bluuebunny/crossref_metadata_2025 huggingface dataset:
Stable Water Isotope Signals and Their Relation to Stratiform and Convective Precipitation in the Tropical Andes
Authors: Landshuter Nadja , Aemisegger Franziska , Mölg Thomas
Published: July 2024

Stratiform and convective precipitation are known to be associated with distinct isotopic fingerprints in the tropics. Such rain type specific isotope signals are of key importance for climate reconstructions derived from climate proxies (e.g., stable isotopes in tree rings). Recently, the relation between rain type and isotope signal in present‐day climate has been intensively discussed. While some studies point out the importance of deep convection, other studies emphasize the role of stratiform precipitation for strongly depleted isotope signals in precipitation. Uncertainties arise from observational studies due to data scarcity while modeling approaches with global climate models cannot explicitly resolve convective processes and rely on parameterizations. High‐resolution climate models are particularly important for studies over complex topography and for the simulation of convective cloud formation and organization. Therefore, we applied the isotope‐enabled version of the high‐resolution climate model from the Consortium for Small‐Scale Modeling (COSMOiso) over the Andes of tropical south Ecuador, South America, to investigate the influence of stratiform and convective rain on the stable oxygen isotope signal of precipitation (δ18OP). Our results highlight the importance of deep convection for depleting the isotopic signal of precipitation and increasing its deuterium excess. Due to the opposing effect of shallow and deep convection on the δ18OP signal, the use of a stratiform fraction might be misleading. We therefore propose to use a shallow and deep convective fraction to analyze the effect of rain types on δ18OP.
A Semi‐Mechanistic Model for Partitioning Evapotranspiration Reveals Transpiration Dominates the Water Flux in Drylands
Authors: Reich E. G. , Samuels‐Crow K. , Bradford J. B. , Litvak M. , Schlaepfer D. R. , Ogle K.
Published: July 2024

Popular evapotranspiration (ET) partitioning methods make assumptions that might not be well‐suited to dryland ecosystems, such as high sensitivity of plant water‐use efficiency (WUE) to vapor pressure deficit (VPD). Our objectives were to (a) create an ET partitioning model that can produce fine‐scale estimates of transpiration (T) in drylands, and (b) use this approach to evaluate how climate controls T and WUE across ecosystem types and timescales along a dryland aridity gradient. We developed a novel, semi‐mechanistic ET partitioning method using a Bayesian approach that constrains abiotic evaporation using process‐based models, and loosely constrains time‐varying WUE within an autoregressive framework. We used this method to estimate daily T and weekly WUE across seven dryland ecosystem types and found that T dominates ET across the aridity gradient. Then, we applied cross‐wavelet coherence analysis to evaluate the temporal coherence between focal response variables (WUE and T/ET) and environmental variables. At yearly scales, we found that WUE at less arid, higher elevation sites was primarily limited by atmospheric moisture demand, and WUE at more arid, lower elevation sites was primarily limited by moisture supply. At sub‐yearly timescales, WUE and VPD were sporadically correlated. Hence, ecosystem‐scale dryland WUE is not always sensitive to changes in VPD at short timescales, despite this being a common assumption in many ET partitioning models. This new ET partitioning method can be used in dryland ecosystems to better understand how climate influences physically and biologically driven water fluxes.
Solar‐Induced Chlorophyll Fluorescence as a Potential Proxy for Gross Primary Production and Methane Emission in a Cool‐Temperate Bog in Northern Japan
Authors: Buareal Kanokrat , Kato Tomomichi , Morozumi Tomoki , Nakashima Naohisa , Tanatarakeree Kitpanuwat , Ueyama Masahito , Hirano Takashi
Published: July 2024

Wetlands play an essential role in the global greenhouse gas budget via carbon dioxide sequestration as well as methane emission. In recent decades, solar‐induced chlorophyll fluorescence (SIF) has been recognized as a remotely sensed proxy of gross primary productivity (GPP), which generates substrates for methane production. To examine the suitability of SIF for estimation of these two fluxes, we conducted ground tower‐based SIF observation with an ultrafine‐resolution spectroradiometer in conjunction with eddy covariance measurement in a cool‐temperate bog. The daily SIF retrieved in the red (687 nm) and far‐red (760 nm) bands (SIFred and SIFfar‐red, respectively) increased nonlinearly with GPP and linearly with absorbed photosynthetically active radiation (APAR). The relatively weak correlation between apparent SIF yield (ΦSIF = SIF/APAR) and light use efficiency implied that both APAR and plant physiology constrained the SIF emission in this wetland. The SIFred/SIFfar‐red ratio showed a significant negative relationship with vegetation greenness indices, and the similar seasonal variation in SIFred and SIFfar‐red indicated that the SIFred reabsorption effect only weakly influenced the SIFred–GPP relationship. Episodic temporal reduction in the water table did not distinctly influence SIF and ΦSIF. Estimation of the methane emission rate was subtly improved by incorporating SIF, which was substituted for GPP as the methanogenesis substrate, in a multivariable regression analysis together with two environmental factors: soil temperature and water table depth. This study illustrates the potential of both SIFred and SIFfar‐red to monitor GPP and to predict methane emission in wetlands.
Seasonal and Fortnight Variations in Internal Solitary Waves in the Indonesian Seas From the SWOT Measurements
Authors: Qiu Bo , Chen Shuiming , Wang Jinbo , Fu Lee‐Lueng
Published: July 2024

Using the wide‐swath sea surface height (SSH) data from the 1‐day repeat calibration/validation phase of the Surface Water and Ocean Topography (SWOT) mission, we explored fine‐scale evolution of nonlinear internal solitary waves (ISWs) in the Banda/Molucca Seas in the Indonesian Archipelagos. Generated in the Ombai Strait and Lifamatola Passage through semidiurnal tide‐topography interaction, respectively, ISWs in the Banda/Molucca Seas have a SSH amplitude of 10–20 cm and exhibit multiple wave packets with the leading wave crest followed by a series of rank‐ordered secondary wave crests. Due to nonlinearity, the ISWs are observed to propagate northward at a speed faster than the regional mode‐1 internal gravity waves and their amplitudes are modulated fortnightly following the regional spring‐neap tidal cycle. On longer timescale, the observed ISW amplitudes are controlled by seasonal upper ocean stratification changes with a weaker stratification favoring a larger amplitude. By converting the SWOT‐measured SSH data to the interior ocean pressure signals, we quantified the depth‐integrated energy flux associated with the northward‐propagating ISWs to be 5 and 2 kW m−1 in the central Banda and Molucca Seas, respectively. Comparisons with past studies indicate that the ISWs contribute to close to 100% and 40% of the tidally‐induced, northward energy fluxes, respectively, across the Banda and Molucca Seas.
Detection of congenital heart disease by neonatologist performed cardiac ultrasound in preterm infants
Authors: MacDonald Bradley , Yim Deane , Ramsay James , Gill Andrew
Published: July 2024

Objective

We aimed to assess the frequency of de novo congenital heart disease (CHD) detection via neonatologist-performed cardiac ultrasounds (NPCU) in premature infants born at <30 weeks of gestation.

Study design

In this cross-sectional study (2004–2023) clinicians completing NPCU flagged de novo suspected CHD. All flagged NPCUs were cross-checked with cardiologists to confirm CHD diagnosis.

Results

There were 2088 out of 3739 infants (56%) with at least one NPCU; 294 (14%) with cardiology referral. CHD diagnosis was confirmed in 109 of the 2088 (5.2%) infants. All major and critical CHD on NPCU imaging were suspected during NPCU and had prompt referral to the cardiology department.

Conclusion

De novo presentation of significant CHD continues to occur in the preterm population, emphasizing the need for recognizing CHD during NPCU. Optimizing NPCU training may benefit patients with early cardiology referral and review.
In vivo CRISPR/Cas9-mediated screen reveals a critical function of TFDP1 and E2F4 transcription factors in hematopoiesis
Authors: Tran Ngoc Tung , Graf Robin , Acevedo-Ochoa Ernesto , Trombke Janine , Weber Timm , Sommermann Thomas , Salomon Claudia , Kühn Ralf , Rajewsky Klaus , Chu Van Trung
Published: July 2024

Hematopoiesis is a continuous process of blood cell production driven by hematopoietic stem and progenitor cells (HSPCs) in the bone marrow. Proliferation and differentiation of HSPCs are regulated by complex transcriptional networks. In order to identify transcription factors with key roles in HSPC-mediated hematopoietic reconstitution, we developed an efficient and robust CRISPR/Cas9-based in vivo genetic screen. Using this experimental system, we identified the TFDP1 transcription factor to be essential for HSPC proliferation and post-transplant hematopoiesis. We further discovered that E2F4, an E2F transcription factor, serves as a binding partner of TFDP1 and is required for HSPC proliferation. Deletion of TFDP1 caused downregulation of genes associated with the cell cycle, with around 50% of these genes being identified as direct targets of TFDP1 and E2F4. Thus, our study expands the transcriptional network governing hematopoietic development through an in vivo CRISPR/Cas9-based genetic screen and identifies TFDP1/E2F4 as positive regulators of cell cycle genes in HSPCs.
Adherence to Mediterranean dietary pattern and the risk of gestational diabetes mellitus: a systematic review and meta-analysis of observational studies
Authors: Jafari Nasab Saeede , Ghanavati Matin , C. T.Clark Cain , Nasirian Maryam
Published: July 2024

Background and aim

Gestational diabetes mellitus (GDM) is one of the most prevalent disorders occurring during pregnancy, which confers significant risk of short and long-term adverse outcomes in both mothers and offspring. Recently, more attention has been paid to the association of pre-pregnancy and early pregnancy healthy dietary patterns, such as Mediterranean dietary pattern with GDM. However, there is a lack of systematic review and meta-analysis summarizing findings in this regard. Hence, we sought to assess the association of MedDiet and GDM in observational studies by performing a systematic review and meta-analysis.

Methods

A comprehensive systematic literature search of observational studies was conducted via PubMed, Scopus, and Google Scholar, up to August 2023. Studies were included in our review if they evaluated the association of MedDiet and GDM, following an observational study design.

Results

Ten studies were included in this study. Combining effect sizes, we found that adherence to MedDiet was inversely associated with GDM risk (OR = 0.64; CI: 0.52–0.78); implying that higher adherence to the MedDiet could reduce the risk of GDM by about 36%. Stratification by the geographic area, Mediterranean countries, time of dietary assessment and study design, showed a consistent significant association between MedDiet and GDM.

Conclusion

We conclude that adhering to diets resembling MedDiet, before or in early pregnancy, could be associated with lower risks or odds of GDM.
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

Poor 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

BUB1 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

Invasion 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

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

Obesity 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

Viruses 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

The 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

Protein-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

The 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

DSR2, 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

Although 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

The 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

Robotics 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

Transcription 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

Protein 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

Cell 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.
Water mediated redox-neutral cleavage of arylalkenes via photoredox catalysis
Authors: Liao Ke , Fang Yuqi , Sheng Lei , Chen Jiean , Huang Yong
Published: July 2024

Cleavage of carbon-carbon bonds remains a challenging task in organic synthesis. Traditional methods for splitting Csp2=Csp2 bonds into two halves typically involve non-redox (metathesis) or oxidative (ozonolysis) mechanisms, limiting their synthetic potential. Disproportionative deconstruction of alkenes, which yields one reduced and one oxidized fragment, remains an unexplored area. In this study, we introduce a redox-neutral approach for deleting a Csp2 carbon unit from substituted arylalkenes, resulting in the formation of an arene (reduction) and a carbonyl product (oxidation). This transformation is believed to proceed through a mechanistic sequence involving visible-light-promoted anti-Markovnikov hydration, followed by photoredox cleavage of Csp3-Csp3 bond in the alcohol intermediate. A crucial consideration in this design is addressing the compatibility between the highly reactive oxy radical species in the latter step and the required hydrogen-atom-transfer (HAT) reagent for both steps. We found that ethyl thioglycolate serves as the optimal hydrogen-atom shuttle, offering remarkable chemoselectivity among multiple potential HAT events in this transformation. By using D2O, we successfully prepared dideuteromethylated (-CD2H) arenes with good heavy atom enrichment. This work presents a redox-neutral alternative for alkene deconstruction, with considerable potential in late-stage modification of complex molecules.
Enhanced elastic stability of a topologically disordered crystalline metal–organic framework
Authors: Meekel Emily G. , Partridge Phillippa , Paraoan Robert A. I. , Levinsky Joshua J. B. , Slater Ben , Hobday Claire L. , Goodwin Andrew L.
Published: July 2024

By virtue of their open network structures and low densities, metal–organic frameworks (MOFs) are soft materials that exhibit elastic instabilities at low applied stresses. The conventional strategy for improving elastic stability is to increase the connectivity of the underlying MOF network, which necessarily increases the material density and reduces the porosity. Here we demonstrate an alternative paradigm, whereby elastic stability is enhanced in a MOF with an aperiodic network topology. We use a combination of variable-pressure single-crystal X-ray diffraction measurements and coarse-grained lattice-dynamical calculations to interrogate the high-pressure behaviour of the topologically aperiodic system TRUMOF-1, which we compare against that of its ordered congener MOF-5. We show that the topology of the former quenches the elastic instability responsible for pressure-induced framework collapse in the latter, much as irregularity in the shapes and sizes of stones acts to prevent cooperative mechanical failure in drystone walls. Our results establish aperiodicity as a counter-intuitive design motif in engineering the mechanical properties of framework structures that is relevant to MOFs and larger-scale architectures alike.
Unlocking saponin biosynthesis in soapwort
Authors: Jo Seohyun , El-Demerdash Amr , Owen Charlotte , Srivastava Vikas , Wu Dewei , Kikuchi Shingo , Reed James , Hodgson Hannah , Harkess Alex , Shu Shengqiang , Plott Chris , Jenkins Jerry , Williams Melissa , Boston Lori-Beth , Lacchini Elia , Qu Tongtong , Goossens Alain , Grimwood Jane , Schmutz Jeremy , Leebens-Mack Jim , Osbourn Anne
Published: July 2024

Soapwort (Saponaria officinalis) is a flowering plant from the Caryophyllaceae family with a long history of human use as a traditional source of soap. Its detergent properties are because of the production of polar compounds (saponins), of which the oleanane-based triterpenoid saponins, saponariosides A and B, are the major components. Soapwort saponins have anticancer properties and are also of interest as endosomal escape enhancers for targeted tumor therapies. Intriguingly, these saponins share common structural features with the vaccine adjuvant QS-21 and, thus, represent a potential alternative supply of saponin adjuvant precursors. Here, we sequence the S. officinalis genome and, through genome mining and combinatorial expression, identify 14 enzymes that complete the biosynthetic pathway to saponarioside B. These enzymes include a noncanonical cytosolic GH1 (glycoside hydrolase family 1) transglycosidase required for the addition of d-quinovose. Our results open avenues for accessing and engineering natural and new-to-nature pharmaceuticals, drug delivery agents and potential immunostimulants.
Archaeological Artefact Database of Finland (AADA)
Authors: Pesonen P. , Moilanen U. , Roose M. , Saipio J. , Tiilikkala J. , Sanwal U. , Immonen V. , Vesakoski O. , Onkamo P.
Published: July 2024

This paper presents the Archaeological Artefact Database of Finland (AADA) of prehistoric (covering period of almost 11,000 years) artefacts in Finland that are categorised by type and are accompanied with photos of the artefacts. The database is intended to contain all typologically classifiable prehistoric artefacts found in Finland and held in Finnish collections. This dataset provides spatio-temporal context for artefacts across different time periods and regions, as it includes approximately 38,000 single artefacts and approximately 10,000 pottery type identifications from the Early Mesolithic to the end of the Iron Age in Finland (c. 8900 calBC - 1300/1500 calAD). In addition, the artefacts are given period-based (subperiod) dating to allow their chronological affiliation. To facilitate data usage, we also offer an R-script to replicate the data visualisation provided in this paper and a Python script to merge the artefact information to the pictures. We further work towards an interactive user interface for data download and visualization.
Mathematical modeling and machine learning-based optimization for enhancing biofiltration efficiency of volatile organic compounds
Authors: Sulaiman Muhammad , Khalaf Osamah Ibrahim , Khan Naveed Ahmad , Alshammari Fahad Sameer , Hamam Habib
Published: July 2024

Biofiltration is a method of pollution management that utilizes a bioreactor containing live material to absorb and destroy pollutants biologically. In this paper, we investigate mathematical models of biofiltration for mixing volatile organic compounds (VOCs) for instance hydrophilic (methanol) and hydrophobic ($$\alpha$$
α
-pinene). The system of nonlinear diffusion equations describes the Michaelis-Menten kinetics of the enzymic chemical reaction. These models represent the chemical oxidation in the gas phase and mass transmission within the air-biofilm junction. Furthermore, for the numerical study of the saturation of $$\alpha$$
α
-pinene and methanol in the biofilm and gas state, we have developed an efficient supervised machine learning algorithm based on the architecture of Elman neural networks (ENN). Moreover, the Levenberg-Marquardt (LM) optimization paradigm is used to find the parameters/ neurons involved in the ENN architecture. The approximation to a solutions found by the ENN-LM technique for methanol saturation and $$\alpha$$
α
-pinene under variations in different physical parameters are allegorized with the numerical results computed by state-of-the-art techniques. The graphical and statistical illustration of indications of performance relative to the terms of absolute errors, mean absolute deviations, computational complexity, and mean square error validates that our results perfectly describe the real-life situation and can further be used for problems arising in chemical engineering.
Microbial inoculum effects on the rumen epithelial transcriptome and rumen epimural metatranscriptome in calves
Authors: Fregulia P. , Park T. , Li W. , Cersosimo L. M. , Zanton G. I.
Published: July 2024

Manipulation of the rumen microbial ecosystem in early life may affect ruminal fermentation and enhance the productive performance of dairy cows. The objective of this experiment was to evaluate the effects of dosing three different types of microbial inoculum on the rumen epithelium tissue (RE) transcriptome and the rumen epimural metatranscriptome (REM) in dairy calves. For this objective, 15 Holstein bull calves were enrolled in the study at birth and assigned to three different intraruminal inoculum treatments dosed orally once weekly from three to six weeks of age. The inoculum treatments were prepared from rumen contents collected from rumen fistulated lactating cows and were either autoclaved (control; ARF), processed by differential centrifugation to create the bacterial-enriched inoculum (BE), or through gravimetric separation to create the protozoal-enriched inoculum (PE). Calves were fed 2.5 L/d pasteurized waste milk 3x/d from 0 to 7 weeks of age and texturized starter until euthanasia at 9 weeks of age, when the RE tissues were collected for transcriptome and microbial metatranscriptome analyses, from four randomly selected calves from each treatment. The different types of inoculum altered the RE transcriptome and REM. Compared to ARF, 9 genes were upregulated in the RE of BE and 92 in PE, whereas between BE and PE there were 13 genes upregulated in BE and 114 in PE. Gene ontology analysis identified enriched GO terms in biological process category between PE and ARF, with no enrichment between BE and ARF. The RE functional signature showed different KEGG pathways related to BE and ARF, and no specific KEGG pathway for PE. We observed a lower alpha diversity index for RE microbiome in ARF (observed genera and Chao1 (p < 0.05)). Five microbial genera showed a significant correlation with the changes in host gene expression: Roseburia (25 genes), Entamoeba (two genes); Anaerosinus, Lachnospira, and Succiniclasticum were each related to one gene. sPLS-DA analysis showed that RE microbial communities differ among the treatments, although the taxonomic and functional microbial profiles show different distributions. Co-expression Differential Network Analysis indicated that both BE and PE had an impact on the abundance of KEGG modules related to acyl-CoA synthesis, type VI secretion, and methanogenesis, while PE had a significant impact on KEGGs related to ectoine biosynthesis and D-xylose transport. Our study indicated that artificial dosing with different microbial inocula in early life alters not only the RE transcriptome, but also affects the REM and its functions.
Sex-specific blood-derived RNA biomarkers for childhood tuberculosis
Authors: Krishnan Preethi , Bobak Carly A. , Hill Jane E.
Published: July 2024

Confirmatory diagnosis of childhood tuberculosis (TB) remains a challenge mainly due to its dependence on sputum samples and the paucibacillary nature of the disease. Thus, only ~ 30% of suspected cases in children are diagnosed and the need for minimally invasive, non-sputum-based biomarkers remains unmet. Understanding host molecular changes by measuring blood-based transcriptomic markers has shown promise as a diagnostic tool for TB. However, the implication of sex contributing to disease heterogeneity and therefore diagnosis remains to be understood. Using publicly available gene expression data (GSE39939, GSE39940; n = 370), we report a sex-specific RNA biomarker signature that could improve the diagnosis of TB disease in children. We found four gene biomarker signatures for male (SLAMF8, GBP2, WARS, and FCGR1C) and female pediatric patients (GBP6, CELSR3, ALDH1A1, and GBP4) from Kenya, South Africa, and Malawi. Both signatures achieved a sensitivity of 85% and a specificity of 70%, which approaches the WHO-recommended target product profile for a triage test. Our gene signatures outperform most other gene signatures reported previously for childhood TB diagnosis.
Exploring pathological link between antimicrobial and amyloid peptides
Authors: Tang Yijing , Zhang Yanxian , Zhang Dong , Liu Yonglan , Nussinov Ruth , Zheng Jie
Published: July 2024

Amyloid peptides (AMYs) and antimicrobial peptides (AMPs) are considered as two distinct families of peptides. In this review, we examine recent developments in the potential interplay between AMYs and AMPs, as well as their pathological implications.
Synthesis of a functionalized and photodegradable fluorene-based polymer for aqueous SWNT dispersion
Authors: Ritaine Dialia , Kertesz Ben A. , Adronov Alex
Published: July 2024

Decoration of single-walled carbon nanotubes with a photocleavable conjugated polymer allows dispersion and triggered release.
Nanopillar array-based electrochemical aptamer sensor for STX sensitivity detection
Authors: Li Jinsong , Zheng Weixian , Gao Ya , Liu Xinyu , Li Zhongbo , Zhang Lijun
Published: July 2024

A nanopillar array-based electrochemical aptasensor was fabricated for the detection of STX. High sensitivity was achieved over 1 pM–3 nM and 3–100 nM with an LOD of 1 pM with no interference from neo-STX, okadaic acid and common metal ions.
Improved estimates of expanded measurement uncertainty
Authors: Analytical Methods Committee, AMCTB No. 114
Published: July 2024

An improved estimate of expanded measurement uncertainty, when this is calculated using ANOVA results from a nested experimental design, is described. In cases where the number of sampling targets is ≪30, more accurate coverage factors are calculated.
Recent advances in dual photoredox/nickel catalyzed alkene carbofunctionalised reactions
Authors: Kommoju Anilkumar , Snehita Kattamuri , Sowjanya Kandi , Mukkamala Saratchandra Babu , Padala Kishor
Published: July 2024

Alkene carbofunctionalization reactions have great potential for synthesizing complex molecules and constructing complex structures in natural products and medicinal chemistry.