Structural basis for tetraspanin functions as revealed by the cryo-EM structure of uroplakin complexes at 6-Å resolution

Tetraspanin uroplakins (UPs) Ia and Ib, together with their single-spanning transmembrane protein partners UP II and IIIa, form a unique crystalline 2D array of 16-nm particles covering almost the entire urothelial surface. A 6 Å–resolution cryo-EM structure of the UP particle revealed that the UP tetraspanins have a rod-shaped structure consisting of four closely packed transmembrane helices that extend into the extracellular loops, capped by a disulfide-stabilized head domain. The UP tetraspanins form the primary complexes with their partners through tight interactions of the transmembrane domains as well as the extracellular domains, so that the head domains of their tall partners can bridge each other at the top of the heterotetramer. The secondary interactions between the primary complexes and the tertiary interaction between the 16-nm particles contribute to the formation of the UP tetraspanin network. The rod-shaped tetraspanin structure allows it to serve as stable pilings in the lipid sea, ideal for docking partner proteins to form structural/signaling networks

Structural analysis of a novel rabbit monoclonal antibody R53 targeting an epitope in HIV-1 gp120 C4 region critical for receptor and co-receptor binding

The fourth conserved region (C4) in the HIV-1 envelope glycoprotein (Env) gp120 is a structural element that is important for its function, as it binds to both the receptor CD4 and the co-receptor CCR5/CXCR4. It has long been known that this region is highly immunogenic and that it harbors B-cell as well as T-cell epitopes. It is the target of a number of antibodies in animal studies, which are called CD4-blockers. However, the mechanism by which the virus shields itself from such antibody responses is not known. Here, we determined the crystal structure of R53 in complex with its epitope peptide using a novel anti-C4 rabbit monoclonal antibody R53. Our data show that although the epitope of R53 covers a highly conserved sequence (433)AMYAPPI(439), it is in the gp120 trimer and in the CD4-bound conformation. Our results suggest a masking mechanism to explain how HIV-1 protects this critical region from the human immune system

Tin-graphene tubes as anodes for lithium-ion batteries with high volumetric and gravimetric energy densities.

Limited by the size of microelectronics, as well as the space of electrical vehicles, there are tremendous demands for lithium-ion batteries with high volumetric energy densities. Current lithium-ion batteries, however, adopt graphite-based anodes with low tap density and gravimetric capacity, resulting in poor volumetric performance metric. Here, by encapsulating nanoparticles of metallic tin in mechanically robust graphene tubes, we show tin anodes with high volumetric and gravimetric capacities, high rate performance, and long cycling life. Pairing with a commercial cathode material LiNi0.6Mn0.2Co0.2O2, full cells exhibit a gravimetric and volumetric energy density of 590 W h Kg-1 and 1,252 W h L-1, respectively, the latter of which doubles that of the cell based on graphite anodes. This work provides an effective route towards lithium-ion batteries with high energy density for a broad range of applications

The Bayes factor and its implementation in JASP: A practical primer

Statistical inference plays a critical role in modern scientific research, however, the dominant method for statistical inference in science, null hypothesis significance testing (NHST), is often misunderstood and misused, which leads to unreproducible findings. To address this issue, researchers propose to adopt the Bayes factor as an alternative to NHST. The Bayes factor is a principled Bayesian tool for model selection and hypothesis testing, and can be interpreted as the strength for both the null hypothesis H0 and the alternative hypothesis H1 based on the current data. Compared to NHST, the Bayes factor has the following advantages: it quantifies the evidence that the data provide for both the H0 and the H1, it is not “violently biased” against H0, it allows one to monitor the evidence as the data accumulate, and it does not depend on sampling plans. Importantly, the recently developed open software JASP makes the calculation of Bayes factor accessible for most researchers in psychology, as we demonstrated for the t-test. Given these advantages, adopting the Bayes factor will improve psychological researchers’ statistical inferences. Nevertheless, to make the analysis more reproducible, researchers should keep their data analysis transparent and open

Rabbit anti-HIV-1 monoclonal antibodies raised by immunization can mimic the antigen-binding modes of antibodies derived from HIV-1-infected humans

The rabbit is a commonly used animal model in studying antibody responses in HIV/AIDS vaccine development. However, no rabbit monoclonal antibodies (MAbs) have been developed previously to study the epitope-specific antibody responses against HIV-1 envelope (Env) glycoproteins, and little is known about how the rabbit immune system can mimic the human immune system in eliciting such antibodies. Here we present structural analyses of two rabbit MAbs, R56 and R20, against the third variable region (V3) of HIV-1 gp120. R56 recognizes the well-studied immunogenic region in the V3 crown, while R20 targets a less-studied region at the C terminus of V3. By comparison of the Fab/epitope complex structures of these two antibodies raised by immunization with that of the corresponding human antibodies derived from patients chronically infected with HIV-1, we found that rabbit antibodies can recognize immunogenic regions of gp120 and mimic the binding modes of human antibodies. This result can provide new insight into the use of the rabbit as an animal model in AIDS vaccine development

5-(4-Pentyl­phen­yl)-1,3,4-thia­diazol-2-amine

The title compound, C13H17N3S, was synthesized by the reaction of 4-pentyl­benzoic acid and thio­semicarbazide. The dihedral angle between the thia­diazole and phenyl rings is 29.9 (2)°. An intra­molecular C—H⋯S inter­action is observed. In the crystal, inter­molecular N—H⋯N hydrogen bonding links the mol­ecules into centrosymmetric dimers

Identification of PTPN22 as a potential genetic biomarker for abdominal aortic aneurysm

Abdominal aortic aneurysm (AAA) is a severe life-threatening disease that is generally asymptomatic and is diagnosed at a very late stage. The genetic component underpinning AAA is considerable, with an estimated heritability of up to 70%. Therefore, identifying genetic biomarkers for AAA is valuable for predicting high-risk populations. We used integrative bioinformatics and cellular AAA model-based validation to reveal that the gene encoding protein tyrosine phosphatase non-receptor type 22 (PTPN22) may be a potentially useful diagnostic biomarker for AAA. Integrative bioinformatics analyses of clinical specimens showed that PTPN22 expression was consistently upregulated in aortic tissues and peripheral blood mononuclear cells (PBMCs) derived from patients with AAA. Moreover, transcriptomics data revealed that PTPN22 is a potential biomarker for AAA with limited diagnostic value in patients with thoracic aortic aneurysm/dissection. Single-cell RNA sequencing-based findings further highlight PTPN22 expression in aortic immune cells and vascular smooth muscle cells (VSMCs) is consistently upregulated in patients with AAA. A cellular AAA model was eventually employed to verify the increase in PTPN22 expression. Collectively, the results indicate that PTPN22 could be a potentially useful diagnostic biomarker for AAA

Towards Vehicle-to-everything Autonomous Driving: A Survey on Collaborative Perception

Vehicle-to-everything (V2X) autonomous driving opens up a promising direction for developing a new generation of intelligent transportation systems. Collaborative perception (CP) as an essential component to achieve V2X can overcome the inherent limitations of individual perception, including occlusion and long-range perception. In this survey, we provide a comprehensive review of CP methods for V2X scenarios, bringing a profound and in-depth understanding to the community. Specifically, we first introduce the architecture and workflow of typical V2X systems, which affords a broader perspective to understand the entire V2X system and the role of CP within it. Then, we thoroughly summarize and analyze existing V2X perception datasets and CP methods. Particularly, we introduce numerous CP methods from various crucial perspectives, including collaboration stages, roadside sensors placement, latency compensation, performance-bandwidth trade-off, attack/defense, pose alignment, etc. Moreover, we conduct extensive experimental analyses to compare and examine current CP methods, revealing some essential and unexplored insights. Specifically, we analyze the performance changes of different methods under different bandwidths, providing a deep insight into the performance-bandwidth trade-off issue. Also, we examine methods under different LiDAR ranges. To study the model robustness, we further investigate the effects of various simulated real-world noises on the performance of different CP methods, covering communication latency, lossy communication, localization errors, and mixed noises. In addition, we look into the sim-to-real generalization ability of existing CP methods. At last, we thoroughly discuss issues and challenges, highlighting promising directions for future efforts. Our codes for experimental analysis will be public at https://github.com/memberRE/Collaborative-Perception.Comment: 19 page