AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control system.In this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s disease.We used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse brain.CHIP overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated tau.CHIP also alleviated the concentration of microglia and astrocytes around plaques.In APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin expression.Levels of HSP70 and HSP40,which have functional relevance to CHIP,were also increased.Single nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of CHIP.Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice.Indeed,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

Carboxyl Terminus Truncated Human Papillomavirus Type 58 L1 Protein Maintains Its Bioactivity and Ability to Form Virus-like Particles

Summary: To prepare carboxyl terminus truncated human papillomavirus type 58 L1(HPV58L1) protein and evaluate its ability to form virus-like particles, the baculovirus and Sf-9 insect cells was used to express HPV58L1 protein, and pFastBac-Htb containing HPV58L1 gene sequence of carboxyl terminus truncation was generated. Then Sf-9 cells were infected with recombinant baculovirus. After being cultured, the post-infected cells expressing-HPV58L1 protein-were harvested and analyzed by SDS-PAGE and Western blot. The ProBond~TM purification system was used for protein purification. The bio-activity of purified protein was identified by mouse erythrocyte hemagglutination assay, and the VLP formation was examined with transmission electron microscope. Our results showed that the recombinant baculovirus was generated and the Sf-9 cells was infected with the recombinant baculovirus, and after collecting, total cellular proteins were extracted. Truncated HPV58L1 protein with MW 58KD was revealed by SDS-PAGE and confirmed by Western blot. The purified L1 proteins under native condition could cause mouse erythrocytes to agglutinate and form VLP. It is concluded that HPV58L1 protein with carboxyl terminus truncation could be efficiently expressed. In baculovirus Sf-9 cells expression system, the purified protein could self-assemble into virions in vitro, and induce agglutination of mouse erythrocytes, indicating that carboxyl terminus truncation does not interfere with the bioactivity of HPV58L1 protein.

Effects of shape of terminus on excitation of surface plasmon modes on metal nanowires

The effects of the shape of a nanowire terminus on the excited surface plasmon polariton （SPP） modes are investigated. The conical terminus and terminus cut at a certain angle are studied. For the first time, the quantitative mode decompositions are carried out to derive the full information about excited SPP modes. It is demonstrated that tuning the shape of the terminus provides an effective method to control the composition of excited SPP modes on metal nanowires. It is especially found that some important patterns, such as the pure TM0 mode and the superposition of TM0 and HE＋1 or HE-1 modes, can be generated by some specific shapes of the terminus, whereas there is no way to produce these patterns using flat-end nanowires.

Redefinition of the Terminus of the Middle America Trench

The terminus of the Middle America Trench has been traditionally represented as an arc, concave towards the continent. Tres Marías Islands are located at the terminus of the Middle America Trench in western Mexico, and their location is not only intriguing but also a key to the re-construction of the position of Baja California peninsula before separation from the North America plate. Previous re-constructions suggested various places around the location of Tres Marías Islands for the position of the tip of the peninsula, and several converge to a position that invades the area occupied by the islands, offering no explanation for the overlap. Before peninsular separation from North America, the Guadalupe trench followed a smooth curve;recreating the position of this paleo-trench yields a baseline for fixing the position of the peninsula, as well as the original position of the Tres Marías Islands fragment. A new tectonic view of the structure of the Middle America Trench terminus is proposed, replacing the traditional arc representation with a series of en echelon blocks, the northernmost terminates at the Tres Marías Escarpment. The long sides of the blocks correspond to previously identified geological faults in the Bahía de Banderas region, while their offshore continuation is supported by topographic observations. As a test of this model I show the corresponding re-construction of the position of Baja California prior to separation from the North America plate and the positional evolution of the peninsula and the Tres Marías fragment from Chron 4n.2 (7.90 Ma) to Chron 3n.4 (5.12 Ma).

MreBCD-associated Cytoskeleton is Required for Proper Segregation of the Chromosomal Terminus during the Division Cycle of Escherichia Coli

Background：In prokaryotic organisms,the mechanism responsible for the accurate partition of newly replicated chromosomes into daughter cells is incompletely understood.Segregation of the replication terminus of the circular prokaryotic chromosome poses special problems that have not previously been addressed.The aim of this study was to investigate the roles of several protein components （MreB,MreC,and MreD） of the prokaryotic cytoskeleton for the faithful transmission of the chromosomal terminus into daughter cells.Methods：Strain LQ1 （mreB：：cat）,LQ2 （mreC：：cat）,and LQ3 （mreD：：cat） were constructed using the Red recombination system.LQ11/pLAU53,LQ12/pLAU53,LQ13/pLAU53,LQ14/pLAU53,and LQ15/pLAU53 strains were generated by Pltransduction of （tetO）240-Gm and （lacO）240-Km cassettes from strains IL2 and IL29.Fluorescence microscopy was performed to observe localization pattern of fluorescently-labeled origin and terminus foci in wild-type and mutant cells.SOS induction was monitored as gfp fluorescence from PsulA-gfp in log phase cells grown in Luria-Bertani medium at 37℃ by measurement of emission at 525 nm with excitation at 470 nm in a microplate fluorescence reader.Results：Mutational deletion of the mreB,mreC,or mreD genes was associated with selective loss of the terminus region in approximately 40％ of the cells within growing cultures.This was accompanied by significant induction of the SOS DNA damage response,suggesting that deletion of terminus sequences may have occurred by chromosomal cleavage,presumably caused by ingrowth of the division septum prior to segregation of the replicated terminal.Conclusions：These results imply a role for the MreBCD cytoskeleton in the resolution of the final products of terminus replication and/ or in the specific movement of newly replicated termini away from midcell prior to completion of septal ingrowth.This would identify a previously unrecognized stage in the overall process of chromosome segregation.

Analyzing geomorphological and topographical controls for the heterogeneous glacier mass balance in the Sikkim Himalayas

Glacier response patterns at the catchment scale are highly heterogeneous and defined by a complex interplay of various dynamics and surface factors.Previous studies have explained heterogeneous responses in qualitative ways but quantitative assessment is lacking yet where an intrazone homogeneous climate assumption can be valid.Hence,in the current study,the reason for heterogeneous mass balance has been explained in quantitative methods using a multiple linear regression model in the Sikkim Himalayan region.At first,the topographical parameters are selected from previously published studies,then the most significant topographical and geomorphological parameters are selected with backward stepwise subset selection methods.Finally,the contributions of selected parameters are calculated by least square methods.The results show that,the magnitude of mass balance lies between-0.003±0.24 to-1.029±0.24 m.w.e.a^(-1) between 2000 and 2020 in the Sikkim Himalaya region.Also,the study shows that,out of the terminus type of the glacier,glacier area,debris cover,ice-mixed debris,slope,aspect,mean elevation,and snout elevation of the glaciers,only the terminus type and mean elevation of the glacier are significantly altering the glacier mass balance in the Sikkim Himalayan region.Mathematically,the mass loss is approximately 0.40 m.w.e.a^(-1) higher in the lake-terminating glaciers compared to the land-terminating glaciers in the same elevation zone.On the other hand,a thousand meters mean elevation drop is associated with 0.179 m.w.e.a-1of mass loss despite the terminus type of the glaciers.In the current study,the model using the terminus type of the glaciers and the mean elevation of the glaciers explains 76% of fluctuation of mass balance in the Sikkim Himalayan region.

Effect of topography on the changes of Urumqi Glacier No.1 in the Chinese Tianshan Mountains

Topography plays an important role in determining the glacier changes.However,topography has often been oversimplified in the studies of the glacier changes.No systematic studies have been conducted to evaluate the relationship between the glacier changes and topographic features.The present study provided a detailed insight into the changes in the two branches(east branch and west branch)of Urumqi Glacier No.1 in the Chinese Tianshan Mountains since 1993 and systematically discussed the effect of topography on the glacier parameters.This study analyzed comprehensive recently observed data(from 1992/1993 to 2018/2019),including mass balance,ice thickness,surface elevation,ice velocity,terminus,and area,and then determined the differences in the changes of the two branches and explored the effect of topography on the glacier changes.We also applied a topographic solar radiation model to analyze the influence of topography on the incoming shortwave radiation(SW_(in))across the entire glacier,focusing on the difference in the SW_(in) between the two branches.The glacier mass balance of the east branch was more negative than that of the west branch from 1992/1993 to 2018/2019,and this was mainly attributed to the lower average altitude of the east branch.Compared with the west branch,the decrease rate of the ice velocity was lower in the east branch owing to its relatively increased slope.The narrow shape of the west branch and its southeast aspect in the earlier period resulted in a larger glacier terminus retreat of the west branch.The spatial variability of the SW_(in) across the glacier surface became much larger as altitude increased.The SW_(in) received by the east branch was slightly larger than that received by the west branch,and the northern aspect could receive more SW_(in),leading to glacier melting.In the future,the difference of the glacier changes between the two branches will continue to exist due to their topographic differences.This work is fundamental to understanding how topographic features affect the glacier changes,and provides information for building different types of relationship between the glacier area and ice volume to promote further studies on the basin-scale glacier classification.

大型自溃闸门

美国加利福尼亚州的一个大型工程修建了自溃闸门系统,不但提高了防洪能力,也增加了水库的蓄水量。

Selective N-terminal modification of peptides and proteins:Recent progresses and applications

Numerous strategies for linking desired chemical probes with target peptides and proteins have been developed and applied in the field of biological chemistry.Approaches for site-specific modification of native amino acid residues in test tubes and biological contexts represent novel biological tools for understanding the role of peptides and proteins.Selective N-terminal modification strategies have been broadly studied especially in the last 10 years,as N-terminal positions are typically solvent exposed and provide chemically distinct sites for many peptide and protein targets,making N terminus distinct from other functional groups.A growing number of chemical and enzymatic techniques have been developed to modify N-terminal amino acids,and those techniques have the potential in the fields of medicine,basic research and applied materials science.This review focuses on appraising modification methodologies with the potential for biological applications from the past 10 years.

Flexible interwoven termini determine the thermal stability of thermosomes

Group II chaperonins,which assemble as double-ring complexes,assist in the refolding of nascent peptides or denatured proteins in an ATP-dependent manner.The mo-lecular mechanism of group II chaperonin assembly and thermal stability is yet to be elucidated.Here,we selected the group II chaperonins(cpn-αand cpn-β),also called thermosomes,from Acidianus tengchongensis and in-vestigated their assembly and thermal stability.We found that the binding of ATP or its analogs contributed to the successful assembly of thermosomes and enhanced their thermal stabilities.Cpn-βis more thermally stable than cpn-α,while the thermal stability of the hetero thermo-some cpn-αβis intermediate.Cryo-electron microscopy reconstructions of cpn-αand cpn-βrevealed the interwo-ven densities of their non-conserved fl exible N/C-termini around the equatorial planes.The deletion or swapping of their termini and pH-dependent thermal stability assays revealed the key role of the termini electrostatic interac-tions in the assembly and thermal stability of the ther-mosomes.