bluuebunny/crossref_metadata_2025 huggingface dataset:
Ciliary localization of a light-activated neuronal GPCR shapes behavior
Authors: Winans Amy M. , Friedmann Drew , Stanley Cherise , Xiao Tong , Liu Tsung-li , Chang Christopher J. , Isacoff Ehud Y.
Published: October 2023

Many neurons in the central nervous system produce a single primary cilium that serves as a specialized signaling organelle. Several neuromodulatory G-protein-coupled receptors (GPCRs) localize to primary cilia in neurons, although it is not understood how GPCR signaling from the cilium impacts circuit function and behavior. We find that the vertebrate ancient long opsin A (VALopA), a Gi-coupled GPCR extraretinal opsin, targets to cilia of zebrafish spinal neurons. In the developing 1-d-old zebrafish, brief light activation of VALopA in neurons of the central pattern generator circuit for locomotion leads to sustained inhibition of coiling, the earliest form of locomotion. We find that a related extraretinal opsin, VALopB, is also Gi-coupled, but is not targeted to cilia. Light-induced activation of VALopB also suppresses coiling, but with faster kinetics. We identify the ciliary targeting domains of VALopA. Retargeting of both opsins shows that the locomotory response is prolonged and amplified when signaling occurs in the cilium. We propose that ciliary localization provides a mechanism for enhancing GPCR signaling in central neurons.
Colloquialism and genre variation in Chinese
Authors: Li Jialei
Published: October 2023

Colloquialization has been identified as one of the most crucial change processes of the English language, through
which written genres gradually shift towards spoken styles. Colloquialism refers to the synchronous features resulting from
colloquialization. There is limited research into the lexical and phrasal patterns indicating colloquialism in Chinese or how
Chinese colloquialism manifests in different spoken and written genres. To extract the lexical and phrasal patterns indicating
colloquialism in Chinese, this study used a corpus-driven approach to determine and compare keywords and phrase frames from two
training Chinese corpora and those keywords and phrase frames with higher frequencies were retained for further testing.
Evaluation of resistance spot weldability and weld performance of zinc-coated martensitic steels
Authors: Pant Pallavi , Fagerstrom Emmitt , Schubert Holger , Hilpert Benjamin , Brewer Luke N.
Published: October 2023

This paper explores the resistance spot weldability of three martensitic (MS) steels of 1500 MPa tensile strength. A weld diameter versus current plot was developed for the three MS steels to investigate their weldable current range and expulsion characteristics. The mechanical performance of the welds was investigated using cross-tension, tensile-shear and hardness tests. It was found that the differences in electrical resistivity during the nugget growth period influenced the expulsion limit and, consequently, the weldable current range. The three MS steels failed in pullout failure mode but exhibited different plug ratios. Finally, the mechanical strength of the three MS steels was observed to be better than the other advanced high-strength steels (AHSS) such as DP600, TRIP1000 and PHS1500 steels.
Influences on the mechanical and physical properties of hot-press moulding alkali-activated slag (HP-FRAASC) composite with various fibers
Authors: Wang Haonian , Xu Lixin , Zang Sirui , Huang Dajian , Wang Song , Guo Qing , Yang Jiale , Jiang Changjun
Published: October 2023

In this study, we will apply the hot-press moulding method for the first time to the preparation of alkali-activated slag composites (AASC) and incorporate 1vol.-%, 3vol.-%, 5vol.-%, and 7vol.-% steel, copper, and carbon fibres into the matrix in order to investigate the characteristics of the HP-AASC and fibre reinforced (HP-FRAASC) in terms of compressive strength, flexural strength, impact toughness, and bulk density of HP-AASC and HP-FRAASC. Results show that the composites have good flexural strength, compressive strength, and impact toughness when the content of steel fibres is 5 vol.-%, copper fibres are 7 vol.-%, and carbon fibres are 1–3 vol.-%. It was observed from each sample of HP-FRAASC and HP-AASC that the HP-AASC samples had lower porosity, better density, and an easy preparation process, which can be used as a suitable preparation method for this material.
Collecting the energy generated by manual workers to monitor their working status and improve their working conditions by using a flexible rack mechanism
Authors: Ren Limin , Zhou Yang , He Yutong , Li Shixun , Sun Xuewen , Fan Liwu , Tan Yisong
Published: October 2023

Currently, an increasing quantity of portable energy harvesting modules are being developed to capture the energy generated by human motion. However, the size and weight of a device can affect the smoothness and comfort of a user’s normal limb movements in the process of collecting energy generated by human movement. Especially on manual workers, this effect will significantly increase their physical exertion, so the design of energy-harvesting devices for wearing on manual workers has higher requirements. The bend knee energy harvester (BKEH) designed in the work presented in this paper used a laboratory-made flexible rack to harvest the energy generated by manual workers’ frequently bent knees during work. It converts the collected energy into electricity for various wearable devices to monitor the working status of manual workers and improve their working conditions. One end of the flexible rack is fixed to the upper thigh. When the user bends the knee, the flexible rack will move downward, causing the gear to rotate, thereby collecting the energy generated by the body’s movement. The BKEH was made of many lightweight materials and weighed only 406 g, greatly reducing the impact on the user’s normal limb movements and physical exertion. Practical experiments showed that the BKEH output open-circuit voltage is up to 80.3 V, the output power reached as high as 3.16 W, and the power density reached as high as 7.9 W kg−1, which can effectively supply sufficient electrical power for wearable devices to work normally. The BKEH has a high practical value and good adaptability to human movement posture and can generate enough voltage and power to allow some wearable devices to work properly. These wearable devices can effectively provide users with the ability to monitor their work status and improve working conditions.
Recognizing and correcting for errors in frequency-dependent modulation spectroscopy
Authors: Wilson N M , Aarnio H , Österbacka R
Published: October 2023

This work shows how to acquire reliable data from frequency dependent continuous-wave modulation spectroscopy. We demonstrate this through the example of continuous-wave photoinduced absorption (cwPA), a characterization technique useful for studying long-lived photoexcitations in thin-film solar cell materials. Experimental errors arising at moderate frequencies in modulation spectroscopy are identified and corrected for. Limitations of the detectors and electronics are seen to cause both signal loss and phase shifts. Imperfect charge collection in the detector leads to wavelength-dependent correction factors, while phase shifts caused by the experimental setup call for frequency-dependent corrections. The methods outlined in this work act as a guide to avoid pitfalls in setting up modulation spectroscopy measurements and correcting for limitations.
Structural, mechanical and thermodynamic stability of the CaIn intermetallic compound for promising hydrogen storage: ab-initio calculations
Authors: Missoum Khadidja , Meskine Saïd , Boukortt Abdelkader , Benaouad Ahlam , Mehtougui Nabila
Published: October 2023

This study was conducted to investigate the structural, elastic, dynamical, mechanical, and thermodynamic properties of the binary intermetallic compound CaIn in various crystallographic phases, utilizing density functional theory (DFT) calculations. The results reveal that the compound is chemically and mechanically stable, as indicated by the formation energy, stability in the phonon dispersion, and elastic constants calculation. The mechanical and thermodynamic properties of our studied compound are only examined in the most stable calculated phase, which is the orthorhombic phase (Pmma). By calculating Pugh’s ratio

B
/
G
,

it has been determined that this compound possesses a brittle character. The quasi-harmonic Debye (QHD) model was employed to analyze various thermodynamic parameters such as Debye temperature, volume variation, isothermal bulk modulus, heat capacity, and thermal expansion coefficient. These findings are expected to encourage further theoretical and experimental studies on the CaIn intermetallic compound for potential applications as a hydrogen storage material and in various other fields.
Hierarchical controlled cyclic quantum teleportation
Authors: Yang Benchao
Published: October 2023

In this paper, a new hierarchical controlled cyclic quantum teleportation scheme is proposed, which can be applied to hierarchical quantum information transmission in a variety of application scenarios. In this scheme, Charlie in the low-level position can only complete simple sending tasks under the control of Bob, while Alice in the middle-level position needs to complete ordinary sending tasks under the control of Charlie and Diana; Bob in the high-level position needs to complete important tasks sent to Charlie under the control of the controller Diana and the high-level controller Eve. Diana and Eve can be regarded as both internal middle and high-level managers as well as different external regulators. Finally, this paper also discusses the number of controllers and their control capabilities, and briefly proposes a simplified hierarchical cyclic quantum teleportation scheme, which provides more options for users with different needs.
Bethe-Heitler lepton pair production in the deuteron breakup reaction*
Authors: Cai 蔡 Mengchu 孟初 , Liu 刘 Tianbo 天博 , Ma 马 Bo-Qiang 伯强
Published: October 2023

We study the lepton pair production via the Bethe-Heitler mechanism in the deuteron breakup reaction. The complete seven-fold differential cross section is calculated with final state interactions taken into account. The deuteron bound state is described by a relativistic covariant deuteron-nucleon vertex. The numerical results indicate that the differential cross section is highly dependent on the lepton's azimuthal angle in regions of small polar angles and exhibits sharp peaks in the distribution over the invariant mass of the generated lepton pair or the two nucleons in the final state. We demonstrate that such a nearly singular feature originates from the collinearity between the produced lepton or antilepton and the incident photon, and it is physically regularized by the lepton mass in our calculation. The final state interaction between the knocked-out nucleon and recoil nucleon redistributes the differential cross section over the missing momentum, with a significant enhancement at a large missing momentum and a suppression in the intermediate region. With a further decomposition of the final state interaction contribution, It is found that the on-shell term dominates the near quasi-elastic region, while the off-shell term dominates the other end. Additionally, we examine the contribution from the interference between the proton amplitude and neutron amplitude, which, as expected, is found negligible even if the proton-neutron rescattering is included. The results of this study can serve as inputs for the analysis and background estimation of multiple exclusive measurements at Jefferson Lab and future electron-ion colliders.
Antibacterial mechanism of Xiuyan jade mineral waste as a natural inorganic antibacterial agent
Authors: Wang Jimei , Wang Xiaoyan , Yang Yang
Published: October 2023

The Xiuyan jade waste exhibits prominent antibacterial properties after mechanical activation; these properties can be further optimized through low-temperature annealing. To elucidate its antibacterial mechanism, analysis methods involving metal-ion leaching monitoring and zeta potential analysis were used. Although the activated waste cannot be easily dissolved in water, Mg2+ and Ca2+ ions precipitated when the waste particles were dispersed in water. The particle surface showed different degrees of electronegativity, which could be the main reason for the antibacterial properties of the material. This study proved the importance of the surface electrical properties of activated waste particles on their properties by observing their adsorption capacity for methylene blue. At the annealing temperature of 270 °C, the Xiuyan jade waste exhibited the highest electronegativity and optimal antibacterial properties as well as the adsorption rate of methylene blue, verifying the significance of electronegativity of activated mineral waste powders on the antibacterial mechanism.
Pre-baked anode based on petroleum coke used as lithium-ion battery anode material
Authors: Gao Zhihan , Wang Bo , Liu Jinhua , Wang Peng , Ma Chunrong , Hou Zhenhua , Han Wenpeng , Zhang Jun , Choy Jin-Ho , Long Yun-Ze
Published: October 2023

Non-calcined petroleum coke can serve as an anode material for lithium-ion batteries (LIBs). Nevertheless, this method results in materials with insufficient conductivities and low Coulombic efficiencies during the initial cycle. To address these challenges, the usage of pre-baked carbon anodes as a material for anodes in LIBs is proposed in this study. The surface features of the pre-baked anode (i.e. wrinkle-like filaments) aid in reducing the volume expansion of the electrode during the lithium-ion insertion–removal process. Furthermore, the treatment increases the particle contact area, improving the conductivity of the pre-baked anode. At a current density of 3 A g−1, the pre-baked anode demonstrated an initial discharge capacity and a stable discharge capacity of 548.7 and 134.5 mAh g−1, respectively, after 100 cycles. The capacity of the anode (after 1000 cycles) consistently varies within a narrow range at a current density of 3 A g−1, indicating the stability of the electrode capacity over extended use. Therefore, this study provides valuable insights into exploring potential applications of pre-baked anode materials.
Preparation of carbon dots-metal nanoparticles nanocomposites and their application in heterogeneous catalysis
Authors: Li Xing , Li Bingcheng , Zhang Qunfeng , Li Xiaonian
Published: October 2023

Since carbon dots (CDs)-metal nanoparticles (MNPs) nanocomposites combine the advantages of both carbon quantum dots (CQDs) and MNPs, they show unique properties and are applied in heterogeneous catalysis. In the nanocomposite catalysts, CDs can act as modifiers to modulate the electronic properties of the metals or produce synergy with the metals. Consequently, the nanocomposite catalysts have good catalytic performance. This paper summarizes the preparation methods of nanocomposite catalysts and focuses on their applications in heterogeneous catalysis. Various specific preparation methods are not only summarized as completely as possible but also are also classified at the macro logic level. The applications of the nanocomposite catalysts in heterogeneous catalysis include photocatalysis, sonocatalysis, electrocatalysis, and thermal catalysis. It also reveals how the nanocomposite catalysts produce excellent catalytic performances in various catalytic reactions. Finally, the existing problems and the direction of future efforts are proposed. It is hoped that this paper will provide a slight reference for the future research of MNPs-CQDs nanocomposite catalysts and their application in the field of catalysis.
Towards a new avenue for rapid synthesis of electrocatalytic electrodes via laser-induced hydrothermal reaction for water splitting
Authors: Sha Yang , Zhu Menghui , Huang Kun , Zhang Yang , Moissinac Francis , Zhang Zhizhou , Cheng Dongxu , Mativenga Paul , Liu Zhu
Published: October 2023

Electrochemical production of hydrogen from water requires the development of electrocatalysts that are active, stable, and low-cost for water splitting. To address these challenges, researchers are increasingly exploring binder-free electrocatalytic integrated electrodes (IEs) as an alternative to conventional powder-based electrode preparation methods, for the former is highly desirable to improve the catalytic activity and long-term stability for large-scale applications of electrocatalysts. Herein, we demonstrate a laser-induced hydrothermal reaction (LIHR) technique to grow NiMoO4 nanosheets on nickel foam, which is then calcined under H2/Ar mixed gases to prepare the IE IE-NiMo-LR. This electrode exhibits superior hydrogen evolution reaction performance, requiring overpotentials of 59, 116 and 143 mV to achieve current densities of 100, 500 and 1000 mA·cm−2. During the 350 h chronopotentiometry test at current densities of 100 and 500 mA·cm−2, the overpotential remains essentially unchanged. In addition, NiFe-layered double hydroxide grown on Ni foam is also fabricated with the same LIHR method and coupled with IE-NiMo-IR to achieve water splitting. This combination exhibits excellent durability under industrial current density. The energy consumption and production efficiency of the LIHR method are systematically compared with the conventional hydrothermal method. The LIHR method significantly improves the production rate by over 19 times, while consuming only 27.78% of the total energy required by conventional hydrothermal methods to achieve the same production.
Vortex detection in atomic Bose–Einstein condensates using neural networks trained on synthetic images
Authors: Kim Myeonghyeon , Kwon Junhwan , Rabga Tenzin , Shin Y
Published: October 2023

Quantum vortices in atomic Bose–Einstein condensates (BECs) are topological defects characterized by quantized circulation of particles around them. In experimental studies, vortices are commonly detected by time-of-flight imaging, where their density-depleted cores are enlarged. In this work, we describe a machine learning-based method for detecting vortices in experimental BEC images, particularly focusing on turbulent condensates containing irregularly distributed vortices. Our approach employs a convolutional neural network (CNN) trained solely on synthetic simulated images, eliminating the need for manual labeling of the vortex positions as ground truth. We find that the CNN achieves accurate vortex detection in real experimental images, thereby facilitating analysis of large experimental datasets without being constrained by specific experimental conditions. This novel approach represents a significant advancement in studying quantum vortex dynamics and streamlines the analysis process in the investigation of turbulent BECs.
Actin polymerization inhibition by targeting ARPC2 affects intestinal stem cell homeostasis
Authors: Zhang Ruzhen , Chen Sheng , Yang Zhifan , Zhang Ning , Guo Kenan , Lv Keyi , Zhou Zimo , Gao Meijiao , Hu Xiancheng , Su Yongping , He Jianming , Wang Fengchao
Published: October 2023

Background

The rapid turnover of the intestinal epithelium is driven by the proliferation and differentiation of intestinal stem cells (ISCs). The dynamics of the F-actin cytoskeleton are critical for maintaining intercellular force and the signal transduction network. However, it remains unclear how direct interference with actin polymerization impacts ISC homeostasis. This study aims to reveal the regulatory effects of the F-actin cytoskeleton on the homeostasis of intestinal epithelium, as well as the potential risks of benproperine (BPP) as an anti-tumor drug.

Methods

Phalloidin fluorescence staining was utilized to test F-actin polymerization. Flow cytometry and IHC staining were employed to discriminate different types of intestinal epithelial cells. Cell proliferation was assessed through bromo-deoxyuridine (BrdU) and 5-ethynyl-2′-deoxyuridine (EdU) incorporation assays. The proliferation and differentiation of intestinal stem cells were replicated in vitro through organoid culture. Epithelial migration was evaluated through BrdU pulse labeling and chasing in mice.

Results

The F-actin content was observed to significantly increase as crypt cells migrated into the villus region. Additionally, actin polymerization in secretory cells, especially in Paneth cells (PCs), was much higher than that in neighboring ISCs. Treatment with the newly identified actin-related protein 2/3 complex subunit 2 (ARPC2) inhibitor BPP led to a dose-dependent increase or inhibition of intestinal organoid growth in vitro and crypt cell proliferation in vivo. Compared with the vehicle group, BPP treatment decreased the expression of Lgr5 ISC feature genes in vivo and in organoid culture. Meanwhile, PC differentiation derived from ISCs and progenitors was decreased by inhibition of F-actin polymerization. Mechanistically, BPP-induced actin polymerization inhibition may activate the Yes1-associated transcriptional regulator pathway, which affects ISC proliferation and differentiation. Accordingly, BPP treatment affected intestinal epithelial cell migration in a dose-dependent manner.

Conclusion

Our findings indicate that the regulation of cytoskeleton reorganization can affect ISC homeostasis. In addition, inhibiting ARPC2 with the Food and Drug Administration-approved drug BPP represents a novel approach to influencing the turnover of intestinal epithelial cells.
A photoactivatable and phenylboronic acid-functionalized nanoassembly for combating multidrug-resistant gram-negative bacteria and their biofilms
Authors: Zhou Xiaoqing , Dong Lanlan , Zhao Baohua , Hu Guangyun , Huang Can , Liu Tengfei , Lu Yifei , Zheng Mengxue , Yu Yanlan , Yang Zengjun , Cheng Shaowen , Xiong Yan , Luo Gaoxing , Qian Wei , Yin Rui
Published: October 2023

Background

Multidrug-resistant (MDR) gram-negative bacteria-related infectious diseases have caused an increase in the public health burden and mortality. Moreover, the formation of biofilms makes these bacteria difficult to control. Therefore, developing novel interventions to combat MDR gram-negative bacteria and their biofilms-related infections are urgently needed. The purpose of this study was to develop a multifunctional nanoassembly (IRNB) based on IR-780 and N, N′-di-sec-butyl-N, N′- dinitroso-1,4-phenylenediamine (BNN6) for synergistic effect on the infected wounds and subcutaneous abscesses caused by gram-negative bacteria.

Methods

The characterization and bacteria-targeting ability of IRNB were investigated. The bactericidal efficacy of IRNB against gram-negative bacteria and their biofilms was demonstrated by crystal violet staining assay, plate counting method and live/dead staining in vitro. The antibacterial efficiency of IRNB was examined on a subcutaneous abscess and cutaneous infected wound model in vivo. A cell counting kit-8 assay, Calcein/PI cytotoxicity assay, hemolysis assay and intravenous injection assay were performed to detect the biocompatibility of IRNB in vitro and in vivo.

Results

Herein, we successfully developed a multifunctional nanoassembly IRNB based on IR-780 and BNN6 for synergistic photothermal therapy (PTT), photodynamic therapy (PDT) and nitric oxide (NO) effect triggered by an 808 nm laser. This nanoassembly could accumulate specifically at the infected sites of MDR gram-negative bacteria and their biofilms via the covalent coupling effect. Upon irradiation with an 808 nm laser, IRNB was activated and produced both reactive oxygen species (ROS) and hyperthermia. The local hyperthermia could induce NO generation, which further reacted with ROS to generate ONOO−, leading to the enhancement of bactericidal efficacy. Furthermore, NO and ONOO− could disrupt the cell membrane, which converts bacteria to an extremely susceptible state and further enhances the photothermal effect. In this study, IRNB showed a superior photothermal-photodynamic-chemo (NO) synergistic therapeutic effect on the infected wounds and subcutaneous abscesses caused by gram-negative bacteria. This resulted in effective control of associated infections, relief of inflammation, promotion of re-epithelization and collagen deposition, and regulation of angiogenesis during wound healing. Moreover, IRNB exhibited excellent biocompatibility, both in vitro and in vivo.

Conclusions

The present research suggests that IRNB can be considered a promising alternative for treating infections caused by MDR gram-negative bacteria and their biofilms.
Investment Tribunals as Courts of Appeal? Determining State Responsibility for Substantive Denial of Justice
Authors: Prislan Vid
Published: October 2023

The contribution looks into the circumstances under which states can held be responsible for the content of judgments rendered by their courts pursuant to the denial of justice standard. The standard has received increased attention in the context of investor-state arbitration, where it has become widely used as a measure for determining the propriety of judicial conduct. Although ostensibly claimed to concern solely the propriety of judicial procedure, in the practice of investment tribunals, the standard has no less frequently been applied to measure the substantive adequacy of domestic courts’ judgments. The contribution examines this emerging practice by mapping the jurisprudence and evaluating the nature of arbitral tribunals’ scrutiny. It also sets out certain normative considerations that should guide the tribunals’ assessment of whether or not a particular judicial outcome is an adequate one from the standpoint of international standards of administration of justice. The contribution advances three arguments: first, that judicial decisions, as the final product of the domestic adjudicative process, can properly be the object of scrutiny by arbitral tribunals; second, that the task of arbitral tribunals must be limited to determining whether the particular decision is supported by adequate reasoning, and does not extend to inquiring whether the substantive outcome – i.e. the judicial decision on its merits – is also reasonable as such; and third, that the substantive review performed under the denial of justice standard necessarily requires the application of deferential standards of review.
Expression of taste sentinels, T1R, T2R, and PLCβ2, on the passageway for olfactory signals in zebrafish
Authors: Birdal Günes , D’Gama Percival P , Jurisch-Yaksi Nathalie , Korsching Sigrun I
Published: October 2023

The senses of taste and smell detect overlapping sets of chemical compounds in fish, e.g. amino acids are detected by both senses. However, so far taste and smell organs appeared morphologically to be very distinct, with a specialized olfactory epithelium for detection of odors and taste buds located in the oral cavity and lip for detection of tastants. Here, we report dense clusters of cells expressing T1R and T2R receptors as well as their signal transduction molecule PLCβ2 in nostrils of zebrafish, i.e. on the entrance funnel through which odor molecules must pass to be detected by olfactory sensory neurons. Quantitative evaluation shows the density of these chemosensory cells in the nostrils to be as high or higher than that in the established taste organs oral cavity and lower lip. Hydrodynamic flow is maximal at the nostril rim enabling high throughput chemosensation in this organ. Taken together, our results suggest a sentinel function for these chemosensory cells in the nostril.
Priorities and Progress in Gram-positive Bacterial Infection Research by the Antibacterial Resistance Leadership Group: A Narrative Review
Authors: Doernberg Sarah B , Arias Cesar A , Altman Deena R , Babiker Ahmed , Boucher Helen W , Creech C Buddy , Cosgrove Sara E , Evans Scott R , Fowler Vance G , Fritz Stephanie A , Hamasaki Toshimitsu , Kelly Brendan J , Leal Sixto M , Liu Catherine , Lodise Thomas P , Miller Loren G , Munita Jose M , Murray Barbara E , Pettigrew Melinda M , Ruffin Felicia , Scheetz Marc H , Shopsin Bo , Tran Truc T , Turner Nicholas A , Williams Derek J , Zaharoff Smitha , Holland Thomas L ,   for the Antibacterial Resistance Leadership Group, Patel Robin , King Heather , Kinamon Tori , Dai Weixiao , Geres Holly , Deckard Nancie , Schuler Carl , Bunn Ivra , Sharma Shrabani , Wickward Cathy , Waller Jason , Wilson Holly , Mehigan Maureen , Ghazaryan Varduhi , Raterman Erica , Samuel Tamika , Lee Marina
Published: October 2023

The Antibacterial Resistance Leadership Group (ARLG) has prioritized infections caused by gram-positive bacteria as one of its core areas of emphasis. The ARLG Gram-positive Committee has focused on studies responding to 3 main identified research priorities: (1) investigation of strategies or therapies for infections predominantly caused by gram-positive bacteria, (2) evaluation of the efficacy of novel agents for infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci, and (3) optimization of dosing and duration of antimicrobial agents for gram-positive infections. Herein, we summarize ARLG accomplishments in gram-positive bacterial infection research, including studies aiming to (1) inform optimal vancomycin dosing, (2) determine the role of dalbavancin in MRSA bloodstream infection, (3) characterize enterococcal bloodstream infections, (4) demonstrate the benefits of short-course therapy for pediatric community-acquired pneumonia, (5) develop quality of life measures for use in clinical trials, and (6) advance understanding of the microbiome. Future studies will incorporate innovative methodologies with a focus on interventional clinical trials that have the potential to change clinical practice for difficult-to-treat infections, such as MRSA bloodstream infections.
Prdm16 mutation determines sex-specific cardiac metabolism and identifies two novel cardiac metabolic regulators
Authors: Kühnisch Jirko , Theisen Simon , Dartsch Josephine , Fritsche-Guenther Raphaela , Kirchner Marieluise , Obermayer Benedikt , Bauer Anna , Kahlert Anne-Karin , Rothe Michael , Beule Dieter , Heuser Arnd , Mertins Philipp , Kirwan Jennifer A , Berndt Nikolaus , MacRae Calum A , Hubner Norbert , Klaassen Sabine
Published: October 2023

Aims

Mutation of the PRDM16 gene causes human dilated and non-compaction cardiomyopathy. The PRDM16 protein is a transcriptional regulator that affects cardiac development via Tbx5 and Hand1, thus regulating myocardial structure. The biallelic inactivation of Prdm16 induces severe cardiac dysfunction with post-natal lethality and hypertrophy in mice. The early pathological events that occur upon Prdm16 inactivation have not been explored.

Methods and results

This study performed in-depth pathophysiological and molecular analyses of male and female Prdm16csp1/wt mice that carry systemic, monoallelic Prdm16 gene inactivation. We systematically assessed early molecular changes through transcriptomics, proteomics, and metabolomics. Kinetic modelling of cardiac metabolism was performed in silico with CARDIOKIN. Prdm16csp1/wt mice are viable up to 8 months, develop hypoplastic hearts, and diminished systolic performance that is more pronounced in female mice. Prdm16csp1/wt cardiac tissue of both sexes showed reductions in metabolites associated with amino acid as well as glycerol metabolism, glycolysis, and the tricarboxylic acid cycle. Prdm16csp1/wt cardiac tissue revealed diminished glutathione (GSH) and increased inosine monophosphate (IMP) levels indicating oxidative stress and a dysregulated energetics, respectively. An accumulation of triacylglycerides exclusively in male Prdm16csp1/wt hearts suggests a sex-specific metabolic adaptation. Metabolic modelling using CARDIOKIN identified a reduction in fatty acid utilization in males as well as lower glucose utilization in female Prdm16csp1/wt cardiac tissue. On the level of transcripts and protein expression, Prdm16csp1/wt hearts demonstrate an up-regulation of pyridine nucleotide-disulphide oxidoreductase domain 2 (Pyroxd2) and the transcriptional regulator pre-B-cell leukaemia transcription factor interacting protein 1 (Pbxip1). The strongest concordant transcriptional up-regulation was detected for Prdm16 itself, probably through an autoregulatory mechanism.

Conclusions

Monoallelic, global Prdm16 mutation diminishes cardiac performance in Prdm16csp1/wt mice. Metabolic alterations and transcriptional dysregulation in Prdm16csp1/wt affect cardiac tissue. Female Prdm16csp1/wt mice develop a more pronounced phenotype, indicating sexual dimorphism at this early pathological window. This study suggests that metabolic dysregulation is an early event in the PRDM16 associated cardiac pathology.
Host–pathogen coevolution promotes the evolution of general, broad-spectrum resistance and reduces foreign pathogen spillover risk
Authors: Hulse Samuel V , Antonovics Janis , Hood Michael E , Bruns Emily L
Published: October 2023

Genetic variation for disease resistance within host populations can strongly impact the spread of endemic pathogens. In plants, recent work has shown that within-population variation in resistance can also affect the transmission of foreign spillover pathogens if that resistance is general. However, most hosts also possess specific resistance mechanisms that provide strong defenses against coevolved endemic pathogens. Here we use a modeling approach to ask how antagonistic coevolution between hosts and their endemic pathogen at the specific resistance locus can affect the frequency of general resistance, and therefore a host’s vulnerability to foreign pathogens. We develop a two-locus model with variable recombination that incorporates both general resistance (effective against all pathogens) and specific resistance (effective against endemic pathogens only). With coevolution, when pathogens can evolve to evade specific resistance, we find that the regions where general resistance can evolve are greatly expanded, decreasing the risk of foreign pathogen invasion. Furthermore, coevolution greatly expands the conditions that maintain polymorphisms at both resistance loci, thereby driving greater genetic diversity within host populations. This genetic diversity often leads to positive correlations between host resistance to foreign and endemic pathogens, similar to those observed in natural populations. However, if resistance loci become linked, the resistance correlations can shift to negative. If we include a third linkage-modifying locus in our model, we find that selection often favors complete linkage. Our model demonstrates how coevolutionary dynamics with an endemic pathogen can mold the resistance structure of host populations in ways that affect its susceptibility to foreign pathogen spillovers, and that the nature of these outcomes depends on resistance costs, as well as the degree of linkage between resistance genes.
Activity of novel β-lactam/β-lactamase inhibitor combinations against serine carbapenemase-producing carbapenem-resistant Pseudomonas aeruginosa
Authors: Lee Su Young , Gill Christian M , Nicolau David P ,   ERACE-PA Global Study Group, Aktas Elif , Alfouzan Wadha , Bourassa Lori , Brink Adrian , Burnham Carey-Ann D , Canton Rafael , Carmeli Yehuda , Falcone Marco , Kiffer Carlos , Marchese Anna , Martinez Octavio , Pournaras Spyros , Satlin Michael , Seifert Harald , Thabit Abrar K , Thomson Kenneth S , Villegas Maria Virginia , Wille Julia , Rezende Thais Teles Freitas , Cekin Zuhal , Malkocoglu Gulsah , Gijón Desirae , Tarakmeh Layla Abdullah , Chu Chun Yat , Opperman Christoffel Johannes , Tootla Hafsah Deepa , Moodley Clinton , Coetzee Jennifer , Vourli Sophia , Dimopoulos George , Attallah Dalya M , Tiseo Giusy , Leonildi Alessandro , Giordano Cesira , Barnini Simona , Menichetti Francesco , Di Pilato Vincenzo , Codda Giulia , Vena Antonio , Giacobbe Daniele Roberto , Westblade Lars , Cardona Armando , Curtis Lauren , Fang Ferric , Thomson Gina
Published: October 2023

Background

Antimicrobial resistance in Pseudomonas aeruginosa is complex and multifaceted. While the novel β-lactamase inhibitors (BLIs) avibactam, relebactam and vaborbactam inhibit serine-based β-lactamases, the comparative potency of the novel β-lactam (BL)/BLI combinations against serine carbapenemase-producing P. aeruginosa is unknown.

Objectives

To compare the in vitro activity of ceftazidime/avibactam, ceftazidime, imipenem/relebactam, imipenem, meropenem/vaborbactam and meropenem against serine β-lactamase-producing P. aeruginosa.

Methods

Carbapenem-resistant P. aeruginosa were collated through the Enhancing Rational Antimicrobials against Carbapenem-resistant P. aeruginosa (ERACE-PA) Global Surveillance. Isolates positive for serine-based carbapenemases were assessed. MICs were determined by broth microdilution to each novel BL/BLI and BL alone.

Results

GES was the most common carbapenemase identified (n = 59) followed by KPC (n = 8). Ceftazidime/avibactam had MIC50/MIC90 values of 4/8 mg/L and 91% of isolates were susceptible. Conversely, ceftazidime alone was active against only 3% of isolates. The MIC50/MIC90 of imipenem/relebactam were 16/>16 mg/L and 13% of all isolates were defined as susceptible. Of the KPC-producing isolates, 38% were susceptible to imipenem/relebactam, compared with 0% to imipenem. The meropenem/vaborbactam MIC50/MIC90 were >16/>16 mg/L, and 6% of isolates were susceptible, which was similar to meropenem alone (MIC50/90, >8/>8 mg/L; 3% susceptible) suggesting the addition of vaborbactam cannot overcome co-expressed, non-enzymatic resistance mechanisms.

Conclusions

Among the novel BL/BLIs, ceftazidime/avibactam displayed better in vitro activity and thus is a rational treatment option for serine carbapenemase-harbouring P. aeruginosa. While imipenem/relebactam displayed some activity, particularly against isolates with blaKPC, meropenem/vaborbactam exhibited poor activity, with MICs similar to meropenem alone.
Ownership networks and labor income
Authors: Huneeus Federico , Larrain Borja , Larrain Mauricio , Prem Mounu
Published: October 2023

We document a novel relationship between networks of firms linked through ownership (i.e., business groups) and labor income using matched employer–employee data for Chile. Business group affiliation is associated with higher wages, even after controlling for firm size and individual worker effects. The group premium is stronger for top workers; hence, group firms have higher wage dispersion. The premium remains present when comparing group firms and matched stand-alone firms, and in within-firm comparisons using transitions in and out of groups. Our results are consistent with workers reaching higher productivity and wages by leveraging their skills on the group’s organizational structure (JEL G32, J31).
The emerging roles of nitric oxide and its associated scavengers—phytoglobins—in plant symbiotic interactions
Authors: Pathak Pradeep Kumar , Yadav Nidhi , Kaladhar Vemula Chandra , Jaiswal Rekha , Kumari Aprajita , Igamberdiev Abir U , Loake Gary J , Gupta Kapuganti Jagadis
Published: October 2023

A key feature in the establishment of symbiosis between plants and microbes is the maintenance of the balance between the production of the small redox-related molecule, nitric oxide (NO), and its cognate scavenging pathways. During the establishment of symbiosis, a transition from a normoxic to a microoxic environment often takes place, triggering the production of NO from nitrite via a reductive production pathway. Plant hemoglobins [phytoglobins (Phytogbs)] are a central tenant of NO scavenging, with NO homeostasis maintained via the Phytogb–NO cycle. While the first plant hemoglobin (leghemoglobin), associated with the symbiotic relationship between leguminous plants and bacterial Rhizobium species, was discovered in 1939, most other plant hemoglobins, identified only in the 1990s, were considered as non-symbiotic. From recent studies, it is becoming evident that the role of Phytogbs1 in the establishment and maintenance of plant–bacterial and plant–fungal symbiosis is also essential in roots. Consequently, the division of plant hemoglobins into symbiotic and non-symbiotic groups becomes less justified. While the main function of Phytogbs1 is related to the regulation of NO levels, participation of these proteins in the establishment of symbiotic relationships between plants and microorganisms represents another important dimension among the other processes in which these key redox-regulatory proteins play a central role.
Identification and quantification of small exon-containing isoforms in long-read RNA sequencing data
Authors: Liu Zhen , Zhu Chenchen , Steinmetz Lars M , Wei Wu
Published: October 2023

Small exons are pervasive in transcriptomes across organisms, and their quantification in RNA isoforms is crucial for understanding gene functions. Although long-read RNA-seq based on Oxford Nanopore Technologies (ONT) offers the advantage of covering transcripts in full length, its lower base accuracy poses challenges for identifying individual exons, particularly microexons (≤ 30 nucleotides). Here, we systematically assess small exons quantification in synthetic and human ONT RNA-seq datasets. We demonstrate that reads containing small exons are often not properly aligned, affecting the quantification of relevant transcripts. Thus, we develop a local-realignment method for misaligned exons (MisER), which remaps reads with misaligned exons to the transcript references. Using synthetic and simulated datasets, we demonstrate the high sensitivity and specificity of MisER for the quantification of transcripts containing small exons. Moreover, MisER enabled us to identify small exons with a higher percent spliced-in index (PSI) in neural, particularly neural-regulated microexons, when comparing 14 neural to 16 non-neural tissues in humans. Our work introduces an improved quantification method for long-read RNA-seq and especially facilitates studies using ONT long-reads to elucidate the regulation of genes involving small exons.
MINRbase: a comprehensive database of nuclear- and mitochondrial-ribosomal-RNA-derived fragments (rRFs)
Authors: Pliatsika Venetia , Cherlin Tess , Loher Phillipe , Vlantis Panagiotis , Nagarkar Parth , Nersisyan Stepan , Rigoutsos Isidore
Published: October 2023

We describe the Mitochondrial and Nuclear rRNA fragment database (MINRbase), a knowledge repository aimed at facilitating the study of ribosomal RNA-derived fragments (rRFs). MINRbase provides interactive access to the profiles of 130 238 expressed rRFs arising from the four human nuclear rRNAs (18S, 5.8S, 28S, 5S), two mitochondrial rRNAs (12S, 16S) or four spacers of 45S pre-rRNA. We compiled these profiles by analyzing 11 632 datasets, including the GEUVADIS and The Cancer Genome Atlas (TCGA) repositories. MINRbase offers a user-friendly interface that lets researchers issue complex queries based on one or more criteria, such as parental rRNA identity, nucleotide sequence, rRF minimum abundance and metadata keywords (e.g. tissue type, disease). A ‘summary’ page for each rRF provides a granular breakdown of its expression by tissue type, disease, sex, ancestry and other variables; it also allows users to create publication-ready plots at the click of a button. MINRbase has already allowed us to generate support for three novel observations: the internal spacers of 45S are prolific producers of abundant rRFs; many abundant rRFs straddle the known boundaries of rRNAs; rRF production is regimented and depends on ‘personal attributes’ (sex, ancestry) and ‘context’ (tissue type, tissue state, disease). MINRbase is available at https://cm.jefferson.edu/MINRbase/.
Ubiquitin signaling and the proteasome drive human DNA–protein crosslink repair
Authors: Essawy Maram , Chesner Lisa , Alshareef Duha , Ji Shaofei , Tretyakova Natalia , Campbell Colin
Published: October 2023

DNA–protein crosslinks (DPCs) are large cytotoxic DNA lesions that form following exposure to chemotherapeutic drugs and environmental chemicals. Nucleotide excision repair (NER) and homologous recombination (HR) promote survival following exposure to DPC-inducing agents. However, it is not known how cells recognize DPC lesions, or what mechanisms selectively target DPC lesions to these respective repair pathways. To address these questions, we examined DPC recognition and repair by transfecting a synthetic DPC lesion comprised of the human oxoguanine glycosylase (OGG1) protein crosslinked to double-stranded M13MP18 into human cells. In wild-type cells, this lesion is efficiently repaired, whereas cells deficient in NER can only repair this lesion if an un-damaged homologous donor is co-transfected. Transfected DPC is subject to rapid K63 polyubiquitination. In NER proficient cells, the DPC is subject to K48 polyubiquitination, and is removed via a proteasome-dependent mechanism. In NER-deficient cells, the DNA–conjugated protein is not subject to K48 polyubiquitination. Instead, the K63 tag remains attached, and is only lost when a homologous donor molecule is present. Taken together, these results support a model in which selective addition of polyubiquitin chains to DNA-crosslinked protein leads to selective recruitment of the proteasome and the cellular NER and recombinational DNA repair machinery.
Anisodine hydrobromide injection in the treatment of acute ischemic stroke: A protocol for systematic review and meta-analysis
Authors: Liu Yunlu , Wang Yang , Wan Feng
Published: October 2023

Background:

Acute ischemic stroke (AIS) is a common disease of the central nervous system, with high mortality, and disability rates. Anisodine hydrobromide (Ani) injection has been used clinically for the treatment of AIS in China. However, no systematic review and meta-analysis have provided rigorous evidence for the clinical use of Ani injection in the treatment of AIS. This study aims to assess the efficacy and safety of Ani injection in the treatment of AIS.

Methods:

Following databases will be searched to identify eligible articles: CNKI, VIP, Wanfang, Chinese Biomedical Literature Database, EMBASE, PubMed, Cochrane, and Web of Science. All databases will be searched from their inception to May, 2023. RevMan software will be used for data analysis.

Results:

The results from meta-synthesis and descriptive analysis of National Institute of Health Stroke Scale, modified Rankin scale, Barthel Index, CT parameters, clinical efficacy rate, and adverse reactions of included articles will provide latest evidence.

Conclusion:

Findings of this study will provide a solid evidence-based basis for the rational and precise application of Ani injection for the treatment of AIS.