bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Production Effect in Memory Reveals a Balanced Bilingual Advantage
Authors: Schwell Ronit , Icht Michal , Reznick Julia , Mama Yaniv
Published: July 2024

Abstract: There is evidence suggesting that bilingual individuals demonstrate an advantage over monolinguals in performing various tasks related to memory and executive functions. The characteristics of this bilingual advantage are not unanimously agreed upon in the literature, and some even doubt it exists. The heterogeneity of the bilingual population may explain this inconsistency. Hence, it is important to identify different subgroups of bilinguals and characterize their cognitive performance. The current study focuses on the production effect, a well-established memory phenomenon, in bilingual young adults differing in their English and Hebrew proficiency levels, and the possible balanced bilingual advantage. The aims of this study are (1) to evaluate the production effect in three groups of bilingual participants: English-dominant bilinguals, Hebrew-dominant bilinguals, and balanced bilinguals, and (2) to examine whether memory advantage depends on varying degrees of bilingualism. One hundred twenty-one bilingual young adults who speak English and Hebrew at different levels participated. All learned lists of familiar words, in English and Hebrew, half by reading aloud and half by silent reading, followed by free recall tests. As expected, a production effect (better memory for aloud words than for silent words) was found for all groups in both languages. Balanced bilinguals remembered more words than did dominant participants, demonstrating a memory advantage in both languages. These findings support the hypothesis that the presence of cognitive advantage in bilingualism depends on the acquisition of a good proficiency level in each of the languages, with direct implications for family language policy and bilingual education.
Singing Does Not Necessarily Improve Memory More Than Reading Aloud
Authors: Whitridge Jedidiah W. , Huff Mark J. , Ozubko Jason D. , Bürkner Paul C. , Lahey Chelsea D. , Fawcett Jonathan M.
Published: July 2024

Abstract: The production effect refers to the finding that words read aloud are better remembered than words read silently. This finding is typically attributed to the presence of additional sensorimotor features appended to the memory trace by the act of reading aloud, which are not present for items read silently. Supporting this perspective, the production effect tends to be larger for singing (the singing superiority effect) than reading aloud, possibly due to the inclusion of further sensorimotor features (e.g., more pronounced tone). However, the singing superiority effect has not always replicated. Across four experiments, we demonstrate a production effect for items read aloud but observe a singing superiority effect only when items are tested in the same color in which they were studied (with foils randomized to color). A series of meta-analytic models revealed the singing superiority effect to be smaller than previously thought and to emerge only when test items are presented in the same color in which they were studied. This outcome is inconsistent with common distinctiveness-based theoretical accounts.
European and US Aeromedical Authority Guidance for Neurocognitive Evaluation of Airline Pilots With Mental Disorders
Authors: Vuorio Alpo , Suhonen-Malm Anna-Stina , Budowle Bruce , Bor Robert
Published: July 2024

Abstract: Commercial airline pilots must exhibit specific neurocognitive skills and aptitudes to perform their safety-critical roles. This review addresses neuropsychological assessment in mental disorders derived from guidance developed by European and US aviation authorities as well as indications in the current literature in relation to major depression and suicidality, self-harm, attention-deficit/hyperactivity disorder, posttraumatic stress disorder, and bipolar disorder in aeromedical evaluations. Several studies show that cognitive functioning may be impaired during major depression. The results of neurocognitive assessments provide useful information about a pilot’s performance. Obstacles to referring crew for neuropsychological testing are the paucity of neuropsychological specialists to undertake assessments and aeromedical examiners’ varied training and experience in assessing mental health problems of pilots in general.
Hydro‐Biogeochemical Controls on Nitrate Removal: Insights From Artificial Emergent Vegetation Experiments in a Recirculating Flume Mesocosm
Authors: Waterman B. R. , Hansen A. T.
Published: July 2024

Environments with aquatic vegetation can mitigate excess nitrogen (N) loads to downstream waters. However, complex interactions between multiple hydro‐biogeochemical processes control N removal within these environments and thus complicate implementation of aquatic vegetation as a management solution. Here, we conducted controlled experiments using a canopy of artificial rigid emergent vegetation in a recirculating flume mesocosm to quantify differences in rates of mass transport and nitrate (NO3−N) removal between the open channel‐canopy interface across a range in nominal water velocities. We found NO3−N removal rates were 86% greater with the canopy present compared to no canopy control experiments and were always greatest at intermediate velocity (6 cms−1). With the canopy present, a hydrodynamically distinct mixing layer formed at the open channel‐canopy interface, and resources, such as carbon (C), CN ratios, and dissolved oxygen, differed between open channel and vegetated canopy. The dimensionless Damköhler (Da) number indicated NO3−N removal rates were reaction limited (Da << 1) for all canopy experiments, yet across all velocities NO3−N removal was more reaction limited in the open channel than the canopy due to higher rates of mixing and less contact time with reactive surfaces. We found significant relationships between NO3−N removal rates and Da with hydrodynamic metrics (mixing zone width and Reynolds number, respectively), suggesting that NO3−N removal in the presence of rigid vegetation can be enhanced by manipulating flow conditions. These findings demonstrate that rigid emergent vegetation‐open channel interfaces create conditions conducive for NO3−N removal and with effective management can improve overall water quality.
Home Waste Audit: A Community Science Activity to Increase Waste Literacy and Reduce Household Waste
Authors: De Frond Hannah , Gutierrez Rafaela F. , Debreceni Susan , Rochman Chelsea M.
Published: July 2024

The amount of household waste produced worldwide is increasing every year. In combination with other actions to reduce waste production and improve waste management, community engagement and community‐focused programs are needed to motivate the public to change their behavior in such a way that reduces their waste generation and increases the accuracy of waste sorting. It is also helpful for people to become more waste literate to empower them to be part of the solution. The Home Waste Audit (HWA) is a community science activity designed to increase waste literacy and reduce household waste. In the HWA, participants record their waste for a set period of time, research their local waste streams, and complete surveys to share perceptions of household waste habits. Here, we present data from a HWA conducted in 2021 as a case study. Before the audit, 60% of participants underestimated their weekly waste generation. Throughout the HWA, weekly waste count among households decreased by 31%. Participants found purchasing items with less/no packaging and avoiding single‐use plastics challenging. Easier changes included learning which items can/cannot be recycled and repurposing waste items. Several changes to waste habits were maintained 1 year after participation. These results demonstrate that the HWA is an effective tool for individuals to be a part of the solution by learning about local waste streams, reducing waste production, and accurately managing their household waste.
Ozone Mortality Burden Changes Driven by Population Aging and Regional Inequity in China in 2013–2050
Authors: Chen Xiaokang , Jiang Zhe , Shen Yanan , Wang Shuxiao , Shindell Drew , Zhang Yuqiang
Published: July 2024

Air pollution exposure is closely linked to population age and socioeconomic status. Population aging and imbalance in regional economy are thus anticipated to have important implications on ozone (O3)‐related health impacts. Here we provide a driver analysis for O3 mortality burden due to respiratory disease in China over 2013–2050 driven by population aging and regional inequity. Unexpectedly, we find that population aging is estimated to result in dramatic rises in annual O3 mortality burden in China; by 56, 101–137, and 298–485 thousand over the periods 2013–2020, 2020–2030, and 2030–2050, respectively. This reflects the exponential rise in baseline mortality rates with increasing age. The aging‐induced mortality burden rise in 2030–2050 is surprisingly large, as it is comparable to the net national mortality burden due to O3 exposure in 2030 (359–399 thousand yr−1). The health impacts of O3 pollution, shown as mortality burden per capita, are inequitably distributed, with more severe effects in less developed provinces than their developed counterparts by 23.1% and 21.5% in 2019 and 2030, respectively. However, the regional inequity in O3 mortality burden is expected to be mitigated in 2050. This temporal variation reflects evolving demographic dividend characterized by a larger proportion of younger individuals in developed regions. These findings are critical for targeted improvement of healthcare services to ensure the sustainability of social development.
Termination of Mid‐to‐Lower Crustal Extrusion on the Eastern Flank of the Eastern Himalayan Syntaxis: Implied From Trans‐Regional Ambient Noise Tomography
Authors: Tian Yining , Jiang Mingming , He Yumei , Ai Yinshuang , Hou Guangbing , Ling Yuan , Thant Myo , Sein Kyaing
Published: July 2024

The Eastern Himalayan Syntaxis (EHS) serves as a natural laboratory for the study of intense continental collision and lateral extrusion tectonics. By aiming at the intricate tectonic dynamics south and southeast of the EHS, we integrate seismic data from new broadband stations in central Myanmar with permanent stations in southeastern Tibet to establish a high‐resolution 3‐D shear wave velocity model through ambient noise surface wave tomography. Our imaging results reveal distinct differences in crustal seismic velocity structures between the West Burma Block, Chuan‐Dian Block, and the Shan Plateau, highlighting the extent of oblique subduction and restricted crustal extrusion. Notably, two north‐south oriented low‐velocity zones in the mid‐to‐lower crust of southeastern Tibet are mainly confined within the Chuan‐Dian Block and terminate near the Red River Fault, with limited extension into the Shan Plateau.
How Did the Merger With a Tropical Depression Amplify the Rapid Weakening of Super Typhoon Hinnamnor (2022)?
Authors: Zheng Minglin , Zhang Ze , Zhang Weimin
Published: July 2024

Grasping the physical interactions when two tropical cyclones (TCs) (TC) are in proximity is essential for boosting the accuracy of TC forecasts. This study dissects an uncommon scenario wherein the merging with Tropical Depression 13 W significantly hastened the rapid weakening of Super Typhoon Hinnamnor (2022), utilizing comparative experiments with and without 13 W in simulation's initial field. The findings reveal strong correlations between the merger, amplified environmental vertical wind shear (VWS), and Hinnamnor's consecutive weakening, unfolding in two stages— “top‐down” (Stage 1) and “bottom‐up” weakening (Stage 2) stage. In Stage 1, 13 W led to downdrafts from upper level, hindering the eyewall updrafts and weakening the warm core. In Stage 2, 13 W merged into Hinnamnor's outer rainband, introduced low‐entropy air into the boundary layer and also vied with the eyewall for energy. This research emphasizes that even minor, less‐intense vortices can have profound impacts on the rapid intensity change in TCs.
Improved Simulation of Antarctic Sea Ice by Parameterized Thickness of New Ice in a Coupled Climate Model
Authors: Fang Yongjie , Yao Junchen , Wu Tongwen , Wu Fanghua , Li Jianglong
Published: July 2024

Sea ice formation over open water exerts critical control on polar atmosphere‐ocean‐ice interactions, but is only crudely represented in sea ice models. In this study, a collection depth parameterization of new ice for flux polynya models is modified by including the sea ice concentration and ice growth rate as additional factors. We evaluated it in a climate model BCC‐CSM2‐MR and found that it improves simulation of Antarctic sea ice concentration and thickness in most of Indian and Atlantic sectors. Disagreement between the observed Antarctic sea ice expansion during 1981–2014 and the modeled decline still exists but is mitigated when the modified scheme is implemented. Further analysis indicates that these improvements are associated with the overcoming of premature closure of open water, which enhances the response of ocean to surface wind intensification during 1981–2014, and consequently slowdowns the sea surface temperature increase and the resulting Antarctic sea ice reduction.
Role of Martian Crustal Fields in Ionospheric Electron Density Distribution and Subsequent South‐North Asymmetry: Insights From Multi‐Year MAVEN Observations During (MYs 33–36)
Authors: Nayak Chinmaya , Yiğit Erdal , Remya Bhanu , Bulusu Jayashree , Devanandhan S. , Singh Satyavir , Dimri A. P. , Padhye Pranjali
Published: July 2024

This study uses Mars Atmosphere and Volatile EvolutioN observations of electron density and magnetic field for a period of four Martian years (MYs 33–36) (∼8 Earth years) to investigate the effects of Martian crustal magnetic fields on the distribution and variability of Mars' ionosphere. The results show a clear enhancement in electron density in the southern hemisphere in the region where the strong crustal magnetic fields are present with the longitudes between 120° and 240° (i.e., the central longitude), which is in agreement with previous studies. On the contrary, the corresponding northern hemisphere region in the central longitudes shows an exactly opposite behavior that the electron density is lower compared to the surrounding longitude regions. These effects are found to be primarily dayside phenomena. As opposed to dayside, the nightside electron density in the central longitudes are slightly reduced at altitudes below 200 km, compared to longitudes on its western and eastern sides. Above 200 km, the nightside effects are not very clear. Significant hemispheric asymmetry is observed in the longitude regions of enhanced crustal magnetic fields compared to other longitude regions during the daytime. This dayside south‐north asymmetry in the central longitude region is observed to be a constant feature across all seasons. However, on the nightside, the south‐north asymmetry remains more or less similar across all longitude regions, during all seasons implying a weakened control of the crustal fields over the nightside ionosphere. Even then, the southern hemisphere retains a stronger nightside ionosphere during all seasons except summer.
Xenolith Petrochronology (San Luis Potosi, Mexico) Constrains Heat Sources for Cenozoic Ultrahigh‐Temperature Metamorphism in the Lower Crust
Authors: Droubi Omar Khalil , Cipar Jacob H. , Smye Andrew J. , Garber Joshua M.
Published: July 2024

Ultrahigh‐temperature (UHT; >900°C) metamorphism drives crustal differentiation and is widely recognized in the rock record, but its geodynamic causes are debated. Previous work on granulite‐facies metapelite xenoliths from San Luis Potosí, Mexico suggests the lower crust experienced a protracted UHT metamorphic event that coincided with the onset of regional extension. To determine the duration, conditions, and heat sources of UHT metamorphism recorded by these xenoliths, this study characterizes the major‐element, trace‐element, and U‐Pb isotopic systematics of quartz, rutile, feldspar, garnet, and zircon by in situ electron microprobe (EPMA) and laser‐ablation inductively coupled‐plasma mass spectrometry (LA‐ICP‐MS), and augments these data with detailed petrography, thermobarometry, phase equilibria modeling, and diffusion modeling. Thermobarometry and phase equilibria modeling suggest peak metamorphic conditions exceeded 0.7 GPa and 900°C. Zircon petrochronology confirms >15 Myr of UHT conditions since its onset at ∼30 Ma. A small population of zircon record elevated temperatures following transition from backarc compression to extension during the waning stages of orogenesis (60–37 Ma). Garnet preserves trace‐element zoning and mineral inclusions consistent with suprasolidus garnet growth and subsequent compositional modification by intracrystalline rare‐earth element diffusion during protracted heating, with diffusion chronometry timescales in agreement with zircon data, followed by fluid‐driven remobilization of trace elements along now‐healed fractures within ∼1 Myr of eruption. In sum, these data are most compatible with lithospheric mantle attenuation or removal as the dominant heat transport mechanism driving synextensional UHT metamorphism and crustal melting, which has bearing on models for crustal differentiation and formation of modern and ancient granulite terranes globally.
Leisure-time physical activity motives and perceived gains for individuals with spinal cord injury
Authors: Watson Paul K. , Stendell Laura , Quel de Oliveira Camila , Middleton James W. , Arora Mohit , Davis Glen M.
Published: July 2024

Study design

Longitudinal cross-sectional.

Objectives

To examine motives to, and perceived gains from, leisure-time physical activity (LTPA) in people with spinal cord injury (SCI).

Setting

Community.

Methods

One hundred and five physically active individuals with SCI undertook an online survey and a semi-structured interview. The Exercise Motives and Gains Inventory was used to examine the movies towards, and the gains from LTPA, and the Leisure-time Physical Activity Questionnaire was administered via interview to gather LTPA data. A cross-sectional analysis, which included descriptive, inferential, and regression statistics, was conducted on all participants, physical activity (PA) guideline adherers and PA guideline non-adherers.

Results

The most common motives for LTPA were improvements in health and fitness, management of appearance and weight, and avoidance of illness. The most common gains from LTPA included improved health, fitness, strength and endurance, increased nimbleness, and enjoyment and revitalisation.

Conclusions

Whilst health enhancement appears to be a significant motivator for LTPA, other psychosocial aspects, such as affiliation and revitalisation, appear to influence engagement and volume of LTPA. Regular LTPA should be encouraged for its health benefits, and emphasis should be placed on promoting its ability to reduce illness, facilitate affiliation, and manage stress.
Whole genome sequencing study of identical twins discordant for psychosis
Authors: Ormond Cathal , Ryan Niamh M. , Hedman Anna M. , Cannon Tyrone D. , Sullivan Patrick F. , Gill Michael , Hultman Christina , Heron Elizabeth A. , Johansson Viktoria , Corvin Aiden
Published: July 2024

Monozygotic (MZ) twins are often thought to have identical genomes, but recent work has shown that early post-zygotic events can result in a spectrum of DNA variants that are different between MZ twins. Such variants may explain phenotypic discordance and contribute to disease etiology. Here we performed whole genome sequencing in 17 pairs of MZ twins discordant for a psychotic disorder (schizophrenia, schizoaffective disorder or bipolar disorder). We examined various classes of rare variants that are discordant within a twin pair. We identified four genes harboring rare, predicted deleterious missense variants that were private to an affected individual in the cohort. Variants in FOXN1 and FLOT2 would have been categorized as damaging from recent schizophrenia and bipolar exome sequencing studies. Additionally, we identified four rare genic copy number variants (CNVs) private to an affected sample, two of which overlapped genes that have shown evidence for association with schizophrenia or bipolar disorder. One such CNV was a 3q29 duplication previously implicated in autism and developmental delay. We have performed the largest MZ twin study for discordant psychotic phenotypes to date. These findings warrant further investigation using other analytical approaches.
TOX2 nuclear-cytosol translocation is linked to leukemogenesis of acute T-cell leukemia by repressing TIM3 transcription
Authors: Li Anzhou , Zhang Junbao , Zhan Liangping , Liu Xiufeng , Zeng Xiliang , Zhu Qian , Wang Zifeng , Li Jiang
Published: July 2024

Nuclear factors TOX and TOX2 upregulate TIM3 expression and lead to T-cell exhaustion in malignancies. Here, we demonstrate two distinct TIM3 expression patterns (high & low) with high TOX and TOX2 levels in T-cell acute lymphoblastic leukemia (T-ALL) specimens and cell lines. However, the mechanisms regulated by TOX and TIM3 signaling in leukemogenesis are unclear. We found that TOX and TOX2 proteins each directly upregulated HAVCR2 transcription, while the cellular localization of TOX2 was different in Jurkat and MOLT3 cells (nucleus) and lymphoblastic cell T2 and normal T cells (cytoplasm). Nuclear TOX and TOX2 formed a protein complex and repressed HAVCR2 promoter activity by recruiting transcriptional corepressor LCOR and deacetylase HDAC3. The nuclear-cytosol translocation of TOX2 was deacetylation-dependent and cooperatively mediated by deacetylase Sirt1 and kinase TBK1. Radiation damage induced TOX2 nuclear translocation and decreased Sirt1, TIM3, and caspase 1 expression in normal T cells. Accordingly, knockdown of TOX, TOX2 or LCOR; HDAC3 inhibition; or TIM3 overexpression induced Jurkat cell apoptosis in vitro and slow growth in vivo. Thus, our findings demonstrate a novel regulatory mechanism involving TOX-TOX2 and the TIM3 pathway in the leukemogenesis of T-ALL.
Endoplasmic reticulum stress—a key guardian in cancer
Authors: Zhang Wenlong , Shi Yidan , Oyang Linda , Cui Shiwen , Li Shizhen , Li Jinyun , Liu Lin , Li Yun , Peng Mingjing , Tan Shiming , Xia Longzheng , Lin Jinguan , Xu Xuemeng , Wu Nayiyuan , Peng Qiu , Tang Yanyan , Luo Xia , Liao Qianjin , Jiang Xianjie , Zhou Yujuan
Published: July 2024

Endoplasmic reticulum stress (ERS) is a cellular stress response characterized by excessive contraction of the endoplasmic reticulum (ER). It is a pathological hallmark of many diseases, such as diabetes, obesity, and neurodegenerative diseases. In the unique growth characteristic and varied microenvironment of cancer, high levels of stress are necessary to maintain the rapid proliferation and metastasis of tumor cells. This process is closely related to ERS, which enhances the ability of tumor cells to adapt to unfavorable environments and promotes the malignant progression of cancer. In this paper, we review the roles and mechanisms of ERS in tumor cell proliferation, apoptosis, metastasis, angiogenesis, drug resistance, cellular metabolism, and immune response. We found that ERS can modulate tumor progression via the unfolded protein response (UPR) signaling of IRE1, PERK, and ATF6. Targeting the ERS may be a new strategy to attenuate the protective effects of ERS on cancer. This manuscript explores the potential of ERS-targeted therapies, detailing the mechanisms through which ERS influences cancer progression and highlighting experimental and clinical evidence supporting these strategies. Through this review, we aim to deepen our understanding of the role of ER stress in cancer development and provide new insights for cancer therapy.
Sequence-to-sequence translation from mass spectra to peptides with a transformer model
Authors: Yilmaz Melih , Fondrie William E. , Bittremieux Wout , Melendez Carlo F. , Nelson Rowan , Ananth Varun , Oh Sewoong , Noble William Stafford
Published: July 2024

A fundamental challenge in mass spectrometry-based proteomics is the identification of the peptide that generated each acquired tandem mass spectrum. Approaches that leverage known peptide sequence databases cannot detect unexpected peptides and can be impractical or impossible to apply in some settings. Thus, the ability to assign peptide sequences to tandem mass spectra without prior information—de novo peptide sequencing—is valuable for tasks including antibody sequencing, immunopeptidomics, and metaproteomics. Although many methods have been developed to address this problem, it remains an outstanding challenge in part due to the difficulty of modeling the irregular data structure of tandem mass spectra. Here, we describe Casanovo, a machine learning model that uses a transformer neural network architecture to translate the sequence of peaks in a tandem mass spectrum into the sequence of amino acids that comprise the generating peptide. We train a Casanovo model from 30 million labeled spectra and demonstrate that the model outperforms several state-of-the-art methods on a cross-species benchmark dataset. We also develop a version of Casanovo that is fine-tuned for non-enzymatic peptides. Finally, we demonstrate that Casanovo’s superior performance improves the analysis of immunopeptidomics and metaproteomics experiments and allows us to delve deeper into the dark proteome.
Multilevel neurium-mimetic individualized graft via additive manufacturing for efficient tissue repair
Authors: Kong Lingchi , Gao Xin , Yao Xiangyun , Xie Haijiao , Kang Qinglin , Sun Wei , You Zhengwei , Qian Yun , Fan Cunyi
Published: July 2024

Complicated peripheral nerve injuries or defects, especially at branching sites, remain a prominent clinical challenge after the application of different treatment strategies. Current nerve grafts fail to match the expected shape and size for delicate and precise branched nerve repair on a case-by-case basis, and there is a lack of geometrical and microscale regenerative navigation. In this study, we develop a sugar painting-inspired individualized multilevel epi-/peri-/endoneurium-mimetic device (SpinMed) to customize natural cues, featuring a selectively protective outer sheath and an instructive core, to support rapid vascular reconstruction and consequent efficient neurite extension along the defect area. The biomimetic perineurium dictates host-guest crosslinking in which new vessels secrete multimerin 1 binding to the fibroin filler surface as an anchor, contributing to the biological endoneurium that promotes Schwann cell homing and remyelination. SpinMed implantation into rat sciatic nerve defects yields a satisfactory outcome in terms of structural reconstruction, with sensory and locomotive function restoration. We further customize SpinMed grafts based on anatomy and digital imaging, achieving rapid repair of the nerve trunk and branches superior to that achieved by autografts and decellularized grafts in a specific beagle nerve defect model, with reliable biosafety. Overall, this intelligent art-inspired biomimetic design offers a facile way to customize sophisticated high-performance nerve grafts and holds great potential for application in translational regenerative medicine.
Modular RNA motifs for orthogonal phase separated compartments
Authors: Stewart Jaimie Marie , Li Shiyi , Tang Anli A. , Klocke Melissa Ann , Gobry Martin Vincent , Fabrini Giacomo , Di Michele Lorenzo , Rothemund Paul W. K. , Franco Elisa
Published: July 2024

Recent discoveries in biology have highlighted the importance of protein and RNA-based condensates as an alternative to classical membrane-bound organelles. Here, we demonstrate the design of pure RNA condensates from nanostructured, star-shaped RNA motifs. We generate condensates using two different RNA nanostar architectures: multi-stranded nanostars whose binding interactions are programmed via linear overhangs, and single-stranded nanostars whose interactions are programmed via kissing loops. Through systematic sequence design, we demonstrate that both architectures can produce orthogonal (distinct and immiscible) condensates, which can be individually tracked via fluorogenic aptamers. We also show that aptamers make it possible to recruit peptides and proteins to the condensates with high specificity. Successful co-transcriptional formation of condensates from single-stranded nanostars suggests that they may be genetically encoded and produced in living cells. We provide a library of orthogonal RNA condensates that can be modularly customized and offer a route toward creating systems of functional artificial organelles for the task of compartmentalizing molecules and biochemical reactions.
Programmable DNA pyrimidine base editing via engineered uracil-DNA glycosylase
Authors: Yi Zongyi , Zhang Xiaoxue , Wei Xiaoxu , Li Jiayi , Ren Jiwu , Zhang Xue , Zhang Yike , Tang Huixian , Chang Xiwen , Yu Ying , Wei Wensheng
Published: July 2024

DNA base editing technologies predominantly utilize engineered deaminases, limiting their ability to edit thymine and guanine directly. In this study, we successfully achieve base editing of both cytidine and thymine by leveraging the translesion DNA synthesis pathway through the engineering of uracil-DNA glycosylase (UNG). Employing structure-based rational design, exploration of homologous proteins, and mutation screening, we identify a Deinococcus radiodurans UNG mutant capable of effectively editing thymine. When fused with the nickase Cas9, the engineered DrUNG protein facilitates efficient thymine base editing at endogenous sites, achieving editing efficiencies up to 55% without enrichment and exhibiting minimal cellular toxicity. This thymine base editor (TBE) exhibits high editing specificity and significantly restores IDUA enzyme activity in cells derived from patients with Hurler syndrome. TBEs represent efficient, specific, and low-toxicity approaches to base editing with potential applications in treating relevant diseases.
Evidence for multi-fragmentation and mass shedding of boulders on rubble-pile binary asteroid system (65803) Didymos
Authors: Pajola M. , Tusberti F. , Lucchetti A. , Barnouin O. , Cambioni S. , Ernst C. M. , Dotto E. , Daly R. T. , Poggiali G. , Hirabayashi M. , Nakano R. , Epifani E. Mazzotta , Chabot N. L. , Della Corte V. , Rivkin A. , Agrusa H. , Zhang Y. , Penasa L. , Ballouz R.-L. , Ivanovski S. , Murdoch N. , Rossi A. , Robin C. , Ieva S. , Vincent J. B. , Ferrari F. , Raducan S. D. , Campo-Bagatin A. , Parro L. , Benavidez P. , Tancredi G. , Karatekin Ö. , Trigo-Rodriguez J. M. , Sunshine J. , Farnham T. , Asphaug E. , Deshapriya J. D. P. , Hasselmann P. H. A. , Beccarelli J. , Schwartz S. R. , Abell P. , Michel P. , Cheng A. , Brucato J. R. , Zinzi A. , Amoroso M. , Pirrotta S. , Impresario G. , Bertini I. , Capannolo A. , Caporali S. , Ceresoli M. , Cremonese G. , Dall’Ora M. , Gai I. , Casajus L. Gomez , Gramigna E. , Manghi R. Lasagni , Lavagna M. , Lombardo M. , Modenini D. , Palumbo P. , Perna D. , Tortora P. , Zannoni M. , Zanotti G.
Published: July 2024

Asteroids smaller than 10 km are thought to be rubble piles formed from the reaccumulation of fragments produced in the catastrophic disruption of parent bodies. Ground-based observations reveal that some of these asteroids are today binary systems, in which a smaller secondary orbits a larger primary asteroid. However, how these asteroids became binary systems remains unclear. Here, we report the analysis of boulders on the surface of the stony asteroid (65803) Didymos and its moonlet, Dimorphos, from data collected by the NASA DART mission. The size-frequency distribution of boulders larger than 5 m on Dimorphos and larger than 22.8 m on Didymos confirms that both asteroids are piles of fragments produced in the catastrophic disruption of their progenitors. Dimorphos boulders smaller than 5 m have size best-fit by a Weibull distribution, which we attribute to a multi-phase fragmentation process either occurring during coalescence or during surface evolution. The density per km2 of Dimorphos boulders ≥1 m is 2.3x with respect to the one obtained for (101955) Bennu, while it is 3.0x with respect to (162173) Ryugu. Such values increase once Dimorphos boulders ≥5 m are compared with Bennu (3.5x), Ryugu (3.9x) and (25143) Itokawa (5.1x). This is of interest in the context of asteroid studies because it means that contrarily to the single bodies visited so far, binary systems might be affected by subsequential fragmentation processes that largely increase their block density per km2. Direct comparison between the surface distribution and shapes of the boulders on Didymos and Dimorphos suggest that the latter inherited its material from the former. This finding supports the hypothesis that some asteroid binary systems form through the spin up and mass shedding of a fraction of the primary asteroid.
Aging drives cerebrovascular network remodeling and functional changes in the mouse brain
Authors: Bennett Hannah C. , Zhang Qingguang , Wu Yuan-ting , Manjila Steffy B. , Chon Uree , Shin Donghui , Vanselow Daniel J. , Pi Hyun-Jae , Drew Patrick J. , Kim Yongsoo
Published: July 2024

Aging is frequently associated with compromised cerebrovasculature and pericytes. However, we do not know how normal aging differentially impacts vascular structure and function in different brain areas. Here we utilize mesoscale microscopy methods and in vivo imaging to determine detailed changes in aged murine cerebrovascular networks. Whole-brain vascular tracing shows an overall ~10% decrease in vascular length and branching density with ~7% increase in vascular radii in aged brains. Light sheet imaging with 3D immunolabeling reveals increased arteriole tortuosity of aged brains. Notably, vasculature and pericyte densities show selective and significant reductions in the deep cortical layers, hippocampal network, and basal forebrain areas. We find increased blood extravasation, implying compromised blood-brain barrier function in aged brains. Moreover, in vivo imaging in awake mice demonstrates reduced baseline and on-demand blood oxygenation despite relatively intact neurovascular coupling. Collectively, we uncover regional vulnerabilities of cerebrovascular network and physiological changes that can mediate cognitive decline in normal aging.
Structure of the MlaC-MlaD complex reveals molecular basis of periplasmic phospholipid transport
Authors: Wotherspoon Peter , Johnston Hannah , Hardy David J. , Holyfield Rachel , Bui Soi , Ratkevičiūtė Giedrė , Sridhar Pooja , Colburn Jonathan , Wilson Charlotte B. , Colyer Adam , Cooper Benjamin F. , Bryant Jack A. , Hughes Gareth W. , Stansfeld Phillip J. , Bergeron Julien R. C. , Knowles Timothy J.
Published: July 2024

The Maintenance of Lipid Asymmetry (Mla) pathway is a multicomponent system found in all gram-negative bacteria that contributes to virulence, vesicle blebbing and preservation of the outer membrane barrier function. It acts by removing ectopic lipids from the outer leaflet of the outer membrane and returning them to the inner membrane through three proteinaceous assemblies: the MlaA-OmpC complex, situated within the outer membrane; the periplasmic phospholipid shuttle protein, MlaC; and the inner membrane ABC transporter complex, MlaFEDB, proposed to be the founding member of a structurally distinct ABC superfamily. While the function of each component is well established, how phospholipids are exchanged between components remains unknown. This stands as a major roadblock in our understanding of the function of the pathway, and in particular, the role of ATPase activity of MlaFEDB is not clear. Here, we report the structure of E. coli MlaC in complex with the MlaD hexamer in two distinct stoichiometries. Utilising in vivo complementation assays, an in vitro fluorescence-based transport assay, and molecular dynamics simulations, we confirm key residues, identifying the MlaD β6-β7 loop as essential for MlaCD function. We also provide evidence that phospholipids pass between the C-terminal helices of the MlaD hexamer to reach the central pore, providing insight into the trajectory of GPL transfer between MlaC and MlaD.
Mapping the molecular landscape of Lotus japonicus nodule organogenesis through spatiotemporal transcriptomics
Authors: Ye Keyi , Bu Fengjiao , Zhong Liyuan , Dong Zhaonian , Ma Zhaoxu , Tang Zhanpeng , Zhang Yu , Yang Xueyong , Xu Xun , Wang Ertao , Lucas William J. , Huang Sanwen , Liu Huan , Zheng Jianshu
Published: July 2024

Legumes acquire nitrogen-fixing ability by forming root nodules. Transferring this capability to more crops could reduce our reliance on nitrogen fertilizers, thereby decreasing environmental pollution and agricultural production costs. Nodule organogenesis is complex, and a comprehensive transcriptomic atlas is crucial for understanding the underlying molecular events. Here, we utilized spatial transcriptomics to investigate the development of nodules in the model legume, Lotus japonicus. Our investigation has identified the developmental trajectories of two critical regions within the nodule: the infection zone and peripheral tissues. We reveal the underlying biological processes and provide gene sets to achieve symbiosis and material exchange, two essential aspects of nodulation. Among the candidate regulatory genes, we illustrate that LjNLP3, a transcription factor belonging to the NIN-LIKE PROTEIN family, orchestrates the transition of nodules from the differentiation to maturation. In summary, our research advances our understanding of nodule organogenesis and provides valuable data for developing symbiotic nitrogen-fixing crops.
A gate tunable transmon qubit in planar Ge
Authors: Sagi Oliver , Crippa Alessandro , Valentini Marco , Janik Marian , Baghumyan Levon , Fabris Giorgio , Kapoor Lucky , Hassani Farid , Fink Johannes , Calcaterra Stefano , Chrastina Daniel , Isella Giovanni , Katsaros Georgios
Published: July 2024

Gate-tunable transmons (gatemons) employing semiconductor Josephson junctions have recently emerged as building blocks for hybrid quantum circuits. In this study, we present a gatemon fabricated in planar Germanium. We induce superconductivity in a two-dimensional hole gas by evaporating aluminum atop a thin spacer, which separates the superconductor from the Ge quantum well. The Josephson junction is then integrated into an Xmon circuit and capacitively coupled to a transmission line resonator. We showcase the qubit tunability in a broad frequency range with resonator and two-tone spectroscopy. Time-domain characterizations reveal energy relaxation and coherence times up to 75 ns. Our results, combined with the recent advances in the spin qubit field, pave the way towards novel hybrid and protected qubits in a group IV, CMOS-compatible material.
Human-centred physical neuromorphics with visual brain-computer interfaces
Authors: Wang Gao , Marcucci Giulia , Peters Benjamin , Braidotti Maria Chiara , Muckli Lars , Faccio Daniele
Published: July 2024

Steady-state visual evoked potentials (SSVEPs) are widely used for brain-computer interfaces (BCIs) as they provide a stable and efficient means to connect the computer to the brain with a simple flickering light. Previous studies focused on low-density frequency division multiplexing techniques, i.e. typically employing one or two light-modulation frequencies during a single flickering light stimulation. Here we show that it is possible to encode information in SSVEPs excited by high-density frequency division multiplexing, involving hundreds of frequencies. We then demonstrate the ability to transmit entire images from the computer to the brain/EEG read-out in relatively short times. High-density frequency multiplexing also allows to implement a photonic neural network utilizing SSVEPs, that is applied to simple classification tasks and exhibits promising scalability properties by connecting multiple brains in series. Our findings open up new possibilities for the field of neural interfaces, holding potential for various applications, including assistive technologies and cognitive enhancements, to further improve human-machine interactions.
Metaproteomic analysis decodes trophic interactions of microorganisms in the dark ocean
Authors: Zhao Zihao , Amano Chie , Reinthaler Thomas , Baltar Federico , Orellana Mónica V. , Herndl Gerhard J.
Published: July 2024

Proteins in the open ocean represent a significant source of organic matter, and their profiles reflect the metabolic activities of marine microorganisms. Here, by analyzing metaproteomic samples collected from the Pacific, Atlantic and Southern Ocean, we reveal size-fractionated patterns of the structure and function of the marine microbiota protein pool in the water column, particularly in the dark ocean (>200 m). Zooplankton proteins contributed three times more than algal proteins to the deep-sea community metaproteome. Gammaproteobacteria exhibited high metabolic activity in the deep-sea, contributing up to 30% of bacterial proteins. Close virus-host interactions of this taxon might explain the dominance of gammaproteobacterial proteins in the dissolved fraction. A high urease expression in nitrifiers suggested links between their dark carbon fixation and zooplankton urea production. In summary, our results uncover the taxonomic contribution of the microbiota to the oceanic protein pool, revealing protein fluxes from particles to the dissolved organic matter pool.
Investigating the response of the butyrate production potential to major fibers in dietary intervention studies
Authors: Van-Wehle Thao , Vital Marius
Published: July 2024

Interventions involving dietary fibers are known to benefit host health. A leading contribution of gut microbiota is commonly recognized with production of short chain fatty acids (SCFA) suspected to play a key role. However, the detailed mechanisms are largely unknown, and apart from a well-described bifidogenic effect of some fibers, results for other bacterial taxa are often incongruent between studies. We performed pooled analyses of 16S rRNA gene data derived from intervention studies (n = 14) based on three fibers, namely, inulin-type fructans (ITF), resistant starch (RS), and arabinoxylan-oligosaccharides (AXOS), harmonizing the bioinformatics workflow to reveal taxa stimulated by those substrates, specifically focusing on the SCFA-production potential. The results showed an increased butyrate production potential after ITF (p < 0.05) and RS (p < 0.1) treatment via an increase in bacteria exhibiting the enzyme butyryl-CoA:acetate CoA-transferase (but) that was governed by Faecalibacterium, Anaerostipes (ITF) and Agathobacter (RS) respectively. AXOS did not promote an increase in butyrate producers, nor were pathways linked to propionate production stimulated by any intervention. A bifidogenic effect was observed for AXOS and ITF, which was only partly associated with the behavior of but-containing bacteria and largely represented a separate response. Low and high Ruminococcus abundances pre-intervention for ITF and RS, respectively, promoted an increase in but-containing taxa (p < 0.05) upon interventions, whereas initial Prevotella abundance was negatively associated with responses of butyrate producers for both fibers. Collectively, our data demonstrate targeted stimulation of specific taxa by individual fibers increasing the potential to synthesize butyrate, where gut microbiota composition pre-intervention strongly controlled outcomes.
The plant-sucking insect selects assembly of the gut microbiota from environment to enhance host reproduction
Authors: Shan Hong-Wei , Xia Xie-Jiang , Feng Yi-Lu , Wu Wei , Li Hong-Jie , Sun Zong-Tao , Li Jun-Min , Chen Jian-Ping
Published: July 2024

Plant-sucking insects have intricate associations with a diverse array of microorganisms to facilitate their adaptation to specific ecological niches. The midgut of phytophagous true bugs is generally structured into four distinct compartments to accommodate their microbiota. Nevertheless, there is limited understanding regarding the origins of these gut microbiomes, the mechanisms behind microbial community assembly, and the interactions between gut microbiomes and their insect hosts. In this study, we conducted a comprehensive survey of microbial communities within the midgut compartments of a bean bug Riptortus pedestris, soybean plant, and bulk soil across 12 distinct geographical fields in China, utilizing high-throughput sequencing of the 16 S rRNA gene. Our findings illuminated that gut microbiota of the plant-sucking insects predominantly originated from the surrounding soil environment, and plants also play a subordinate role in mediating microbial acquisition for the insects. Furthermore, our investigation suggested that the composition of the insect gut microbiome was probably shaped by host selection and/or microbe-microbe interactions at the gut compartment level, with marginal influence from soil and geographical factors. Additionally, we had unveiled a noteworthy dynamic in the acquisition of core bacterial taxa, particularly Burkholderia, which were initially sourced from the environment and subsequently enriched within the insect midgut compartments. This bacterial enrichment played a significant role in enhancing insect host reproduction. These findings contribute to our evolving understanding of microbiomes within the insect-plant-soil ecosystem, shedding additional light on the intricate interactions between insects and their microbiomes that underpin the ecological significance of microbial partnerships in host adaptation.
Emotional and cognitive influences on alcohol consumption in middle-aged and elderly Tanzanians: a population-based study
Authors: Liu Shuyan , Kazonda Patrick , Leyna Germana H. , Rohr Julia K. , Fawzi Wafaie W. , Shinde Sachin , Abioye Ajibola Ibraheem , Francis Joel M. , Probst Charlotte , Sando David , Mwanyka-Sando Mary , Killewo Japhet , Bärnighausen Till
Published: July 2024

Alcohol consumption in Tanzania exceeds the global average. While sociodemographic difference in alcohol consumption in Tanzania have been studied, the relationship between psycho-cognitive phenomena and alcohol consumption has garnered little attention. Our study examines how depressive symptoms and cognitive performance affect alcohol consumption, considering sociodemographic variations. We interviewed 2299 Tanzanian adults, with an average age of 53 years, to assess their alcohol consumption, depressive symptoms, cognitive performance, and sociodemographic characteristics using a zero-inflated negative binomial regression model. The logistic portion of our model revealed that the likelihood alcohol consumption increased by 8.4% (95% confidence interval [CI] 3.6%, 13.1%, p < 0.001) as depressive symptom severity increased. Conversely, the count portion of the model indicated that with each one-unit increase in the severity of depressive symptoms, the estimated number of drinks decreased by 2.3% (95% CI [0.4%, 4.0%], p = .016). Additionally, the number of drinks consumed decreased by 4.7% (95% CI [1.2%, 8.1%], p = .010) for each increased cognitive score. Men exhibited higher alcohol consumption than women, and Christians tended to consume more than Muslims. These findings suggest that middle-aged and elderly adults in Tanzania tend to consume alcohol when they feel depressed but moderate their drinking habits by leveraging their cognitive abilities.