Detergent-insoluble PFN1 inoculation expedites disease onset and progression in PFN1 transgenic rats

Accumulating evidence suggests a gain of elusive toxicity in pathogenically mutated PFN1. The prominence of PFN1 aggregates as a pivotal pathological hallmark in PFN1 transgenic rats underscores the crucial involvement of protein aggregation in the initiation and progression of neurodegeneration. Detergent-insoluble materials were extracted from the spinal cords of paralyzed rats afflicted with ALS and were intramuscularly administered to asymptomatic recipient rats expressing mutant PFN1, resulting in an accelerated development of PFN1 inclusions and ALS-like phenotypes. This effect diminished when the extracts derived from wildtype PFN1 transgenic rats were employed, as detergent-insoluble PFN1 was detected exclusively in mutant PFN1 transgenic rats. Consequently, the factor influencing the progression of ALS pathology in recipient rats is likely associated with the presence of detergent-insoluble PFN1 within the extracted materials. Noteworthy is the absence of disease course modification upon administering detergent-insoluble extracts to rats that already displayed PFN1 inclusions, suggesting a seeding rather than augmenting role of such extracts in initiating neuropathological changes. Remarkably, pathogenic PFN1 exhibited an enhanced affinity for the molecular chaperone DNAJB6, leading to the sequestration of DNAJB6 within protein inclusions, thereby depleting its availability for cellular functions. These findings shed light on a novel mechanism that underscores the prion-like characteristics of pathogenic PFN1 in driving neurodegeneration in the context of PFN1-related ALS

PIH1D3-knockout rats exhibit full ciliopathy features and dysfunctional pre-assembly and loading of dynein arms in motile cilia

Background: Recessive mutation of the X-linked gene, PIH1 domain-containing protein 3 (PIH1D3), causes familial ciliopathy. PIH1D3 deficiency is associated with the defects of dynein arms in cilia, but how PIH1D3 specifically affects the structure and function of dynein arms is not understood yet. To gain insights into the underlying mechanisms of the disease, it is crucial to create a reliable animal model. In humans, rats, and mice, one copy of the PIH1D3 gene is located on the X chromosome. Interestingly, mice have an additional, intronless copy of the Pih1d3 gene on chromosome 1. To develop an accurate disease model, it is best to manipulate the X-linked PIH1D3 gene, which contains essential regulatory sequences within the introns for precise gene expression. This study aimed to develop a tailored rat model for PIH1D3-associated ciliopathy with the ultimate goal of uncovering the intricate molecular mechanisms responsible for ciliary defects in the disease.Methods: Novel Pih1d3-knockout (KO) rats were created by using TALEN-mediated non-homologous DNA recombination within fertilized rat eggs and, subsequently, underwent a comprehensive characterization through a battery of behavioral and pathological assays. A series of biochemical and histological analyses were conducted to elucidate the identity of protein partners that interact with PIH1D3, thus shedding light on the intricate molecular mechanisms involved in this context.Results: PIH1D3-KO rats reproduced the cardinal features of ciliopathy including situs inversus, defects in spermatocyte survival and mucociliary clearance, and perinatal hydrocephalus. We revealed the novel function of PIH1D3 in cerebrospinal fluid circulation and elucidated the mechanism by which PIH1D3 deficiency caused communicating hydrocephalus. PIH1D3 interacted with the proteins required for the pre-assembly and uploading of outer (ODA) and inner dynein arms (IDA), regulating the integrity of dynein arm structure and function in cilia.Conclusion: PIH1D3-KO rats faithfully reproduced the cardinal features of ciliopathy associated with PIH1D3 deficiency. PIH1D3 interacted with the proteins responsible for the pre-assembly and uploading of dynein arms in cilia, and its deficiency led to dysfunctional cilia and, thus, to ciliopathy by affecting the pre-assembly and uploading of dynein arms. The resultant rat model is a valuable tool for the mechanistic study of PIH1D3-caused diseases

A heterozygous moth genome provides insights into herbivory and detoxification

How an insect evolves to become a successful herbivore is of profound biological and practical importance. Herbivores are often adapted to feed on a specific group of evolutionarily and biochemically related host plants1, but the genetic and molecular bases for adaptation to plant defense compounds remain poorly understood2. We report the first whole-genome sequence of a basal lepidopteran species, Plutella xylostella, which contains 18,071 protein-coding and 1,412 unique genes with an expansion of gene families associated with perception and the detoxification of plant defense compounds. A recent expansion of retrotransposons near detoxification-related genes and a wider system used in the metabolism of plant defense compounds are shown to also be involved in the development of insecticide resistance. This work shows the genetic and molecular bases for the evolutionary success of this worldwide herbivore and offers wider insights into insect adaptation to plant feeding, as well as opening avenues for more sustainable pest management.Minsheng You … Simon W Baxter … et al

A Dynamic Heterogeneous Information Network Embedding Method Based on Meta-Path and Improved Rotate Model

Aiming at the current situation of network embedding research focusing on dynamic homogeneous network embedding and static heterogeneous information network embedding but lack of dynamic information utilization, this paper proposes a dynamic heterogeneous information network embedding method based on the meta-path and improved Rotate model; this method first uses meta-paths to model the semantic relationships involved in the heterogeneous information network, then uses GCNs to get local node embedding, and finally uses meta-path-level aggression mechanisms to aggregate local representations of nodes, which can solve the heterogeneous information utilization issues. In addition, a temporal processing component based on a time decay function is designed, which can effectively handle temporal information. The experimental results on two real datasets show that the method has good performance in networks with different characteristics. Compared to current mainstream methods, the accuracy of downstream clustering and node classification tasks can be improved by 0.5~41.8%, which significantly improves the quality of embedding, and it also has a shorter running time than most comparison algorithms

The observations on Polar Stratospheric Clouds at Zhongshan Station, Antarctica

A lidar system (694 nm) was used to measure the stratospheric aerosol layer at Zhongshan Station (69°22'S, 76°22'E) in 1993. A total of 53 sets of lidar data presented in this paper were obtained over a period of 224 days between March 27 and November 5, 1993. The average vertical profiles of stratospheric aerosol backscattering ratio and the integrated backscatter coefficient over the 12 km - 30 km altitude range were reversed from the return signal of lidar. The results of observations show that the stratospheric aerosol content more noticeable enhanced in 1993 than that in 1990 due to Mt. Pinatubo eruption in Philippines in June of 1991. Polar Stratospheric Clouds (PSCs) were observed from late May until early August. The vertical profiles of stratospheric aerosol backscattering ratio at Antarctica in 1993 show a clear double-layer structure. One layer is at an altitude of about 12 km, the other is at an altitude of about 25 km . The upper layer is varied with season

Effects of macropore size on structural and electrochemical properties of hierarchical porous carbons

Hierarchical porous carbons (HPCs) were synthesized by a colloid crystal template method with phenolic resin as carbon source and triblock copolymer Pluronic F127 as a soft template. The obtained HPCs with tunable macropore size of 242-420 nm exhibit large BET surface areas (similar to 900 m(2) g(-1)) and large pore volumes (similar to 1.2 cm(3) g(-1)). With an increase in the diameters of silica template, the BET surface areas and pore volumes of HPCs decrease. The electrochemical properties of the HPCs with various macropore sizes used as supercapacitor electrodes materials were evaluated using cyclic voltammetry, galvanostatic charge-discharge, and electrochemical impedance spectroscopy techniques. The results show the HPC with the macropore size of 242 nm possesses the largest specific capacitance among the HPCs. The excellent capacitive behavior of HPC-242 can be attributed to its faster ion transport behavior and better ion-accessible surface area

Heavy metal exposure has adverse effects on the growth and development of preschool children

The purpose of this study was to investigate the associations between levels of lead (Pb), cadmium (Cd), chromium (Cr), and manganese (Mn) in the PM2.5 and blood and physical growth, and development parameters including birth length and weight, height, weight, body mass index (BMI), head circumference, and chest circumference in preschool children from Guiyu (e-waste exposure area) and Haojiang (the reference area). A total of 470 preschool children from Guiyu and Haojiang located in southeast coast of China were recruited and required to undergo physical examination and blood tests during the study period. Birth length and weight were obtained by birth records and questionnaire. Pb and Cd in both PM2.5 and blood were significantly higher in Guiyu than Haojiang. Remarkably, the children of Guiyu had significantly lower birth weight and length, BMI, and chest circumference when compare to their peers from the reference area (all p valu

Effect of phenolic resin infiltration content on the structural and electrochemical properties of hierarchical porous carbons

Hierarchical porous (micro-, meso- and macro-porous) carbons (HPCs) are synthesized by a facile replica template method with phenolic resin (PR) as a carbon source and hollow mesoporous silica as a hard template. The morphology of the HPCs can be easily controlled by altering the mass ratio of PR to SiO2 spheres. Structural characterizations reveal that a well-defined HPC with a large surface area of 1141 m(2) g(-1) is formed when PR/SiO2 is 1:1. With further increasing PR infiltration content, macropores of carbons disappear while solid structures appear. A possible formation mechanism for the morphological transformation of HPCs is proposed. The effect of phenolic resin infiltration content on the electrochemical properties of HPCs-based materials as supercapacitor electrodes is further evaluated. The HPCs-1(PR/SiO2 = 1) electrode exhibits the highest specific capacitance of 256 F g(-1) due to its faster diffusion of electrolyte ions and lower charge transfer resistance. The relationship between the morphology and the electrochemical behavior of HPCs is also elucidated.21236003, NSFC, National Natural Science Foundation of China; 21322607, NSFC, National Natural Science Foundation of China; 21371057, NSFC, National Natural Science Foundation of Chin

Effect of Al–5Ti–1B–La intermediate alloy on microstructure and mechanical properties of A356.2 aluminum alloy

This study delves into the effects of Al–5Ti–1B–1La intermediate alloy, a newly developed refinement agent, on the microstructure and mechanical properties of A356.2 aluminum-silicon alloy modified by Al–10Sr. The decomposition of Ti2Al20La, where La element was concentrated in the Al–5Ti–1B–1La intermediate alloy, hardly affected the conventional nucleation mechanism of TiAl3–TiB2; nonetheless, the La element significantly refined the dendritic arms of α-Al. Notably, the secondary dendrite arm spacing was reduced from 49 μm to 27 μm, when 0.025 wt% ∼0.2 wt% Al–5Ti–1B–1La intermediate alloy and 0.014 wt% Al–10Sr modifier was incorporated to the A356.2 aluminum alloy. Although the room-temperature ultimate tensile strength was increased only by 30 MPa, the elongation was remarkably improved from 10% to 26%. The hardness of the alloy was also enhanced from 75 HBW to 84 HBW. The experimental outcomes underscore the efficacy of minimal La element incorporation in enhancing the performance of Al–5Ti–1B intermediate alloy, and the findings are significant for improving the serviceability of automobile wheels made from A356.2 aluminum alloy. The method used in this study can also be employed to regulate the microstructure and enhance mechanical properties of other sub-eutectic aluminum-silicon alloys

Structural characteristics of pressure balanced plug valve and treatment methods for internal leakage

Most of the imported Serck Audco pressure balanced plug valves are adopted for the bypass throttle valves, vent valves and station ESD vent valves of the block valve on the trunk line of PetroChina West-to-East Gas Pipeline. Internal leakage faults of plug valves for station ESD high-pressure venting occur frequently, but the conventional treatment appears not to be satisfactory. Through the analysis on structural characteristics of sealing and pressure balance of the imported plug valves, treatment methods such as grease filling, disassembly for maintenance, valve replacement, and return for repair were put forward based on field practical experience. The root causes of frequent internal leakage of plug valve attribute to abrasion and scratch on surface of plug valve body that may result in sealing failure. During field disassembly and maintenance, the clearance between the plug and the valve body was hard to be restored to its original state. It is hardly possible to reach the original fit accuracy after manual grinding, and the repair effect may be worse after several times of disassembly. So the disassembly and maintenance should be treated with caution. Return for repair might be able to eliminate the abrasion and scratch on the plug surface, and the internal leakage problem of the valve was verified by the site test and proved to be solvable. But for domestic plug valves or imported plug valves repaired by domestic manufacturers, the additional pressure relief nozzle at the large end of the plug is required to eliminate the plug self-locking phenomenon. The pressure relief nozzle at the large end is in direct contact with the medium fluid, and impurities cannot be prevented from entering the bottom of the large end under the working condition that the valve is used for pipeline medium containing large amounts of impurities. Research should be carried out in these aspects for the localization development of plug valves