bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the artificially intelligent workplace: an ethical framework for evaluating experimental technologies in workplace settings
Authors: Hosseini Ziagul , Nyholm Sven , Le Blanc Pascale M. , Preenen Paul T. Y. , Demerouti Evangelia
Published: February 2023

Experimental technologies, including AI and robots, are revolutionising many types of work. For example, the logistics warehouse sector is witnessing a wave of new technologies, such as automated picking tools, collaborative robots and exoskeletons, affecting jobs and employees. Notably, it is not always possible to predict the effects of such new technologies, since they have inherent uncertainties and unintended consequences. Hence, their introduction into workplaces can be conceived as a social experiment. This paper aims to sketch a set of ethical guidelines for introducing experimental technologies into workplaces. It builds on Van de Poel's general framework for assessing new experimental technologies and translates that framework into a more specific context of work. We discuss its five principles: non-maleficence, beneficence, responsibility, autonomy, and justice. Each of these principles is applied to workplaces in general, and specifically to the logistics warehouse setting as a case study. A particular focus in our discussion is put on the distinctive potential harms and goods of work.
The Rural Landscapes of Archaic Cyprus
Authors: Kearns Catherine
Published: February 2023

The ninth to the fifth centuries BCE saw a series of significant historical transformations across Cyprus, especially in the growth of towns and in developments in the countryside. In this book, Catherine Kearns argues that changing patterns of urban and rural sedentism drove social changes as diverse communities cultivated new landscape practices. Climatic changes fostered uneven relationships between people, resources like land, copper, and wood, and increasingly important places like rural sanctuaries and cemeteries. Bringing together a range of archaeological, textual, and scientific evidence, the book examines landscapes, environmental history, and rural practices to argue for their collective instrumentality in the processes driving Iron Age political formations. It suggests how rural households managed the countryside, interacted with the remains of earlier generations, and created gathering spaces alongside the development of urban authorities. Offering new insights into landscape archaeologies, Dr Kearns contributes to current debates about society's relationships with changing environments.
The Potency of Pastoral in the Hispanic Baroque
Authors: Holloway Anne
Published: February 2023

A careful re-evaluation of pastoral poetics in the early modern Hispanic literature of Spain and Latin America.
The Medieval Military Engineer
Authors: Purton Peter
Published: February 2023

Sheds light on the skills and techniques of the medieval military engineer, over a thousand year sweep.
Transient leading-edge vortex development on a wing rolling in uniform flow
Authors: Wabick Kevin J. , Johnson Kyle C. , Berdon Randall L. , Thurow Brian S. , Buchholz James H.J.
Published: February 2023

Plenoptic particle image velocimetry and surface pressure measurements were used to analyse the early development of leading-edge vortices (LEVs) created by a flat-plate wing of aspect ratio 2 rolling in a uniform flow parallel to the roll axis. Four cases were constructed by considering two advance coefficients,

$J=0.54$

and 1.36, and two wing radii of gyration,

$R_g/c=2.5$

and 3.25. In each case, the wing pitch angle was articulated such as to achieve an angle of attack of

$33^{\circ }$

at the radius of gyration of the wing. The sources and sinks of vorticity were quantified for a chordwise rectangular control region, using a vorticity transport framework in a non-inertial coordinate system attached to the wing. Within this framework, terms associated with Coriolis acceleration provide a correction to tilting and spanwise convective fluxes measured in the rotating frame and, for the present case, have insignificant values. For the baseline case (

$J=0.54, R_g/c=3.25$

), three distinct spanwise regions were observed within the LEV, with distinct patterns of vortex evolution and vorticity transport mechanisms in each region. Reducing the radius of gyration to

$R_g/c=2.5$

resulted in a more stable vortex with the inboard region extending over a broader spanwise range. Increasing advance ratio eliminated the conical vortex, resulting in transport processes resembling the mid-span region of the baseline case. Although the circulation of the LEV system was generally stronger at the larger advance coefficient, the shear-layer contribution was diminished.
Inertial and viscous dynamics of jump-to-contact between fluid drops under van der Waals attraction
Authors: Beaty Edward , Lister John R.
Published: February 2023

When two small fluid drops are sufficiently close, the van der Waals force overcomes surface tension and deforms the surfaces into contact, initiating coalescence. The dynamics of surface deformation across an inviscid gap falls into two distinct regimes (Stokes and inertial–viscous) characterized by the forces that balance the van der Waals attraction at leading order (viscosity, and both inertia and viscosity). The previously studied Stokes regime holds for very viscous drops but fails for less viscous drops as inertia becomes significant before contact is reached. We show that the subsequent inertial–viscous dynamics is self-similar as contact is approached, with the gap width decreasing as

$t{'^{3/8}}$

and the radial scale of the deformed region decreasing as

$t{'^{1/2}}$

as

$t{'}\to 0$

, for time until contact

$t'$

. The self-similar behaviour is universal and is the generic asymptotic behaviour observed in time-dependent simulations. The unique self-similar gap profile of the inertial–viscous regime suggests new initial conditions for the coalescence of the drops after contact.
AllBRICQS: The All-sky BRIght, Complete Quasar Survey
Authors: Onken Christopher A. , Wolf Christian , Hon Wei Jeat , Lai (賴民希) Samuel , Tisserand Patrick , Webster Rachel
Published: February 2023

We describe the first results from the All-sky BRIght, Complete Quasar Survey (AllBRICQS), which aims to discover the last remaining optically bright quasars. We present 156 spectroscopically confirmed quasars (140 newly identified) having$|b|>10^{\circ}$. 152 of the quasars haveGaiaDR3 magnitudes brighter than$B_{P}=16.5$or$R_{P}=16$mag, while four are slightly fainter. The quasars span a redshift range of$z=0.07-3.93$. In particular, we highlight the properties of J0529-4351 at$z=3.93$, which, if unlensed, is one of the most intrinsically luminous quasars in the Universe. The AllBRICQS sources have been selected by combining data from theGaiaandWISEall-sky satellite missions, and we successfully identify quasars not flagged as candidates byGaiaData Release 3. We expect the completeness to be$\approx$96% within our magnitude and latitude limits, while the preliminary results indicate a selection purity of$\approx$96%. The optical spectroscopy used for source classification will also enable detailed quasar characterisation, including black hole mass measurements and identification of foreground absorption systems. The AllBRICQS sources will greatly enhance the number of quasars available for high-signal-to-noise follow-up with present and future facilities.
Can a urease inhibitor improve the efficacy of nitrogen use under perennial ryegrass temperate grazing conditions?
Authors: Murray Á. , Gilliland T. J. , Delaby L. , Patton D. , Creighton P. , Forrestal P. J. , McCarthy B.
Published: February 2023

This study sought to compare the efficiency of different nitrogen (N) fertilizer forms applied to perennial ryegrass swards that were rotationally grazed by dairy cows or sheep under Irish conditions for two or three years. A 3 × 2 factorial random complete block design plot arrangement was used to compare calcium ammonium nitrate (CAN), urea and urea + N-(n-butyl) thiophosphoric triamide (urea + NBPT) at 150 and 250 kg N/ha per year. Zero nitrogen plots were also added to allow for N efficiency to be calculated. The study was conducted at four sites, giving three years of data collection at two sites and two years at the other two sites. All four sites observed similar responses to N fertilizer type and N fertilizer rate. Significant differences were observed between the 150 kg N/ha and 250 kg N/ha treatments for pre-grazing herbage yield (1346 and 1588 kg DM/ha, respectively; P < 0.001) and total herbage production (12 290 and 14 448 kg DM/ha, respectively; P < 0.001). There was no difference but a tendency for pre-grazing herbage yield to be higher for CAN and urea + NBPT than urea (1485, 1480 and 1436 kg DM/ha, for CAN, urea + NBPT and urea, respectively; P = 0.091). Total herbage production was significantly higher for CAN and urea + NBPT than urea (13 478, 13 542 and 13 087 kg DM/ha, respectively; P = 0.004). In conclusion, there was an overall benefit detected over the 10 site-years from using urea protected with NBPT v. using urea.
The internal structure of the syllable in Russian and in Hebrew: Evidence from monolingual kindergarteners
Authors: Kogan Nadya , Saiegh-Haddad Elinor
Published: February 2023

Notwithstanding remarkable phonological differences, the CV syllable is the most frequent syllable type in both Russian and Hebrew. This led to the prediction that the internal structure of the CVC syllable in the two languages, as reflected in phonological awareness tasks, might be similar. The study tested phonological awareness in two groups of monolingual kindergarteners: Hebrew-speaking (N = 35) and Russian-speaking (N = 20) in order to shed light on the underlying structure of the CVC syllable in the two languages. Phonological awareness tasks targeted awareness of the sub-syllabic structure (structured and unstructured) and phoneme awareness (initial and final). A linear mixed model analysis revealed that children in both groups showed greater facility with body-coda CV-C than with onset-rime C-VC syllable splitting and higher scores on final than on initial phoneme isolation tasks. The unstructured tasks also reflected the cohesion of the CV body in both languages. The findings demonstrate a similar internal representation of the CVC syllable in Russian and in Hebrew speakers as reflected in phonological awareness among preschoolers.
State Regulation and Class Struggle in the Beedi Industry of Post-Colonial Malabar, 1947–1970
Authors: Thekke Kalathil Suramya
Published: February 2023

In post-independence India, as in many developing post-colonial nations, the capitalist class was dependent on the state to discipline the laborforce, and the rapid uptake of capitalist production methods prompted the new government to intervene aggressively in industrial labor relations. The main goal of postcolonial labor policy was to maintain peaceful labor relations at any cost in order to foster economic development. The newly elected government failed to help capitalists increase their profits through productivity growth, so the way forward was to impose restrictions on labor. Pro-capital labor legislation initially enabled capitalists to curb the mobility and resistance of workers. In due course, however, irrespective of how consistently or effectively labor regulations and repressive measures were enforced, the reaction of the working class heightened its political consciousness, and thus aggravated frictions between capital and labor. When the state resorted to labor welfare laws as a new strategy to reduce these conflicts, employers often fragmented production among smaller units (such as workshops and households) in order to dodge labor regulations. As a reaction to this production decentralization, the working-class movement created impediments to the process of continual capital accumulation.
Farmer perceived challenges toward conservation practice usage in the margins of the Corn Belt, USA
Authors: Adhikari Ram Kumar , Wang Tong , Jin Hailong , Ulrich-Schad Jessica D. , Sieverding Heidi L. , Clay David
Published: February 2023

While conservation practices promote soil health and reduce the negative environmental effects from agricultural production, their adoption rates are generally low. To facilitate farmer adoption, we carried out a survey to identify potential challenges faced by farmers regarding conservation tillage and cover crop adoption in the western margin of the US Corn Belt. We found farmers' top two concerns regarding conservation tillage were delayed planting, caused by slow soil warming in spring, and increased dependence on herbicide and fungicides. Narrow planting window and lack of time/labor were perceived by farmers as the two primary challenges for cover crop adoption. Some sense of place factors, including the commonly included dimensions of attachment, identity and dependence, played a role in farmers' perceived challenges. For example, respondents more economically dependent on farming perceived greater challenges. We found that farmers' challenge perceptions regarding reduced yield and lack of time/labor significantly decreased as years of usage increased, implying that time and experience could dilute some challenges faced by farmers. Our findings indicate that social network use, technical guidance and economic subsidies are likely to address the concerns of farmers and facilitate their adoption of conservation practices.
Dust Detection Over East Asia From Multispectral and Multi‐Temporal Himawari‐8/AHI Thermal Infrared Observations
Authors: Shi Jianjun , Yang Shizhi , Cui Shengcheng , Luo Tao , Li Xuebin , Lu Wenqiang , Han Lu
Published: February 2023

The frequent outbreak of dust storms every spring is one of the extreme weathers in East Asia. Geostationary meteorological satellite thermal infrared (TIR) imagery provides observations for high‐frequency, all‐day, large‐scale monitoring of dust sources and transport. This study proposes an integrated method to detect dust over East Asia by using the multispectral and multi‐temporal Himawari‐8/Advanced Himawari Imager (AHI) TIR observations, based on a Feedforward Neural Network (FNN) model and the Robust Principal Component Analysis based Anomalous Dust Detection (ADD) method. The FNN model is trained to map the multispectral Brightness Temperatures (BTs) to the three category probabilities (i.e., cloud, dust, and clear sky), and the ADD method calculates the dust score by normalizing multi‐temporal BT difference anomalous variation. The Integrated Dust Index (IDI) reflects the quantified dust confidence of the AHI pixel, which is defined as the sum of the dust probability and the dust score. The IDI was evaluated using 2 months of the Sentinel‐5P TROPOMI Ultraviolet Aerosol Index and achieved a total dust detection accuracy above 90%. A comparison with Cloud Aerosol Lidar and Infrared Pathfinder Satellite Observation nighttime observations shows that the IDI can also detect dust at night. The times series IDI of the massive 14–16 March 2021 dust storm show its capabilities to trace dust sources and monitor dust transport.
GOLD Synoptic Observations of Thermospheric Annual and Semiannual Variations in Composition During Solar Minimum Years
Authors: Gan Quan , Qian Liying , Pedatella Nicholas M. , Wu Yen‐Jung , Correira John , Wang Wenbin , McClintock William E. , Eastes Richard W.
Published: February 2023

This study investigates thermospheric seasonal variations composed of annual and semiannual oscillations (AO and SAO) in the column density ratio of atomic oxygen to molecular nitrogen observed by Global‐scale Observations of Limb and Disk. On the basis of multiple analysis approaches, it is revealed that the AO is the predominant component at middle latitudes, while the SAO tends to be increasingly important toward the lower latitudes. The SAO is also evident in the southern mid‐latitudes. Quantitative analyses demonstrate that AO (SAO) peaks around winter solstices (equinoxes). Additionally, the seasonal variation at low‐latitudes exhibits greater amplitudes in the early morning and around noon, whereas it gradually weakens from early morning toward late afternoon at mid‐latitudes. A hypothesis is that seasonal variations are likely modulated by atmospheric tides, including those generated in the thermosphere and those propagating upward from the lower atmosphere.
Role of Extreme Indian Ocean Dipole in Regulating Three‐Dimensional Freshwater Content in the Southeast Indian Ocean
Authors: Chen Gengxin , Han Weiqing , Ma Xueying , Li Yuanlong , Zhang Tiecheng , Wang Dongxiao
Published: February 2023

The tropical Southeast Indian Ocean (SEIO) is a key area linking the global freshwater and heat exchanges. The Indian Ocean Dipole (IOD) fundamentally modulates the Indian Ocean circulation and thus regulates the basin‐wide freshwater balance. However, our knowledge of this effect remains limited. Using observational‐based data sets, this study suggests that extreme positive IOD events have notable signatures on the three‐dimensional freshwater content of the SEIO, leading to the vertically opposite salinity anomalies in the surface and subsurface layers. The wind changes led to the northwestward extension of the South Equatorial Current and intensified Sumatra‐Java upwelling. The changing horizontal and vertical currents jointly result in the complicated salinity anomalies. The Equatorial Undercurrent serves as the conduit for water exchange between the equator and the SEIO. This work highlights a strong coupling between the equatorial circulation and the three‐dimensional freshwater inventory of the SEIO within the framework of the IOD.
Simulation of Centrifugally Driven Convection in Jovian Inner Magnetosphere Using the Rice Convection Model
Authors: Wang Yuxian , Yang Jian , Guo Xiaocheng , Wang Chi , Blanc Michel
Published: February 2023

The dynamics of the Jovian inner magnetosphere are dominated by centrifugally driven convection. We use the newly developed Rice Convection Model‐Jupiter to simulate the interchange instability and the plasma transport in the Jovian inner magnetosphere (L < 20 RJ). The model explicitly incorporates the active Io plasma source and its related pickup effect. A series of runs are performed to parametrically investigate how ionospheric conductances and Io source rate affect the convection system. Simulation results show that the iogenic plasma is transported outward in the form of elongated fingers. The outflow radial velocity in the quasi‐steady state increases with further distances, reaching a value of over ∼30 km/s at L = 20 RJ, and is in general higher than that of the inflow. It is found that the interchange instability and the convection can be significantly affected by the conductance and Io source rate. A larger Pedersen conductance or a lower source rate produces a slower radial inflow/outflow and a less prominent corotation lag of the outflow throughout the inner magnetosphere, while the angular velocity for the inflow is always near zero and not significantly affected. Furthermore, a uniform Hall conductance () exerts little influence on the convection system, while the inhomogeneity of can significantly regulate the plasma convection.
Recovery of the Alberta Basin Sedimentary Structures in Southern‐Central Alberta Using Nonlinear Inversions of Receiver Functions
Authors: Zhang Cheng , Gu Yu Jeffrey , Dokht Ramin M. H. , Chen Yunfeng
Published: February 2023

Secondary converted waves from receiver functions are highly sensitive to physical properties below the Earth's surface. When modeled properly, the waveforms of converted waves offer direct constraints on the impedance contrast, depth, and P‐to‐S velocity ratio pertaining to sedimentary, crustal and mantle interfaces. In this study we introduce a nonlinear waveform inversion algorithm that matches the first 5 s of receiver functions recorded in the Alberta Basin within the Western Canada Sedimentary Basin (WCSB). Our algorithm searches for the optimal thickness of the sedimentary cover and shear velocities of appropriately selected layers within and below it. Combining inversions with forward simulations, we determine the supracrustal stratigraphy from 80 regional broadband seismic stations in the WCSB. The inverted models show east tapering sedimentary layers with their thicknesses ranging from ∼6 km beneath the foothills of the Canadian Rocky Mountains to 3–4 km beneath the Alberta Basin. This finding is consistent with the sedimentary strata determined from regional well‐logging data. The sedimentary layer contains low velocity zones of variable thicknesses and amplitudes that, depending on the locations, may be caused by mechanisms involving deposition, composition or deformation history. Our shear velocity models near the top of the basement complement the existing sonic‐logs or single component seismic data and offer new constraints on the subsidence history of the WCSB. The resolved range of depths (0–14 km) effectively bridges the gap between the vertical scales of well logging (0–6 km) and those of traditional broadband analysis (>10 km) involving receiver functions and surface waves.
Long-term cardiovascular consequences of adolescent anorexia nervosa
Authors: Springall Gabriella A. C. , Caughey Michelle , Zannino Diana , Kyprianou Kypros , Mynard Jonathan P. , Rudolph Subashini , Cheong Jeanie , Yeo Michele , Cheung Michael M. H.
Published: February 2023

Background

Anorexia nervosa (AN) is associated with maladaptive cardiovascular changes. This study investigated whether individuals who recovered from AN during adolescence experience long-term cardiovascular risk in early adulthood.

Methods

Former AN patients discharged from the Royal Children’s and Monash Children’s Hospital Eating Disorder Services in Melbourne, Australia underwent cardiovascular testing. Measurements were performed using an oscillometric device for blood pressure and pulse wave velocity, ultrasound for carotid wall structure/function, resting electrocardiogram for heart-rate variability, and the EndoPat 2000 (Itamar) system for endothelial function. Patient measures were compared to healthy controls and/or normal thresholds.

Results

Ninety-one percent of the former AN patients (N = 22) and controls (N = 66) were female, aged approximately 25 years, with a healthy body mass index. The mean time interval from AN recovery to participation was 7.4 years. Pulse wave velocity was lower in the former AN patients than controls. Carotid intima–media thickness was not different; however, carotid distensibility and compliance were lower, and the elastic modulus higher in the former AN patients. Greater vagal tone was observed and endothelial dysfunction was evident in 46% of the former patients.

Conclusions

Young adults who recovered from adolescent AN exhibit persistent cardiovascular adaptations. Routine cardiovascular monitoring could manage potential disease risk.

Impact

Cardiovascular complications are common in patients with anorexia nervosa (AN) and population studies have revealed that developmental adaptations in response to undernutrition have long-term consequences for cardiovascular health.

In this study of young adults treated for AN during adolescence, there was evidence of increased carotid artery stiffness, reduced aortic stiffness, vagal hyperactivity, and endothelial dysfunction in early adulthood when compared to healthy controls.

It is important to consider the cardiovascular health of patients with AN beyond achieving medical stability.

Interventions that monitor cardiovascular health could minimise the burden of future cardiovascular disease.
Alcohol-specific transcriptional dynamics of memory reconsolidation and relapse
Authors: Goltseker Koral , Garay Patricia , Bonefas Katherine , Iwase Shigeki , Barak Segev
Published: February 2023

Relapse, a critical issue in alcohol addiction, can be attenuated by disruption of alcohol-associated memories. Memories are thought to temporarily destabilize upon retrieval during the reconsolidation process. Here, we provide evidence for unique transcriptional dynamics underpinning alcohol memory reconsolidation. Using a mouse place-conditioning procedure, we show that alcohol-memory retrieval increases the mRNA expression of immediate-early genes in the dorsal hippocampus and medial prefrontal cortex, and that alcohol seeking is abolished by post-retrieval non-specific inhibition of gene transcription, or by downregulating ARC expression using antisense-oligodeoxynucleotides. However, since retrieval of memories for a natural reward (sucrose) also increased the same immediate-early gene expression, we explored for alcohol-specific transcriptional changes using RNA-sequencing. We revealed a unique transcriptional fingerprint activated by alcohol memories, as the expression of this set of plasticity-related genes was not altered by sucrose-memory retrieval. Our results suggest that alcohol memories may activate two parallel transcription programs: one is involved in memory reconsolidation in general, and another is specifically activated during alcohol-memory processing.
A lncRNA-encoded mitochondrial micropeptide exacerbates microglia-mediated neuroinflammation in retinal ischemia/reperfusion injury
Authors: Zheng Xintong , Wang Mingwei , Liu Shuting , Chen Haiqiao , Li Yifei , Yuan Fa , Yang Ludong , Qiu Suo , Wang Hongwei , Xie Zhi , Xiang Mengqing
Published: February 2023

As a common pathology of many ocular disorders such as diabetic retinopathy and glaucoma, retinal ischemia/reperfusion (IR) triggers inflammation and microglia activation that lead to irreversible retinal damage. The detailed molecular mechanism underlying retinal IR injury, however, remains poorly understood at present. Here we report the bioinformatic identification of a lncRNA 1810058I24Rik (181-Rik) that was shown to encode a mitochondrion-located micropeptide Stmp1. Its deficiency in mice protected retinal ganglion cells from retinal IR injury by attenuating the activation of microglia and the Nlrp3 inflammasome pathway. Moreover, its genetic knockout in mice or knockdown in primary microglia promoted mitochondrial fusion, impaired mitochondrial membrane potential, and reactive oxygen species (ROS) production, diminished aerobic glycolysis, and ameliorated inflammation. It appears that 181-Rik may trigger the Nlrp3 inflammasome activation by controlling mitochondrial functions through inhibiting expression of the metabolic sensor uncoupling protein 2 (Ucp2) and activating expression of the Ca2+ sensors S100a8/a9. Together, our findings shed new light on the molecular pathogenesis of retinal IR injury and may provide a fresh therapeutic target for IR-associated neurodegenerative diseases.
ERK1/2-dependent TSPO overactivation associates with the loss of mitophagy and mitochondrial respiration in ALS
Authors: Magrì Andrea , Lipari Cristiana Lucia Rita , Risiglione Pierpaolo , Zimbone Stefania , Guarino Francesca , Caccamo Antonella , Messina Angela
Published: February 2023

Mitochondrial dysfunction and the loss of mitophagy, aimed at recycling irreversibly damaged organelles, contribute to the onset of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease affecting spinal cord motor neurons. In this work, we showed that the reduction of mitochondrial respiration, exactly oxygen flows linked to ATP production and maximal capacity, correlates with the appearance of the most common ALS motor symptoms in a transgenic mouse model expressing SOD1 G93A mutant. This is the result of the equal inhibition in the respiration linked to complex I and II of the electron transport chain, but not their protein levels. Since the overall mitochondrial mass was unvaried, we investigated the expression of the Translocator Protein (TSPO), a small mitochondrial protein whose overexpression was recently linked to the loss of mitophagy in a model of Parkinson’s disease. Here we clearly showed that levels of TSPO are significantly increased in ALS mice. Mechanistically, this increase is linked to the overactivation of ERK1/2 pathway and correlates with a decrease in the expression of the mitophagy-related marker Atg12, indicating the occurrence of impairments in the activation of mitophagy. Overall, our work sets out TSPO as a key regulator of mitochondrial homeostasis in ALS.
ASAP1 activates the IQGAP1/CDC42 pathway to promote tumor progression and chemotherapy resistance in gastric cancer
Authors: Xie Wangkai , Han Zheng , Zuo Ziyi , Xin Dong , Chen Hua , Huang Juanjuan , Zhu Siyu , Lou Han , Yu Zhiqiang , Chen Chenbin , Chen Sian , Hu Yuanbo , Huang Jingjing , Zhang Fabiao , Ni Zhonglin , Shen Xian , Xue Xiangyang , Lin Kezhi
Published: February 2023

Abnormal expression and remodeling of cytoskeletal regulatory proteins are important mechanisms for tumor development and chemotherapy resistance. This study systematically analyzed the relationship between differential expression of cytoskeleton genes and prognosis in gastric cancer (GC). We found the Arf GTP-activating protein ASAP1 plays a key role in cytoskeletal remodeling and prognosis in GC patients. Here we analyzed the expression level of ASAP1 in tissue microarrays carrying 564 GC tissues by immunohistochemistry. The results showed that ASAP1 expression was upregulated in GC cells and can be served as a predictor of poor prognosis. Moreover, ASAP1 promoted the proliferation, migration, and invasion of GC cells both in vitro and in vivo. We also demonstrated that ASAP1 inhibited the ubiquitin-mediated degradation of IQGAP1 and thus enhanced the activity of CDC42. The activated CDC42 upregulated the EGFR-MAPK pathway, thereby promoting the resistance to chemotherapy in GC. Taken together, our results revealed a novel mechanism by which ASAP1 acts in the progression and chemotherapy resistance in GC. This may provide an additional treatment option for patients with GC.
DNALI1 deficiency causes male infertility with severe asthenozoospermia in humans and mice by disrupting the assembly of the flagellar inner dynein arms and fibrous sheath
Authors: Wu Huan , Liu Yiyuan , Li Yuqian , Li Kuokuo , Xu Chuan , Gao Yang , Lv Mingrong , Guo Rui , Xu Yuping , Zhou Ping , Wei Zhaolian , Hua Rong , He Xiaojin , Cao Yunxia
Published: February 2023

The axonemal dynein arms (outer (ODA) and inner dynein arms (IDAs)) are multiprotein structures organized by light, intermediate, light intermediate (LIC), and heavy chain proteins. They hydrolyze ATP to promote ciliary and flagellar movement. Till now, a variety of dynein protein deficiencies have been linked with asthenospermia (ASZ), highlighting the significance of these structures in human sperm motility. Herein, we detected bi-allelic DNALI1 mutations [c.663_666del (p.Glu221fs)], in an ASZ patient, which resulted in the complete loss of the DNALI1 in the patient’s sperm. We identified loss of sperm DNAH1 and DNAH7 rather than DNAH10 in both DNALI1663_666del patient and Dnali1−/− mice, demonstrating that mammalian DNALI1 is a LIC protein of a partial IDA subspecies. More importantly, we revealed that DNALI1 loss contributed to asymmetries in the most fibrous sheath (FS) of the sperm flagellum in both species. Immunoprecipitation revealed that DNALI1 might interact with the cytoplasmic dynein complex proteins in the testes. Furthermore, DNALI1 loss severely disrupted the transport and assembly of the FS proteins, especially AKAP3 and AKAP4, during flagellogenesis. Hence, DNALI1 may possess a non-classical molecular function, whereby it regulates the cytoplasmic dynein complex that assembles the flagella. We conclude that a DNALI deficiency-induced IDAs injury and an asymmetric FS-driven tail rigid structure alteration may simultaneously cause flagellum immotility. Finally, intracytoplasmic sperm injection (ICSI) can effectively resolve patient infertility. Collectively, we demonstrate that DNALI1 is a newly causative gene for AZS in both humans and mice, which possesses multiple crucial roles in modulating flagellar assembly and motility.
Community science designed ribosomes with beneficial phenotypes
Authors: Krüger Antje , Watkins Andrew M. , Wellington-Oguri Roger , Romano Jonathan , Kofman Camila , DeFoe Alysse , Kim Yejun , Anderson-Lee Jeff , Fisker Eli , Townley Jill ,   Eterna Participants, d’Aquino Anne E. , Das Rhiju , Jewett Michael C.
Published: February 2023

Functional design of ribosomes with mutant ribosomal RNA (rRNA) can expand opportunities for understanding molecular translation, building cells from the bottom-up, and engineering ribosomes with altered capabilities. However, such efforts are hampered by cell viability constraints, an enormous combinatorial sequence space, and limitations on large-scale, 3D design of RNA structures and functions. To address these challenges, we develop an integrated community science and experimental screening approach for rational design of ribosomes. This approach couples Eterna, an online video game that crowdsources RNA sequence design to community scientists in the form of puzzles, with in vitro ribosome synthesis, assembly, and translation in multiple design-build-test-learn cycles. We apply our framework to discover mutant rRNA sequences that improve protein synthesis in vitro and cell growth in vivo, relative to wild type ribosomes, under diverse environmental conditions. This work provides insights into rRNA sequence-function relationships and has implications for synthetic biology.
Long-lived electronic spin qubits in single-walled carbon nanotubes
Authors: Chen Jia-Shiang , Trerayapiwat Kasidet Jing , Sun Lei , Krzyaniak Matthew D. , Wasielewski Michael R. , Rajh Tijana , Sharifzadeh Sahar , Ma Xuedan
Published: February 2023

Electron spins in solid-state systems offer the promise of spin-based information processing devices. Single-walled carbon nanotubes (SWCNTs), an all-carbon one-dimensional material whose spin-free environment and weak spin-orbit coupling promise long spin coherence times, offer a diverse degree of freedom for extended range of functionality not available to bulk systems. A key requirement limiting spin qubit implementation in SWCNTs is disciplined confinement of isolated spins. Here, we report the creation of highly confined electron spins in SWCNTs via a bottom-up approach. The record long coherence time of 8.2 µs and spin-lattice relaxation time of 13 ms of these electronic spin qubits allow demonstration of quantum control operation manifested as Rabi oscillation. Investigation of the decoherence mechanism reveals an intrinsic coherence time of tens of milliseconds. These findings evident that combining molecular approaches with inorganic crystalline systems provides a powerful route for reproducible and scalable quantum materials suitable for qubit applications.
Long-lifetime water-washable ceramic catalyst filter for air purification
Authors: Kwon Hyuk Jae , Yang Dong Sik , Koo Min Seok , Ji Sang Min , Jeong Joonseon , Oh Sehyeong , Kuk Su Keun , Heo Hyeon-su , Ham Dong Jin , Kim Mijong , Choi Hyoungwoo , Lee Jong-Min , Shur Joong-Won , Lee Woo-Jin , Bin Chang-Ook , Timofeev Nikolay , Wu Huiqing , Wang Liming , Lee Taewoo , Jacob Daniel J. , Lee Hyun Chul
Published: February 2023

Particulate matter (PM) and volatile organic compounds (VOCs) are recognised as hazardous air pollutants threatening human health. Disposable filters are generally used for air purification despite frequent replacement and waste generation problems. However, the development of a novel regenerable and robust filter for long-term use is a huge challenge. Here, we report on a new class of facile water-washing regenerable ceramic catalyst filters (CCFs), developed to simultaneously remove PM (>95%) and VOCs (>82%) in single-pass and maximized space efficiency by coating the inner and outer filter channels with an inorganic membrane and a Cu2O/TiO2 photocatalyst, respectively. The CCFs reveal four-fold increase in the maximum dust loading capacity (approximately 20 g/L) in relation to conventional filters (5 g/L), and can be reused after ten regeneration capability with simple water washing retaining initial PM and VOC removal performances. Thus, the CCFs can be well-suited for indoor and outdoor air purification for 20 years, which shows a huge increase in lifetime compared to the 6-month lifespan of conventional filters. Finally, we believe that the development and implementation of CCFs for air purification can open new avenues for sustainable technology through renewability and zero-waste generation.
Local inversion-symmetry breaking in a bismuthate high-Tc superconductor
Authors: Griffitt S. , Spaić M. , Joe J. , Anderson Z. W. , Zhai D. , Krogstad M. J. , Osborn R. , Pelc D. , Greven M.
Published: February 2023

The doped perovskite BaBiO3exhibits a maximum superconducting transition temperature (Tc) of 34 K and was the first high-Tcoxide to be discovered, yet pivotal questions regarding the nature of both the metallic and superconducting states remain unresolved. Although it is generally thought that superconductivity in the bismuthates is of the conventionals-wave type, the pairing mechanism is still debated, with strong electron-phonon coupling and bismuth valence or bond disproportionation possibly playing a role. Here we use diffuse x-ray scattering and Monte Carlo modeling to study the local structure of Ba1-xKxBiO3across its insulator-metal boundary. We find no evidence for either long- or short-range disproportionation, which resolves a major conundrum, as disproportionation and the related polaronic effects are likely not relevant for the metallic and superconducting states. Instead, we uncover nanoscale structural correlations that break inversion symmetry, with far-reaching implications for the electronic physics. This unexpected finding furthermore establishes that the bismuthates belong to the broader classes of materials with hidden spin-orbit coupling and a tendency towards inversion-breaking displacements.
Efficient and stable organic solar cells enabled by multicomponent photoactive layer based on one-pot polymerization
Authors: Liu Bin , Sun Huiliang , Lee Jin-Woo , Jiang Zhengyan , Qiao Junqin , Wang Junwei , Yang Jie , Feng Kui , Liao Qiaogan , An Mingwei , Li Bolin , Han Dongxue , Xu Baomin , Lian Hongzhen , Niu Li , Kim Bumjoon J. , Guo Xugang
Published: February 2023

Degradation of the kinetically trapped bulk heterojunction film morphology in organic solar cells (OSCs) remains a grand challenge for their practical application. Herein, we demonstrate highly thermally stable OSCs using multicomponent photoactive layer synthesized via a facile one-pot polymerization, which show the advantages of low synthetic cost and simplified device fabrication. The OSCs based on multicomponent photoactive layer deliver a high power conversion efficiency of 11.8% and exhibit excellent device stability for over 1000 h (>80% of their initial efficiency retention), realizing a balance between device efficiency and operational lifetime for OSCs. In-depth opto-electrical and morphological properties characterizations revealed that the dominant PM6-b-L15 block polymers with backbone entanglement and the small fraction of PM6 and L15 polymers synergistically contribute to the frozen fine-tuned film morphology and maintain well-balanced charge transport under long-time operation. These findings pave the way towards the development of low-cost and long-term stable OSCs.
Chemoproteomic discovery of a human RNA ligase
Authors: Yuan Yizhi , Stumpf Florian M. , Schlor Lisa A. , Schmidt Olivia P. , Saumer Philip , Huber Luisa B. , Frese Matthias , Höllmüller Eva , Scheffner Martin , Stengel Florian , Diederichs Kay , Marx Andreas
Published: February 2023

RNA ligases are present across all forms of life. While enzymatic RNA ligation between 5′-PO4 and 3′-OH termini is prevalent in viruses, fungi, and plants, such RNA ligases are yet to be identified in vertebrates. Here, using a nucleotide-based chemical probe targeting human AMPylated proteome, we have enriched and identified the hitherto uncharacterised human protein chromosome 12 open reading frame 29 (C12orf29) as a human enzyme promoting RNA ligation between 5′-PO4 and 3′-OH termini. C12orf29 catalyses ATP-dependent RNA ligation via a three-step mechanism, involving tandem auto- and RNA AMPylation. Knock-out of C12ORF29 gene impedes the cellular resilience to oxidative stress featuring concurrent RNA degradation, which suggests a role of C12orf29 in maintaining RNA integrity. These data provide the groundwork for establishing a human RNA repair pathway.
Sugar transporter Slc37a2 regulates bone metabolism in mice via a tubular lysosomal network in osteoclasts
Authors: Ng Pei Ying , Ribet Amy B. P. , Guo Qiang , Mullin Benjamin H. , Tan Jamie W. Y. , Landao-Bassonga Euphemie , Stephens Sébastien , Chen Kai , Yuan Jinbo , Abudulai Laila , Bollen Maike , Nguyen Edward T. T. T. , Kular Jasreen , Papadimitriou John M. , Søe Kent , Teasdale Rohan D. , Xu Jiake , Parton Robert G. , Takayanagi Hiroshi , Pavlos Nathan J.
Published: February 2023

Osteoclasts are giant bone-digesting cells that harbor specialized lysosome-related organelles termed secretory lysosomes (SLs). SLs store cathepsin K and serve as a membrane precursor to the ruffled border, the osteoclast’s ‘resorptive apparatus’. Yet, the molecular composition and spatiotemporal organization of SLs remains incompletely understood. Here, using organelle-resolution proteomics, we identify member a2 of the solute carrier 37 family (Slc37a2) as a SL sugar transporter. We demonstrate in mice that Slc37a2 localizes to the SL limiting membrane and that these organelles adopt a hitherto unnoticed but dynamic tubular network in living osteoclasts that is required for bone digestion. Accordingly, mice lacking Slc37a2 accrue high bone mass owing to uncoupled bone metabolism and disturbances in SL export of monosaccharide sugars, a prerequisite for SL delivery to the bone-lining osteoclast plasma membrane. Thus, Slc37a2 is a physiological component of the osteoclast’s unique secretory organelle and a potential therapeutic target for metabolic bone diseases.
SVEP1 is an endogenous ligand for the orphan receptor PEAR1
Authors: Elenbaas Jared S. , Pudupakkam Upasana , Ashworth Katrina J. , Kang Chul Joo , Patel Ved , Santana Katherine , Jung In-Hyuk , Lee Paul C. , Burks Kendall H. , Amrute Junedh M. , Mecham Robert P. , Halabi Carmen M. , Alisio Arturo , Di Paola Jorge , Stitziel Nathan O.
Published: February 2023

Sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1) is an extracellular matrix protein that causally promotes vascular disease and associates with platelet reactivity in humans. Here, using a human genomic and proteomic approach, we identify a high affinity, disease-relevant, and potentially targetable interaction between SVEP1 and the orphan receptor Platelet and Endothelial Aggregation Receptor 1 (PEAR1). This interaction promotes PEAR1 phosphorylation and disease associated AKT/mTOR signaling in vascular cells and platelets. Mice lacking SVEP1 have reduced platelet activation, and exogenous SVEP1 induces PEAR1-dependent activation of platelets. SVEP1 and PEAR1 causally and concordantly relate to platelet phenotypes and cardiovascular disease in humans, as determined by Mendelian Randomization. Targeting this receptor-ligand interaction may be a viable therapeutic strategy to treat or prevent cardiovascular and thrombotic disease.
CvkR is a MerR-type transcriptional repressor of class 2 type V-K CRISPR-associated transposase systems
Authors: Ziemann Marcus , Reimann Viktoria , Liang Yajing , Shi Yue , Ma Honglei , Xie Yuman , Li Hui , Zhu Tao , Lu Xuefeng , Hess Wolfgang R.
Published: February 2023

Certain CRISPR-Cas elements integrate into Tn7-like transposons, forming CRISPR-associated transposon (CAST) systems. How the activity of these systems is controlled in situ has remained largely unknown. Here we characterize the MerR-type transcriptional regulator Alr3614 that is encoded by one of the CAST (AnCAST) system genes in the genome of cyanobacteriumAnabaenasp. PCC 7120. We identify a number of Alr3614 homologs across cyanobacteria and suggest naming these regulators CvkR for Cas V-K repressors. Alr3614/CvkR is translated from leaderless mRNA and represses the AnCAST core modulescas12kandtnsB directly, and indirectly the abundance of the tracr-CRISPR RNA. We identify a widely conserved CvkR binding motif 5’-AnnACATnATGTnnT-3’. Crystal structure of CvkR at 1.6 Å resolution reveals that it comprises distinct dimerization and potential effector-binding domains and that it assembles into a homodimer, representing a discrete structural subfamily of MerR regulators. CvkR repressors are at the core of a widely conserved regulatory mechanism that controls type V-K CAST systems.
Phosphoproteomics reveals rewiring of the insulin signaling network and multi-nodal defects in insulin resistance
Authors: Fazakerley Daniel J. , van Gerwen Julian , Cooke Kristen C. , Duan Xiaowen , Needham Elise J. , Díaz-Vegas Alexis , Madsen Søren , Norris Dougall M. , Shun-Shion Amber S. , Krycer James R. , Burchfield James G. , Yang Pengyi , Wade Mark R. , Brozinick Joseph T. , James David E. , Humphrey Sean J.
Published: February 2023

The failure of metabolic tissues to appropriately respond to insulin (“insulin resistance”) is an early marker in the pathogenesis of type 2 diabetes. Protein phosphorylation is central to the adipocyte insulin response, but how adipocyte signaling networks are dysregulated upon insulin resistance is unknown. Here we employ phosphoproteomics to delineate insulin signal transduction in adipocyte cells and adipose tissue. Across a range of insults causing insulin resistance, we observe a marked rewiring of the insulin signaling network. This includes both attenuated insulin-responsive phosphorylation, and the emergence of phosphorylation uniquely insulin-regulated in insulin resistance. Identifying dysregulated phosphosites common to multiple insults reveals subnetworks containing non-canonical regulators of insulin action, such as MARK2/3, and causal drivers of insulin resistance. The presence of several bona fide GSK3 substrates among these phosphosites led us to establish a pipeline for identifying context-specific kinase substrates, revealing widespread dysregulation of GSK3 signaling. Pharmacological inhibition of GSK3 partially reverses insulin resistance in cells and tissue explants. These data highlight that insulin resistance is a multi-nodal signaling defect that includes dysregulated MARK2/3 and GSK3 activity.
Reciprocal modulation of ammonia and melanin production has implications for cryptococcal virulence
Authors: Baker Rosanna P. , Casadevall Arturo
Published: February 2023

The fungus Cryptococcus neoformans is the causative agent of cryptococcosis, a disease that is uniformly lethal unless treated with antifungal drugs, yet current regimens are hindered by host toxicity and pathogen resistance. An attractive alternative approach to combat this deadly disease is the direct targeting of pathogen-derived virulence mechanisms. C. neoformans expresses multiple virulence factors that have been studied previously as isolated entities. Among these, are urease, which increases phagosomal pH and promotes brain invasion, and melanization, which protects against immune cells and antifungal treatments. Here we report a reciprocal interdependency between these two virulence factors. Cells hydrolyzing urea release ammonia gas which acts at a distance to raise pH and increase melanization rates for nearby cells, which in turn reduces secretion of urease-carrying extracellular vesicles. This reciprocal relationship manifests as an emergent property that may explain why targeting isolated virulence mechanisms for drug development has been difficult and argues for a more holistic approach that considers the virulence composite.