bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of distinct roses suitable for future breeding by phenotypic and genotypic evaluations of 192 rose germplasms
Authors: Guan Huilin , Huang Bingyao , Yan Xinyue , Zhao Jiaxing , Yang Shaozong , Wu Quanshu , Bao Manzhu , Bendahmane Mohammed , Fu Xiaopeng
Published: January 2024

Rose (Rosa) is a prominent ornamental plant that holds substantial economic and social significance. Roses originating from different regions exhibit intricate phenotypic and genetic characteristics, but the majority of rose genetic resources are poorly characterized. In this study, 192 genotypes of the genus Rosa were examined using 33 phenotypic traits and 10 pairs of SSR markers. Compared to wild species, both old garden and modern roses exhibited a significant level of diversity, with flower color having the highest degree of diversity and style morphology having the lowest degree of diversity. This phenomenon may be attributed to the limited utilization of wild roses due to their simpler ornamental traits and the frequent phenotypic and molecular infiltration between old garden roses and modern roses. Following a inaugural comprehensive evaluation employing principal component analysis, R. chinensis ‘Zihongxiang’, R. hybrida ‘Burgundy Iceberg’, R. hybrida ‘Conrad F. Meyer’, R. rugosa ‘Gaohong’ and R. floribunda ‘Sheherazad’ were selected as core germplasm resources for future breeding. Moreover, three tetraploid roses, namely R. hybrida ‘Midnight Blue’, R. floribunda ‘Sheherazad’, and R. hybrida ‘Couture Rose Tilia’, with significant differences in both phenotypic and molecular profiles were selected and reciprocally intercrossed. Ultimately, two populations were obtained exhibiting significant variation in flower size, annual stem color, stem pickle density, and leaf number. Furthermore, our results indicated that the traits of flower diameter, flower height, petal width, and petal number may potentially be controlled by two major-effect loci. In conclusion, this study provides novel insights into the evolutionary patterns of Rosa germplasm resources. It paves the way for identifying core genotypes that carry distinct ornamental characteristics and possess immense value for breeding novel varieties in the future.
Involvement of citrus shoots in response and tolerance to abiotic stress
Authors: Vives-Peris Vicente , Pérez-Clemente Rosa M. , Gómez-Cadenas Aurelio , López-Climent María F.
Published: January 2024

Traditionally, the root system has been regarded as the primary component influencing citrus tolerance. Aerial tissues also play a crucial role in abiotic stress tolerance, as they are responsible for vital physiological processes, such as photosynthesis and transpiration. In addition, these tissues are directly exposed to various stress conditions, including extreme temperatures (heat and cold), high light irradiation, and ultraviolet (UV) exposure. In the current climate change scenario, optimizing both citrus rootstocks and grafted scions is crucial to ensure fruit quality and crop yield. Various approaches have been used to investigate the significance of aerial tissues, including in vitro systems, isolated aerial tissue growth, reciprocal grafting, and girdling. This review highlights recent research on the role of aerial tissues in citrus plants under various abiotic stress conditions. Studying and optimizing the genotypes used as scions in grafted citrus plants under abiotic stress conditions is crucial and may contribute to the development of new crop management strategies and breeding programs. Furthermore, this knowledge could be extended to other crops, enabling the development of more resilient and productive agricultural systems.
Bad Godots
Authors: Gontarski S. E.
Published: January 2024

This Element focuses on the machinery of commercial theatre, on extra-authorial interventions into the creative process and on the people and institutional forces that foster them. Such a process challenges the autonomy of the artwork and authorial integrity. The primary focus of this Element is then on the hybrid genre of theatre where collective esthetics tends to override and so to supersede individual creation. The essay pays special attention to Samuel Beckett's first professionally produced play, Waiting for Godot, primarily its English language premieres in the US, UK, and the Republic of Ireland. Its implications, however, reach far beyond the genetic and production histories of a single theatrical work to deal with the nature of authorship in a monetized culture, the process of realizing dramatic texts in such a culture, and Samuel Beckett's engagement with such machinery of art.
Peer Assessment in Writing Instruction
Authors: Yu Shulin
Published: January 2024

This Element traces the evolution of peer assessment in writing instruction and illustrates how peer assessment can be used to promote the teaching and learning of writing in various sociocultural and educational contexts. Specifically, this Element aims to present a critical discussion of the major themes and research findings in the existing studies on peer assessment regarding the three assessment paradigms (assessment of, for, and as learning), and to identify whether and how peer assessment has served the purposes of assessment of, for, and as learning, respectively in writing instruction. This Element highlights the contextual factors that shape the effect of peer assessment in writing instruction and concludes with directions for future research and implications regarding how peer assessment can be successfully used to improve students' writing development.
Weathering alteration in the Antarctic environment as seen in the Miller Range (MIL) 090030 Martian meteorite
Authors: Coloma Leire , Aramendia Julene , Huidobro Jennifer , Población Iratxe , García-Florentino Cristina , Castro Kepa , Arana Gorka , Madariaga Juan Manuel
Published: January 2024

The analysis of Martian meteorites is a key research to understand the mineralogical composition of Mars. However, they suffer different types of alteration due to the environment where they fall on Earth. These differences should be identified in order to characterize correctly the original Martian compounds. Most of the meteorites found on Earth are collected in Antarctica where the environmental conditions are such that, in general and based on many previous investigations, produce fewer alterations compared with other terrestrial environments such as hot deserts. In this study, the weathering alterations of minerals from the MIL 090030 Martian Nakhlite found in Antarctica were analyzed to determine which minerals are formed by Antarctic environmental conditions. It was confirmed that the south-polar region environment can contaminate Martian meteorites and, in this study, several minerals like halite, nitratine and niter, were detected as weathering alteration products that have not been referenced in the literature before.
Repentance, Atonement, and Aquinas
Authors: Schmidt Taylor Greggory
Published: January 2024

Repentance is central to the message of Christianity. Yet, repentance has received little analysis in recent scholarship despite being emphasized by the church fathers. In particular, there has been minimal effort to understand the necessity of repentance in light of Christ’s atoning work. With this as the background, I explore fundamental questions such as repentance’s definition, scope, and role in salvation history. Furthermore, I attempt to more precisely outline repentance’s role in Christ’s salvific work. Underpinning the project is my view that repentance should be understood as metanoia or transformation. This transformation of repentance is ordered toward divine metanoia – participation in Christ. In developing repentance, I put forward a synthesis of Thomas Aquinas’s framework of penance and John McLeod Campbell’s account of Christ’s vicarious repentance. Through this synthesis, I attempt to make sense of the relationship between repentance and atonement. I finish by suggesting that it would be appropriate to conclude that Thomas would endorse a vicarious repentance account of the atonement and hint at how it might fit into broader soteriologies.
Loser Takes All: Graham Greene’s Theological Puzzle Box
Authors: Comerford Peter J.
Published: January 2024

Graham Greene’s novella Loser Takes All has been unfairly ignored in the critical literature. Rather than the mere frivolity it is taken to be, it is a humorous examination of some serious theological issues. By means of an inversion of Pascal’s Great Wager, Greene makes the case that attempts to rationalize the mystery that is the object of our faith will cheapen and diminish that faith. In the course of so doing, he alludes to and has fun with his earlier works, particularly Brighton Rock, and critiques the inversion of the Wager by Albert Camus. He shows the influence of Miguel de Unamuno, who years later would influence Greene’s Monsignor Quixote. Greene also invokes a poem by Charles Baudelaire, which Greene has quoted in many works, that the possibility of damnation adds meaning to life, though it may drift into what von Balthasar called Greene’s indulgence of the mystique of sin.
THE EARLY BRONZE AGE CEMETERY AT ÇEŞME–BOYALIK IN COASTAL WESTERN ANATOLIA
Authors: Şahoğlu Vasıf
Published: January 2024

Early Bronze Age burial practices in western Anatolia have been much discussed, and the general developmental stages of these traditions have been defined by scholars over the course of years. The first half of the third millennium sees the use of a variety of grave types, namely, stone cist, pithos and simple pit burials; meanwhile, during the second half of the millennium, pithos burials seem to predominate. Short-term rescue excavations at Boyalık, in Çeşme District, Izmir Province, reveal the presence of a new type of burial tradition in coastal western Anatolia dating to the middle of the third millennium BC. The cemetery revealed the use of rock-cut chamber tombs for the first time in this region. This paper presents the unique graves and their finds from Boyalık cemetery and discusses the implications of this new tradition for the third-millennium archaeology of the wider Aegeo-Anatolian region.
Resisting Biographical Illusions: Pandurang Khankhoje, Indian Revolutionaries and the Anxiety to be Remembered
Authors: Cháirez-Garza Jesús F.
Published: January 2024

Recently, there has been a growing discussion concerning the way historians should approach the study of Indian revolutionaries both within and outside the subcontinent. Described as ‘the revolutionary turn’, this area of research has not only explored the porosity and ambiguity in defining individuals as revolutionaries but has also questioned the way such revolutionaries sought to write themselves into history as a political act. Continuing this line of interrogation, this article examines the retrospective political claims of heroic revolutionary belonging by analysing the autobiographical notes left by Pandurang Khankhoje, a peripatetic Indian who left his country pursuing dreams of revolution. While in the last decade Khankhoje has become an iconic character in writing histories about global solidarities and anti-colonial resistance, this article asks to what extent can historians believe self-described revolutionary narratives. As this article shows, these narratives privilege what Pierre Bourdieu has called ‘biographical illusion’, the organisation of life as a history that unfolds coherently and chronologically from beginning to end. Political or ideological differences and inconsistencies are flattened in the name of global ideologies or solidarities. As an attempt to disrupt these narratives, this article will focus on the silences, absences and ‘unreliability’ of the experiences and sources used to understand the work and lives of Indian revolutionaries abroad, such as Khankhoje, Lala Har Dayal and M. N. Roy. This article argues that the story of revolutionaries reveals important details about how they understood the racial, political and gender structures of different societies in the early twentieth century.
ARE UNOBSERVABLES SEPARABLE?
Authors: Babii Andrii , Florens Jean-Pierre
Published: January 2024

It is common to assume in empirical research that observables and unobservables are additively separable, especially when the former are endogenous. This is because it is widely recognized that identification and estimation challenges arise when interactions between the two are allowed for. Starting from a nonseparable IV model, where the instrumental variable is independent of unobservables, we develop a novel nonparametric test of separability of unobservables. The large-sample distribution of the test statistics is nonstandard and relies on a Donsker-type central limit theorem for the empirical distribution of nonparametric IV residuals, which may be of independent interest. Using a dataset drawn from the 2015 U.S. Consumer Expenditure Survey, we find that the test rejects the separability in Engel curves for some commodities.
Leaky-wave antenna on substrate-integrated waveguide with radiation pattern controlled by DC voltage
Authors: Machac Jan , Svanda Milan , Kabourek Vaclav
Published: January 2024

This paper presents the application of a substrate-integrated waveguide (SIW) for the design of a leaky-wave antenna (LWA). The antenna radiates through a wide slot in the top wall of the SIW structure in the forward direction. The effective width of the slot is varied by changing capacitances of two arrays of varactors connected between slot edges and inserted conducting strips. The radiation pattern of the antenna is by this way controlled by DC bias, which sets the capacitances of varactors. The maximum radiation direction in elevation can be varied within 35° by changing the DC bias from 2 to 12 V. This elevation angle is measured from the broad side direction perpendicular to the antenna substrate. The measured antenna characteristics are in accord with those predicted by simulation. The antenna can be simply fabricated by a planar circuit board technology.
Combining soft robotics and telerehabilitation for improving motor function after stroke
Authors: Proietti Tommaso , Nuckols Kristin , Grupper Jesse , Schwerz de Lucena Diogo , Inirio Bianca , Porazinski Kelley , Wagner Diana , Cole Tazzy , Glover Christina , Mendelowitz Sarah , Herman Maxwell , Breen Joan , Lin David , Walsh Conor
Published: January 2024

Telerehabilitation and robotics, either traditional rigid or soft, have been extensively studied and used to improve hand functionality after a stroke. However, a limited number of devices combined these two technologies to such a level of maturity that was possible to use them at the patients’ home, unsupervised. Here we present a novel investigation that demonstrates the feasibility of a system that integrates a soft inflatable robotic glove, a cloud-connected software interface, and a telerehabilitation therapy. Ten chronic moderate-to-severe stroke survivors independently used the system at their home for 4 weeks, following a software-led therapy and being in touch with occupational therapists. Data from the therapy, including automatic assessments by the robot, were available to the occupational therapists in real-time, thanks to the cloud-connected capability of the system. The participants used the system intensively (about five times more movements per session than the standard care) for a total of more than 8 hr of therapy on average. We were able to observe improvements in standard clinical metrics (FMA +3.9 ± 4.0, p < .05, COPM-P + 2.5 ± 1.3, p < .05, COPM-S + 2.6 ± 1.9, p < .05, MAL-AOU +6.6 ± 6.5, p < .05) and range of motion (+88%) at the end of the intervention. Despite being small, these improvements sustained at follow-up, 2 weeks after the end of the therapy. These promising results pave the way toward further investigation for the deployment of combined soft robotic/telerehabilitive systems at-home for autonomous usage for stroke rehabilitation.
Incentivizing Responses in International Organization Elite Surveys: Evidence from the World Bank
Authors: Heinzel Mirko , Weaver Catherine , Briggs Ryan
Published: January 2024

Scholars of International Organizations (IOs) increasingly use elite surveys to study the preferences and decisions of policymakers. When designing these surveys, one central concern is low statistical power, because respondents are typically recruited from a small and inaccessible population. However, much of what we know about how to incentivize elites to participate in surveys is based on anecdotal reflections, rather than systematic evidence on which incentives work best. In this article, we study the efficacy of three incentives in a preregistered experiment with World Bank staff. These incentives were the chance to win an Amazon voucher, a donation made to a relevant charity, and a promise to provide a detailed report on the findings. We find that no incentive outperformed the control group, and the monetary incentive decreased the number of respondents on average by one-third compared to the control group (from around 8% to around 5%).
Noise and mental health: evidence, mechanisms, and consequences
Authors: Hahad Omar , Kuntic Marin , Al-Kindi Sadeer , Kuntic Ivana , Gilan Donya , Petrowski Katja , Daiber Andreas , Münzel Thomas
Published: January 2024

The recognition of noise exposure as a prominent environmental determinant of public health has grown substantially. While recent years have yielded a wealth of evidence linking environmental noise exposure primarily to cardiovascular ailments, our understanding of the detrimental effects of noise on the brain and mental health outcomes remains limited. Despite being a nascent research area, an increasing body of compelling research and conclusive findings confirms that exposure to noise, particularly from sources such as traffic, can potentially impact the central nervous system. These harms of noise increase the susceptibility to mental health conditions such as depression, anxiety, suicide, and behavioral problems in children and adolescents. From a mechanistic perspective, several investigations propose direct adverse phenotypic changes in brain tissue by noise (e.g. neuroinflammation, cerebral oxidative stress), in addition to feedback signaling by remote organ damage, dysregulated immune cells, and impaired circadian rhythms, which may collectively contribute to noise-dependent impairment of mental health. This concise review linking noise exposure to mental health outcomes seeks to fill research gaps by assessing current findings from studies involving both humans and animals.
Treatment-free remission after a second TKI discontinuation attempt in patients with Chronic Myeloid Leukemia re-treated with dasatinib – interim results from the DAstop2 trial
Authors: Flygt Hjalmar , Söderlund Stina , Richter Johan , Saussele Susanne , Koskenvesa Perttu , Stenke Leif , Mustjoki Satu , Dimitrijevic Andreja , Stentoft Jesper , Majeed Waleed , Roy Lydia , Wolf Dominik , Dreimane Arta , Gjertsen Bjørn Tore , Gedde-Dahl Tobias , Ahlstrand Erik , Markevärn Berit , Hjorth-Hansen Henrik , Janssen Jeroen , Olsson-Strömberg Ulla
Published: January 2024

Tyrosine kinase inhibitor (TKI) discontinuation in chronic myeloid leukemia (CML) has become part of routine care for patients with a sustained deep molecular response (DMR). Approximately 50% experience a molecular relapse upon TKI cessation. Most of them quickly regain DMR upon TKI resumption. Whether these patients can achieve a second treatment-free remission (TFR) remains unclear. DAstop2 (ClinicalTrials.gov ID: NCT03573596) is a prospective study including patients with a failed first TFR attempt re-treated with any TKI for ≥ one year. Upon entering the study, patients received the TKI dasatinib for additional two years. Patients with sustained DMR for ≥1 year qualified for a second TKI stop. Ninety-four patients were included between Oct 2017-Dec 2021. At the time of data analysis, 62 patients had attempted a 2nd stop. After a median follow-up of 27 months from 2nd stop, TFR rates were 61, 56 and 46% at 6, 12 and 24 months respectively. No progression to advanced stage disease was seen and 87% had re-achieved MR4 within a median of 3 months from TKI re-initiation. In summary, we show that a 2nd TFR attempt after dasatinib treatment is safe, feasible and TFR rates seem in the range of those reported in trials of a first TKI stop.
Porous nanocomposites with enhanced intrinsic piezoresistive sensitivity for bioinspired multimodal tactile sensors
Authors: Zhang Jianpeng , Wei Song , Liu Caichao , Shang Chao , He Zhaoqiang , Duan Yu , Peng Zhengchun
Published: January 2024

In this work, we propose porous fluororubber/thermoplastic urethane nanocomposites (PFTNs) and explore their intrinsic piezoresistive sensitivity to pressure. Our experiments reveal that the intrinsic sensitivity of the PFTN-based sensor to pressure up to 10 kPa increases up to 900% compared to the porous thermoplastic urethane nanocomposite (PTN) counterpart and up to 275% compared to the porous fluororubber nanocomposite (PFN) counterpart. For pressures exceeding 10 kPa, the resistance-pressure relationship of PFTN follows a logarithmic function, and the sensitivity is 221% and 125% higher than that of PTN and PFN, respectively. With the excellent intrinsic sensitivity of the thick PFTN film, a single sensing unit with integrated electrode design can imitate human skin for touch detection, pressure perception and traction sensation. The sensing range of our multimodal tactile sensor reaches ~150 Pa, and it exhibits a linear fit over 97% for both normal pressure and shear force. We also demonstrate that an electronic skin, made of an array of sensing units, is capable of accurately recognizing complex tactile interactions including pinch, spread, and tweak motions.
EEG-vigilance regulation is associated with and predicts ketamine response in major depressive disorder
Authors: Ip Cheng-Teng , de Bardeci Mateo , Kronenberg Golo , Pinborg Lars Hageman , Seifritz Erich , Brunovsky Martin , Olbrich Sebastian
Published: January 2024

Ketamine offers promising new therapeutic options for difficult-to-treat depression. The efficacy of treatment response, including ketamine, has been intricately linked to EEG measures of vigilance. This research investigated the interplay between intravenous ketamine and alterations in brain arousal, quantified through EEG vigilance assessments in two distinct cohorts of depressed patients (original dataset: n = 24; testing dataset: n = 24). Clinical response was defined as a decrease from baseline of >33% on the Montgomery–Åsberg Depression Rating Scale (MADRS) 24 h after infusion. EEG recordings were obtained pre-, start-, end- and 24 h post- infusion, and the resting EEG was automatically scored using the Vigilance Algorithm Leipzig (VIGALL). Relative to placebo (sodium chloride 0.9%), ketamine increased the amount of low-vigilance stage B1 at end-infusion. This increase in B1 was positively related to serum concentrations of ketamine, but not to norketamine, and was independent of clinical response. In contrast, treatment responders showed a distinct EEG pattern characterized by a decrease in high-vigilance stage A1 and an increase in low-vigilance B2/3, regardless of whether placebo or ketamine had been given. Furthermore, pretreatment EEG differed between responders and non-responders with responders showing a higher percentage of stage A1 (53% vs. 21%). The logistic regression fitted on the percent of A1 stages was able to predict treatment outcomes in the testing dataset with an area under the ROC curve of 0.7. Ketamine affects EEG vigilance in a distinct pattern observed only in responders. Consequently, the percentage of pretreatment stage A1 shows significant potential as a predictive biomarker of treatment response.

Clinical Trials Registration:https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-000952-17/CZ

Registration number: EudraCT Number: 2013-000952-17.
Farnesyl-transferase inhibitors show synergistic anticancer effects in combination with novel KRAS-G12C inhibitors
Authors: Baranyi Marcell , Molnár Eszter , Hegedűs Luca , Gábriel Zsófia , Petényi Flóra Gréta , Bordás Fanni , Léner Violetta , Ranđelović Ivan , Cserepes Mihály , Tóvári József , Hegedűs Balázs , Tímár József
Published: January 2024

Background

Inhibition of mutant KRAS challenged cancer research for decades. Recently, allele-specific inhibitors were approved for the treatment of KRAS-G12C mutant lung cancer. However, de novo and acquired resistance limit their efficacy and several combinations are in clinical development. Our study shows the potential of combining G12C inhibitors with farnesyl-transferase inhibitors.

Methods

Combinations of clinically approved farnesyl-transferase inhibitors and KRAS G12C inhibitors are tested on human lung, colorectal and pancreatic adenocarcinoma cells in vitro in 2D, 3D and subcutaneous xenograft models of lung adenocarcinoma. Treatment effects on migration, proliferation, apoptosis, farnesylation and RAS signaling were measured by histopathological analyses, videomicroscopy, cell cycle analyses, immunoblot, immunofluorescence and RAS pulldown.

Results

Combination of tipifarnib with sotorasib shows synergistic inhibitory effects on lung adenocarcinoma cells in vitro in 2D and 3D. Mechanistically, we present antiproliferative effect of the combination and interference with compensatory HRAS activation and RHEB and lamin farnesylation. Enhanced efficacy of sotorasib in combination with tipifarnib is recapitulated in the subcutaneous xenograft model of lung adenocarcinoma. Finally, combination of additional KRAS G1C and farnesyl-transferase inhibitors also shows synergism in lung, colorectal and pancreatic adenocarcinoma cellular models.

Discussion

Our findings warrant the clinical exploration of KRAS-G12C inhibitors in combination with farnesyl-transferase inhibitors.
Caspase-dependent apoptosis in Riboflavin Transporter Deficiency iPSCs and derived motor neurons
Authors: Marioli Chiara , Muzzi Maurizio , Colasuonno Fiorella , Fiorucci Cristian , Cicolani Nicolò , Petrini Stefania , Bertini Enrico , Tartaglia Marco , Compagnucci Claudia , Moreno Sandra
Published: January 2024

Riboflavin Transporter Deficiency (RTD) is a rare genetic, childhood-onset disease. This pathology has a relevant neurological involvement, being characterized by motor symptoms, ponto-bulbar paralysis and sensorineural deafness. Such clinical presentation is associated with muscle weakness and motor neuron (MN) degeneration, so that RTD is considered part of the MN disease spectrum. Based on previous findings demonstrating energy dysmetabolism and mitochondrial impairment in RTD induced Pluripotent Stem cells (iPSCs) and iPSC-derived MNs, here we address the involvement of intrinsic apoptotic pathways in disease pathogenesis using these patient-specific in vitro models by combined ultrastructural and confocal analyses. We show impaired neuronal survival of RTD iPSCs and MNs. Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) documents severe alterations in patients’ cells, including deranged mitochondrial ultrastructure, and altered plasma membrane and nuclear organization. Occurrence of aberrantly activated apoptosis is confirmed by immunofluorescence and TUNEL assays. Overall, our work provides evidence of a role played by mitochondrial dysfunction in RTD, and identifies neuronal apoptosis as a contributing event in disease pathogenesis, indicating intrinsic apoptosis pathways as possible relevant targets for more effective therapeutical approaches.
Glial senescence enhances α-synuclein pathology owing to its insufficient clearance caused by autophagy dysfunction
Authors: Hong Bin , Ohtake Yosuke , Itokazu Takahide , Yamashita Toshihide
Published: January 2024

Parkinson’s disease (PD) is characterized by the pathological accumulation of α-synuclein (α-syn) and loss of dopaminergic neurons in the substantia nigra. Aging is a significant risk factor for PD. The accumulation of senescent glial cells in the aged brain contributes to PD progression by inducing chronic neuroinflammatory processes. However, although the insufficient degradation of α-syn aggregates results in PD deterioration, the possible alteration in the ability of α-syn clearance in senescent glia has received little attention. In this study, we investigated how aging and glial senescence affect the capacity of α-syn clearance. We found that following the intra-striatal injection of human α-syn (hu-α-syn) preformed fibril, hu-α-syn pathology persisted more in aged mice compared with younger mice and that aged microglia exhibited greater accumulation of hu-α-syn than younger microglia. Moreover, in vitro assay revealed that the clearance of hu-α-syn was primarily dependent on the autophagy-lysosome system rather than on the ubiquitin-proteasome system and that the capacity of hu-α-syn clearance was diminished in senescent glia because of autophagy-lysosome system dysfunction. Overall, this study provides new insights into the role of senescent glia in PD pathogenesis.
Phosphorylated α-synuclein deposited in Schwann cells interacting with TLR2 mediates cell damage and induces Parkinson’s disease autonomic dysfunction
Authors: Li Yangxia , Tong Qing , Wang Ye , Cheng Yue , Geng Yao , Tian Tian , Yuan Yongsheng , Fan Yi , Lu Ming , Zhang Kezhong
Published: January 2024

Despite the significant frequency of autonomic dysfunction (AutD) in Parkinson’s disease (PD) patients, its pathogenesis and diagnosis are challenging. Here, we aimed to further explore the mechanism of phosphorylated α-synuclein (p-α-syn) deposited in vagus nerve Schwann cells (SCs) causing SCs damage and PD AutD. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg) was administrated to C57BL/6 mice twice a week for 35 days. Following the final injection, locomotor functions, gastrointestinal symptoms, urine functions, and cardiovascular system functions were evaluated. Meanwhile, we examined p-α-syn deposited in vagus nerve SCs, Toll-like receptor 2 (TLR2) activation, and SCs loss using immunofluorescence, western blot, and Luxol fast blue staining. In vitro, the rat SCs line RSC96 cells were exposed to α-synuclein preformed fibril (α-syn PFF), and cell viability was detected by CCK8. Co-IP was used to identify the interaction between p-α-syn and TLR2. Furthermore, the role of TLR2 in p-α-syn-mediated SCs damage was confirmed by the administration of CU-CPT22, a specific blocker of TLR2. In vivo, apart from dyskinesia, MPTP mice exhibited constipation, urinary dysfunction, and cardiovascular failure, which were associated with the deposition of p-α-syn in vagus nerve SCs, TLR2 activation, and vagus nerve demyelination. In vitro, stimulation of α-syn PFF induced a time-dependent loss of viability, and p-α-syn deposited in RSC96 cells induced a cellular inflammatory response by interacting with TLR2, resulting in cell dysfunction and apoptosis. However, both SCs inflammatory response and cell viability were alleviated after inhibition of TLR2. Furthermore, 1 h fecal pellets and water content, the frequency of 1 h urine, blood pressure, heart rate, and heart rate variability of mice in the MPTP + CU-CPT22 group were also improved. Our results support the perspective that p-α-syn interacts with TLR2 induced SCs damage and is involved in PD AutD, which sheds fresh light on the mechanism of PD AutD and indicates a promising treatment for PD AutD targeting SCs p-α-syn/ TLR2 signaling pathway.
Large anomalous transverse transport properties in atomically thin 2D Fe3GaTe2
Authors: Marfoua Brahim , Hong Jisang
Published: January 2024

Anomalous transverse conductivities, such as anomalous Hall conductivity (AHC), anomalous Nernst conductivity (ANC), and anomalous thermal Hall conductivity (ATHC), play a crucial role in the emerging field of spintronics. Motivated by the recent fabrication of two-dimensional (2D) ferromagnetic thin film Fe3GaTe2, we investigate the thickness-dependent anomalous transverse conductivities of the 2D Fe3GaTe2 system (from one to four layers). The atomically ultrathin 2D Fe3GaTe2 system shows above-room-temperature ferromagnetism with a large perpendicular magnetic anisotropy energy. Furthermore, we obtain a large AHC of −485 S/cm in the four-layer thickness, and this is further enhanced to −550 S/cm with small electron doping. This AHC is seven times larger than the measured AHC in thicker 2D Fe3GaTe2 (178 nm). The ANC also reaches 0.55 A/K.m in the four-layer structure. Along with these, the four-layer system exhibits a large ATHC (−0.105 ~ −0.135 W/K.m). This ATHC is comparable to the large ATHC found in Weyl semimetal Co3Sn2S2. Based on our results, the atomically ultrathin 2D Fe3GaTe2 system shows outstanding anomalous transverse conductivities and can be utilized as a potential platform for future spintronics and spin caloritronic device applications.
Indirect H2O2 synthesis without H2
Authors: Fink Arthur G. , Delima Roxanna S. , Rousseau Alexandra R. , Hunt Camden , LeSage Natalie E. , Huang Aoxue , Stolar Monika , Berlinguette Curtis P.
Published: January 2024

Industrial hydrogen peroxide (H2O2) is synthesized using carbon-intensive H2 gas production and purification, anthraquinone hydrogenation, and anthrahydroquinone oxidation. Electrochemical hydrogenation (ECH) of anthraquinones offers a carbon-neutral alternative for generating H2O2 using renewable electricity and water instead of H2 gas. However, the H2O2 formation rates associated with ECH are too low for commercialization. We report here that a membrane reactor enabled us to electrochemically hydrogenate anthraquinone (0.25 molar) with a current efficiency of 70% at current densities of 100 milliamperes per square centimeter. We also demonstrate continuous H2O2 synthesis from the hydrogenated anthraquinones over the course of 48 h. This study presents a fast rate of electrochemically-driven anthraquinone hydrogenation (1.32 ± 0.14 millimoles per hour normalized per centimeter squared of geometric surface of electrode), and provides a pathway toward carbon-neutral H2O2 synthesis.
SiFT: uncovering hidden biological processes by probabilistic filtering of single-cell data
Authors: Piran Zoe , Nitzan Mor
Published: January 2024

Cellular populations simultaneously encode multiple biological attributes, including spatial configuration, temporal trajectories, and cell-cell interactions. Some of these signals may be overshadowed by others and harder to recover, despite the great progress made to computationally reconstruct biological processes from single-cell data. To address this, we present SiFT, a kernel-based projection method for filtering biological signals in single-cell data, thus uncovering underlying biological processes. SiFT applies to a wide range of tasks, from the removal of unwanted variation in the data to revealing hidden biological structures. We demonstrate how SiFT enhances the liver circadian signal by filtering spatial zonation, recovers regenerative cell subpopulations in spatially-resolved liver data, and exposes COVID-19 disease-related cells, pathways, and dynamics by filtering healthy reference signals. SiFT performs the correction at the gene expression level, can scale to large datasets, and compares favorably to state-of-the-art methods.
Elucidation of unusual biosynthesis and DnaN-targeting mode of action of potent anti-tuberculosis antibiotics Mycoplanecins
Authors: Fu Chengzhang , Liu Yunkun , Walt Christine , Rasheed Sari , Bader Chantal D. , Lukat Peer , Neuber Markus , Haeckl F. P. Jake , Blankenfeldt Wulf , Kalinina Olga V. , Müller Rolf
Published: January 2024

DNA polymerase III sliding clamp (DnaN) was recently validated as a new anti-tuberculosis target employing griselimycins. Three (2 S,4 R)−4-methylproline moieties of methylgriselimycin play significant roles in target binding and metabolic stability. Here, we identify the mycoplanecin biosynthetic gene cluster by genome mining using bait genes from the 4-methylproline pathway. We isolate and structurally elucidate four mycoplanecins comprising scarce homo-amino acids and 4-alkylprolines. Evaluating mycoplanecin E against Mycobacterium tuberculosis surprisingly reveals an excitingly low minimum inhibition concentration at 83 ng/mL, thus outcompeting griselimycin by approximately 24-fold. We show that mycoplanecins bind DnaN with nanomolar affinity and provide a co-crystal structure of mycoplanecin A-bound DnaN. Additionally, we reconstitute the biosyntheses of the unusual l-homoleucine, l-homonorleucine, and (2 S,4 R)−4-ethylproline building blocks by characterizing in vitro the full set of eight enzymes involved. The biosynthetic study, bioactivity evaluation, and drug target validation of mycoplanecins pave the way for their further development to tackle multidrug-resistant mycobacterial infections.
An extensive disulfide bond network prevents tail contraction in Agrobacterium tumefaciens phage Milano
Authors: Sonani Ravi R. , Palmer Lee K. , Esteves Nathaniel C. , Horton Abigail A. , Sebastian Amanda L. , Kelly Rebecca J. , Wang Fengbin , Kreutzberger Mark A. B. , Russell William K. , Leiman Petr G. , Scharf Birgit E. , Egelman Edward H.
Published: January 2024

A contractile sheath and rigid tube assembly is a widespread apparatus used by bacteriophages, tailocins, and the bacterial type VI secretion system to penetrate cell membranes. In this mechanism, contraction of an external sheath powers the motion of an inner tube through the membrane. The structure, energetics, and mechanism of the machinery imply rigidity and straightness. The contractile tail of Agrobacterium tumefaciens bacteriophage Milano is flexible and bent to varying degrees, which sets it apart from other contractile tail-like systems. Here, we report structures of the Milano tail including the sheath-tube complex, baseplate, and putative receptor-binding proteins. The flexible-to-rigid transformation of the Milano tail upon contraction can be explained by unique electrostatic properties of the tail tube and sheath. All components of the Milano tail, including sheath subunits, are crosslinked by disulfides, some of which must be reduced for contraction to occur. The putative receptor-binding complex of Milano contains a tailspike, a tail fiber, and at least two small proteins that form a garland around the distal ends of the tailspikes and tail fibers. Despite being flagellotropic, Milano lacks thread-like tail filaments that can wrap around the flagellum, and is thus likely to employ a different binding mechanism.
Structural and functional insights into the lipid regulation of human anion exchanger 2
Authors: Zhang Weiqi , Ding Dian , Lu Yishuo , Chen Hongyi , Jiang Peijun , Zuo Peng , Wang Guangxi , Luo Juan , Yin Yue , Luo Jianyuan , Yin Yuxin
Published: January 2024

Anion exchanger 2 (AE2) is an electroneutral Na+-independent Cl-/HCO3- exchanger belongs to the SLC4 transporter family. The widely expressed AE2 participates in a variety of physiological processes, including transepithelial acid-base secretion and osteoclastogenesis. Both the transmembrane domains (TMDs) and the N-terminal cytoplasmic domain (NTD) are involved in regulation of AE2 activity. However, the regulatory mechanism remains unclear. Here, we report a 3.2 Å cryo-EM structure of the AE2 TMDs in complex with PIP2 and a 3.3 Å full-length mutant AE2 structure in the resting state without PIP2. We demonstrate that PIP2 at the TMD dimer interface is involved in the substrate exchange process. Mutation in the PIP2 binding site leads to the displacement of TM7 and further stabilizes the interaction between the TMD and the NTD. Reduced substrate transport activity and conformation similar to AE2 in acidic pH indicating the central contribution of PIP2 to the function of AE2.
Bioinspired handheld time-share driven robot with expandable DoFs
Authors: Wang Yunjiang , Hu Xinben , Cui Luhang , Xiao Xuan , Yang Keji , Zhu Yongjian , Jin Haoran
Published: January 2024

Handheld robots offer accessible solutions with a short learning curve to enhance operator capabilities. However, their controllable degree-of-freedoms are limited due to scarce space for actuators. Inspired by muscle movements stimulated by nerves, we report a handheld time-share driven robot. It comprises several motion modules, all powered by a single motor. Shape memory alloy (SMA) wires, acting as “nerves”, connect to motion modules, enabling the selection of the activated module. The robot contains a 202-gram motor base and a 0.8 cm diameter manipulator comprised of sequentially linked bending modules (BM). The manipulator can be tailored in length and integrated with various instruments in situ, facilitating non-invasive access and high-dexterous operation at remote surgical sites. The applicability was demonstrated in clinical scenarios, where a surgeon held the robot to conduct transluminal experiments on a human stomach model and an ex vivo porcine stomach. The time-share driven mechanism offers a pragmatic approach to build a multi-degree-of-freedom robot for broader applications.
Compositional and temporal division of labor modulates mixed sugar fermentation by an engineered yeast consortium
Authors: Shin Jonghyeok , Liao Siqi , Kuanyshev Nurzhan , Xin Yongping , Kim Chanwoo , Lu Ting , Jin Yong-Su
Published: January 2024

Synthetic microbial communities have emerged as an attractive route for chemical bioprocessing. They are argued to be superior to single strains through microbial division of labor (DOL), but the exact mechanism by which DOL confers advantages remains unclear. Here, we utilize a synthetic Saccharomyces cerevisiae consortium along with mathematical modeling to achieve tunable mixed sugar fermentation to overcome the limitations of single-strain fermentation. The consortium involves two strains with each specializing in glucose or xylose utilization for ethanol production. By controlling initial community composition, DOL allows fine tuning of fermentation dynamics and product generation. By altering inoculation delay, DOL provides additional programmability to parallelly regulate fermentation characteristics and product yield. Mathematical models capture observed experimental findings and further offer guidance for subsequent fermentation optimization. This study demonstrates the functional potential of DOL in bioprocessing and provides insight into the rational design of engineered ecosystems for various applications.
Photocatalytic ethylene production by oxidative dehydrogenation of ethane with dioxygen on ZnO-supported PdZn intermetallic nanoparticles
Authors: Wang Pu , Zhang Xingyu , Shi Run , Zhao Jiaqi , Waterhouse Geoffrey I. N. , Tang Junwang , Zhang Tierui
Published: January 2024

The selective oxidative dehydrogenation of ethane (ODHE) is attracting increasing attention as a method for ethylene production. Typically, thermocatalysts operating at high temperatures are needed for C–H activation in ethane. In this study, we describe a low temperature ( < 140 °C) photocatalytic route for ODHE, using O2 as the oxidant. A photocatalyst containing PdZn intermetallic nanoparticles supported on ZnO is prepared, affording an ethylene production rate of 46.4 mmol g–1 h–1 with 92.6% ethylene selectivity under 365 nm irradiation. When we employ a simulated shale gas feed, the photocatalytic ODHE system achieves nearly 20% ethane conversion while maintaining an ethylene selectivity of about 87%. The robust interface between the PdZn intermetallic nanoparticles and ZnO support plays a crucial role in ethane activation through a photo-assisted Mars-van Krevelen mechanism, followed by a rapid lattice oxygen replenishment to complete the reaction cycle. Our findings demonstrate that photocatalytic ODHE is a promising method for alkane-to-alkene conversions under mild conditions.
Direct 4D printing of ceramics driven by hydrogel dehydration
Authors: Wang Rong , Yuan Chao , Cheng Jianxiang , He Xiangnan , Ye Haitao , Jian Bingcong , Li Honggeng , Bai Jiaming , Ge Qi
Published: January 2024

4D printing technology combines 3D printing and stimulus-responsive materials, enabling construction of complex 3D objects efficiently. However, unlike smart soft materials, 4D printing of ceramics is a great challenge due to the extremely weak deformability of ceramics. Here, we report a feasible and efficient manufacturing and design approach to realize direct 4D printing of ceramics. Photocurable ceramic elastomer slurry and hydrogel precursor are developed for the fabrication of hydrogel-ceramic laminates via multimaterial digital light processing 3D printing. Flat patterned laminates evolve into complex 3D structures driven by hydrogel dehydration, and then turn into pure ceramics after sintering. Considering the dehydration-induced deformation and sintering-induced shape retraction, we develop a theoretical model to calculate the curvatures of bent laminate and sintered ceramic part. Then, we build a design flow for direct 4D printing of various complex ceramic objects. This approach opens a new avenue for the development of ceramic 4D printing technology.
A contact-electro-catalysis process for producing reactive oxygen species by ball milling of triboelectric materials
Authors: Wang Ziming , Dong Xuanli , Li Xiao-Fen , Feng Yawei , Li Shunning , Tang Wei , Wang Zhong Lin
Published: January 2024

Ball milling is a representative mechanochemical strategy that uses the mechanical agitation-induced effects, defects, or extreme conditions to activate substrates. Here, we demonstrate that ball grinding could bring about contact-electro-catalysis (CEC) by using inert and conventional triboelectric materials. Exemplified by a liquid-assisted-grinding setup involving polytetrafluoroethylene (PTFE), reactive oxygen species (ROS) are produced, despite PTFE being generally considered as catalytically inert. The formation of ROS occurs with various polymers, such as polydimethylsiloxane (PDMS) and polypropylene (PP), and the amount of generated ROS aligns well with the polymers’ contact-electrification abilities. It is suggested that mechanical collision not only maximizes the overlap in electron wave functions across the interface, but also excites phonons that provide the energy for electron transition. We expect the utilization of triboelectric materials and their derived CEC could lead to a field of ball milling-assisted mechanochemistry using any universal triboelectric materials under mild conditions.
Thermo-optic epsilon-near-zero effects
Authors: Wu Jiaye , Clementi Marco , Huang Chenxingyu , Ye Feng , Fu Hongyan , Lu Lei , Zhang Shengdong , Li Qian , Brès Camille-Sophie
Published: January 2024

Nonlinear epsilon-near-zero (ENZ) nanodevices featuring vanishing permittivity and CMOS-compatibility are attractive solutions for large-scale-integrated systems-on-chips. Such confined systems with unavoidable heat generation impose critical challenges for semiconductor-based ENZ performances. While their optical properties are temperature-sensitive, there is no systematic analysis on such crucial dependence. Here, we experimentally report the linear and nonlinear thermo-optic ENZ effects in indium tin oxide. We characterize its temperature-dependent optical properties with ENZ frequencies covering the telecommunication O-band, C-band, and 2-μm-band. Depending on the ENZ frequency, it exhibits an unprecedented 70–93-THz-broadband 660–955% enhancement over the conventional thermo-optic effect. The ENZ-induced fast-varying large group velocity dispersion up to 0.03–0.18 fs2nm−1 and its temperature dependence are also observed for the first time. Remarkably, the thermo-optic nonlinearity demonstrates a 1113–2866% enhancement, on par with its reported ENZ-enhanced Kerr nonlinearity. Our work provides references for packaged ENZ-enabled photonic integrated circuit designs, as well as a new platform for nonlinear photonic applications and emulations.