WNK1 contributed to B cell proliferation. Administration of a single dose of a WNK inhibitor transiently reduced B cell motility and polarity in the lymph nodes of live mice. These results indicate that WNK1 signaling maintains B cell responsiveness to CXCL13 and suggest that pharmacological inhibition of WNK1, which is involved in cancer progression and blood pressure regulation, may affect humoral immunity.

Early impaired relaxation of the left ventricle in isolated, uncomplicated prehypertension without left ventricular hypertrophy can be detected by exercise electrocardiography

Nearly fifty percent of patients with isolated, uncomplicated prehypertension have impaired relaxation of the left ventricle even in the absences of left ventricular hypertrophy. Such early impairment of the left ventricular relaxation can be detected by exercise electrocardiography. Transient increase, in the area of the negative terminal deflection of the P wave in lead V1 (&gt;0.04mVaec) during and/or early recovery suggested transient increase in the left atrial pressure due to unmasking of the early impairment of the left ventricular relaxation by exercise induced tachycardia.

Offsetting Dense Particle Sedimentation in Microfluidic Systems.

Sedimentation is an undesirable phenomenon that complicates the design of microsystems that exploit dense microparticles as delivery tools, especially in biotechnological applications. It often informs the integration of continuous mixing modules, consequently impacting the system footprint, cost, and complexity. The impact of sedimentation is significantly worse in systems designed with the intent of particle metering or binary encapsulation in droplets. Circumventing this problem involves the unsatisfactory adoption of gel microparticles as an alternative. This paper presents two solutions-a hydrodynamic solution that changes the particle sedimentation trajectory relative to a flow-rate dependent resultant force, and induced hindered settling (i-HS), which exploits Richardson-Zaki (RZ) corrections of Stokes' law. The hydrodynamic solution was validated using a multi-well fluidic multiplexing and particle metering manifold. Computational image analysis of multiplex metering efficiency using this method showed an average reduction in well-to-well variation in particle concentration from 45% (Q = 1 mL/min, n = 32 total wells) to 17% (Q = 10 mL/min, n = 48 total wells). By exploiting a physical property (cloud point) of surfactants in the bead suspension in vials, the i-HS achieved a 58% reduction in the sedimentation rate. This effect results from the surfactant phase change, which increases the turbidity (transient increase in particle concentration), thereby exploiting the RZ theories. Both methods can be used independently or synergistically to eliminate bead settling in microsystems or to minimize particle sedimentation.

Bidirectional Effect of Long-Term Δ9-Tetrahydrocannabinol Treatment on mTOR Activity and Metabolome.

Brain aging is associated with cognitive decline, reduced synaptic plasticity, and altered metabolism. The activity of mechanistic target of rapamycin (mTOR) has a major impact on aging by regulating cellular metabolism. Although reduced mTOR signaling has a general antiaging effect, it can negatively affect the aging brain by reducing synaptogenesis and thus cognitive functions. Increased mTOR activity facilitates aging and is responsible for the amnestic effect of the cannabinoid receptor 1 agonist Δ9-tetrahydrocannabinol (THC) in higher doses. Long-term low-dose Δ9-THC had an antiaging effect on the brain by restoring cognitive abilities and synapse densities in old mice. Whether changes in mTOR signaling and metabolome are associated with its positive effects on the aging brain is an open question. Here, we show that Δ9-THC treatment has a tissue-dependent and dual effect on mTOR signaling and the metabolome. In the brain, Δ9-THC treatment induced a transient increase in mTOR activity and in the levels of amino acids and metabolites involved in energy production, followed by an increased synthesis of synaptic proteins. Unexpectedly, we found a similar reduction in the mTOR activity in adipose tissue and in the level of amino acids and carbohydrate metabolites in blood plasma as in animals on a low-calorie diet. Thus, long-term Δ9-THC treatment first increases the level of energy and synaptic protein production in the brain, followed by a reduction in mTOR activity and metabolic processes in the periphery. Our study suggests that a dual effect on mTOR activity and the metabolome could be the basis for an effective antiaging and pro-cognitive medication.

Probability-oriented disturbance estimation-triggered control via collaborative and adaptive Bayesian optimization for reentry vehicles

The paper investigates the performance improvement issue for reentry vehicles under uncertainties from the perspective of probability. The disturbance estimation-triggered control (DETC) proves to achieve transient performance increase compared with the standard disturbance-observer control methods, and the presented approach further exploits the probability-oriented transient performance improvement based on the collaborative and adaptive Bayesian optimization (CABO) technique, which constructs the main contribution of the paper. Based on the attitude dynamics of reentry vehicles, the DETC method is first introduced to guarantee the tracking stability and robustness against the uncertainties including the aerodynamic perturbation and wind effects. Meanwhile, the performance improvement is analyzed theoretically. Then, by virtue of the CABO algorithm, the CABO-based DETC is presented by combining the performance and probability indexes. Finally, the simulation results verify the effectiveness of the proposed control scheme and parameters influence is also discussed.

Coordination of shoot apical meristem shape and identity by APETALA2 during floral transition in Arabidopsis

Plants flower in response to environmental signals. These signals change the shape and developmental identity of the shoot apical meristem (SAM), causing it to form flowers and inflorescences. We show that the increases in SAM width and height during floral transition correlate with changes in size of the central zone (CZ), defined by CLAVATA3 expression, and involve a transient increase in the height of the organizing center (OC), defined by WUSCHEL expression. The APETALA2 (AP2) transcription factor is required for the rapid increases in SAM height and width, by maintaining the width of the OC and increasing the height and width of the CZ. AP2 expression is repressed in the SAM at the end of floral transition, and extending the duration of its expression increases SAM width. Transcriptional repression by SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1) represents one of the mechanisms reducing AP2 expression during floral transition. Moreover, AP2 represses SOC1 transcription, and we find that reciprocal repression of SOC1 and AP2 contributes to synchronizing precise changes in meristem shape with floral transition.

N-Acetylcysteine Ineffective in Alleviating Hangover from Binge Drinking: A Clinical Study.

Alcohol hangover (veisalgia) is a fairly common phenomenon. The pathogenesis of veisalgia is not understood and treatment has not yet been established. Occasionally, students take N-acetylcysteine (NAC) before binge drinking to alleviate hangover. The aim of this study was to evaluate the effect of NAC on serum levels of electrolytes, enzymes, oxidative stress biomarkers and symptoms of veisalgia in binge drinking. In this randomized, double-blind, placebo-controlled study, healthy students were randomly assigned into two groups: one receiving NAC and the other receiving a placebo. Blood samples were taken before drinking, 30 min after a 1.5 h long drinking session, and the subsequent morning. Serum levels of electrolytes, urea, enzymes, ethanol, 8-Hydroxydeoxyguanosine (8-OHdG) and N-epsilon-hexanoyl-lysine were measured. The participants completed the Acute Hangover Severity Scale (AHSS) assessment based on symptoms, and 40 students (20 male), aged 23 ± 2 years, were included in the study. Their mean blood ethanol concentration was 1.4 g/kg. Serum sodium levels were increased after drinking, and urea decreased the following morning compared to their levels before drinking in both groups. Serum 8-OHdG levels were increased after drinking and remained elevated until the following morning, compared to the levels before drinking, in both groups. NAC had no effect on sodium, urea and 8-OHdG levels or the symptoms of veisalgia. In conclusion, binge drinking causes a transient increase in serum sodium and as a prolonged increase in oxidative marker 8-OHdG levels. NAC had no effect on the sodium and 8-OHdG levels.

Dopaminergic cAMP signaling in mouse olfactory bulb astrocytes

Cyclic AMP (cAMP) is an important second messenger in virtually all animal cell types, including astrocytes. In the brain, it modulates energy metabolism, development and synaptic plasticity. Dopamine receptors are G protein-coupled receptors that affect cAMP production by adenylyl cyclases. They are divided into two subgroups, D1-like receptors linked to Gs proteins stimulating cAMP production and D2-like receptors linked to Gi/o proteins inhibiting cAMP production. In the present study, we investigated the effect of dopamine receptor activation on cAMP dynamics in astrocytes of the mouse olfactory bulb, the brain region with the largest population of dopaminergic neurons. Using the genetically encoded cAMP sensor Flamindo2 we visualized changes in the cytosolic cAMP concentration and showed that dopamine application results in a transient increase in cAMP. This cAMP increase could be mimicked by the D1-like receptor agonist A 68930 and was inhibited by the D1-like receptor antagonist SCH 23390, whereas D2-like receptor ligands had no effect on the astrocytic cAMP concentration. Thus, olfactory bulb astrocytes express D1-like receptors that are linked to cAMP production.

Imaging-Guided Metabolic Radiosensitization of Pediatric Rhabdoid Tumors.

Tumor hypoxia leads to increased resistance to radiation therapy (RT), resulting in markedly worse clinical outcomes in the treatment and management of pediatric malignant rhabdoid tumors (MRT). To alleviate hypoxia in MRT, we repurposed an FDA approved, mitochondrial oxidative phosphorylation (OXPHOS) inhibitor, Atovaquone (AVO), to inhibit oxygen consumption and thereby enhance the sensitivity of tumor cells to low dose RT in MRT by hypoxia alleviation. Additionally, to better understand the tumor response induced by AVO and optimize the combination with RT, we employed an emerging, noninvasive imaging modality, known as multispectral optoacoustic tomography (MSOT), to monitor and evaluate real-time dynamic changes in tumor hypoxia and vascular perfusion. Oxygen-Enhanced (OE)-MSOT could measure the change of tumor oxygenation in the MRT xenograft models after AVO and RT treatments, indicating its potential as a response biomarker. OE-MSOT showed that treating MRT mouse models with AVO resulted in a transient increase in oxygen saturation (ΔsO 2 ) in tumors when the mice were subjected to oxygen challenge, while RT or saline treated groups produced no change. In AVO+RT combination groups, the tumors showed an increase in ΔsO 2 after AVO administration followed by a significant decrease after RT, that correlated with a strong anti-tumor response, demarcated by complete regression of tumors, with no relapse on long-term monitoring. These observations were histologically validated. In MRT models of acquired AVO resistance, combination therapy failed to alleviate tumoral hypoxia and elicit any therapeutic benefit. Together, our data highlights the utility of repurposing anti-malarial AVO as an anticancer adjuvant for enabling low dose RT for pediatric patients.

Revisiting the fluid requirement during the critical phase of dengue: Does it actually follow a bell-shaped curve?&amp;nbsp;

Plasma leakage due to a transient increase in capillary permeability is the hallmark of dengue haemorrhagic fever. There is no specific antiviral agent for dengue. Therefore, the mainstay of management during the plasma leakage phase is the judicious use of intravenous fluid to ensure adequate organ perfusion and to prevent fluid overload. The current practice guidelines for dengue are empirical. They are mostly based on expert opinions. The rates and amounts of fluid to be administered during the critical phase of the disease have not been studied in randomised controlled trials. It is hypothesised that the rate of fluid leakage during the critical phase follows a bell-shaped curve. Based on this concept, both WHO and Sri Lankan guidelines recommend starting fluid at a lower rate, increasing the rate until the midpoint of the CP, and gradually reducing the infusion rate thereafter. However, the authors believe that the more fluid you give during the critical phase, the more will leak out into the third space. Thus increasing the complications of fluid overload without improving the effective plasma volume. Therefore, administering fluids at an escalating rate may be superfluous and could result in fluid overload.