bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct observations of X-rays produced by upward positive lightning
Authors: Oregel-Chaumont Toma , Šunjerga Antonio , Hettiarachchi Pasan , Cooray Vernon , Rubinstein Marcos , Rachidi Farhad
Published: April 2024

X-rays have been observed in natural downward cloud-to-ground lightning for over 20 years and in rocket-triggered lightning for slightly less. In both cases, this energetic radiation has been detected during the stepped and dart leader phases of downward negative flashes. More recently, X-rays have also been reported during the dart leader phase of upward negative flashes. In this study, we present the observations of four upward positive lightning flashes from the Säntis Tower (2.5 km ASL) in Switzerland. These consist of the simultaneous records of electric current passing through the tower, and electric field strength and X-ray flux 20 m from the tower base. One of the flashes was captured by a high-speed camera operating at 24,000 frames per second, stills from which are also presented. We detected X-rays during the initial phase of upward negative leader propagation, which can be associated with the leader-stepping process from electric field and current waveforms. To the best of our knowledge, this is the first time that such measurements are reported in the literature. The obtained time-synchronised data confirm that the X-ray emissions detected are associated with the initial steps of the upward negative leader. The frequency and energy of X-ray pulses appear to decrease as functions of time, with pulses disappearing altogether within the first millisecond of the leader initiation. X-ray emission also appears to be correlated with the maximum current-derivative and the electric field change of leader steps, consistent with cold electron runaway. These observations contribute to improving our understanding of upward lightning, which is a primary source of damage to tall structures such as wind turbines and telecommunications towers, as well as aircraft during takeoff and landing.
Research on the hydraulic support face guard mechanism and coupling characteristic of rib spalling in large mining heights
Authors: Zeng Qingliang , Ma Xiaoqi , Wan Lirong , Zhu Yanpeng , Yue Yanping
Published: April 2024

In view of the problem of poor coupling adaptability and easy rib spalling of coal wall in large mining height comprehensive mining, based on the effective inhibition effect of face guard mechanism on coal wall spalling, the structural characteristics and bearing capacity of different structural forms of the face guard mechanism are compared and analyzed. According to the surrounding rock adaptability of the face guard mechanism, established a numerical analysis model for rigid-flexible coupling of the face guard mechanism under different spalling forms. In order to accurately simulate the stress state of the protective mechanism, a variable stiffness spring damping system is used to replace the hydraulic cylinder. The load-bearing performance and response characteristics of the face guard mechanism under rib spalling coupling conditions were analyzed by applying uniform normal load and impact load to the face guard. The findings indicated that, the integral-type face guard mechanism has a better effect on suppressing rib spalling. When the face guard mechanism bears the static load of the coal wall, the entire response process of the face guard jack can be divided into three stages: initial support, increasing resistance bearing, constant resistance bearing; both the impact load position and the coupling state of the rib spalling will affect the characteristics of force transmission at the face guard mechanism’s hinge point, the hinge point between the extensible canopy and the primary face guard is most sensitive to biased load. The research results can provide reference for optimizing the face guard mechanism of large mining height hydraulic support and improving the reliability of coal wall support.
Outcome of right ventricular microaxial pump support in patients undergoing cardiac surgery
Authors: Marta Medina , Zada Mahmoud , Theuerkauf Nils , Duerr Georg Daniel , Zimmer Sebastian , Treede Hendrik , Oezkur Mehmet
Published: April 2024

Right ventricular failure (RVF) after cardiac surgery is associated with an in-hospital mortality rate of up to 75%. Microaxial flow pumps are one of the mechanical circulatory supports (MCS) options available for the treatment of RVF, however the specifics of timing and indication for MCS, as well as predictors for survival, remain unclear due to a dearth of published data. We evaluated the clinical outcome of patients treated with Impella-RP for predictors of mortality and the hemodynamic effects of the pump. This is a single-center retrospective observational study involving adult patients who underwent cardiac surgery with cardiopulmonary bypass between January 2019 and December 2020 in cardiac surgery and required therapeutic management of RVF with an Impella-RP. Overall, 18 patients were included and analyzed for factors that could be associated with mortality, or that could be predictors of patient outcomes for this population. Treatment of RVF with Impella-RP improved the patient hemodynamics significantly and had a survival rate of 61% within 30 days. Patients with isolated CABG or better liver function before implantation had a better survival rate, which may indicate that underlying disease and timing of implantation are significant for successful treatment of RVF.
Oriented feature pyramid network for small and dense wheat heads detection and counting
Authors: Yu Junwei , Chen Weiwei , Liu Nan , Fan Chao
Published: April 2024

Wheat head detection and counting using deep learning techniques has gained considerable attention in precision agriculture applications such as wheat growth monitoring, yield estimation, and resource allocation. However, the accurate detection of small and dense wheat heads remains challenging due to the inherent variations in their size, orientation, appearance, aspect ratios, density, and the complexity of imaging conditions. To address these challenges, we propose a novel approach called the Oriented Feature Pyramid Network (OFPN) that focuses on detecting rotated wheat heads by utilizing oriented bounding boxes. In order to facilitate the development and evaluation of our proposed method, we introduce a novel dataset named the Rotated Global Wheat Head Dataset (RGWHD). This dataset is constructed by manually annotating images from the Global Wheat Head Detection (GWHD) dataset with oriented bounding boxes. Furthermore, we incorporate a Path-aggregation and Balanced Feature Pyramid Network into our architecture to effectively extract both semantic and positional information from the input images. This is achieved by leveraging feature fusion techniques at multiple scales, enhancing the detection capabilities for small wheat heads. To improve the localization and detection accuracy of dense and overlapping wheat heads, we employ the Soft-NMS algorithm to filter the proposed bounding boxes. Experimental results indicate the superior performance of the OFPN model, achieving a remarkable mean average precision of 85.77% in oriented wheat head detection, surpassing six other state-of-the-art models. Moreover, we observe a substantial improvement in the accuracy of wheat head counting, with an accuracy of 93.97%. This represents an increase of 3.12% compared to the Faster R-CNN method. Both qualitative and quantitative results demonstrate the effectiveness of the proposed OFPN model in accurately localizing and counting wheat heads within various challenging scenarios.
Risk factors for liver dysfunction and their clinical importance after gastric cancer surgery
Authors: Sumiyoshi Shutaro , Kubota Takeshi , Ohashi Takuma , Nishibeppu Keiji , Kiuchi Jun , Shimizu Hiroki , Arita Tomohiro , Yamamoto Yusuke , Konishi Hirotaka , Morimura Ryo , Kuriu Yoshiaki , Shiozaki Atsushi , Ikoma Hisashi , Fujiwara Hitoshi , Otsuji Eigo
Published: April 2024

Postoperative hepatobiliary enzyme abnormalities often present as postoperative liver dysfunction in patients with gastric cancer (GC). This study aimed to identify the risk factors for postoperative liver dysfunction and their clinical impact after GC surgery. We retrospectively analyzed the data of 124 patients with GC who underwent laparoscopic or robotic surgery at Kyoto Prefectural University of Medicine between 2017 and 2019. Twenty (16.1%) patients with GC developed postoperative liver dysfunction (Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 ≥ Grade 3). Univariate analyses identified robotic surgery as a risk factor for postoperative liver dysfunction (P = 0.005). There was no correlation between the postoperative liver dysfunction status and postoperative complications or postoperative hospital stays. Patients with postoperative liver dysfunction did not have significantly worse overall survival (P = 0.296) or recurrence-free survival (P = 0.565) than those without postoperative liver dysfunction. Robotic surgery is a risk factor for postoperative liver dysfunction; however, postoperative liver dysfunction does not affect short or long-term outcomes.
Hal-Py-SO3H as a novel and recyclable catalyst for highly efficient synthesis of xanthene and spiropyran derivatives
Authors: Abdolmaleki Mohammad , Daraie Mansoureh , Mirjafary Zohreh
Published: April 2024

The aim of this research is to synthesize a new sulfonic acid catalyst based on halloysite nanotubes (Hal-Py-SO3H) and characterize it as a solid acid nanocatalyst by various analytical techniques such as Fourier-Transformed Infrared spectroscopy (FTIR), Thermal gravimetric Analysis (TGA), X-ray Diffraction (XRD) analysis, Scanning Electron Microscopy (SEM), Vibrating Energy-Dispersive X-ray analysis (EDX), Transmission electron microscopy (TEM) and X-ray atomic mapping. Furthermore, this new catalyst was evaluated in synthesizing spiropyran derivatives via multicomponent reactions (MCRs) and Xanthen derivatives under environmentally sustainable conditions. The main advantages of this approach include green conditions, excellent yields, quick reaction rates, and ease of preparation. Additionally it was observed that the catalyst exhibited robust stability even after multiple recycling processes, indicating its potential for practical applications in sustainable chemical transformations.
Utility of oligonucleotide in upregulating circular RNA production in a cellular model
Authors: Ni Lu , Yamada Takeshi , Nakatani Kazuhiko
Published: April 2024

Circular RNAs (circRNAs), are a covalently closed, single-stranded RNA without 5′- and 3′-termini, commonly stem from the exons of precursor mRNAs (pre-mRNAs). They have recently garnered interest, with studies uncovering their pivotal roles in regulating various aspects of cell functions and disease progressions. A notable feature of circRNA lies in the mechanism of its biogenesis involving a specialized form of splicing: back-splicing. A splicing process that relies on interactions between introns flanking the circularizing exon to bring the up and downstream splice sites in proximity through the formation of a prerequisite hairpin structure, allowing the spliceosomes to join the two splice sites together to produce a circular RNA molecule. Based on this mechanism, we explored the feasibility of facilitating the formation of such a prerequisite hairpin structure by utilizing a newly designed oligonucleotide, CircuLarIzation Promoting OligoNucleotide (CLIP-ON), to promote the production of circRNA in cells. CLIP-ON was designed to hybridize with and physically bridge two distal sequences in the flanking introns of the circularizing exons. The feasibility of CLIP-ON was confirmed in HeLa cells using a model pre-mRNA, demonstrating the applicability of CLIP-ON as a trans-acting modulator to upregulate the production of circRNAs in a cellular environment.
Enhancing astaxanthin biosynthesis and pathway expansion towards glycosylated C40 carotenoids by Corynebacterium glutamicum
Authors: Göttl Vanessa L. , Meyer Florian , Schmitt Ina , Persicke Marcus , Peters-Wendisch Petra , Wendisch Volker F. , Henke Nadja A.
Published: April 2024

Astaxanthin, a versatile C40 carotenoid prized for its applications in food, cosmetics, and health, is a bright red pigment with powerful antioxidant properties. To enhance astaxanthin production in Corynebacterium glutamicum, we employed rational pathway engineering strategies, focused on improving precursor availability and optimizing terminal oxy-functionalized C40 carotenoid biosynthesis. Our efforts resulted in an increased astaxanthin precursor supply with 1.5-fold higher β-carotene production with strain BETA6 (18 mg g−1 CDW). Further advancements in astaxanthin production were made by fine-tuning the expression of the β-carotene hydroxylase gene crtZ and β-carotene ketolase gene crtW, yielding a nearly fivefold increase in astaxanthin (strain ASTA**), with astaxanthin constituting 72% of total carotenoids. ASTA** was successfully transferred to a 2 L fed-batch fermentation with an enhanced titer of 103 mg L−1 astaxanthin with a volumetric productivity of 1.5 mg L−1 h−1. Based on this strain a pathway expansion was achieved towards glycosylated C40 carotenoids under heterologous expression of the glycosyltransferase gene crtX. To the best of our knowledge, this is the first time astaxanthin-β-d-diglucoside was produced with C. glutamicum achieving high titers of microbial C40 glucosides of 39 mg L−1. This study showcases the potential of pathway engineering to unlock novel C40 carotenoid variants for diverse industrial applications.
Investigating cortical activity during cybersickness by fNIRS
Authors: Yeo Sang Seok , Park Seo Yoon , Yun Seong Ho
Published: April 2024

This study investigated brain responses during cybersickness in healthy adults using functional near-infrared spectroscopy (fNIRS). Thirty participants wore a head-mounted display and observed a virtual roller coaster scene that induced cybersickness. Cortical activation during the virtual roller coaster task was measured using fNIRS. Cybersickness symptoms were evaluated using a Simulator Sickness Questionnaire (SSQ) administered after the virtual rollercoaster. Pearson correlations were performed for cybersickness symptoms and the beta coefficients of hemodynamic responses. The group analysis of oxyhemoglobin (HbO) and total hemoglobin (HbT) levels revealed deactivation in the bilateral angular gyrus during cybersickness. In the Pearson correlation analyses, the HbO and HbT beta coefficients in the bilateral angular gyrus had a significant positive correlation with the total SSQ and disorientation. These results indicated that the angular gyrus was associated with cybersickness. These findings suggest that the hemodynamic response in the angular gyrus could be a biomarker for evaluating cybersickness symptoms.
The autophagy inhibitor NSC185058 suppresses mTORC1-mediated protein anabolism in cultured skeletal muscle
Authors: Ryan Patrick J. , Uranga Selina , Stanelle Sean T. , Lewis Megan H. , O’Reilly Colleen L. , Cardin Jessica M. , Deaver J. William , Morton Aaron B. , Fluckey James D.
Published: April 2024

The mammalian target of rapamycin (mTOR), and specifically the mTOR complex 1 (mTORC1) is the central regulator of anabolism in skeletal muscle. Among the many functions of this kinase complex is the inhibition of the catabolic process of autophagy; however, less work has been done in investigating the role of autophagy in regulating mTORC1 signaling. Using an in vitro model to better understand the pathways involved, we activated mTORC1 by several different means (growth factors, leucine supplementation, or muscle contraction), alone or with the autophagy inhibitor NSC185058. We found that inhibiting autophagy with NSC185058 suppresses mTORC1 activity, preventing any increase in cellular protein anabolism. These decrements were the direct result of action on the mTORC1 kinase, which we demonstrate, for the first time, cannot function when autophagy is inhibited by NSC185058. Our results indicate that, far from being a matter of unidirectional action, the relationship between mTORC1 and the autophagic cascade is more nuanced, with autophagy serving as an mTORC1 input, and mTORC1 inhibition of autophagy as a form of homeostatic feedback to regulate anabolic signaling. Future studies of cellular metabolism will have to consider this fundamental intertwining of protein anabolism and catabolism, and how it ultimately serves to regulate muscle proteostasis.
Unraveling the rapid CO2 mineralization experiment using the Paraná flood basalts of South America
Authors: Ferreira Alanielson , Santos Roberto Ventura , de Almeida Tarcísio Silva , Camargo Maryene Alves , Filho José André , Miranda Caetano Rodrigues , dos Passos Saulo de Tarso Alves , Baptista Alvaro David Torrez , Tassinari Colombo Celso Gaeta , Rubio Valentina Alzate , Capistrano Gabriel Godinho
Published: April 2024

CO2 capture and storage in geological reservoirs have the potential to significantly mitigate the effects of anthropogenic gas emissions on global climate. Here, we report the results of the first laboratory experiments of CO2 injection in continental flood basalts of South America. The results show that the analyzed basalts have a mineral assemblage, texture and composition that efficiently allows a fast carbonate precipitation that starts 72 h after injection. Based on the availability of calcium, chemical monitoring indicates an estimated CO2 storage of ~ 75%. The carbonate precipitation led to the precipitation of aragonite (75.9%), dolomite (19.6%), and calcite (4.6%).
The genetic status and rescue measure for a geographically isolated population of Amur tigers
Authors: Ning Yao , Liu Dongqi , Gu Jiayin , Zhang Yifei , Roberts Nathan James , Guskov Valentin Yu , Sun Jiale , Liu Dan , Gong Ming , Qi Jinzhe , He Zhijian , Shi Chunmei , Jiang Guangshun
Published: April 2024

The Amur tiger is currently confronted with challenges of anthropogenic development, leading to its population becoming fragmented into two geographically isolated groups: smaller and larger ones. Small and isolated populations frequently face a greater extinction risk, yet the small tiger population’s genetic status and survival potential have not been assessed. Here, a total of 210 samples of suspected Amur tiger feces were collected from this small population, and the genetic background and population survival potentials were assessed by using 14 microsatellite loci. Our results demonstrated that the mean number of alleles in all loci was 3.7 and expected heterozygosity was 0.6, indicating a comparatively lower level of population genetic diversity compared to previously reported studies on other subspecies. The genetic estimates of effective population size (Ne) and the Ne/N ratio were merely 7.6 and 0.152, respectively, representing lower values in comparison to the Amur tiger population in Sikhote-Alin (the larger group). However, multiple methods have indicated the possibility of genetic divergence within our isolated population under study. Meanwhile, the maximum kinship recorded was 0.441, and the mean inbreeding coefficient stood at 0.0868, both of which are higher than those observed in other endangered species, such as the African lion and the grey wolf. Additionally, we have identified a significant risk of future extinction if the lethal equivalents were to reach 6.26, which is higher than that of other large carnivores. Further, our simulation results indicated that an increase in the number of breeding females would enhance the prospects of this population. In summary, our findings provide a critical theoretical basis for further bailout strategies concerning Amur tigers.
The new record of drought and warmth in the Amazon in 2023 related to regional and global climatic features
Authors: Espinoza Jhan-Carlo , Jimenez Juan Carlos , Marengo José Antonio , Schongart Jochen , Ronchail Josyane , Lavado-Casimiro Waldo , Ribeiro João Vitor M.
Published: April 2024

In 2023 Amazonia experienced both historical drought and warm conditions. On October 26th 2023 the water levels at the port of Manaus reached its lowest record since 1902 (12.70 m). In this region, October monthly maximum and minimum temperature anomalies also surpassed previous record values registered in 2015 (+ 3 °C above the normal considering the 1981–2020 average). Here we show that this historical dry and warm situation in Amazonia is associated with two main atmospheric mechanisms: (i) the November 2022–February 2023 southern anomaly of vertical integrated moisture flux (VIMF), related to VIMF divergence and extreme rainfall deficit over southwestern Amazonia, and (ii) the June–August 2023 downward motion over northern Amazonia related to extreme rainfall deficit and warm conditions over this region. Anomalies of both atmospheric mechanisms reached record values during this event. The first mechanism is significantly correlated to negative sea surface temperature (SST) anomalies in the equatorial Pacific (November–February La Niña events). The second mechanism is significantly correlated to positive SST anomalies in the equatorial Pacific, related to the impacts of June–September El Niño on the Walker Circulation. While previous extreme droughts were linked to El Niño (warmer North Tropical Atlantic SST) during the austral summer (winter and spring), the transition from La Niña 2022–23 to El Niño 2023 appears to be a key climatic driver in this record-breaking dry and warm situation, combined to a widespread anomalous warming over the worldwide ocean.
Gender-specific link between sleep quality and body composition components: a cross-sectional study on the elderly
Authors: Kohanmoo Ali , Kazemi Asma , Zare Morteza , Akhlaghi Masoumeh
Published: April 2024

Sleep duration has been associated with overweight/obesity. Since sleep quality and body composition alter during aging, we conducted this study to determine if sleep quality is linked to body composition components in elderly people. This is a cross-sectional study conducted on 305 Iranian community-dwelling elderly aged ≥ 65 years. Sleep quality and body composition components were evaluated using Pittsburgh sleep quality index and bioelectric impedance analysis, respectively. The association of sleep quality and body composition components was examined using linear regression analysis. The prevalence of poor sleep quality and overweight/obesity was 48.9% and 54.4% in men and 77.0% and 79.3% in women, respectively. Women had significantly higher scores in most PSQI items than men, indicating their worse sleep quality compared to men. Women also had significantly higher body mass index (BMI), body fat percentage, and visceral adipose tissue and lower skeletal muscle and fat-free mass percentages than men. In the adjusted regression model, men showed positive associations between the third tertile of poor sleep quality and BMI (B = 1.35; 95% CI 0.08–2.61) and waist circumference (B = 4.14; 95% CI 0.39–7.89), but they did not demonstrate an association between sleep quality and body composition components. In the adjusted regression model for women, there were positive associations for BMI (B = 1.21; 95% CI 0.34–2.07), waist circumference (B = 2.95; 95% CI 0.99–4.91), body fat percentage (B = 2.75; 95% CI 1.06–4.45), and visceral adipose tissue (B = 7.80; 95% CI 1.73–13.87); also there were negative associations for skeletal muscle (B =  − 1.40; 95% CI − 2.39 – – 0.41) and fat-free mass (B =  − 2.76; 95% CI − 4.46 – –1.07) percentages. Except for waist circumference, other variables differed between men and women (P < 0.001). Weight management, prevention of muscle wasting, and improvement of sleep quality should be considered in a consortium when designing healthcare strategies for the elderly.
Association between dietary inflammation index and asthma COPD overlap
Authors: Wang Shidong , Wang Yaokun , Hu Xiaoyan , Lu Linmin
Published: April 2024

There are few studies on the relationship between dietary habits and asthma–COPD overlap (ACO). In this study, we aimed to investigate the association between dietary inflammation index (DII) score and ACO. Data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2020. The DII score was first calculated and the demographic characteristics of the grouping based on the DII quartile were assessed. The weighted logistic regression model was used to study the relationship between DII and ACO. Subgroup analysis was used to further explore the differences in different subgroups. Restricted cubic spline (RCS) plot was used to show the general trend of DII score and disease risk, and threshold effect analysis was used to determine the inflection point. In a comparison of baseline characteristics, the highest ACO prevalence was found in the fourth quartile array of people in DII. An adjusted weighted logistic regression model showed that DII was positively correlated with the incidence of ACO. Subgroup analysis showed that the association was more pronounced in women, non-Hispanics, people with cardiovascular disease, and people without diabetes. The RCS graph shows that overall, the risk of ACO increases with the increase of DII score. Threshold effect analysis showed that the inflection point was 3.779, and the risk was more significant after the DII score was greater than the inflection point value (OR 2.001, 95% CI 1.334–3.001, P < 0.001). Higher DII scores were positively associated with ACO risk. These results further support diet as an intervention strategy for ACO prevention and treatment.
Expression of GCaMP6s in the dentate gyrus induces tonic–clonic seizures
Authors: Teng Sasa , Wang Wanqi , Wen Jia Jun Joel , Wang Jingxuan , Turi Gergely F. , Peng Yueqing
Published: April 2024

GCaMP is a genetically encoded calcium indicator (GECI) widely used in neuroscience research. It measures intracellular Ca2+ level by fluorescence changes as it directly binds to Ca2+. In this process, the effect of this calcium buffer on the intracellular calcium signaling and cell physiology is often not taken into consideration. However, growing evidence from calcium imaging studies shows GCaMP expression under certain conditions can generate aberrant activity, such as seizures. In this study, we examined the effect of GCaMP6 expression in the dentate gyrus (DG) on epileptogenesis. We found that viral expression of GCaMP6s but not GCaMP6f in the DG induces tonic–clonic seizures several weeks after viral injection. Cell-type specific expression of GCaMP6s revealed the granule cells (GCs) as the key player in GCaMP6s-induced epilepsy. Finally, by using slice electrophysiology, we demonstrated that GCaMP6s expression increases neuronal excitability in the GCs. Together, this study highlights the ability of GCaMP6s in DG-associated epileptogenesis.
Improvement in variance estimation using transformed auxiliary variable under simple random sampling
Authors: Ali Hameed , Asim Syed Muhammad , Ijaz Muhammad , Zaman Tolga , Iftikhar Soofia
Published: April 2024

This paper offers a novel approach to formulate efficient ratio estimator of the population variance using a transformed auxiliary variable. The impact of transformation on auxiliary information has also been discussed. It is observed that incorporating a transformed auxiliary variable result in a high gain in efficiency. Theoretical properties of the newly developed estimators have been derived. The empirical and simulation studies show that the suggested estimators outperformed the existing estimators.
Reversing valproic acid-induced autism-like behaviors through a combination of low-frequency repeated transcranial magnetic stimulation and superparamagnetic iron oxide nanoparticles
Authors: Afshari Masoud , Gharibzadeh Shahriar , Pouretemad Hamidreza , Roghani Mehrdad
Published: April 2024

Transcranial magnetic stimulation (TMS) is a neurostimulation device used to modulate brain cortex activity. Our objective was to enhance the therapeutic effectiveness of low-frequency repeated TMS (LF-rTMS) in a rat model of autism spectrum disorder (ASD) induced by prenatal valproic acid (VPA) exposure through the injection of superparamagnetic iron oxide nanoparticles (SPIONs). For the induction of ASD, we administered prenatal VPA (600 mg/kg, I.P.) on the 12.5th day of pregnancy. At postnatal day 30, SPIONs were injected directly into the lateral ventricle of the brain. Subsequently, LF-rTMS treatment was applied for 14 consecutive days. Following the treatment period, behavioral analyses were conducted. At postnatal day 60, brain tissue was extracted, and both biochemical and histological analyses were performed. Our data revealed that prenatal VPA exposure led to behavioral alterations, including changes in social interactions, increased anxiety, and repetitive behavior, along with dysfunction in stress coping strategies. Additionally, we observed reduced levels of SYN, MAP2, and BDNF. These changes were accompanied by a decrease in dendritic spine density in the hippocampal CA1 area. However, LF-rTMS treatment combined with SPIONs successfully reversed these dysfunctions at the behavioral, biochemical, and histological levels, introducing a successful approach for the treatment of ASD.
Cobalt complexes modulate plasmid conjugation in Escherichia coli and Klebsiella pneumoniae
Authors: Alav Ilyas , Pordelkhaki Parisa , de Resende Pedro Ernesto , Partington Hannah , Gibbons Simon , Lord Rianne M. , Buckner Michelle M. C.
Published: April 2024

Antimicrobial resistance genes (ARG), such as extended-spectrum β-lactamase (ESBL) and carbapenemase genes, are commonly carried on plasmids. Plasmids can transmit between bacteria, disseminate globally, and cause clinically important resistance. Therefore, targeting plasmids could reduce ARG prevalence, and restore the efficacy of existing antibiotics. Cobalt complexes possess diverse biological activities, including antimicrobial and anticancer properties. However, their effect on plasmid conjugation has not been explored yet. Here, we assessed the effect of four previously characterised bis(N-picolinamido)cobalt(II) complexes lacking antibacterial activity on plasmid conjugation in Escherichia coli and Klebsiella pneumoniae. Antimicrobial susceptibility testing of these cobalt complexes confirmed the lack of antibacterial activity in E. coli and K. pneumoniae. Liquid broth and solid agar conjugation assays were used to screen the activity of the complexes on four archetypical plasmids in E. coli J53. The cobalt complexes significantly reduced the conjugation of RP4, R6K, and R388 plasmids, but not pKM101, on solid agar in E. coli J53. Owing to their promising activity, the impact of cobalt complexes was tested on the conjugation of fluorescently tagged extended-spectrum β-lactamase encoding pCTgfp plasmid in E. coli and carbapenemase encoding pKpQILgfp plasmid in K. pneumoniae, using flow cytometry. The complexes significantly reduced the conjugation of pKpQILgfp in K. pneumoniae but had no impact on pCTgfp conjugation in E. coli. The cobalt complexes did not have plasmid-curing activity, suggesting that they target conjugation rather than plasmid stability. To our knowledge, this is the first study to report reduced conjugation of clinically relevant plasmids with cobalt complexes. These cobalt complexes are not cytotoxic towards mammalian cells and are not antibacterial, therefore they could be optimised and employed as inhibitors of plasmid conjugation.
Enhanced plant-derived vesicles for nucleotide delivery for cancer therapy
Authors: Corvigno Sara , Liu Yuan , Bayraktar Emine , Stur Elaine , Bayram Nazende Nur , Ahumada Adrian Lankenau , Nagaraju Supriya , Rodriguez-Aguayo Cristian , Chen Hu , Vu Thanh Chung , Wen Yunfei , Liang Han , Zhao Li , Lee Sanghoon , Lopez-Berestein Gabriel , Sood Anil K.
Published: April 2024

Small RNAs (microRNAs [miRNAs] or small interfering RNAs [siRNAs]) are effective tools for cancer therapy, but many of the existing carriers for their delivery are limited by low bioavailability, insufficient loading, impaired transport across biological barriers, and low delivery into the tumor microenvironment. Extracellular vesicle (EV)–based communication in mammalian and plant systems is important for many physiological and pathological processes, and EVs show promise as carriers for RNA interference molecules. However, some fundamental issues limit their use, such as insufficient cargo loading and low potential for scaling production. Plant-derived vesicles (PDVs) are membrane-coated vesicles released in the apoplastic fluid of plants that contain biomolecules that play a role in several biological mechanisms. Here, we developed an alternative approach to deliver miRNA for cancer therapy using PDVs. We isolated vesicles from watermelon and formulated a hybrid, exosomal, polymeric system in which PDVs were combined with a dendrimer bound to miRNA146 mimic. Third generation PAMAM was chosen due to its high branching structure and versatility for loading molecules of interest. We performed several in vivo experiments to demonstrate the therapeutic efficacy of our compound and explored in vitro biological mechanisms underlying the anti-tumor effects of miRNA146, which are mostly related to its anti-angiogenic activity.
Exploration of the two-dimensional transition metal phosphide MoP2 as anode for Na/K ion batteries
Authors: Jin Junjie , Schwingenschlögl Udo
Published: April 2024

Transition metal phosphides are regarded to be potential anode materials for alkali metal ion batteries with abundant availability of the constituent elements. However, the volume changes and resulting structure deterioration during the charge-discharge process are challenges. Using evolutionary search combined with ab initio calculations, we discover a dynamically, thermally, and mechanically stable MoP2 monolayer, which turns out to be an excellent anode material for Na-ion batteries providing a high specific capacity of 339 mA h g−1, low diffusion barrier of 0.12 eV, and low open-circuit voltage of 0.48 V. The volume expansion (125%) is found to be decisively smaller than in the case of black phosphorus (443%), for example.
Synaptic ribbon dynamics after noise exposure in the hearing cochlea
Authors: Ismail Mohamad Noura , Santra Peu , Park Yesai , Matthews Ian R. , Taketa Emily , Chan Dylan K.
Published: April 2024

Moderate noise exposure induces cochlear synaptopathy, the loss of afferent ribbon synapses between cochlear hair cells and spiral ganglion neurons, which is associated with functional hearing decline. Prior studies have demonstrated noise-induced changes in the distribution and number of synaptic components, but the dynamic changes that occur after noise exposure have not been directly visualized. Here, we describe a live imaging model using RIBEYE-tagRFP to enable direct observation of pre-synaptic ribbons in mature hearing mouse cochleae after synaptopathic noise exposure. Ribbon number does not change, but noise induces an increase in ribbon volume as well as movement suggesting unanchoring from synaptic tethers. A subgroup of basal ribbons displays concerted motion towards the cochlear nucleus with subsequent migration back to the cell membrane after noise cessation. Understanding the immediate dynamics of synaptic damage after noise exposure may facilitate identification of specific target pathways to treat cochlear synaptopathy.
Functional and structural reorganization in brain tumors: a machine learning approach using desynchronized functional oscillations
Authors: Falcó-Roget Joan , Cacciola Alberto , Sambataro Fabio , Crimi Alessandro
Published: April 2024

Neuroimaging studies have allowed for non-invasive mapping of brain networks in brain tumors. Although tumor core and edema are easily identifiable using standard MRI acquisitions, imaging studies often neglect signals, structures, and functions within their presence. Therefore, both functional and diffusion signals, as well as their relationship with global patterns of connectivity reorganization, are poorly understood. Here, we explore the functional activity and the structure of white matter fibers considering the contribution of the whole tumor in a surgical context. First, we find intertwined alterations in the frequency domain of local and spatially distributed resting-state functional signals, potentially arising within the tumor. Second, we propose a fiber tracking pipeline capable of using anatomical information while still reconstructing bundles in tumoral and peritumoral tissue. Finally, using machine learning and healthy anatomical information, we predict structural rearrangement after surgery given the preoperative brain network. The generative model also disentangles complex patterns of connectivity reorganization for different types of tumors. Overall, we show the importance of carefully designing studies including MR signals within damaged brain tissues, as they exhibit and relate to non-trivial patterns of both structural and functional (dis-)connections or activity.
Allosteric activation unveils protein-mass modulation of ATP phosphoribosyltransferase product release
Authors: Read Benjamin J. , Mitchell John B. O. , da Silva Rafael G.
Published: April 2024

Heavy-isotope substitution into enzymes slows down bond vibrations and may alter transition-state barrier crossing probability if this is coupled to fast protein motions. ATP phosphoribosyltransferase from Acinetobacter baumannii is a multi-protein complex where the regulatory protein HisZ allosterically enhances catalysis by the catalytic protein HisGS. This is accompanied by a shift in rate-limiting step from chemistry to product release. Here we report that isotope-labelling of HisGS has no effect on the nonactivated reaction, which involves negative activation heat capacity, while HisZ-activated HisGS catalytic rate decreases in a strictly mass-dependent fashion across five different HisGS masses, at low temperatures. Surprisingly, the effect is not linked to the chemical step, but to fast motions governing product release in the activated enzyme. Disruption of a specific enzyme-product interaction abolishes the isotope effects. Results highlight how altered protein mass perturbs allosterically modulated thermal motions relevant to the catalytic cycle beyond the chemical step.
Superconducting diode effect sign change in epitaxial Al-InAs Josephson junctions
Authors: Lotfizadeh Neda , Schiela William F. , Pekerten Barış , Yu Peng , Elfeky Bassel Heiba , Strickland William M. , Matos-Abiague Alex , Shabani Javad
Published: April 2024

There has recently been a surge of interest in studying the superconducting diode effect (SDE) partly due to the possibility of uncovering the intrinsic properties of a material system. A change of sign of the SDE at finite magnetic field has previously been attributed to different mechanisms. Here, we observe the SDE in epitaxial Al-InAs Josephson junctions with strong Rashba spin-orbit coupling (SOC). We show that this effect strongly depends on the orientation of the in-plane magnetic field. In the presence of a strong magnetic field, we observe a change of sign in the SDE. Simulation and measurement of supercurrent suggest that depending on the superconducting widths, WS, this sign change may not necessarily be related to 0–π or topological transitions. We find that the strongest sign change in junctions with narrow WS is consistent with SOC-induced asymmetry of the critical current under magnetic-field inversion, while in wider WS, the sign reversal could be related to 0–π transitions and topological superconductivity.
Activation of telecom emitters in silicon upon ion implantation and ns pulsed laser annealing
Authors: Andrini Greta , Zanelli Gabriele , Ditalia Tchernij Sviatoslav , Corte Emilio , Nieto Hernández Elena , Verna Alessio , Cocuzza Matteo , Bernardi Ettore , Virzì Salvatore , Traina Paolo , Degiovanni Ivo P. , Genovese Marco , Olivero Paolo , Forneris Jacopo
Published: April 2024

Recent demonstrations of optically active telecom emitters show that silicon is a compelling candidate for solid-state quantum photonic platforms. In particular, the fabrication of a defect known as the G center has been shown in carbon-rich silicon upon conventional thermal annealing. However, the high-yield controlled fabrication of these emitters at the wafer scale still requires the identification of a suitable thermodynamic pathway enabling its activation following ion implantation. Here we demonstrate the activation of G centers in high-purity silicon substrates upon nanosecond pulsed laser annealing. The proposed method enables non-invasive, localized activation of G centers by the supply of short non-stationary pulses, thus overcoming the limitations of conventional rapid thermal annealing related to the structural metastability of the emitters. A finite-element analysis highlights the strong non-stationarity of the technique, offering radically different defect-engineering capabilities with respect to conventional longer thermal treatments, paving the way to the direct and controlled fabrication of emitters embedded in integrated photonic circuits and waveguides.
Exacerbated summer European warming not captured by climate models neglecting long-term aerosol changes
Authors: Schumacher Dominik L. , Singh Jitendra , Hauser Mathias , Fischer Erich M. , Wild Martin , Seneviratne Sonia I.
Published: April 2024

In much of western-central Europe, summer temperatures have surged three times faster than the global mean warming since 1980, yet this is not captured by most climate model simulations. Here we disentangle this warming into thermodynamic and circulation-induced contributions, and show that the latter is the main reason why numerically simulated warming is weaker than observed. Crucially, regional climate models from the Coordinated Regional Downscaling Experiment with constant aerosol forcings systematically show the strongest discrepancies from observations: in these simulations, the regional brightening and associated thermodynamic warming due to aerosol reductions is not represented. We estimate an effect of ~0.5 °C over western-central Europe for our model ensemble, and the discrepancy to climate models with evolving aerosols increases in future projections. To better reap the benefits of regional high-resolution simulations, it is thus imperative to represent the relevant external forcings and associated responses across the entire climate model chain.
Observational constraint on a feedback from supercooled clouds reduces projected warming uncertainty
Authors: Cesana Grégory V. , Ackerman Andrew S. , Fridlind Ann M. , Silber Israel , Del Genio Anthony D. , Zelinka Mark D. , Chepfer Hélène , Khadir Théodore , Roehrig Romain
Published: April 2024

The increase of carbon-dioxide-doubling-induced warming (climate sensitivity) in the latest climate models is primarily attributed to a larger extratropical cloud feedback. This is thought to be partly driven by a greater ratio of supercooled liquid-phase clouds to all clouds, termed liquid phase ratio. We use an instrument simulator approach to show that this ratio has increased in the latest climate models and is overestimated rather than underestimated as previously thought. In our analysis of multiple models, a greater ratio corresponds to stronger negative cloud feedback, in contradiction with single-model-based studies. We trace this unexpected result to a cloud feedback involving a shift from supercooled to warm clouds as climate warms, which corresponds to greater cloud amount and optical depth and weakens the extratropical cloud feedback. Better constraining this ratio in climate models – and thus this supercooled cloud feedback – impacts their climate sensitivities by up to 1 ˚C and reduces inter-model spread.
Genomics reveals heterogeneous Plasmodium falciparum transmission and selection signals in Zambia
Authors: Fola Abebe A. , He Qixin , Xie Shaojun , Thimmapuram Jyothi , Bhide Ketaki P. , Dorman Jack , Ciubotariu Ilinca I. , Mwenda Mulenga C. , Mambwe Brenda , Mulube Conceptor , Hawela Moonga , Norris Douglas E. , Moss William J. , Bridges Daniel J. , Carpi Giovanna
Published: April 2024

Background

Genomic surveillance is crucial for monitoring malaria transmission and understanding parasite adaptation to interventions. Zambia lacks prior nationwide efforts in malaria genomic surveillance among African countries.

Methods

We conducted genomic surveillance of Plasmodium falciparum parasites from the 2018 Malaria Indicator Survey in Zambia, a nationally representative household survey of children under five years of age. We whole-genome sequenced and analyzed 241 P. falciparum genomes from regions with varying levels of malaria transmission across Zambia and estimated genetic metrics that are informative about transmission intensity, genetic relatedness between parasites, and selection.

Results

We provide genomic evidence of widespread within-host polygenomic infections, regardless of epidemiological characteristics, underscoring the extensive and ongoing endemic malaria transmission in Zambia. Our analysis reveals country-level clustering of parasites from Zambia and neighboring regions, with distinct separation in West Africa. Within Zambia, identity by descent (IBD) relatedness analysis uncovers local spatial clustering and rare cases of long-distance sharing of closely related parasite pairs. Genomic regions with large shared IBD segments and strong positive selection signatures implicate genes involved in sulfadoxine-pyrimethamine and artemisinin combination therapies drug resistance, but no signature related to chloroquine resistance. Furthermore, differences in selection signatures, including drug resistance loci, are observed between eastern and western Zambian parasite populations, suggesting variable transmission intensity and ongoing drug pressure.

Conclusions

Our findings enhance our understanding of nationwide P. falciparum transmission in Zambia, establishing a baseline for analyzing parasite genetic metrics as they vary over time and space. These insights highlight the urgency of strengthening malaria control programs and surveillance of antimalarial drug resistance.
Limitations in metabolic plasticity after traumatic injury are only moderately exacerbated by physical activity restriction
Authors: Bruzina Angela S. , Raymond-Pope Christiana J. , Murray Kevin J. , Lillquist Thomas J. , Castelli Katelyn M. , Bijwadia Shefali R. , Call Jarrod A. , Greising Sarah M.
Published: April 2024

Following traumatic musculoskeletal injuries, prolonged bedrest and loss of physical activity may limit muscle plasticity and drive metabolic dysfunction. One specific injury, volumetric muscle loss (VML), results in frank loss of muscle and is characterized by whole-body and cellular metabolic dysfunction. However, how VML and restricted physical activity limit plasticity of the whole-body, cellular, and metabolomic environment of the remaining uninjured muscle remains unclear. Adult mice were randomized to posterior hindlimb compartment VML or were age-matched injury naïve controls, then randomized to standard or restricted activity cages for 8-wks. Activity restriction in naïve mice resulted in ~5% greater respiratory exchange ratio (RER); combined with VML, carbohydrate oxidation was ~23% greater than VML alone, but lipid oxidation was largely unchanged. Activity restriction combined with VML increased whole-body carbohydrate usage. Together there was a greater pACC:ACC ratio in the muscle remaining, which may contribute to decreased fatty acid synthesis. Further, β-HAD activity normalized to mitochondrial content was decreased following VML, suggesting a diminished capacity to oxidize fatty acids. The muscle metabolome was not altered by the restriction of physical activity. The combination of VML and activity restriction resulted in similar ( ~ 91%) up- and down-regulated metabolites and/or ratios, suggesting that VML injury alone is regulating changes in the metabolome. Data supports possible VML-induced alterations in fatty acid metabolism are exacerbated by activity restriction. Collectively, this work adds to the sequalae of VML injury, exhausting the ability of the muscle remaining to oxidize fatty acids resulting in a possible accumulation of triglycerides.