Interactions of antagonists with subtypes of inositol 1,4,5-trisphosphate (IP3) receptor

BACKGROUND AND PURPOSE

Inositol 1,4,5-trisphosphate receptors (IP₃Rs) are intracellular Ca²⁺ channels. Interactions of the commonly used antagonists of IP₃Rs with IP₃R subtypes are poorly understood.

EXPERIMENTAL APPROACH

IP₃-evoked Ca²⁺ release from permeabilized DT40 cells stably expressing single subtypes of mammalian IP₃R was measured using a luminal Ca²⁺ indicator. The effects of commonly used antagonists on IP₃-evoked Ca²⁺ release and ³H-IP₃ binding were characterized.

KEY RESULTS

Functional analyses showed that heparin was a competitive antagonist of all IP₃R subtypes with different affinities for each (IP₃R3 > IP₃R1 ≥ IP₃R2). This sequence did not match the affinities for heparin binding to the isolated N-terminal from each IP₃R subtype. 2-aminoethoxydiphenyl borate (2-APB) and high concentrations of caffeine selectively inhibited IP₃R1 without affecting IP₃ binding. Neither Xestospongin C nor Xestospongin D effectively inhibited IP₃-evoked Ca²⁺ release via any IP₃R subtype.

CONCLUSIONS AND IMPLICATIONS

Heparin competes with IP₃, but its access to the IP₃-binding core is substantially hindered by additional IP₃R residues. These interactions may contribute to its modest selectivity for IP₃R3. Practicable concentrations of caffeine and 2-APB inhibit only IP₃R1. Xestospongins do not appear to be effective antagonists of IP₃Rs.     

Assessment of Circulating Biochemical Markers in Mice Receiving Cinnamon and Glycyrrhizin Under Carbon Tetrachloride Induced Hepatic Injury

The study evaluated the hepatoprotective activity of plant extracts of cinnamon and glycyrrhizin in distinct dosage ways to minimize the oxidative stress induced by carbon tetrachloride (CCl₄) in BALB/cJ inbred albino mice. Fifteen albino mice were divided into five groups, each group containing three mice. Group A was referred as positive control while group B, C, D and E were injected intraperitoneally with 1 mL/kg body weight of CCl₄ twice a week for 1 month. Group C and D were treated orally with isolated extracts of cinnamon @50 mg/kg and glycyrrhizin @50 mg/kg respectively on daily basis for 1 month. However, group E was treated orally with combination dose of cinnamon @50 mg/kg + glycyrrhizin @50 mg/kg body weight. The increase in the levels of alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP), triglyceride (TG), malondialdehyde (MDA) and glucose were recorded in CCl₄ induced liver injury in mice while there is decrease in the levels of total protein (TP), reduced glutathione (GSH), Superoxide dismutase (SOD) and catalase (CAT) in CCL₄ intoxicated mice. Isolated therapy of plant extracts of cinnamon and glycyrrhizin decreased the levels of ALT, AST, ALP, MDA, TG and glucose whereas increase in TP, GSH, SOD and CAT was observed in plant extracts treated mice. The best restoration of all the above said parameters near to control was observed in group of mice treated with combination dose of cinnamon and glycyrrhizin @50 mg/kg. Therefore, the present study declared the antioxidative, anti-inflammatory and hepatoprotective activity of standardized extracts of cinnamon and glycyrrhizin and their potent defensive property.

     

Early infection in post-autologous hematopoietic stem cell transplant patients: Princess Noorah Oncology Center experience

Objectives:To assess local epidemiology and risk factors for bacterial, fungal, and viral infections among the autologous bone marrow transplant population.Methods:This study is a retrospective correlational cohort design comprising 150 adult patients who underwent autologous transplants at Princess Noorah Oncology Center, Jeddah, Saudi Arabia between 2014 and 2020.Results:The study findings indicate that bacterial infection prevalence differed significantly across the different disease status pre-salvage as patients with the relapsed disease were more likely to have bacterial infections. The median of engraftment days differed significantly between those who had a bacterial infection and those who did not. Interestingly, previous pneumonia infection had a positive relationship with the number of hospital stays.Conclusions:Bacterial infections are the dominant type of infection among the autologous patient population. The research reflects authentic practice and reports unique characteristics of autologous transplant patients in terms of the prevalence and types of infection these patients experience.     

Removal of toluene as a toxic VOC from methane gas using a non-thermal plasma dielectric barrier discharge reactor

Methane is the main component of biogas, which could be used as a renewable energy source for electricity, source of heat, and biofuel production after upgrading from biogas. It also contains toxic compounds which cause environmental and human health problems. Therefore, in this work, the removal of a toxic compound (toluene) from methane gas was studied using a dielectric barrier discharge (DBD) reactor. It was observed that the removal of the toxic compound could be achieved from methane carrier gas using a dielectric barrier discharge reactor, and it depends on plasma input power. The maximum removal of the toxic compound was 85.9% at 40 W and 2.86 s. The major gaseous products were H₂ and lower hydrocarbons (LHC) and the yield of these products also increases with input power. In the current study, the yield of gaseous products depends on the decomposition of toxic compounds and methane, because the decomposition of methane also produces H₂ and lower hydrocarbons. The percentage yield of H₂ increases from 0.43–4.74%. Similarly, the yield of LHC increases from 0.56–7.54% under the same reaction conditions. Hence, input power promoted the decomposition of the toxic compound and enhanced the yield of gaseous products.

The removal of toluene as a toxic volatile organic compound from methane gas, which is the major component of biogas, is carried out using a non-thermal plasma dielectric barrier discharge reactor.     

Investigating the Impact of Cu2+ Doping on the Morphological,Structural, Optical,and Electrical Properties of CoFe2O4 Nanoparticles for Use in Electrical Devices

This study investigated the production of Cu²⁺-doped CoFe₂O₄ nanoparticles (CFO NPs) using a facile sol−gel technique. The impact of Cu²⁺ doping on the lattice parameters, morphology, optical properties, and electrical properties of CFO NPs was investigated for applications in electrical devices. The XRD analysis revealed the formation of spinel-phased crystalline structures of the specimens with no impurity phases. The average grain size, lattice constant, cell volume, and porosity were measured in the range of 4.55–7.07 nm, 8.1770–8.1097 Å, 546.7414–533.3525 ų, and 8.77–6.93%, respectively. The SEM analysis revealed a change in morphology of the specimens with a rise in Cu²⁺ content. The particles started gaining a defined shape and size with a rise in Cu²⁺ doping. The Cu_0.12Co_0.88Fe₂O₄ NPs revealed clear grain boundaries with the least agglomeration. The energy band gap declined from 3.98 eV to 3.21 eV with a shift in Cu²⁺ concentration from 0.4 to 0.12. The electrical studies showed that doping a trace amount of Cu²⁺ improved the electrical properties of the CFO NPs without producing any structural distortions. The conductivity of the Cu²⁺-doped CFO NPs increased from 6.66 × 10⁻¹⁰ to 5.26 × 10⁻⁶ ℧ cm⁻¹ with a rise in Cu²⁺ concentration. The improved structural and electrical characteristics of the prepared Cu²⁺-doped CFO NPs made them a suitable candidate for electrical devices, diodes, and sensor technology applications.     

Effect of the Source-to-Substrate Distance on Structural,Optoelectronic, and Thermoelectric Properties of Zinc Sulfide Thin Films

Zinc sulfide (ZnS) thin films with variable structural, optical, electrical, and thermoelectric properties were obtained by changing the source-to-substrate (SSD) distance in the physical-vapor-thermal-coating (PVTC) system. The films crystallized into a zinc-blende cubic structure with (111) preferred orientation. The films had a wide 3.54 eV optical band gap. High-quality homogenous thin films were obtained at 60 mm SSD. The sheet resistance and resistivity of the films decreased from 10¹¹ to 10¹⁰ Ω/Sq. and from 10⁶ to 10⁵ Ω-cm, when SSD was increased from 20 mm to 60 mm, respectively. The phase and band gap were also verified by first principles that were in agreement with the experimental results. Thermoelectric characteristics were studied by using the semi-classical Boltzmann transport theory. The high quality, wide band gap, and reduced electrical resistance make ZnS a suitable candidate for the window layer in solar cells.     

Bimodal optomotor response to plaids in blowflies: mechanisms of component selectivity and evidence for pattern selectivity

Many animals estimate their self-motion and the movement of external objects by exploiting panoramic patterns of visual motion. To probe how visual systems process compound motion patterns, superimposed visual gratings moving in different directions, plaid stimuli, have been successfully used in vertebrates. Surprisingly, nothing is known about how visually guided insects process plaids. Here, we explored in the blowfly how the well characterized yaw optomotor reflex and the activity of identified visual interneurons depend on plaid stimuli. We show that contrary to previous expectations, the yaw optomotor reflex shows a bimodal directional tuning for certain plaid stimuli. To understand the neural correlates of this behavior, we recorded the responses of a visual interneuron supporting the reflex, the H1 cell, which was also bimodally tuned to the plaid direction. Using a computational model, we identified the essential neural processing steps required to capture the observed response properties. These processing steps have functional parallels with mechanisms found in the primate visual system, despite different biophysical implementations. By characterizing other visual neurons supporting visually guided behaviors, we found responses that ranged from being bimodally tuned to the stimulus direction (component-selective), to responses that appear to be tuned to the direction of the global pattern (pattern-selective). Our results extend the current understanding of neural mechanisms of motion processing in insects, and indicate that the fly employs a wider range of behavioral responses to multiple motion cues than previously reported.     

Le burn out, conséquences et solutions : enquête chez les personnels d’anesthésie–réanimation de quatre hôpitaux universitaires marocains

Background

Burn out syndrome consists in physical and mental exhaustion observed in professionals whose work involves continuous contact with other people in response to chronic stress. Anesthesists reanimators staff are considered to be vulnerable to experiencing burn out. After analyzing the prevalence and risk factors in an anterior article, we tried through this work to evaluate the consequences of burn out and to have a preventive or curative approach for this syndrome among medical and paramedical staff in intensive care unit.

Methods

A multicenter analytical cross-sectional study was conducted among practitioners in many Anesthesia and Intensive Care units in Moroccan University Hospitals (Rabat, Casablanca, Fez and Marrakech). Practitioners were invited to fill a self-questioning which envisaged eventual consequences of burn out, and they were invited to suggest solutions to this problem and to express their comments on subject.

Results

Our 202 practitioners who present burn out, accused irritability, discontent, and angriness in respectively 34,3%, 41,7%, and 34,1% case; 59,7% complains sleep confusion, 60,68% developed addict attitudes and 55,5% have relational problem. Proposed resolutions stressed the importance of the optimization of work organization and the motivation of personal, one of the precautionary lanes would consist on the combination of different therapeutic approaches (individual, collective and organizational).

Discussion/Conclusion

Burn out appears to be a reality in intensive care unit. Introduction of preventive strategies, while underlining the importance of work organization and communication seem to be necessary.