Neurexin and neuroligins jointly regulate synaptic degeneration at the Drosophila neuromuscular junction based on TEM studies

The Drosophila larval neuromuscular junction (NMJ) is a well-known model system and is often used to study synapse development. Here, we show synaptic degeneration at NMJ boutons, primarily based on transmission electron microscopy (TEM) studies. When degeneration starts, the subsynaptic reticulum (SSR) swells, retracts and folds inward, and the residual SSR then degenerates into a disordered, thin or linear membrane. The axon terminal begins to degenerate from the central region, and the T-bar detaches from the presynaptic membrane with clustered synaptic vesicles to accelerate large-scale degeneration. There are two degeneration modes for clear synaptic vesicles. In the first mode, synaptic vesicles without actin filaments degenerate on the membrane with ultrafine spots and collapse and disperse to form an irregular profile with dark ultrafine particles. In the second mode, clear synaptic vesicles with actin filaments degenerate into dense synaptic vesicles, form irregular dark clumps without a membrane, and collapse and disperse to form an irregular profile with dark ultrafine particles. Last, all residual membranes in NMJ boutons degenerate into a linear shape, and all the residual elements in axon terminals degenerate and eventually form a cluster of dark ultrafine particles. Swelling and retraction of the SSR occurs prior to degradation of the axon terminal, which degenerates faster and with more intensity than the SSR. NMJ bouton degeneration occurs under normal physiological conditions but is accelerated in Drosophila neurexin (dnrx) dnrx273, Drosophila neuroligin (dnlg) dnlg1 and dnlg4 mutants and dnrx83;dnlg3 and dnlg2;dnlg3 double mutants, which suggests that both neurexin and neuroligins play a vital role in preventing synaptic degeneration

Multilayer Mo2N-Ag/SiNx films for demanding applications: Morphology, structure and temperature-cycling tribological properties

Nowadays there is the need to avoid the excessive consumption of liquid lubricant oils, as they are harmful to the environment and hard to disposal. Self-lubricant films have been seen as the sustainable solution to achieve a long-term lubrication under high temperature-cycling conditions. In this manuscript, multilayer Mo2N-Ag/SiNx films with a fixed modulation ratio (thickness of Mo2N-Ag to SiNx) of 3:1, with changing modulation period (Λ, thickness of Mo2N-Ag and SiNx) from 8 to 200 nm were produced to achieve an effective balance between the lubricious phase diffusion control and the adequate formation of the low friction tribo-layers. Results showed that a dual-phase of fcc-Mo2N and fcc-Ag co-existed in Mo2N-Ag layers, while the SiNx layer exhibited an amorphous character. Both room temperature (RT) lubricant and wear-resistance properties of the films were improved by increasing Λ from 8 to 64 nm, while a further increase of Λ degraded the wear-resistance properties. The multilayer film at Λ = 64 nm exhibited an excellent RT-500 °C temperature-cycling tribological properties. Mechanical properties and the synergistic effect of both modulation layers were the cause for the improvement of the tribological properties.Supported by the National Natural Science Foundation of China, China (51801081, 52071159, 52171071, 52172090); Portugal National Funds through FCT project, Portugal (2021.04115); Outstanding University Young Teachers of ‘‘Qing Lan Project” of Jiangsu Province, China; Excellent Talents of ‘‘Shenlan Project” of Jiangsu University of Science and Technology, China; China Merchants Marine Scientific Research and Innovation Fund, China. Filipe Fernandes acknowledges the funding received in the aim of the projects: MCTool21 - ref. ‘‘POCI-01-0247- FEDER-045940”, CEMMPRE – ref. ‘‘UIDB/00285/2020” and SMARTLUB – ref. ‘‘POCI- 01-0145-FEDER-031807”.info:eu-repo/semantics/publishedVersio

Phosphorylation of Synaptojanin Differentially Regulates Endocytosis of Functionally Distinct Synaptic Vesicle Pools

The rapid replenishment of synaptic vesicles through endocytosis is crucial for sustaining synaptic transmission during intense neuronal activity. Synaptojanin (Synj), a phosphoinositide phosphatase, is known to play an important role in vesicle recycling by promoting the uncoating of clathrin following synaptic vesicle uptake. Synj has been shown to be a substrate of the minibrain (Mnb) kinase, a fly homolog of the dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A); however, the functional impacts of Synj phosphorylation by Mnb are not well understood. Here we identify that Mnb phosphorylates Synj at S1029 in Drosophila. We find that phosphorylation of Synj at S1029 enhances Synj phosphatase activity, alters interaction between Synj and endophilin, and promotes efficient endocytosis of the active cycling vesicle pool (also referred to as exo-endo cycling pool) at the expense of reserve pool vesicle endocytosis. Dephosphorylated Synj, on the other hand, is deficient in the endocytosis of the active recycling pool vesicles but maintains reserve pool vesicle endocytosis to restore total vesicle pool size and sustain synaptic transmission. Together, our findings reveal a novel role for Synj in modulating reserve pool vesicle endocytosis and further indicate that dynamic phosphorylation and dephosphorylation of Synj differentially maintain endocytosis of distinct functional synaptic vesicle pools. SIGNIFICANCE STATEMENT Synaptic vesicle endocytosis sustains communication between neurons during a wide range of neuronal activities by recycling used vesicle membrane and protein components. Here we identify that Synaptojanin, a protein with a known role in synaptic vesicle endocytosis, is phosphorylated at S1029 in vivo by the Minibrain kinase. We further demonstrate that the phosphorylation status of Synaptojanin at S1029 differentially regulates its participation in the recycling of distinct synaptic vesicle pools. Our results reveal a new role for Synaptojanin in maintaining synaptic vesicle pool size and in reserve vesicle endocytosis. As Synaptojanin and Minibrain perturbations are associated with various neurological disorders, such as Parkinson's, autism, and Down syndrome, understanding mechanisms modulating Synaptojanin function provides valuable insights into processes affecting neuronal communication

Motorcycle ownership and injury in China

Background. China has made tremendous progress in its economic development in the past two decades. Accompanying this economic development has been an evident shift in the modes of transport, from walking and cycling to the use of motorcycles and, increasingly, four-wheel vehicles. Such changes are likely to have also produced changes in the patterns and numbers of road traffic injuries, including increases in motorcycle injuries. However, such changes have not been well documented. The work described in this paper sought, therefore, to document the changes in motorcycle ownership, motorcyclist mortality and injury rates in China since 1987. Methods. National traffic ownership and injury data from 1987 to 2001 were obtained from the National Bureau for Traffic Administration. Additionally, traffic ownership and injury records from 1997 to 2001 were collected from local police offices from 20 counties in Guangxi Region. Population data were obtained from the national and county statistics bureaus. Motorcycle ownership, fatality and injury trends over time were calculated. Results. Nationally, motorcycles accounted for 23.4% of all registered motor vehicles in 1987, increasing to 63.2% in 2001. Motorcyclist fatalities and injuries increased 5.5-fold and 9.3-fold, respectively, between 1987 and 2001. In 1987, 7.5% of all traffic fatalities and 8.8% of all traffic injuries were sustained by motorcyclists, with the corresponding proportions increasing to 18.9% and 22.8%, respectively, in 2001. The changing proportions of both traffic fatalities and injuries sustained by motorcyclists were positively correlated with the change in the proportion of motorcycles among all motor vehicles. In the 20 counties in Guangxi, motorcyclist fatality and injury rates also increased between 1997 and 2001. Moreover, these rates were considerably higher than the national rates. Conclusions. Motorcyclist injury in China is a serious public health problem. Motorcyclist fatalities and injuries are likely to continue to increase unless appropriate intervention programmes are implemented

The gut microbiome in atherosclerotic cardiovascular disease

The gut microbiota may play a role in cardiovascular diseases. Here, the authors perform a metagenome-wide association study on stools from individuals with atherosclerotic cardiovascular disease and healthy controls, identifying microbial strains and functions associated with the disease

Three-dimensional discrete element simulation of ballast direct shear testing in vibration field

To reveal the mechanical properties of ballast particles under the disturbance of dynamic loading, a 3D DEM model for ballast direct shear test was established in a horizontal vibration field. Based on 3D scanning technology, the morphological characteristics of ballast particles were rebuilt in the numerical model by Voronoi tessellation. By calibrating with experimental results of ballast static direct experiments, meso-mechanical parameters for ballast particles were also obtained. On this basis, ballast sample’s shear strength and volume changing under dynamic condition were studied. Numerical results showed that the ballast shear strength in vibration field were smaller than that under static shear condition. Vibration amplitude was the main factor affecting the dynamic shear strength of ballast, as vibration amplitude increased from 0.1 to 0.48 mm, the peak shear stress of the ballast sample decreased from 185 to 102 kPa; while as the vibration frequency increased from 10 to 60 Hz, the dynamic shear strength of ballast didn’t change obviously. Dilatancy feature of ballast was confirmed by volume change before and after shearing process. For the static and low frequency dynamic shear condition, the volume of the ballast sample increased monotonously; while as the vibration frequency exceeded a critical value, the volume of the ballast sample increased first and then decreased during the shearing process. Moreover, increasing the amplitude could effectively reduce this critical frequency. For the dynamic condition that the shear direction was not coincident with the vibration direction, as the angle between these two directions changed from 90° (perpendicular to each other) to 0° (same direction), the smaller the angle was, the more the shear strength decreased

Tribological Properties of Mo2N Films at Elevated Temperature

Mo2N films were synthesized using the reactive magnetron sputtering system in a mixture of argon and nitrogen, and the tribological properties were investigated at different testing temperatures against an Al2O3 counterpart. The relative intensity ratio (RIR) method was used to calculate the weight fraction of the tribo-film (MoO3) on the wear tracks of the films. The results showed that the average friction coefficient first increased from 0.30 at 25 °C to 0.53 at 200 °C, and then decreased to 0.29 at 550 °C, while the wear rate decreased from 2.1 × 10−6 mm3/Nmm at 25 °C to 5.3 × 10−7 mm3/Nmm at 200 °C and then increased to 3.1 × 10−5 mm3/Nmm at 550 °C. The weight fraction of tribo-film was mainly attributed to changes in the average friction coefficient and the wear rate. Besides this, the relative humidity also influenced the tribological properties at 25–200 °C