Normal-Mode-Analysis-Guided Investigation of Crucial Intersubunit Contacts in the cAMP-Dependent Gating in HCN Channels

Abstract Protein structures define a complex network of atomic interactions in three dimensions. Direct visualization of the structure and analysis of the interaction potential energy are not straightforward approaches to pinpoint the atomic contacts that are crucial for protein function. We used the tetrameric hyperpolarization-activated cAMP-regulated (HCN) channel as a model system to study the intersubunit contacts in cAMP-dependent gating. To obtain a systematic survey of the contacts between each pair of residues, we used normal-mode analysis, a computational approach for studying protein dynamics, and constructed the covariance matrix for C-α atoms. The significant contacts revealed by covariance analysis were further investigated by means of mutagenesis and functional assays. Among the mutant channels that show phenotypes different from those of the wild-type, we focused on two mutant channels that express opposite changes in cAMP-dependent gating. Subsequent biochemical assays on isolated C-terminal fragments, including the cAMP binding domain, revealed only minimal effects on cAMP binding, suggesting the necessity of interpreting the cAMP-dependent allosteric regulation at the whole-channel level. For this purpose, we applied the patch-clamp fluorometry technique and observed correlated changes in the dynamic, state-dependent cAMP binding in the mutant channels. This study not only provides further understanding of the intersubunit contacts in allosteric coupling in the HCN channel, it also illustrates an effective strategy for delineating important atomic contacts within a structure

The relationship between sleep quality and occupational well-being in employees: The mediating role of occupational self-efficacy

ObjectiveThis study aimed to examine the impact of sleep quality on occupational well-being in employees by primarily focusing on the mediating role of occupational self-efficacy.MethodsA total of 487 junior staff completed a set of questionnaires comprised Pittsburgh Sleep Quality Index scale, Occupational Self-efficacy Scale, and occupational well-being measurements.ResultsThe results revealed that both sleep quality and occupational self-efficacy were significantly correlated with occupational well-being. The structural equation modeling analysis and the bootstrap test indicated that occupational self-efficacy partially mediated the effect of poor sleep quality on occupational well-being.DiscussionThese findings expand upon existing research on the relationship between sleep quality and well-being among occupational workers, shed light on the correlation of poor sleep quality with occupational well-being, and are valuable in promoting the occupational well-being of employees

New aneurysm formation after endovascular embolization of a vertebral epidural AV fistula: a rare sequelae of NF AV fistulae

BackgroundNeurofibromatosis type 1 (NF-1) is a dominant genetic disorder often accompanied by lesions of the neurovascular system. Patients with NF-1 are predisposed to unique vertebral artery fistula (AVF).Case descriptionWe report on a rare case of multiple neurovascular abnormalities in a 47-year-old man with neurofibromatosis. He was admitted due to a sudden headache and was found to have suffered a subarachnoid hemorrhage from a left vertebral arteriovenous fistula. He underwent two endovascular procedures complicated by a delayed extraspinal mass 7 days after treatment. Angiography revealed a new vascular abnormality, and although we performed another embolization, it failed to respond to further embolization.ConclusionVascular abnormalities in patients with NF-1 can be complex. Endovascular intervention remains feasible for NF-1 related AVF, however, partial occlusion of the fistula should be avoided to limit and iatrogenic damage to the blood vessels

The effects of object size on spatial orientation: an eye movement study

IntroductionThe processing of visual information in the human brain is divided into two streams, namely, the dorsal and ventral streams, object identification is related to the ventral stream and motion processing is related to the dorsal stream. Object identification is interconnected with motion processing, object size was found to affect the information processing of motion characteristics in uniform linear motion. However, whether the object size affects the spatial orientation is still unknown.MethodsThirty-eight college students were recruited to participate in an experiment based on the spatial visualization dynamic test. Eyelink 1,000 Plus was used to collect eye movement data. The final direction difference (the difference between the final moving direction of the target and the final direction of the moving target pointing to the destination point), rotation angle (the rotation angle of the knob from the start of the target movement to the moment of key pressing) and eye movement indices under conditions of different object sizes and motion velocities were compared.ResultsThe final direction difference and rotation angle under the condition of a 2.29°-diameter moving target and a 0.76°-diameter destination point were significantly smaller than those under the other conditions (a 0.76°-diameter moving target and a 0.76°-diameter destination point; a 0.76°-diameter moving target and a 2.29°-diameter destination point). The average pupil size under the condition of a 2.29°-diameter moving target and a 0.76°-diameter destination point was significantly larger than the average pupil size under other conditions (a 0.76°-diameter moving target and a 0.76°-diameter destination point; a 0.76°-diameter moving target and a 2.29°-diameter destination point).DiscussionA relatively large moving target can resist the landmark attraction effect in spatial orientation, and the influence of object size on spatial orientation may originate from differences in cognitive resource consumption. The present study enriches the interaction theory of the processing of object characteristics and motion characteristics and provides new ideas for the application of eye movement technology in the examination of spatial orientation ability

Temporary Cultivation and Live Transport with Water Based on Gradient Cooling of Grass Carp (Ctenopharyngodon idellas)

The study investigated the semi-hibernation and critical temperature of grass carp based on gradient cooling, and explore the effects of temperature (12–24 ℃) on the survival of grass carp and the concentration of ammonia nitrogen in the water. The temperature was reduced from room temperature (23–25 ℃) to the semi-dormant temperature (16 ℃) at cooling rate of 1, 3, or 5 ℃/h. The control group was reared at room temperature, and sampling was conducted after 0, 12, 24, 36, and 48 h. Serum biochemical and antioxidant parameters were measured to obtain the maximum cooling rate for grass crap. The results showed that the semi-dormant temperature of grass carp was 16 ℃, the critical temperature was 6–8 ℃, and the optimal cooling rate was 3 ℃/h. At 16 ℃, grass carp exhibited delayed stress response and decreased metabolism, and lower concentrations of ammonia nitrogen in the water. Except for aspartate aminotransferase level, the maximum values of other serum biochemical indexes at the cooling rate of 3 ℃/h, were significantly lower than those at 1 and 5 ℃/h (P < 0.05). The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) exhibited a trend of initially increasing and then decreasing with survival time, whereas the content of malondialdehyde (MDA) showed an opposite trend, reaching a minimum value of 5.27 mmol/mg after 36 h. Compared to the control group, the contents of all biochemical and antioxidant indexes in the three cooling groups showed significant changes with survival time. Therefore, cooling grass carp at a rate of 3 ℃/h could reduce the stress response and allowed it to enter a semi-hibernation state at a more suitable time. The results from this study provide key parameters for the temporary cultivation and transport of grass carp, as well as useful guidelines for reducing the transport mortality

Application of intraoperative infrared thermography in bypass surgery for adult moyamoya syndrome: A preliminary study

Background and objectivesCerebral revascularization surgery is the mainstay of treatment for moyamoya syndrome (MMS) today, and intraoperative determination of the patency of the revascularized vessel is a critical factor in the success of the procedure. Currently, major imaging modalities include intraoperative indocyanine green (ICG) videoangiography (ICG-VA), digital subtraction angiography (DSA), and vascular ultrasound Doppler. Infrared thermography is a modern imaging modality with non-contact devices for the acquisition and analysis of thermal data. We aimed to investigate the feasibility and advantages of infrared thermography in determining anastomotic patency during MMS surgery.MethodsIndocyanine green videoangiography and infrared thermography were performed simultaneously in 21 patients with MMS who underwent bypass surgery. The detection result of vessel patency was compared, and the feasibility and advantages of infrared thermography were assessed.ResultsThe patency of the anastomosis was accurately determined in 21 patients using either ICG angiography or infrared thermography. In 20 patients, the results of infrared thermography showed that the vascular anastomosis was unobstructed, and there was an agreement with the subsequent results of ICG-VA. In one patient, we suspected inadequate patency after testing the anastomosis with infrared thermography, and the results of ICG-VA evaluation of the anastomosis confirmed that there was indeed an anastomotic obstruction.ConclusionCompared with ICG-VA, infrared thermography might offer an alternative non-invasive, contrast-free option in assessing anastomosis patency compared with ICG-VA, and it is likely to become more widely used in the clinic in the near future

Optimization of tensile strength for new type acetone-urea-formaldehyde furan resin using uniform design

In this study, the 24 h tensile strength of new type acetone-urea-formaldehyde furan resin (nitrogen content 3%) was investigated by uniform design optimization. Four independent variables such as acetone : formaldehyde molar ratio (mol/mol), solution pH value, reaction temperature (℃) and reaction time (min) were considered in the experiments. U*13(134) uniform design was employed and the equation of 24 h tensile strength model was obtained after 13 experimentations. The 24 h tensile strength was optimized by applying single factor experiments and stepwise non-linear regression analysis. Minitab (Minitab 15 trial version) and MATLAB (R2010a trial version) were used for data analysis. The t-value and p-value indicate that the major impact factors include the interaction effect of solution pH value and reaction temperature (X2X3), the linear terms of acetone : formaldehyde molar ratio (X1), reaction time (X4) followed by the square effects of acetone/formaldehyde molar ratio (X1X1). The optimized results were achieved with the acetone: formaldehyde molar ratio (mol/mol) at 3:1, solution pH value at 6.0, reaction temperature at 70 ℃, and reaction time at 140 min, respectively. This method can not only significantly reduce the number and cost of the tests, but also provide a good experimental design strategy for the development of furan resin. The investigation shows that the predicted results of 24 h tensile strength are consistent well with the experimental ones