bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plastic pollution fosters more microbial growth in lakes than natural organic matter
Authors: Sheridan Eleanor A. , Fonvielle Jérémy A. , Cottingham Samuel , Zhang Yi , Dittmar Thorsten , Aldridge David C. , Tanentzap Andrew J. 
Published: July 2022

AbstractPlastic debris widely pollutes freshwaters. Abiotic and biotic degradation of plastics releases carbon-based substrates that are available for heterotrophic growth, but little is known about how these novel organic compounds influence microbial metabolism. Here we found leachate from plastic shopping bags was chemically distinct and more bioavailable than natural organic matter from 29 Scandinavian lakes. Consequently, plastic leachate increased bacterial biomass acquisition by 2.29-times when added at an environmentally-relevant concentration to lake surface waters. These results were not solely attributable to the amount of dissolved organic carbon provided by the leachate. Bacterial growth was 1.72-times more efficient with plastic leachate because the added carbon was more accessible than natural organic matter. These effects varied with both the availability of alternate, especially labile, carbon sources and bacterial diversity. Together, our results suggest that plastic pollution may stimulate aquatic food webs and highlight where pollution mitigation strategies could be most effective.
Nonvolatile ferroelectric domain wall memory integrated on silicon
Authors: Sun Haoying , Wang Jierong , Wang Yushu , Guo Changqing , Gu Jiahui , Mao Wei , Yang Jiangfeng , Liu Yuwei , Zhang Tingting , Gao Tianyi , Fu Hanyu , Zhang Tingjun , Hao Yufeng , Gu Zhengbin , Wang Peng , Huang Houbing , Nie Yuefeng 
Published: July 2022

AbstractFerroelectric domain wall memories have been proposed as a promising candidate for nonvolatile memories, given their intriguing advantages including low energy consumption and high-density integration. Perovskite oxides possess superior ferroelectric prosperities but perovskite-based domain wall memory integrated on silicon has rarely been reported due to the technical challenges in the sample preparation. Here, we demonstrate a domain wall memory prototype utilizing freestanding BaTiO3 membranes transferred onto silicon. While as-grown BaTiO3 films on (001) SrTiO3 substrate are purely c-axis polarized, we find they exhibit distinct in-plane multidomain structures after released from the substrate and integrated onto silicon due to the collective effects from depolarizing field and strain relaxation. Based on the strong in-plane ferroelectricity, conductive domain walls with reading currents up to nanoampere are observed and can be both created and erased artificially, highlighting the great potential of the integration of perovskite oxides with silicon for ferroelectric domain wall memories.
Lactational delivery of Triclosan promotes non-alcoholic fatty liver disease in newborn mice
Authors: Weber André A. , Yang Xiaojing , Mennillo Elvira , Ding Jeffrey , Watrous Jeramie D. , Jain Mohit , Chen Shujuan , Karin Michael , Tukey Robert H. 
Published: July 2022

AbstractHere we show that Triclosan (TCS), a high-volume antimicrobial additive that has been detected in human breastmilk, can be efficiently transferred by lactation to newborn mice, causing significant fatty liver (FL) during the suckling period. These findings are relevant since pediatric non-alcoholic fatty liver disease (NAFLD) is escalating in the United States, with a limited mechanistic understanding. Lactational delivery stimulated hepatosteatosis, triglyceride accumulation, endoplasmic reticulum (ER) stress, signs of inflammation, and liver fibrosis. De novo lipogenesis (DNL) induced by lactational TCS exposure is shown to be mediated in a PERK-eIF2α-ATF4-PPARα cascade. The administration of obeticholic acid (OCA), a potent FXR agonist, as well as activation of intestinal mucosal-regenerative gp130 signaling, led to reduced liver ATF4 expression, PPARα signaling, and DNL when neonates were exposed to TCS. It is yet to be investigated but mother to child transmission of TCS or similar toxicants may underlie the recent increases in pediatric NAFLD.
Decoding kinase-adverse event associations for small molecule kinase inhibitors
Authors: Gong Xiajing , Hu Meng , Liu Jinzhong , Kim Geoffrey , Xu James , McKee Amy , Palmby Todd , de Claro R. Angelo , Zhao Liang 
Published: July 2022

AbstractSmall molecule kinase inhibitors (SMKIs) are being approved at a fast pace under expedited programs for anticancer treatment. In this study, we construct a multi-domain dataset from a total of 4638 patients in the registrational trials of 16 FDA-approved SMKIs and employ a machine-learning model to examine the relationships between kinase targets and adverse events (AEs). Internal and external (datasets from two independent SMKIs) validations have been conducted to verify the usefulness of the established model. We systematically evaluate the potential associations between 442 kinases with 2145 AEs and made publicly accessible an interactive web application “Identification of Kinase-Specific Signal” (https://gongj.shinyapps.io/ml4ki). The developed model (1) provides a platform for experimentalists to identify and verify undiscovered KI-AE pairs, (2) serves as a precision-medicine tool to mitigate individual patient safety risks by forecasting clinical safety signals and (3) can function as a modern drug development tool to screen and compare SMKI target therapies from the safety perspective.
Molecular mechanism of toxin neutralization in the HipBST toxin-antitoxin system of Legionella pneumophila
Authors: Zhen Xiangkai , Wu Yongyu , Ge Jinli , Fu Jiaqi , Ye Le , Lin Niannian , Huang Zhijie , Liu Zihe , Luo Zhao-qing , Qiu Jiazhang , Ouyang Songying 
Published: July 2022

AbstractToxin-antitoxin (TA) systems are ubiquitous genetic modules in bacteria and archaea. Here, we perform structural and biochemical characterization of the Legionella pneumophila effector Lpg2370, demonstrating that it is a Ser/Thr kinase. Together with two upstream genes, lpg2370 constitutes the tripartite HipBST TA. Notably, the toxin Lpg2370 (HipTLp) and the antitoxin Lpg2369 (HipSLp) correspond to the C-terminus and N-terminus of HipA from HipBA TA, respectively. By determining crystal structures of autophosphorylated HipTLp, its complex with AMP-PNP, and the structure of HipTLp-HipSLp complex, we identify residues in HipTLp critical for ATP binding and those contributing to its interactions with HipSLp. Structural analysis reveals that HipSLp binding induces a loop-to-helix shift in the P-loop of HipTLp, leading to the blockage of ATP binding and inhibition of the kinase activity. These findings establish the L. pneumophila effector Lpg2370 as the HipBST TA toxin and elucidate the molecular basis for HipT neutralization in HipBST TA.
A device-independent quantum key distribution system for distant users
Authors: Zhang Wei , van Leent Tim , Redeker Kai , Garthoff Robert , Schwonnek René , Fertig Florian , Eppelt Sebastian , Rosenfeld Wenjamin , Scarani Valerio , Lim Charles C.-W. , Weinfurter Harald 
Published: July 2022

AbstractDevice-independent quantum key distribution (DIQKD) enables the generation of secret keys over an untrusted channel using uncharacterized and potentially untrusted devices1–9. The proper and secure functioning of the devices can be certified by a statistical test using a Bell inequality10–12. This test originates from the foundations of quantum physics and also ensures robustness against implementation loopholes13, thereby leaving only the integrity of the users’ locations to be guaranteed by other means. The realization of DIQKD, however, is extremely challenging—mainly because it is difficult to establish high-quality entangled states between two remote locations with high detection efficiency. Here we present an experimental system that enables for DIQKD between two distant users. The experiment is based on the generation and analysis of event-ready entanglement between two independently trapped single rubidium atoms located in buildings 400 metre apart14. By achieving an entanglement fidelity of $$ {\mathcal F} \,\ge 0.892(23)$$

ℱ

≥
0.892

(

23

)

and implementing a DIQKD protocol with random key basis15, we observe a significant violation of a Bell inequality of S = 2.578(75)—above the classical limit of 2—and a quantum bit error rate of only 0.078(9). For the protocol, this results in a secret key rate of 0.07 bits per entanglement generation event in the asymptotic limit, and thus demonstrates the system’s capability to generate secret keys. Our results of secure key exchange with potentially untrusted devices pave the way to the ultimate form of quantum secure communications in future quantum networks.
PI3K drives the de novo synthesis of coenzyme A from vitamin B5
Authors: Dibble Christian C. , Barritt Samuel A. , Perry Grace E. , Lien Evan C. , Geck Renee C. , DuBois-Coyne Sarah E. , Bartee David , Zengeya Thomas T. , Cohen Emily B. , Yuan Min , Hopkins Benjamin D. , Meier Jordan L. , Clohessy John G. , Asara John M. , Cantley Lewis C. , Toker Alex 
Published: July 2022

AbstractIn response to hormones and growth factors, the class I phosphoinositide-3-kinase (PI3K) signalling network functions as a major regulator of metabolism and growth, governing cellular nutrient uptake, energy generation, reducing cofactor production and macromolecule biosynthesis1. Many of the driver mutations in cancer with the highest recurrence, including in receptor tyrosine kinases, Ras, PTEN and PI3K, pathologically activate PI3K signalling2,3. However, our understanding of the core metabolic program controlled by PI3K is almost certainly incomplete. Here, using mass-spectrometry-based metabolomics and isotope tracing, we show that PI3K signalling stimulates the de novo synthesis of one of the most pivotal metabolic cofactors: coenzyme A (CoA). CoA is the major carrier of activated acyl groups in cells4,5 and is synthesized from cysteine, ATP and the essential nutrient vitamin B5 (also known as pantothenate)6,7. We identify pantothenate kinase 2 (PANK2) and PANK4 as substrates of the PI3K effector kinase AKT8. Although PANK2 is known to catalyse the rate-determining first step of CoA synthesis, we find that the minimally characterized but highly conserved PANK49 is a rate-limiting suppressor of CoA synthesis through its metabolite phosphatase activity. Phosphorylation of PANK4 by AKT relieves this suppression. Ultimately, the PI3K–PANK4 axis regulates the abundance of acetyl-CoA and other acyl-CoAs, CoA-dependent processes such as lipid metabolism and proliferation. We propose that these regulatory mechanisms coordinate cellular CoA supplies with the demands of hormone/growth-factor-driven or oncogene-driven metabolism and growth.
Effects of polyethylene oxide particles on the photo-physical properties and stability of FA-rich perovskite solar cells
Authors: Koech Richard K. , Olanrewaju Yusuf A. , Ichwani Reisya , Kigozi Moses , Oyewole Deborah O. , Oyelade Omolara V. , Sanni Dahiru M. , Adeniji Sharafadeen A. , Colin-Ulloa Erika , Titova Lyubov V. , Martin Julia L. , Grimm Ronald L. , Bello Abdulhakeem , Oyewole Oluwaseun K. , Ntsoenzok Esidor , Soboyejo Winston O. 
Published: July 2022

AbstractIn this paper, we use Polyethylene Oxide (PEO) particles to control the morphology of Formamidinium (FA)-rich perovskite films and achieve large grains with improved optoelectronic properties. Consequently, a planar perovskite solar cell (PSC) is fabricated with additions of 5 wt% of PEO, and the highest PCE of 18.03% was obtained. This solar cell is also shown to retain up to 80% of its initial PCE after about 140 h of storage under the ambient conditions (average relative humidity of 62.5 ± 3.25%) in an unencapsulated state. Furthermore, the steady-state PCE of the PEO-modified PSC device remained stable for long (over 2500 s) under continuous illumination. This addition of PEO particles is shown to enable the tuning of the optoelectronic properties of perovskite films, improvements in the overall photophysical properties of PSCs, and an increase in resistance to the degradation of PSCs.
Long lasting anxiety following early life stress is dependent on glucocorticoid signaling in zebrafish
Authors: Chin Jacqueline S. R. , Phan Tram-Anh N. , Albert Lydia T. , Keene Alex C. , Duboué Erik R. 
Published: July 2022

AbstractChronic adversity in early childhood is associated with increased anxiety and a propensity for substance abuse later in adulthood, yet the effects of early life stress (ELS) on brain development remain poorly understood. The zebrafish, Danio rerio, is a powerful model for studying neurodevelopment and stress. Here, we describe a zebrafish model of ELS and identify a role for glucocorticoid signaling during a critical window in development that leads to long-term changes in brain function. Larval fish subjected to chronic stress in early development exhibited increased anxiety-like behavior and elevated glucocorticoid levels later in life. Increased stress-like behavior was only observed when fish were subjected to ELS within a precise time window in early development, revealing a temporal critical window of sensitivity. Moreover, enhanced anxiety-like behavior only emerges after two months post-ELS, revealing a developmentally specified delay in the effects of ELS. ELS leads to increased levels of baseline cortisol, and resulted in a dysregulation of cortisol receptors’ mRNA expression, suggesting long-term effects on cortisol signaling. Together, these findings reveal a ‘critical window’ for ELS to affect developmental reprogramming of the glucocorticoid receptor pathway, resulting in chronic elevated stress.
Characterization of plant growth-promoting rhizobacteria (PGPR) in Persian walnut associated with drought stress tolerance
Authors: Lotfi Naser , Soleimani Ali , Çakmakçı Ramazan , Vahdati Kourosh , Mohammadi Parisa 
Published: July 2022

AbstractThere is a lack of information on the rhizosphere of nut-bearing trees where microbial populations can benefit roots and tree growth. The current research aimed at discovering plant growth-promoting rhizobacteria (PGPR) in the rhizosphere of soil samples from around the root zone of six walnut trees, each of which was considered as a genotype, i.e. ‘TT1’, ‘TT2’, ‘SS2’, ‘ZM1’, ‘Chandler’ and ‘Haward’. The trees grew in different arid and semiarid regions of Iran and Turkey. The strains were isolated and identified based on different morphological and biochemical markers. Drought-stress tolerance was assessed in the case of each isolate through their transfer to culture medium, containing polyethylene glycol (PEG6000) at 0 and 373.80 g L−1. Resilient strains were analyzed for measuring their ability to produce siderophore, hydrogen cyanide (HCN), Indole-3-acetic acid (IAA) and Gibberellic acid (GA3). In sum, 211 isolates were identified, of which a large number belonged to the Bacillus genus and, specifically, 78% of the strains were able to grow under drought stress conditions. The genus Arthrobacter was only detected in the rhizosphere of ‘ZM1’, ‘Haward’ and ‘TT1’ genotypes. In 4% of the strains, IAA production exceeded 53 mg L−1, while a high level of phosphorus solubility was verified in 6% of the strains. No strain was found to have the capability of producing HCN. The strains were screened for drought-tolerance, which resulted in the discovery of two promising strains, i.e. ZM39 and Cha43. Based on molecular identification through amplification and sequencing of the 16S rDNA gene, these two strains seemed to belong to Bacillus velezensis and Bacillus amyloliquefaciens, respectively. The discovery of new PGPR strains could probably assist walnut trees in improving their mechanisms of adaptation to drought stress.
Vasoactive inotropic score as a predictor of long-term mortality in patients after off-pump coronary artery bypass grafting
Authors: Kwon Ji-Hye , Yoo Seung Yeon , Kim Seonwoo , Won Hojeong , Kim Wooksung , Her Sukyoung , Bang Yu Jeong , Park Jungchan , Lee Jong-Hwan , Cho Hyun Sung , Min Jeong-Jin 
Published: July 2022

AbstractIncreased vasoactive-inotropic score (VIS) is a reliable predictor of mortality and morbidity after cardiac surgery. Here, we retrospectively evaluated the association between VIS and adverse outcomes in adult patients after off-pump coronary artery bypass grafting (OPCAB). We included 2149 patients who underwent OPCAB. The maximal VIS was calculated for the initial 48 postoperative hours using standard formulae. The primary outcome was 1-year death. The composite adverse outcome was death, resuscitation or mechanical support, myocardial infarction, revascularization, new-onset atrial fibrillation, infection requiring antibacterial therapy, acute kidney injury, and stroke. Path-analysis was conducted using lactate and prognostic nutritional index (PNI). VIS was associated with 1-year death (odds ratio [OR] 1.07 [1.04–1.10], p < 0.001) and 1-year composite outcome (OR 1.02 [1.0–1.03], p = 0.008). In path-analysis, high VIS showed a direct effect on the increased risk of 1-year death and composite outcome. In the pathway using lactate as a mediating variable, VIS showed an indirect effect on the composite outcome but no significant effect on death. Low PNI directly affected the increased risk of 1-year death and composite outcome, and had an indirect effect on both outcomes, even when VIS was used as a mediating variable. In patients undergoing OPCAB, high VIS independently predicted morbidity and 1-year death. Patients with increased lactate levels following high VIS had an increased risk of postoperative complications, although not necessarily resulting in death. However, patients with poor preoperative nutritional status had an increased risk of unfavourable outcomes, including death, implying the importance of preoperative nutritional support.
Chromatography columns packed with thermoresponsive-cationic-polymer-modified beads for therapeutic drug monitoring
Authors: Nagase Kenichi , Takagi Hikaru , Nakada Hideo , Ishikawa Haruki , Nagata Yoshiko , Aomori Tohru , Kanazawa Hideko 
Published: July 2022

AbstractTherapeutic drug monitoring, which is used to determine appropriate drug doses, is critical in pharmacological therapy. In this study, we developed thermoresponsive chromatography columns with various cationic properties for effective therapeutic drug monitoring. Thermoresponsive cationic copolymer poly(N-isopropylacrylamide-co–n-butyl methacrylate-co–N,N-dimethylaminopropyl acrylamide) (P(NIPAAm-co-BMA-co-DMAPAAm))-modified silica beads, which were used as the chromatographic stationary phase, were prepared by modifying the radical initiator of the silica beads, followed by radical polymerization. Characterization of the prepared silica beads demonstrated that thermoresponsive polymers with various cationic properties successfully modified the beads. The elution behavior of several steroids in the prepared bead-packed columns at various temperatures indicated that the optimal column operating temperature was 30 °C. Appropriate measurement conditions for 13 drugs were investigated by varying the cationic properties of the columns and the pH of the mobile phase. Drug concentrations in serum samples were determined using the developed columns and mobile phases with a suitable pH. Voriconazole concentrations in human serum samples were determined using the developed columns with all-aqueous mobile phases. We anticipate that the developed chromatography columns can be used for therapeutic drug monitoring because drug concentrations can be measured using all-aqueous mobile phases that are suitable in clinical settings.
Identification of candidate enhancers controlling the transcriptome during the formation of interphalangeal joints
Authors: Nowosad Karol , Brouwer Rutger W. W. , Odrzywolski Adrian , Korporaal Anne L. , Gielniewski Bartłomiej , Wojtaś Bartosz , van IJcken Wilfred F. J. , Grosveld Frank , Huylebroeck Danny , Tylzanowski Przemko 
Published: July 2022

AbstractThe formation of the synovial joint begins with the visible emergence of a stripe of densely packed mesenchymal cells located between distal ends of the developing skeletal anlagen called the interzone. Recently the transcriptome of the early synovial joint was reported. Knowledge about enhancers would complement these data and lead to a better understanding of the control of gene transcription at the onset of joint development. Using ChIP-sequencing we have mapped the H3-signatures H3K27ac and H3K4me1 to locate regulatory elements specific for the interzone and adjacent phalange, respectively. This one-stage atlas of candidate enhancers (CEs) was used to map the association between these respective joint tissue specific CEs and biological processes. Subsequently, integrative analysis of transcriptomic data and CEs identified new putative regulatory elements of genes expressed in interzone (e.g.,GDF5,BMP2andDACT2) and phalange (e.g.,MATN1,HAPLN1andSNAI1). We also linked such CEs to genes known as crucial in synovial joint hypermobility and osteoarthritis, as well as phalange malformations. These analyses show that the CE atlas can serve as resource for identifying, and as starting point for experimentally validating, putative disease-causing genomic regulatory regions in patients with synovial joint dysfunctions and/or phalange disorders, and enhancer-controlled synovial joint and phalange formation.
Label-free, real-time detection of perineural invasion and cancer margins in a murine model of head and neck cancer surgery
Authors: Tam Kenric , Alhiyari Yazeed , Huang Shan , Han Albert , Stafsudd Oscar , Shori Ramesh , John Maie St. 
Published: July 2022

AbstractSurgical management of head and neck cancer requires a careful balance between complete resection of malignancy and preservation of function. Surgeons must also determine whether to resect important cranial nerves that harbor perineural invasion (PNI), as sacrificing nerves can result in significant morbidity including facial paralysis. Our group has previously reported that Dynamic Optical Contrast Imaging (DOCI), a novel non-invasive imaging system, can determine margins between malignant and healthy tissues. Herein, we use an in vivo murine model to demonstrate that DOCI can accurately identify cancer margins and perineural invasion, concordant with companion histology. Eight C3H/HeJ male mice were injected subcutaneously into the bilateral flanks with SCCVIISF, a murine head and neck cancer cell line. DOCI imaging was performed prior to resection to determine margins. Both tumor and margins were sent for histologic sectioning. After validating that DOCI can delineate HNSCC margins, we investigated whether DOCI can identify PNI. In six C3H/HeJ male mice, the left sciatic nerve was injected with PBS and the right with SCCVIISF. After DOCI imaging, the sciatic nerves were harvested for histologic analysis. All DOCI images were acquired intraoperatively and in real-time (10 s per channel), with an operatively relevant wide field of view. DOCI values distinguishing cancer from adjacent healthy tissue types were statistically significant (P < 0.05). DOCI imaging was also able to detect perineural invasion with 100% accuracy compared to control (P < 0.05). DOCI allows for intraoperative, real-time visualization of malignant and healthy tissue margins and perineural invasion to help guide tumor resection.