AYVM to AYMM transition on HER2 exon 20 insertion induces TKI resistance in NSCLC.

Pyrotinib, a novel pan-HER tyrosine kinase inhibitor, has demonstrated substantial anti-tumor activity in non-small cell lung cancer (NSCLC) patients harboring HER2 mutations. However, the inevitable resistance to pyrotinib necessitates an in-depth understanding of the underlying mechanisms. In this study, potential resistance-associated mutations were identified through genomic sequencing of clinically paired samples and were validated using in vitro and in vivo models.

Coupling sensor to enzyme in the voltage sensing phosphatase.

Voltage-sensing phosphatases (VSPs) dephosphorylate phosphoinositide (PIP) signaling lipids in response to membrane depolarization. VSPs possess an S4-containing voltage sensor domain (VSD), resembling that of voltage-gated cation channels, and a lipid phosphatase domain (PD). The mechanism by which voltage turns on enzyme activity is unclear.

Structural basis of the recognition of adeno-associated virus by the neurological system-related receptor carbonic anhydrase IV.

Carbonic anhydrase IV (Car4) is a newly identified receptor that allows adeno-associated virus (AAV) 9P31 to cross the blood-brain barrier and achieve efficient infection in the central nervous system (CNS) in mouse models. However, the molecular mechanism by which engineered AAV capsids with 7-mer insertion in the variable region (VR) VIII recognize these novel cellular receptors is unknown. Here we report the cryo-EM structures of AAV9P31 and its complex with Mus musculus Car4 at atomic resolution by utilizing the block-based reconstruction (BBR) method.

Using gait videos to automatically assess anxiety.

Background: In recent years, the number of people with anxiety disorders has increased worldwide. Methods for identifying anxiety through objective clues are not yet mature, and the reliability and validity of existing modeling methods have not been tested. The objective of this paper is to propose an automatic anxiety assessment model with good reliability and validity.

Volatile Profiling and Transcriptome Sequencing Provide Insights into the Biosynthesis of α-Pinene and β-Pinene in Hance Leaves.

Hance is a pinene-rich deciduous plant species in the Altingiaceae family that is used as a medicinal plant in China. However, the regulatory mechanisms underlying α-pinene and β-pinene biosynthesis in leaves remain unknown. Here, a joint analysis of the volatile compounds and transcriptomes of leaves was performed to comprehensively explore the terpene synthase (TPS) that may participate in α-pinene and β-pinene biosynthesis.

Reliability and validity analysis of personality assessment model based on gait video.

Personality affects an individual's academic achievements, occupational tendencies, marriage quality and physical health, so more convenient and objective personality assessment methods are needed. Gait is a natural, stable, and easy-to-observe body movement that is closely related to personality. The purpose of this paper is to propose a personality assessment model based on gait video and evaluate the reliability and validity of the multidimensional model.

Comparing the Effectiveness of Brain Structural Imaging, Resting-state fMRI, and Naturalistic fMRI in Recognizing Social Anxiety Disorder in Children and Adolescents.

Social anxiety disorder (SAD) is a common anxiety disorder in childhood and adolescence. Studies on SAD in adults have reported both structural and functional aberrancies of the brain at the group level. However, evidence has shown differences in anxiety-related brain abnormalities between adolescents and adults.

Structures of tweety homolog proteins TTYH2 and TTYH3 reveal a Ca-dependent switch from intra- to intermembrane dimerization.

Tweety homologs (TTYHs) comprise a conserved family of transmembrane proteins found in eukaryotes with three members (TTYH1-3) in vertebrates. They are widely expressed in mammals including at high levels in the nervous system and have been implicated in cancers and other diseases including epilepsy, chronic pain, and viral infections. TTYHs have been reported to form Ca- and cell volume-regulated anion channels structurally distinct from any characterized protein family with potential roles in cell adhesion, migration, and developmental signaling.

Physical basis for distinct basal and mechanically gated activity of the human K channel TRAAK.

TRAAK is a mechanosensitive two-pore domain K (K2P) channel localized to nodes of Ranvier in myelinated neurons. TRAAK deletion in mice results in mechanical and thermal allodynia, and gain-of-function mutations cause the human neurodevelopmental disorder FHEIG. TRAAK displays basal and stimulus-gated activities typical of K2Ps, but the mechanistic and structural differences between these modes are unknown.

Identifying Psychological Symptoms Based on Facial Movements.

Many methods have been proposed to automatically identify the presence of mental illness, but these have mostly focused on one specific mental illness. In some non-professional scenarios, it would be more helpful to understand an individual's mental health status from all perspectives. We recruited 100 participants.

Structural basis for pH gating of the two-pore domain K channel TASK2.

TASK2 (also known as KCNK5) channels generate pH-gated leak-type K currents to control cellular electrical excitability. TASK2 is involved in the regulation of breathing by chemosensory neurons of the retrotrapezoid nucleus in the brainstem and pH homeostasis by kidney proximal tubule cells. These roles depend on channel activation by intracellular and extracellular alkalization, but the mechanistic basis for TASK2 gating by pH is unknown.

See your mental state from your walk: Recognizing anxiety and depression through Kinect-recorded gait data.

As the challenge of mental health problems such as anxiety and depression increasing today, more convenient, objective, real-time assessing techniques of mental state are in need. The Microsoft Kinect camera is a possible option for contactlessly capturing human gait, which could reflect the walkers' mental state. So we tried to propose a novel method for monitoring individual's anxiety and depression based on the Kinect-recorded gait pattern.

Erratum: PKM2 methylation by CARM1 activates aerobic glycolysis to promote tumorigenesis.

This corrects the article DOI: 10.1038/ncb3630.

Electrophilic probes for deciphering substrate recognition by O-GlcNAc transferase.

O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential human glycosyltransferase that adds O-GlcNAc modifications to numerous proteins. However, little is known about the mechanism with which OGT recognizes various protein substrates. Here we report on GlcNAc electrophilic probes (GEPs) to expedite the characterization of OGT-substrate recognition.

PKM2 methylation by CARM1 activates aerobic glycolysis to promote tumorigenesis.

Metabolic reprogramming is a hallmark of cancer. Herein we discover that the key glycolytic enzyme pyruvate kinase M2 isoform (PKM2), but not the related isoform PKM1, is methylated by co-activator-associated arginine methyltransferase 1 (CARM1). PKM2 methylation reversibly shifts the balance of metabolism from oxidative phosphorylation to aerobic glycolysis in breast cancer cells.

Structural insights into the substrate binding adaptability and specificity of human O-GlcNAcase.

The O-linked β-N-acetyl glucosamine (O-GlcNAc) modification dynamically regulates the functions of numerous proteins. A single human enzyme O-linked β-N-acetyl glucosaminase (O-GlcNAcase or OGA) hydrolyzes this modification. To date, it remains largely unknown how OGA recognizes various substrates.

Structures of human O-GlcNAcase and its complexes reveal a new substrate recognition mode.

Human O-GlcNAcase (hOGA) is the unique enzyme responsible for the hydrolysis of the O-linked β-N-acetyl glucosamine (O-GlcNAc) modification, an essential protein glycosylation event that modulates the function of numerous cellular proteins in response to nutrients and stress. Here we report crystal structures of a truncated hOGA, which comprises the catalytic and stalk domains, in apo form, in complex with an inhibitor, and in complex with a glycopeptide substrate. We found that hOGA forms an unusual arm-in-arm homodimer in which the catalytic domain of one monomer is covered by the stalk domain of the sister monomer to create a substrate-binding cleft.

Emotion recognition using Kinect motion capture data of human gaits.

Automatic emotion recognition is of great value in many applications, however, to fully display the application value of emotion recognition, more portable, non-intrusive, inexpensive technologies need to be developed. Human gaits could reflect the walker's emotional state, and could be an information source for emotion recognition. This paper proposed a novel method to recognize emotional state through human gaits by using Microsoft Kinect, a low-cost, portable, camera-based sensor.

Molecular basis for the formation of ribonucleoprotein complex of Crimean-Congo hemorrhagic fever virus.

Negative-sense single-strand RNA (-ssRNA) viruses comprise a large family of pathogens that cause severe human infectious diseases. All -ssRNA viruses encode a nucleocapsid protein (NP) to encapsidate the viral genome, which, together with polymerase, forms a ribonucleoprotein complex (RNP) that is packaged into virions and acts as the template for viral replication and transcription. In our previous work, we solved the monomeric structure of NP encoded by Crimean-Congo hemorrhagic fever virus (CCHFV), which belongs to the Nairovirus genus within the Bunyaviridae family, and revealed its unusual endonuclease activity.

Crystal Structure of the Core Region of Hantavirus Nucleocapsid Protein Reveals the Mechanism for Ribonucleoprotein Complex Formation.

Unlabelled: Hantaviruses, which belong to the genus Hantavirus in the family Bunyaviridae, infect mammals, including humans, causing either hemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS) in humans with high mortality. Hantavirus encodes a nucleocapsid protein (NP) to encapsidate the genome and form a ribonucleoprotein complex (RNP) together with viral polymerase. Here, we report the crystal structure of the core domains of NP (NPcore) encoded by Sin Nombre virus (SNV) and Andes virus (ANDV), which are two representative members that cause HCPS in the New World.

Bunyamwera virus possesses a distinct nucleocapsid protein to facilitate genome encapsidation.

Bunyamwera virus (BUNV), which belongs to the genus Orthobunyavirus, is the prototypical virus of the Bunyaviridae family. Similar to other negative-sense single-stranded RNA viruses, bunyaviruses possess a nucleocapsid protein (NP) to facilitate genomic RNA encapsidation and virus replication. The structures of two NPs of members of different genera within the Bunyaviridae family have been reported.

Phylogenetic diversity and metabolic potential of activated sludge microbial communities in full-scale wastewater treatment plants.

The activated sludge process is an essential process for treating domestic and industrial wastewaters in most wastewater treatment plants (WWTPs). This process consists of a mixture of general and special microorganisms in a form of a complex enrichment population. Thus, the exploration of activated sludge microbial communities is crucial to improve the performance of activated sludge process.

Complete genome of Pseudomonas mendocina NK-01, which synthesizes medium-chain-length polyhydroxyalkanoates and alginate oligosaccharides.

Pseudomonas mendocina NK-01 can synthesize medium-chain-length polyhydroxyalkanoate (PHA(MCL)) and alginate oligosaccharides (AO) simultaneously from glucose under conditions of limited nitrogen. Here, we report the complete sequence of the 5.4-Mbp genome of Pseudomonas mendocina NK-01, which was isolated from farmland soil in Tianjin, China.

Balanced multiwavelets with interpolatory property.

Balanced multiwavelets with interpolatory property are discussed in this paper. This kind of multiwavelets can have a sampling property like Shannon's sampling theorem. It has been shown that the corresponding matrix-valued refinable mask has special structure, and an orthogonal multifilter bank {H(z),G(z)} can be reduced to a scalar valued conjugate quadrature filter (CQF) a(z) .