bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural and behavioral markers of inhibitory control predict symptom improvement during internet-delivered cognitive behavioral therapy for depression
Authors: Thai Michelle , Olson Elizabeth A. , Nickels Stefanie , Dillon Daniel G. , Webb Christian A. , Ren Boyu , Killgore William D. S. , Rauch Scott L. , Rosso Isabelle M. , Pizzagalli Diego A. 
Published: July 2024

AbstractPoor inhibitory control contributes to deficits in emotion regulation, which are often targeted by treatments for major depressive disorder (MDD), including cognitive behavioral therapy (CBT). Brain regions that contribute to inhibitory control and emotion regulation overlap; thus, inhibitory control might relate to response to CBT. In this study, we examined whether baseline inhibitory control and resting state functional connectivity (rsFC) within overlapping emotion regulation-inhibitory control regions predicted treatment response to internet-based CBT (iCBT). Participants with MDD were randomly assigned to iCBT (N = 30) or a monitored attention control (MAC) condition (N = 30). Elastic net regression was used to predict post-treatment Patient Health Questionnaire-9 (PHQ-9) scores from baseline variables, including demographic variables, PHQ-9 scores, Flanker effects (interference, sequential dependency, post-error slowing), and rsFC between the dorsal anterior cingulate cortex, bilateral anterior insula (AI), and right temporoparietal junction (TPJ). Essential prognostic predictor variables retained in the elastic net regression included treatment group, gender, Flanker interference response time (RT), right AI-TPJ rsFC, and left AI-right AI rsFC. Prescriptive predictor variables retained included interactions between treatment group and baseline PHQ-9 scores, age, gender, Flanker RT, sequential dependency effects on accuracy, post-error accuracy, right AI-TPJ rsFC, and left AI-right AI rsFC. Inhibitory control and rsFC within inhibitory control-emotion regulation regions predicted reduced symptom severity following iCBT, and these effects were stronger in the iCBT group than in the MAC group. These findings contribute to a growing literature indicating that stronger inhibitory control at baseline predicts better outcomes to psychotherapy, including iCBT.
BUB1b impairs chemotherapy sensitivity via resistance to ferroptosis in lung adenocarcinoma
Authors: Ding Yanguang , Gao Jian , Chen Jun , Ren Jinmei , Jiang Jiahao , Zhang Zhiqiang , Tong Xin , Zhao Jun 
Published: July 2024

AbstractBUB1 mitotic checkpoint serine/threonine kinase B (BUB1b) has been unequivocally identified as an oncogene in various cancers. However, the potential mechanism by which BUB1b orchestrates the progression of lung adenocarcinoma (LUAD) remains unclear. Here we found that both the transcript and protein levels of BUB1b were dramatically upregulated in tumor tissues and contributed to the dismal prognosis of LUAD patients. Moreover, gain- and loss-of-function assays, conducted both in vitro and in vivo, confirmed that BUB1b enhanced the viability of LUAD cells. Mechanistically, BUB1b forms a complex with OTUD3 and NRF2 and stabilizes the downstream NRF2 signaling pathway to facilitate insensitivity to ferroptosis and chemotherapy. In BALB/c nude mice bearing subcutaneous tumors that overexpress BUB1b, a combined strategy of ML385 targeting and chemotherapy achieved synergistic effects, inhibiting tumor growth and obviously improving survival. Taken together our study uncovered the underlying mechanism by which BUB1b promotes the progression of LUAD and proposed a novel strategy to enhance the efficacy of chemotherapy.
PRMT6 facilitates EZH2 protein stability by inhibiting TRAF6-mediated ubiquitination degradation to promote glioblastoma cell invasion and migration
Authors: Wang Ji , Shen Shiquan , You Jian , Wang Zhaotao , Li Yan , Chen Yanming , Tuo Yonghua , Chen Danmin , Yu Haoming , Zhang Jingbo , Wang Fangran , Pang Xiao , Xiao Zongyu , Lan Qing , Wang Yezhong 
Published: July 2024

AbstractInvasion and migration are the key hallmarks of cancer, and aggressive growth is a major factor contributing to treatment failure and poor prognosis in glioblastoma. Protein arginine methyltransferase 6 (PRMT6), as an epigenetic regulator, has been confirmed to promote the malignant proliferation of glioblastoma cells in previous studies. However, the effects of PRMT6 on glioblastoma cell invasion and migration and its underlying mechanisms remain elusive. Here, we report that PRMT6 functions as a driver element for tumor cell invasion and migration in glioblastoma. Bioinformatics analysis and glioma sample detection results demonstrated that PRMT6 is highly expressed in mesenchymal subtype or invasive gliomas, and is significantly negatively correlated with their prognosis. Inhibition of PRMT6 (using PRMT6 shRNA or inhibitor EPZ020411) reduces glioblastoma cell invasion and migration in vitro, whereas overexpression of PRMT6 produces opposite effects. Then, we identified that PRMT6 maintains the protein stability of EZH2 by inhibiting the degradation of EZH2 protein, thereby mediating the invasion and migration of glioblastoma cells. Further mechanistic investigations found that PRMT6 inhibits the transcription of TRAF6 by activating the histone methylation mark (H3R2me2a), and reducing the interaction between TRAF6 and EZH2 to enhance the protein stability of EZH2 in glioblastoma cells. Xenograft tumor assay and HE staining results showed that the expression of PRMT6 could promote the invasion of glioblastoma cells in vivo, the immunohistochemical staining results of mouse brain tissue tumor sections also confirmed the regulatory relationship between PRMT6, TRAF6, and EZH2. Our findings illustrate that PRMT6 suppresses TRAF6 transcription via H3R2me2a to enhance the protein stability of EZH2 to facilitate glioblastoma cell invasion and migration. Blocking the PRMT6-TRAF6-EZH2 axis is a promising strategy for inhibiting glioblastoma cell invasion and migration.
Impacts of keratoconus on quality of life: a qualitative study
Authors: Fan Leo , Kandel Himal , Watson Stephanie L. 
Published: July 2024

Abstract
Background/Aims
To identify the domains of quality of life (QoL) in people with keratoconus.

Methods
Semi structured in-depth in person and telephone interviews were conducted with participants diagnosed with keratoconus and recruited from the Sydney Eye Hospital, Sydney, Australia. Thematic analysis of interview content was conducted using inductive and deductive processes. Data was collected until thematic saturation was obtained.

Results
33 patients with keratoconus with median age 37 (range 18 to 65) years and majority male (n = 25; 75.8%) were interviewed and a total of 2551 quotes coded. Thematic analysis resulted in 7 broad themes, Driving (199 references), Career (259 references), Symptoms (647 references), Enjoyment (149 references), Relationships (250 references), Financial (104 references) and Healthcare (881 references). Most references described a negative relationship between keratoconus and these 7 domains. The diverse QoL issues expressed included frustration with treatment effectiveness, fear of disease progression, inconvenience with contact lenses, forced career changes and job loss, cost of contact lenses, and feelings of isolation and discrimination. Themes and subthemes described a complex and varied relationship between keratoconus and QoL.

Conclusion
Severe quality of life impairment was experienced by keratoconus patients despite treatment. Keratoconus diminishes various aspects of individual’s QoL. Therapies able to improve QoL are still needed for keratoconus.
Obesity increases genomic instability at DNA repeat-mediated endogenous mutation hotspots
Authors: Kompella Pallavi , Wang Guliang , Durrett Russell E. , Lai Yanhao , Marin Celeste , Liu Yuan , Habib Samy L. , DiGiovanni John , Vasquez Karen M. 
Published: July 2024

AbstractObesity is associated with increased cancer risk, yet the underlying mechanisms remain elusive. Obesity-associated cancers involve disruptions in metabolic and cellular pathways, which can lead to genomic instability. Repetitive DNA sequences capable of adopting alternative DNA structures (e.g., H-DNA) stimulate mutations and are enriched at mutation hotspots in human cancer genomes. However, it is not known if obesity impacts DNA repeat-mediated endogenous mutation hotspots. We address this gap by measuring mutation frequencies in obese and normal-weight transgenic reporter mice carrying either a control human B-DNA- or an H-DNA-forming sequence (from a translocation hotspot in c-MYC in Burkitt lymphoma). Here, we discover that H-DNA-induced DNA damage and mutations are elevated in a tissue-specific manner, and DNA repair efficiency is reduced in obese mice compared to those on the control diet. These findings elucidate the impact of obesity on cancer-associated endogenous mutation hotspots, providing mechanistic insight into the link between obesity and cancer.
Soft jamming of viral particles in nanopores
Authors: Chazot-Franguiadakis Léa , Eid Joelle , Delecourt Gwendoline , Kolbeck Pauline J. , Brugère Saskia , Molcrette Bastien , Socol Marius , Mougel Marylène , Salvetti Anna , Démery Vincent , Lacroix Jean-Christophe , Bennevault Véronique , Guégan Philippe , Castelnovo Martin , Montel Fabien 
Published: July 2024

AbstractViruses have remarkable physical properties and complex interactions with their environment. However, their aggregation in confined spaces remains unexplored, although this phenomenon is of paramount importance for understanding viral infectivity. Using hydrodynamical driving and optical detection, we developed a method to detect the transport of single virus in real time through synthetic nanopores. We unveiled a jamming phenomenon specifically associated with virus confinement under flow. We showed that the interactions of viral particles with themselves and with the pore surface were critical for clog formation. Based on the detailed screening of the physical and chemical determinants, we proposed a simple dynamical model that recapitulated all the experimental observations. Our results pave the way for the study of jamming phenomena in the presence of more complex interactions.
Complex trait susceptibilities and population diversity in a sample of 4,145 Russians
Authors: Usoltsev Dmitrii , Kolosov Nikita , Rotar Oxana , Loboda Alexander , Boyarinova Maria , Moguchaya Ekaterina , Kolesova Ekaterina , Erina Anastasia , Tolkunova Kristina , Rezapova Valeriia , Molotkov Ivan , Melnik Olesya , Freylikhman Olga , Paskar Nadezhda , Alieva Asiiat , Baranova Elena , Bazhenova Elena , Beliaeva Olga , Vasilyeva Elena , Kibkalo Sofia , Skitchenko Rostislav , Babenko Alina , Sergushichev Alexey , Dushina Alena , Lopina Ekaterina , Basyrova Irina , Libis Roman , Duplyakov Dmitrii , Cherepanova Natalya , Donner Kati , Laiho Paivi , Kostareva Anna , Konradi Alexandra , Shlyakhto Evgeny , Palotie Aarno , Daly Mark J. , Artomov Mykyta 
Published: July 2024

AbstractThe population of Russia consists of more than 150 local ethnicities. The ethnic diversity and geographic origins, which extend from eastern Europe to Asia, make the population uniquely positioned to investigate the shared properties of inherited disease risks between European and Asian ancestries. We present the analysis of genetic and phenotypic data from a cohort of 4,145 individuals collected in three metro areas in western Russia. We show the presence of multiple admixed genetic ancestry clusters spanning from primarily European to Asian and high identity-by-descent sharing with the Finnish population. As a result, there was notable enrichment of Finnish-specific variants in Russia. We illustrate the utility of Russian-descent cohorts for discovery of novel population-specific genetic associations, as well as replication of previously identified associations that were thought to be population-specific in other cohorts. Finally, we provide access to a database of allele frequencies and GWAS results for 464 phenotypes.
Allosteric nanobodies to study the interactions between SOS1 and RAS
Authors: Fischer Baptiste , Uchański Tomasz , Sheryazdanova Aidana , Gonzalez Simon , Volkov Alexander N. , Brosens Elke , Zögg Thomas , Kalichuk Valentina , Ballet Steven , Versées Wim , Sablina Anna A. , Pardon Els , Wohlkönig Alexandre , Steyaert Jan 
Published: July 2024

AbstractProtein-protein interactions (PPIs) are central in cell metabolism but research tools for the structural and functional characterization of these PPIs are often missing. Here we introduce broadly applicable immunization (Cross-link PPIs and immunize llamas, ChILL) and selection strategies (Display and co-selection, DisCO) for the discovery of diverse nanobodies that either stabilize or disrupt PPIs in a single experiment. We apply ChILL and DisCO to identify competitive, connective, or fully allosteric nanobodies that inhibit or facilitate the formation of the SOS1•RAS complex and modulate the nucleotide exchange rate on this pivotal GTPase in vitro as well as RAS signalling in cellulo. One of these connective nanobodies fills a cavity that was previously identified as the binding pocket for a series of therapeutic lead compounds. The long complementarity-determining region (CDR3) that penetrates this binding pocket serves as pharmacophore for extending the repertoire of potential leads.
Enantioselective de novo construction of 3‑oxindoles via organocatalyzed formal [3 + 2] annulation from simple arylamines
Authors: Wang Yong , Li Yanyan , Chen Haohua , Lan Yu , Pi Chao , Wu Yangjie , Cui Xiuling 
Published: July 2024

AbstractThe de novo construction of enantioenriched 3-hydroxyindolenines and 3-oxindoles from easily available starting materials has been highly desired. Herein, an enantioselectively intermolecular direct [3 + 2] annulation of aryl amine with 2,3-diketoesters to construct 3-hydroxyindolenines with a chiral tertiary alcohol has been disclosed. The results of control experiments and DFT calculation revealed that π − π interaction plays a pivotal role in the enantioselectivity-determining process of [3 + 2] annulation. The following unusual concerted [1,2]-ester migration provides a family of chiral 3-oxindoles in good to excellent yields with excellent enantioselectivity.
The structural basis of the activation and inhibition of DSR2 NADase by phage proteins
Authors: Wang Ruiwen , Xu Qi , Wu Zhuoxi , Li Jialu , Guo Hao , Liao Tianzhui , Shi Yuan , Yuan Ling , Gao Haishan , Yang Rong , Shi Zhubing , Li Faxiang 
Published: July 2024

AbstractDSR2, a Sir2 domain-containing protein, protects bacteria from phage infection by hydrolyzing NAD+. The enzymatic activity of DSR2 is triggered by the SPR phage tail tube protein (TTP), while suppressed by the SPbeta phage-encoded DSAD1 protein, enabling phages to evade the host defense. However, the molecular mechanisms of activation and inhibition of DSR2 remain elusive. Here, we report the cryo-EM structures of apo DSR2, DSR2-TTP-NAD+ and DSR2-DSAD1 complexes. DSR2 assembles into a head-to-head tetramer mediated by its Sir2 domain. The C-terminal helical regions of DSR2 constitute four partner-binding cavities with opened and closed conformation. Two TTP molecules bind to two of the four C-terminal cavities, inducing conformational change of Sir2 domain to activate DSR2. Furthermore, DSAD1 competes with the activator for binding to the C-terminal cavity of DSR2, effectively suppressing its enzymatic activity. Our results provide the mechanistic insights into the DSR2-mediated anti-phage defense system and DSAD1-dependent phage immune evasion.
Chiral inversion induced by aromatic interactions in short peptide assembly
Authors: Qi Kai , Qi Hao , Wang Muhan , Ma Xiaoyue , Wang Yan , Yao Qiang , Liu Wenliang , Zhao Yurong , Wang Jiqian , Wang Yuefei , Qi Wei , Zhang Jun , Lu Jian R. , Xu Hai 
Published: July 2024

AbstractAlthough hydrophobic interactions provide the main driving force for initial peptide aggregation, their role in regulating suprastructure handedness of higher-order architectures remains largely unknown. We here interrogate the effects of hydrophobic amino acids on handedness at various assembly stages of peptide amphiphiles. Our studies reveal that relative to aliphatic side chains, aromatic side chains set the twisting directions of single β-strands due to their strong steric repulsion to the backbone, and upon packing into multi-stranded β-sheets, the side-chain aromatic interactions between strands form the aromatic ladders with a directional preference. This ordering not only leads to parallel β-sheet arrangements but also induces the chiral flipping over of single β-strands within a β-sheet. In contrast, the lack of orientational hydrophobic interactions in the assembly of aliphatic peptides implies no chiral inversion upon packing into β-sheets. This study opens an avenue to harness peptide aggregates with targeted handedness via aromatic side-chain interactions.
Triboiontronics with temporal control of electrical double layer formation
Authors: Li Xiang , Li Roujuan , Li Shaoxin , Wang Zhong Lin , Wei Di 
Published: July 2024

AbstractThe nanoscale electrical double layer plays a crucial role in macroscopic ion adsorption and reaction kinetics. In this study, we achieve controllable ion migration by dynamically regulating asymmetric electrical double layer formation. This tailors the ionic-electronic coupling interface, leading to the development of triboiontronics. Controlling the charge-collecting layer coverage on dielectric substrates allows for charge collection and adjustment of the substrate-liquid contact electrification property. By dynamically managing the asymmetric electrical double layer formation between the dielectric substrate and liquids, we develop a direct-current triboiontronic nanogenerator. This nanogenerator produces a transferred charge density of 412.54 mC/m2, significantly exceeding that of current hydrovoltaic technology and conventional triboelectric nanogenerators. Additionally, incorporating redox reactions to the process enhances the peak power and transferred charge density to 38.64 W/m2 and 540.70 mC/m2, respectively.
A droplet robotic system enabled by electret-induced polarization on droplet
Authors: Zhang Ruotong , Zhang Chengzhi , Fan Xiaoxue , Au Yeung Christina C. K. , Li Huiyanchen , Lin Haisong , Shum Ho Cheung 
Published: July 2024

AbstractRobotics for scientific research are evolving from grasping macro-scale solid materials to directly actuating micro-scale liquid samples. However, current liquid actuation mechanisms often restrict operable liquid types or compromise the activity of biochemical samples by introducing interfering mediums. Here, we propose a robotic liquid handling system enabled by a novel droplet actuation mechanism, termed electret-induced polarization on droplet (EPD). EPD enables all-liquid actuation in principle and experimentally exhibits generality for actuating various inorganic/organic liquids with relative permittivity ranging from 2.25 to 84.2 and volume from 500 nL to 1 mL. Moreover, EPD is capable of actuating various biochemical samples without compromising their activities, including various body fluids, living cells, and proteins. A robotic system is also coupled with the EPD mechanism to enable full automation. EPD’s high adaptability with liquid types and biochemical samples thus promotes the automation of liquid-based scientific experiments across multiple disciplines.
Elf1 promotes transcription-coupled repair in yeast by using its C-terminal domain to bind TFIIH
Authors: Selvam Kathiresan , Xu Jun , Wilson Hannah E. , Oh Juntaek , Li Qingrong , Wang Dong , Wyrick John J. 
Published: July 2024

AbstractTranscription coupled-nucleotide excision repair (TC-NER) removes DNA lesions that block RNA polymerase II (Pol II) transcription. A key step in TC-NER is the recruitment of the TFIIH complex, which initiates DNA unwinding and damage verification; however, the mechanism by which TFIIH is recruited during TC-NER, particularly in yeast, remains unclear. Here, we show that the C-terminal domain (CTD) of elongation factor-1 (Elf1) plays a critical role in TC-NER in yeast by binding TFIIH. Analysis of genome-wide repair of UV-induced cyclobutane pyrimidine dimers (CPDs) using CPD-seq indicates that the Elf1 CTD in yeast is required for efficient TC-NER. We show that the Elf1 CTD binds to the pleckstrin homology (PH) domain of the p62 subunit of TFIIH in vitro, and identify a putative TFIIH-interaction region (TIR) in the Elf1 CTD that is important for PH binding and TC-NER. The Elf1 TIR shows functional, structural, and sequence similarities to a conserved TIR in the mammalian UV sensitivity syndrome A (UVSSA) protein, which recruits TFIIH during TC-NER in mammalian cells. These findings suggest that the Elf1 CTD acts as a functional counterpart to mammalian UVSSA in TC-NER by recruiting TFIIH in response to Pol II stalling at DNA lesions.
How antisense transcripts can evolve to encode novel proteins
Authors: Iyengar Bharat Ravi , Grandchamp Anna , Bornberg-Bauer Erich 
Published: July 2024

AbstractProtein coding features can emerge de novo in non coding transcripts, resulting in emergence of new protein coding genes. Studies across many species show that a large fraction of evolutionarily novel non-coding RNAs have an antisense overlap with protein coding genes. The open reading frames (ORFs) in these antisense RNAs could also overlap with existing ORFs. In this study, we investigate how the evolution an ORF could be constrained by its overlap with an existing ORF in three different reading frames. Using a combination of mathematical modeling and genome/transcriptome data analysis in two different model organisms, we show that antisense overlap can increase the likelihood of ORF emergence and reduce the likelihood of ORF loss, especially in one of the three reading frames. In addition to rationalising the repeatedly reported prevalence of de novo emerged genes in antisense transcripts, our work also provides a generic modeling and an analytical framework that can be used to understand evolution of antisense genes.
Engineering mouse cell fate controller by rational design
Authors: Huang Tao , Liu Dong , Wang Xiaomin , Kuang Junqi , Wu Manqi , Wang Beibei , Liang Zechuan , Fan Yixin , Chen Bo , Ma Zhaoyi , Fu Yu , Zhang Wenhui , Ming Jin , Qin Yue , Zhao Chengchen , Wang Bo , Pei Duanqing 
Published: July 2024

AbstractCell fate is likely regulated by a common machinery, while components of this machine remain to be identified. Here we report the design and testing of engineered cell fate controller NanogBiD, fusing BiD or BRG1 interacting domain of SS18 with Nanog. NanogBiD promotes mouse somatic cell reprogramming efficiently in contrast to the ineffective native protein under multiple testing conditions. Mechanistic studies further reveal that it facilitates cell fate transition by recruiting the intended Brg/Brahma-associated factor (BAF) complex to modulate chromatin accessibility and reorganize cell state specific enhancers known to be occupied by canonical Nanog, resulting in precocious activation of multiple genes including Sall4, miR-302, Dppa5a and Sox15 towards pluripotency. Although we have yet to test our approach in other species, our findings suggest that engineered chromatin regulators may provide much needed tools to engineer cell fate in the cells as drugs era.