bluuebunny/crossref_metadata_2025 huggingface dataset:
HPPD inhibitor-susceptible soybean growth, yield, and economic return following isoxaflutole and mesotrione applied postemergence
Authors: Stephenson Daniel O. , Miller Donnie K. , Bond Jason A. , Deliberto Michael A.
Published: August 2022

The use of different herbicide-resistant soybean technologies in proximity could lead to injury and yield loss due to an application error. Research was initiated to evaluate the effect of 6.25%, 12.5%, and 100% doses of isoxaflutole and mesotrione field use doses applied postemergence to 4-hyroxyphenylpyruvate (HPPD) inhibitor-susceptible soybean, representing physical drift or misapplication doses. Visible injury manifested as chlorosis with slight necrosis, progressing to necrosis and height reduction, with visible height reduction as the only symptom. Isoxaflutole at 6.25% and 12.5% injured V2 soybean more than V1 or V4 soybean at all evaluation dates. This is supported by soybean height data at 14, 28, and 42 d after treatment (DAT). Following the 100% dose, maximum injury occurred at 28 DAT with V1, V2, and V4 soybean injured 90%, 85%, and 72%, but injury declined over time. All isoxaflutole treatments reduced yield at least 310 kg ha−1, with no differences among application timings or between the two lowest doses for a revenue loss of US$147 ha−1 to US$623 ha−1. Visible injury following mesotrione manifested as chlorosis and necrosis advancing to visible height reduction. Following mesotrione at 6.25% and 12.5%, injury ranged from 20% to 36% among application timings and did not differ at 3 to 21 DAT. Soybean heights at 28 and 42 DAT do not support injury observations; therefore, the greater injury was due to chlorosis and necrosis. Following mesotrione at 100%, sensitivity decreased at 3 to 14 DAT when applied to later growth stages, with no differences at 42 DAT. Yields did not differ among application timings, but yield losses were at least 240 kg ha−1, with revenue losses of US$60 ha−1 and US$373 ha−1. Producers are cautioned to prevent off-target movement or errant application of isoxaflutole or mesotrione to HPPD inhibitor-susceptible soybean.
Markovian Models for Microplastic Transport in Open‐Channel Flows
Authors: Xing Liming , Bolster Diogo , Liu Haifei , Sherman Thomas , Richter David H. , Rocha‐Brownell Kyle , Ru Zhiming
Published: August 2022

The ubiquity of microplastics in marine environments is of growing concern and is increasingly receiving widespread attention. Due to the role of rivers and streams as suppliers of microplastics to the marine environment, it is essential to accurately capture their movements at these scales, but modeling and experimental knowledge in such settings is still limited. In this work, three Markov models, including a continuous time random walk model, Bernoulli model, and spatial Markov model (SMM), are implemented to investigate polyethylene particles transport in open‐channel flows. First, a three‐dimensional high‐resolution direct numerical simulation (DNS) fully resolves a canonical open‐channel flow, and particle transport is simulated using idealized point particles. Then, a series of laboratory transport experiments are conducted in a circulating water tank, and particle image velocimetry methods are used to obtain particle‐tracking data. We find that the correlated Bernoulli model and SMM can successfully reproduce the transport of both DNS and laboratory experiments, particularly in the prediction of measured breakthrough curves, which highlights the importance of correlation between the successive steps. A major benefit of these models is a computational cost that is several orders of magnitude less than, for example, DNS, which demonstrates their high‐efficiency and effectiveness. Therefore, this research offers new insights into the transport of microplastics in open‐channel systems like rivers and streams, which is necessary to prevent and reduce the environmental hazards of microplastics.
Integrated Assessment of Urban Overheating Impacts on Human Life
Authors: Nazarian N. , Krayenhoff E. S. , Bechtel B. , Hondula D. M. , Paolini R. , Vanos J. , Cheung T. , Chow W. T. L. , de Dear R. , Jay O. , Lee J. K. W. , Martilli A. , Middel A. , Norford L. K. , Sadeghi M. , Schiavon S. , Santamouris M.
Published: August 2022

Urban overheating, driven by global climate change and urban development, is a major contemporary challenge that substantially impacts urban livability and sustainability. Overheating represents a multifaceted threat to the well‐being, performance, and health of individuals as well as the energy efficiency and economy of cities, and it is influenced by complex interactions between building, city, and global scale climates. In recent decades, extensive discipline‐specific research has characterized urban heat and assessed its implications on human life, including ongoing efforts to bridge neighboring disciplines. The research horizon now encompasses complex problems involving a wide range of disciplines, and therefore comprehensive and integrated assessments are needed that address such interdisciplinarity. Here, our objective is to go beyond a review of existing literature and instead provide a broad overview and integrated assessments of urban overheating, defining holistic pathways for addressing the impacts on human life. We (a) detail the characterization of heat hazards and exposure across different scales and in various disciplines, (b) identify individual sensitivities to urban overheating that increase vulnerability and cause adverse impacts in different populations, (c) elaborate on adaptive capacities that individuals and cities can adopt, (d) document the impacts of urban overheating on health and energy, and (e) discuss frontiers of theoretical and applied urban climatology, built environment design, and governance toward reduction of heat exposure and vulnerability at various scales. The most critical challenges in future research and application are identified, targeting both the gaps and the need for greater integration in overheating assessments.
Centennial Memory of the Arctic Ocean for Future Arctic Climate Recovery in Response to a Carbon Dioxide Removal
Authors: Oh Ji‐Hoon , An Soon‐Il , Shin Jongsoo , Kug Jong‐Seong
Published: August 2022

Under the ongoing and potential risks from anthropogenic warming, net negative carbon dioxide (CO2) emissions are inevitable to stabilize or recover the Earth's climate. It is important not only to understand climate irreversibility in response to CO2 removal but also to understand how fast each component of the climate system will recover to its original state. Based on idealized CO2 ramp‐up and ‐down ensemble simulations, here we show that the initial buoyancy states of the Arctic Ocean, such as upper ocean salinity and density, are vital to determining how fast Arctic and global mean temperatures will recover on a centennial time scale. The denser initial Arctic oceanic condition is linked to faster recovery of the Atlantic meridional overturning circulation (AMOC) in the ramp‐down period, which is further accelerated by strong positive AMOC‐salt‐advection feedback. Faster AMOC recovery can delay Arctic temperature recovery by transporting warmer water into the northern subpolar Atlantic during the ramp‐down period. In addition, denser Arctic water enhances vertical mixing, which also results in delayed Arctic cooling under a strong vertical temperature gradient in the subpolar‐to‐polar Atlantic. Our findings suggest that the Arctic's initial states have a centennial memory for the future Arctic and global climate changes.
Caves Offer Temperate Hope for Future Moon Exploration
Authors: Kish Stacy
Published: August 2022

Large caves near the Moon’s equator maintain a temperate, stable daily temperature around 17�C.
New Insights From the 2003 Halloween Storm Into the Colaba 1600 nT Magnetic Depression During the 1859 Carrington Storm
Authors: Ohtani Shinichi
Published: August 2022

The present study investigates the cause of a sharp horizontal (H) magnetic depression observed on the dayside during the 2003 Halloween storm, and discusses if the same process could cause the 1,600 nT H depression observed at Colaba during the 1859 Carrington storm. For the Halloween H depression, it is found that (a) it developed in correlation with southward interplanetary magnetic field (IMF) BZ in the sheath region of a coronal mass ejection; (b) its magnitude decreased significantly with decreasing magnetic latitude; (c) it was highly correlated with westward and eastward sub‐auroral zone magnetic deflections at earlier and later local times, respectively; and (d) the westward auroral electrojet (AEJ) enhanced simultaneously in the entire nightside auroral zone, whereas the enhancement of the dayside eastward AEJ was unclear. These features suggest that the dayside R1‐sense wedge current system, which was driven by dayside magnetic reconnection, was the cause of the H depression, and the associated field‐aligned currents closed primarily with the westward AEJ through the nightside. The Colaba H depression also took place on the dayside and lasted for ∼2 hr. Furthermore, it took place within a few hours after the storm commencement, and the westward AEJ enhanced simultaneously in the dawn sector. These similarities suggest that the dayside wedge current system was also the cause of this historical event. The sharp recovery of the Colaba H depression, which has been a challenge to explain, may be attributed to the decay of this current system due to a northward IMF turning.
AMPK suppresses Th2 cell responses by repressing mTORC2
Authors: Pandit Mahesh , Timilshina Maheshwor , Gu Ye , Acharya Suman , Chung Yeonseok , Seo Sang-Uk , Chang Jae-Hoon
Published: August 2022

Allergic inflammation is a T helper 2 (Th2) cell-driven pathophysiological phenomenon, but the mechanism by which the metabolic cascade affects Th2 cell differentiation remains unclear. In this study, we investigated the roles of AMP-activated protein kinase (AMPK) and intracellular energy sensors in Th2 cell differentiation and the pathogenesis of allergic inflammation. Accordingly, T-cell-specific AMPK or Sirtuin 1 (Sirt1)-knockout mice were subjected to allergic inflammation, and their Th2 cell responses were investigated. The results demonstrated that inducing allergic inflammation in AMPK- and Sirt1-knockout mice increased Th2 cell responses and exacerbated allergic phenotypes. Furthermore, treatment with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMPK, ameliorated allergic inflammation in mice. Mechanistically, our findings revealed that AMPK repressed mechanistic target of rapamycin complex 2 (mTORC2), which downregulated the expression of suppressor of cytokine signaling 5 (SOCS5) in CD4+ T cells. In addition, the loss of AMPK signaling reduced SOCS5 expression and increased interleukin-4-STAT6–GATA3 axis-mediated Th2 cell differentiation. Finally, the T-cell-specific deletion of Rictor, a member of mTORC2, in Sirt1T-KO mice led to the reversal of allergic exacerbation to the level in control mice. Overall, our findings suggest that AMPK in CD4+ T cells inhibits the differentiation of Th2 cells by repressing mTORC2 and thus serves as a potential target for Th2 cell-associated diseases.
Advances in human oxytocin measurement: challenges and proposed solutions
Authors: Tabak Benjamin A. , Leng Gareth , Szeto Angela , Parker Karen J. , Verbalis Joseph G. , Ziegler Toni E. , Lee Mary R. , Neumann Inga D. , Mendez Armando J.
Published: August 2022

Oxytocin, a neuropeptide known for its role in reproduction and socioemotional processes, may hold promise as a therapeutic agent in treating social impairments in patient populations. However, research has yet to uncover precisely how to manipulate this system for clinical benefit. Moreover, inconsistent use of standardized and validated oxytocin measurement methodologies—including the design and study of hormone secretion and biochemical assays—present unresolved challenges. Human studies measuring peripheral (i.e., in plasma, saliva, or urine) or central (i.e., in cerebrospinal fluid) oxytocin concentrations have involved very diverse methods, including the use of different assay techniques, further compounding this problem. In the present review, we describe the scientific value in measuring human endogenous oxytocin concentrations, common issues in biochemical analysis and study design that researchers face when doing so, and our recommendations for improving studies using valid and reliable methodologies.
Classical epithelial-mesenchymal transition (EMT) and alternative cell death process-driven blebbishield metastatic-witch (BMW) pathways to cancer metastasis
Authors: Jinesh Goodwin G. , Brohl Andrew S.
Published: August 2022

Metastasis is a pivotal event that accelerates the prognosis of cancer patients towards mortality. Therapies that aim to induce cell death in metastatic cells require a more detailed understanding of the metastasis for better mitigation. Towards this goal, we discuss the details of two distinct but overlapping pathways of metastasis: a classical reversible epithelial-to-mesenchymal transition (hybrid-EMT)-driven transport pathway and an alternative cell death process-driven blebbishield metastatic-witch (BMW) transport pathway involving reversible cell death process. The knowledge about the EMT and BMW pathways is important for the therapy of metastatic cancers as these pathways confer drug resistance coupled to immune evasion/suppression. We initially discuss the EMT pathway and compare it with the BMW pathway in the contexts of coordinated oncogenic, metabolic, immunologic, and cell biological events that drive metastasis. In particular, we discuss how the cell death environment involving apoptosis, ferroptosis, necroptosis, and NETosis in BMW or EMT pathways recruits immune cells, fuses with it, migrates, permeabilizes vasculature, and settles at distant sites to establish metastasis. Finally, we discuss the therapeutic targets that are common to both EMT and BMW pathways.
Validity and reliability of the 2-minute walk test in individuals with spinal cord injury
Authors: Willi Romina , Widmer Mario , Merz Nora , Bastiaenen Caroline H. G. , Zörner Björn , Bolliger Marc
Published: August 2022

Study design

Multicentre-observational study.

Objectives

The 6-minute walk test (6mWT) is an established assessment of walking function in individuals with spinal cord injury (SCI). However, walking 6 min can be demanding for severely impaired individuals. The 2-minute walk test (2mWT) could be an appropriate alternative that has already been validated in other neurological disorders. The aim of this study was to assess construct validity and test-rest reliability of the 2mWT in individuals with SCI. In addition, the influence of walking performance on sensitivity to change of the 2mWT was assessed.

Setting

Swiss Paraplegic Center Nottwil, Switzerland; Balgrist University Hospital, Zürich, Switzerland.

Methods

Fifty individuals (aged 18–79) with SCI (neurological level of injury: C1-L3, AIS: A-D) were assessed on two test days separated by 1 to 7 days. The first assessment consisted of a 2mWT familiarization, followed by a 2mWT and 10-meter walk test (10MWT) (including the Walking Index for Spinal Cord Injury (WISCI II)) in randomized order. The second assessment consisted of 2mWT and 6mWT in randomized order. Tests were separated by at least 30 min of rest.

Results

The interclass correlation coefficient between the 2mWT assessed on the first and second test day was excellent (r = 0.980, p < 0.001). The 2mWT correlated very strongly with the 6mWT (r = 0.992, p < 0.001) and the 10MWT (r = 0.964, p < 0.001), and moderately with the WISCI II (r = 0.571, p < 0.001). Sensitivity to change was slightly affected by walking performance.

Conclusion

The 2mWT is a valid and reliable alternative to the 6mWT to measure walking function in individuals with SCI.

Trial registration

NCT04555759.
CHK2 activation contributes to the development of oxaliplatin resistance in colorectal cancer
Authors: Hsieh Chi-Che , Hsu Sen-Huei , Lin Chih-Yu , Liaw Hung-Jiun , Li Ting-Wei , Jiang Kuan-Ying , Chiang Nai-Jung , Chen Shang-Hung , Lin Bo-Wen , Chen Po-Chuan , Chan Ren-Hao , Lin Peng-Chan , Yeh Yu-Min , Shen Che-Hung
Published: August 2022

Background

Colorectal cancer (CRC), the most common cancer type, causes high morbidity and mortality. Patients who develop drug resistance to oxaliplatin-based regimens have short overall survival. Thus, identifying molecules involved in the development of oxaliplatin resistance is critical for designing therapeutic strategies.

Methods

A proteomic screen was performed to reveal altered protein kinase phosphorylation in oxaliplatin-resistant (OR) CRC tumour spheroids. The function of CHK2 was characterised using several biochemical techniques and evident using in vitro cell and in vivo tumour models.

Results

We revealed that the level of phospho-CHK2(Thr68) was elevated in OR CRC cells and in ~30% of tumour samples from patients with OR CRC. We demonstrated that oxaliplatin activated several phosphatidylinositol 3-kinase-related kinases (PIKKs) and CHK2 downstream effectors and enhanced CHK2/PARP1 interaction to facilitate DNA repair. A phosphorylation mimicking CHK2 mutant, CHK2T68D, but not a kinase-dead CHK2 mutant, CHK2D347A, promoted DNA repair, the CHK2/PARP1 interaction, and cell growth in the presence of oxaliplatin. Finally, we showed that a CHK2 inhibitor, BML-277, reduced protein poly(ADP-ribosyl)ation (PARylation), FANCD2 monoubiquitination, homologous recombination and OR CRC cell growth in vitro and in vivo.

Conclusion

Our findings suggest that CHK2 activity is critical for modulating oxaliplatin response and that CHK2 is a potential therapeutic target for OR CRC.
A novel age-related gene expression signature associates with proliferation and disease progression in breast cancer
Authors: Ingebriktsen L. M. , Finne K. , Akslen L. A. , Wik E.
Published: August 2022

Background and objective

Breast cancer (BC) diagnosed at ages <40 years presents with more aggressive tumour phenotypes and poorer clinical outcome compared to older BC patients. Here, we explored transcriptional BC alterations to gain a better understanding of age-related tumour biology, also subtype-stratified.

Methods

We studied publicly available global BC mRNA expression (n = 3999) and proteomics data (n = 113), exploring differentially expressed genes, enriched gene sets, and gene networks in the young compared to older patients.

Results

We identified transcriptional patterns reflecting increased proliferation and oncogenic signalling in BC of the young, also in subtype-stratified analyses. Six up-regulated hub genes built a novel age-related score, significantly associated with aggressive clinicopathologic features. A high 6 Gene Proliferation Score (6GPS) demonstrated independent prognostic value when adjusted for traditional clinicopathologic variables and the molecular subtypes. The 6GPS significantly associated also with disease-specific survival within the luminal, lymph node-negative and Oncotype Dx intermediate subset.

Conclusions

We here demonstrate evidence of higher tumour cell proliferation in young BC patients, also when adjusting for molecular subtypes, and identified a novel age-based six-gene signature pointing to aggressive tumour features, tumour proliferation, and reduced survival—also in patient subsets with expected good prognosis.
HPV self-sampling among long-term non-attenders to cervical cancer screening in Norway: a pragmatic randomised controlled trial
Authors: Aasbø Gunvor , Tropè Ameli , Nygård Mari , Christiansen Irene Kraus , Baasland Ingrid , Iversen Grete Alrek , Munk Ane Cecilie , Christiansen Marit Halonen , Presthus Gro Kummeneje , Undem Karina , Bjørge Tone , Castle Philip E. , Hansen Bo T.
Published: August 2022

Background

Cervical cancer screening participation is suboptimal in most settings. We assessed whether human papillomavirus (HPV) self-sampling may increase screening participation among long-term non-attenders in Norway.

Methods

A pragmatic randomised controlled trial with participation as the primary outcome was initiated in the national cervical screening programme in March 2019. A random sample of 6000 women aged 35–69 years who had not attended screening for at least 10 years were randomised 1:1:1 to receive either (i) a reminder to attend regular screening (control), (ii) an offer to order a self-sampling kit (opt-in) for HPV testing or (iii) a self-sampling kit unsolicited (send-to-all) for HPV testing.

Results

Total participation was 4.8%, 17.0% and 27.7% among control, opt-in and send-to-all (P < 0.0001; participation difference (%) send-to-all vs. control: 22.9 (95%CI: 20.7, 25.2); opt-in vs. control: 12.3 (95%CI: 10.3, 14.2); send-to-all vs. opt-in: 10.7 (95% CI: 8.0, 13.3)). High-risk HPV was detected in 11.5% of self-samples and 9.2% of clinician-collected samples (P = 0.40). Most women (92.5%) who returned a positive self-sample attended the clinic for triage testing. Of the 933 women screened, 33 (3.5%) had CIN2 + (1.1%, 3.7%, 3.8% among control, opt-in, and send-to-all, respectively), and 11 (1.2%) had cervical cancer (0%, 1.2%, 1.3% among control, opt-in, send-to-all, respectively).

Conclusion

Opt-in and send-to-all self-sampling increased screening participation among long-term, higher-risk non-attenders.

Clinical trial registration

ClinicalTrials.gov NCT03873376.
Creation of Philadelphia chromosome by CRISPR/Cas9-mediated double cleavages on BCR and ABL1 genes as a model for initial event in leukemogenesis
Authors: Tamai Minori , Fujisawa Shinichi , Nguyen Thao T. T. , Komatsu Chiaki , Kagami Keiko , Kamimoto Kenji , Omachi Kohei , Kasai Shin , Harama Daisuke , Watanabe Atsushi , Akahane Koshi , Goi Kumiko , Naka Kazuhito , Kaname Tadashi , Teshima Takanori , Inukai Takeshi
Published: August 2022

The Philadelphia (Ph) chromosome was the first translocation identified in leukemia. It is supposed to be generated by aberrant ligation between two DNA double-strand breaks (DSBs) at the BCR gene located on chromosome 9q34 and the ABL1 gene located on chromosome 22q11. Thus, mimicking the initiation process of translocation, we induced CRISPR/Cas9-mediated DSBs simultaneously at the breakpoints of the BCR and ABL1 genes in a granulocyte-macrophage colony-stimulating factor (GM-CSF) dependent human leukemia cell line. After transfection of two single guide RNAs (sgRNAs) targeting intron 13 of the BCR gene and intron 1 of the ABL1 gene, a factor-independent subline was obtained. In the subline, p210 BCR::ABL1 and its reciprocal ABL1::BCR fusions were generated as a result of balanced translocation corresponding to the Ph chromosome. Another set of sgRNAs targeting intron 1 of the BCR gene and intron 1 of the ABL1 gene induced a factor-independent subline expressing p190 BCR::ABL1. Both p210 and p190 BCR::ABL1 induced factor-independent growth by constitutively activating intracellular signaling pathways for transcriptional regulation of cell cycle progression and cell survival that are usually regulated by GM-CSF. These observations suggested that simultaneous DSBs at the BCR and ABL1 gene breakpoints are initiation events for oncogenesis in Ph+ leukemia. (200/200 words).
CD36 aggravates podocyte injury by activating NLRP3 inflammasome and inhibiting autophagy in lupus nephritis
Authors: Lv Fu , He Yingxin , Xu Hongde , Li Yongchun , Han Lipei , Yan Lijie , Lang Hui , Zhao Yafei , Zhao Zhanzheng , Qi Yuanyuan
Published: August 2022

A major cause of proteinuria in lupus nephritis (LN) is podocyte injury, and determining potential therapeutic targets to prevent podocyte injury is important from a clinical perspective in the treatment of LN. CD36 is involved in podocyte injury in several glomerulopathies and was reported to be a vital candidate gene in LN. Here, we determined the role of CD36 in the podocyte injury of LN and the underlying mechanisms. We observed that CD36 and NLRP3 (NLR family pyrin domain containing 3) were upregulated in the podocytes of lupus nephritis patients and MRL/lpr mice with renal impairment. In vitro, CD36, NLRP3 inflammasome, and autophagy were elevated accompanied with increased podocyte injury stimulated by IgG extracted from lupus nephritis patients compared that from healthy donors. Knocking out CD36 with the CRISPR/cas9 system decreased the NLRP3 inflammasome levels, increased the autophagy levels and alleviated podocyte injury. By enhancing autophagy, NLRP3 inflammasome was decreased and podocyte injury was alleviated. These results demonstrated that, in lupus nephritis, CD36 promoted podocyte injury by activating NLRP3 inflammasome and inhibiting autophagy by enhancing which could decrease NLRP3 inflammasome and alleviate podocyte injury.
Multiplex viral tropism assay in complex cell populations with single-cell resolution
Authors: Keng Choong Tat , Guo Ke , Liu Yu-Chi , Shen Kimberle Yanyin , Lim Daryl Shern , Lovatt Matthew , Ang Heng Pei , Mehta Jodhbir S. , Chew Wei Leong
Published: August 2022

Gene therapy constitutes one of the most promising mode of disease treatments. Two key properties for therapeutic delivery vectors are its transduction efficiency (how well the vector delivers therapeutic cargo to desired target cells) and specificity (how well it avoids off-target delivery into unintended cells within the body). Here we developed an integrated bioinformatics and experimental pipeline that enables multiplex measurement of transduction efficiency and specificity, particularly by measuring how libraries of delivery vectors transduce libraries of diverse cell types. We demonstrated that pairing high-throughput measurement of AAV identity with high-resolution single-cell RNA transcriptomic sequencing maps how natural and engineered AAV variants transduce individual cells within human cerebral and ocular organoids. We further demonstrate that efficient AAV transduction observed in organoids is recapitulated in vivo in non-human primates. This library-on-library technology will be important for determining the safety and efficacy of therapeutic delivery vectors.
Delineating Mycobacterium abscessus population structure and transmission employing high-resolution core genome multilocus sequence typing
Authors: Diricks Margo , Merker Matthias , Wetzstein Nils , Kohl Thomas A. , Niemann Stefan , Maurer Florian P.
Published: August 2022

Mycobacterium abscessus is an emerging multidrug-resistant non-tuberculous mycobacterium that causes a wide spectrum of infections and has caused several local outbreaks worldwide. To facilitate standardized prospective molecular surveillance, we established a novel core genome multilocus sequence typing (cgMLST) scheme. Whole genome sequencing data of 1991 isolates were employed to validate the scheme, re-analyze global population structure and set genetic distance thresholds for cluster detection and taxonomic identification. We confirmed and amended the nomenclature of the main dominant circulating clones and found that these also correlate well with traditional 7-loci MLST. Dominant circulating clones could be linked to a corresponding reference genome with less than 250 alleles while 99% of pairwise comparisons between epidemiologically linked isolates were below 25 alleles and 90% below 10 alleles. These thresholds can be used to guide further epidemiological investigations. Overall, the scheme will help to unravel the apparent global spread of certain clonal complexes and as yet undiscovered transmission routes.
Americans experience a false social reality by underestimating popular climate policy support by nearly half
Authors: Sparkman Gregg , Geiger Nathan , Weber Elke U.
Published: August 2022

Pluralistic ignorance—a shared misperception of how others think or behave—poses a challenge to collective action on problems like climate change. Using a representative sample of Americans (N = 6119), we examine whether Americans accurately perceive national concern about climate change and support for mitigating policies. We find a form of pluralistic ignorance that we describe as a false social reality: a near universal perception of public opinion that is the opposite of true public sentiment. Specifically, 80–90% of Americans underestimate the prevalence of support for major climate change mitigation policies and climate concern. While 66–80% Americans support these policies, Americans estimate the prevalence to only be between 37–43% on average. Thus, supporters of climate policies outnumber opponents two to one, while Americans falsely perceive nearly the opposite to be true. Further, Americans in every state and every assessed demographic underestimate support across all polices tested. Preliminary evidence suggests three sources of these misperceptions: (i) consistent with a false consensus effect, respondents who support these policies less (conservatives) underestimate support by a greater degree; controlling for one’s own personal politics, (ii) exposure to more conservative local norms and (iii) consuming conservative news correspond to greater misperceptions.
Genome-wide mutational signatures in low-coverage whole genome sequencing of cell-free DNA
Authors: Wan Jonathan C. M. , Stephens Dennis , Luo Lingqi , White James R. , Stewart Caitlin M. , Rousseau Benoît , Tsui Dana W. Y. , Diaz Luis A.
Published: August 2022

Mutational signatures accumulate in somatic cells as an admixture of endogenous and exogenous processes that occur during an individual’s lifetime. Since dividing cells release cell-free DNA (cfDNA) fragments into the circulation, we hypothesize that plasma cfDNA might reflect mutational signatures. Point mutations in plasma whole genome sequencing (WGS) are challenging to identify through conventional mutation calling due to low sequencing coverage and low mutant allele fractions. In this proof of concept study of plasma WGS at 0.3–1.5x coverage from 215 patients and 227 healthy individuals, we show that both pathological and physiological mutational signatures may be identified in plasma. By applying machine learning to mutation profiles, patients with stage I-IV cancer can be distinguished from healthy individuals with an Area Under the Curve of 0.96. Interrogating mutational processes in plasma may enable earlier cancer detection, and might enable the assessment of cancer risk and etiology.
A PfSPZ vaccine immunization regimen equally protective against homologous and heterologous controlled human malaria infection
Authors: Mordmüller Benjamin , Sulyok Zita , Sulyok Mihály , Molnar Zsofia , Lalremruata Albert , Calle Carlos Lamsfus , Bayon Patricia Granados , Esen Meral , Gmeiner Markus , Held Jana , Heimann Henri-Lynn , Woldearegai Tamirat Gebru , Ibáñez Javier , Flügge Judith , Fendel Rolf , Kreidenweiss Andrea , KC Natasha , Murshedkar Tooba , Chakravarty Sumana , Riyahi Pouria , Billingsley Peter F. , Church L. W. Preston , Richie Thomas L. , Sim B. Kim Lee , Hoffman Stephen L. , Kremsner Peter G.
Published: August 2022

Immunization with radiation-attenuated Plasmodium falciparum (Pf) sporozoites (SPZ) in PfSPZ Vaccine, has provided better vaccine efficacy (VE) against controlled human malaria infection (CHMI) with the same parasites as in the vaccine (homologous) than with genetically distant parasites (heterologous). We sought to identify an immunization regimen that provided similar VE against CHMI with homologous and heterologous Pf for at least 9 weeks in malaria-naïve adults. Such a regimen was identified in part 1 (optimization), an open label study, and confirmed in part 2 (verification), a randomized, double-blind, placebo-controlled study in which VE was assessed by cross-over repeat CHMI with homologous (PfNF54) and heterologous (Pf7G8) PfSPZ at 3 and 9–10 weeks. VE was calculated using Bayesian generalized linear regression. In part 1, vaccination with 9 × 105 PfSPZ on days 1, 8, and 29 protected 5/5 (100%) subjects against homologous CHMI at 3 weeks after the last immunization. In part 2, the same 3-dose regimen protected 5/6 subjects (83%) against heterologous CHMI at both 3 and 9–10 weeks after the last immunization. Overall VE was 78% (95% predictive interval: 57–92%), and against heterologous and homologous was 79% (95% PI: 54–95%) and 77% (95% PI: 50–95%) respectively. PfSPZ Vaccine was safe and well tolerated. A 4-week, 3-dose regimen of PfSPZ Vaccine provided similar VE for 9–10 weeks against homologous and heterologous CHMI. The trial is registered with ClinicalTrials.gov, NCT02704533.
Inflammation triggers ILC3 patrolling of the intestinal barrier
Authors: Jarade Angélique , Garcia Zacarias , Marie Solenne , Demera Abdi , Prinz Immo , Bousso Philippe , Di Santo James P. , Serafini Nicolas
Published: August 2022

An orchestrated cellular network, including adaptive lymphocytes and group 3 innate lymphoid cells (ILC3s), maintains intestinal barrier integrity and homeostasis. T cells can monitor environmental insults through constitutive circulation, scanning tissues and forming immunological contacts, a process named immunosurveillance. In contrast, the dynamics of intestinal ILC3s are unknown. Using intravital imaging, we observed that villus ILC3s were largely immotile at steady state but acquired migratory ‘patrolling’ attributes and enhanced cytokine expression in response to inflammation. We showed that T cells, the chemokine CCL25 and bacterial ligands regulated intestinal ILC3 behavior and that loss of patrolling behavior by interleukin-22 (IL-22)-producing ILC3s altered the intestinal barrier through increased epithelial cell death. Collectively, we identified notable differences between the behavior of ILC3s and T cells, with a prominent adaptation of intestinal ILC3s toward mucosal immunosurveillance after inflammation.
Differences in CD80 and CD86 transendocytosis reveal CD86 as a key target for CTLA-4 immune regulation
Authors: Kennedy Alan , Waters Erin , Rowshanravan Behzad , Hinze Claudia , Williams Cayman , Janman Daniel , Fox Thomas A. , Booth Claire , Pesenacker Anne M. , Halliday Neil , Soskic Blagoje , Kaur Satdip , Qureshi Omar S. , Morris Emma C. , Ikemizu Shinji , Paluch Christopher , Huo Jiandong , Davis Simon J. , Boucrot Emmanuel , Walker Lucy S. K. , Sansom David M.
Published: August 2022

CD28 and CTLA-4 (CD152) play essential roles in regulating T cell immunity, balancing the activation and inhibition of T cell responses, respectively. Although both receptors share the same ligands, CD80 and CD86, the specific requirement for two distinct ligands remains obscure. In the present study, we demonstrate that, although CTLA-4 targets both CD80 and CD86 for destruction via transendocytosis, this process results in separate fates for CTLA-4 itself. In the presence of CD80, CTLA-4 remained ligand bound, and was ubiquitylated and trafficked via late endosomes and lysosomes. In contrast, in the presence of CD86, CTLA-4 detached in a pH-dependent manner and recycled back to the cell surface to permit further transendocytosis. Furthermore, we identified clinically relevant mutations that cause autoimmune disease, which selectively disrupted CD86 transendocytosis, by affecting either CTLA-4 recycling or CD86 binding. These observations provide a rationale for two distinct ligands and show that defects in CTLA-4-mediated transendocytosis of CD86 are associated with autoimmunity.
Continuous and binary sets of responses differ in the field
Authors: Rivera-Garrido Noelia , Ramos-Sosa M. P. , Accerenzi Michela , Brañas-Garza Pablo
Published: August 2022

This paper conducts a pre-registered study aimed to compare binary and continuous set of responses in survey questionnaires. Binary responses consist of two possible opposing response options (Yes/No). Continuous responses are numerical, where respondents can indicate an option on a 0–10 horizontal blind line. We study whether feasible sets of binary and continuous responses yield the same outcome (distribution) and have the same cost (duration in minutes). We collect data from 360 households in Honduras that were randomly assigned to Yes/No questions or given a slider (0–10 visual scale) to mark their responses, therefore, we providecausal evidence. We find that respondents are 13% more likely to respond “Yes” and spend 2.1 min less in the binary setting. Additionally, the results suggest that the type of question matters.
A processing-in-pixel-in-memory paradigm for resource-constrained TinyML applications
Authors: Datta Gourav , Kundu Souvik , Yin Zihan , Lakkireddy Ravi Teja , Mathai Joe , Jacob Ajey P. , Beerel Peter A. , Jaiswal Akhilesh R.
Published: August 2022

The demand to process vast amounts of data generated from state-of-the-art high resolution cameras has motivated novel energy-efficient on-device AI solutions. Visual data in such cameras are usually captured in analog voltages by a sensor pixel array, and then converted to the digital domain for subsequent AI processing using analog-to-digital converters (ADC). Recent research has tried to take advantage of massively parallel low-power analog/digital computing in the form of near- and in-sensor processing, in which the AI computation is performed partly in the periphery of the pixel array and partly in a separate on-board CPU/accelerator. Unfortunately, high-resolution input images still need to be streamed between the camera and the AI processing unit, frame by frame, causing energy, bandwidth, and security bottlenecks. To mitigate this problem, we propose a novel Processing-in-Pixel-in-memory (P2M) paradigm, that customizes the pixel array by adding support for analog multi-channel, multi-bit convolution, batch normalization, and Rectified Linear Units (ReLU). Our solution includes a holistic algorithm-circuit co-design approach and the resulting P2M paradigm can be used as a drop-in replacement for embedding memory-intensive first few layers of convolutional neural network (CNN) models within foundry-manufacturable CMOS image sensor platforms. Our experimental results indicate that P2M reduces data transfer bandwidth from sensors and analog to digital conversions by$${\sim }\,21\times$$∼21×, and the energy-delay product (EDP) incurred in processing a MobileNetV2 model on a TinyML use case for visual wake words dataset (VWW) by up to$$\mathord {\sim }\,11\times$$∼11×compared to standard near-processing or in-sensor implementations, without any significant drop in test accuracy.
Abundance, chemical structure, and light absorption properties of humic-like substances (HULIS) and other organic fractions of forest aerosols in Hokkaido
Authors: Afsana Sonia , Zhou Ruichen , Miyazaki Yuzo , Tachibana Eri , Deshmukh Dhananjay Kumar , Kawamura Kimitaka , Mochida Michihiro
Published: August 2022

Atmospheric organic aerosol (OA) are considered as a significant contributor to the light absorption of OA, but its relationship with abundance, composition and sources are not understood well. In this study, the abundance, chemical structural characteristics, and light absorption property of HULIS and other low-to-high polar organics in PM0.95 collected in Tomakomai Experimental Forest (TOEF) were investigated with consideration of their possible sources. HULIS were the most abundant (51%), and correlation analysis revealed that biogenic secondary organic aerosols significantly contribute to HULIS. The mass spectra obtained using a high-resolution aerosol mass spectrometer (HR-AMS) showed that HULIS and highly polar water-soluble organic matter (HP-WSOM) were substantially oxygenated organic aerosol fractions, whereas water-insoluble organic matter (WISOM) had a low O/C ratio and more hydrocarbon-like structures. The WISOM fraction was the predominant light-absorbing organics. HULIS and WISOM showed a noticeable seasonal change in mass absorption efficiency (MAE365), which was highest in winter. Further, HULIS were shown to be less absorbing than those reported for urban sites. The findings in this study provide insights into the contribution of biogenic secondary OA on aerosol property and radiative forcing under varying contributions from other types of OA.
Honey DNA metabarcoding revealed foraging resource partitioning between Korean native and introduced honey bees (Hymenoptera: Apidae)
Authors: Mohamadzade Namin Saeed , Kim Min-Jung , Son Minwoong , Jung Chuleui
Published: August 2022

Honey DNA metabarcoding provides information of floral sources of honey and foraging plant preferences of honey bees. We evaluated the floral composition of honey from two different species of honey bees, Apis cerana honey (ACH) and A. mellifera honey (AMH) in a mixed apiary located in a semi-forest environment to understand the floral preference and level of interspecific competition on floral resource. Three honey samples were collected from different hives of each species in mid-August. In total, 56 plant taxa were identified across the honey samples and among them, 38 taxonomic units were found in ACH compared with a total of 33 in AMH. The number of major plants (> 1% of reads) in honey samples was 9 and 11 in ACH and AMH respectively indicating the higher diversity of plant taxa in AMH. 23 taxonomic units were found exclusively in ACH, 18 taxonomic units were found only in AMH and 15 taxonomic units were shared between ACH and AMH indicating that 73% of the taxonomic units were present only in honey originated from one of the honeybee species. Qualitative and quantitative analyses of the shared major plants revealed the division of floral resource between these co-existing honey bee species pointing to a low level of interspecific competition between these two important pollinators.
EEG temporal–spatial transformer for person identification
Authors: Du Yang , Xu Yongling , Wang Xiaoan , Liu Li , Ma Pengcheng
Published: August 2022

An increasing number of studies have been devoted to electroencephalogram (EEG) identity recognition since EEG signals are not easily stolen. Most of the existing studies on EEG person identification have only addressed brain signals in a single state, depending upon specific and repetitive sensory stimuli. However, in reality, human states are diverse and rapidly changing, which limits their practicality in realistic settings. Among many potential solutions, transformer is widely used and achieves an excellent performance in natural language processing, which demonstrates the outstanding ability of the attention mechanism to model temporal signals. In this paper, we propose a transformer-based approach for the EEG person identification task that extracts features in the temporal and spatial domains using a self-attention mechanism. We conduct an extensive study to evaluate the generalization ability of the proposed method among different states. Our method is compared with the most advanced EEG biometrics techniques and the results show that our method reaches state-of-the-art results. Notably, we do not need to extract any features manually.
Propagation rules of shock waves in confined space under different initial pressure environments
Authors: Wang F. Q. , Wang Q. , Wang Y. J. , Li Z. M. , Li R. , Li X. C. , Yang L. A. , Lu J. W.
Published: August 2022

In this paper, an initial pressure adjustable explosion vessel was developed, and the effect of negative pressure, positive pressure (0.2–1.8 atm) different initial ambient pressure on the explosive shock wave generated by the explosion of explosives was studied. The relationships between the specific impulse, shock wave velocity, the amount of explosive gas products and the ambient pressure were analyzed for different initial pressure environments. It was found that: the overpressure of the blast shock wave decreases with the initial ambient pressure of the explosion, and there exists a negative pressure environment with a dramatic pressure decrease near 0.6 atm, defined as the super-sensitive negative pressure Pcr. The propagation velocity of an explosive wave increases with a decrease in the ambient pressure, and the propagation velocity at a pressure of 1.8 atm is four times less than the velocity at a pressure of 0.2 atm. The production of explosive gas products did not change. The greater the initial pressure of the environment where the explosive is located, the smaller the ratio of the gas generated by the explosion to the initial force gas in the explosion vessel is, and the greater the impact on the propagation of shock waves is. The maximum attenuation of the first specific impulse i1 is 72.97% and the maximum attenuation of the second specific impulse i2 is 72.39%. The experiments provide reference data for high-altitude military confrontation, high-altitude weapons and ammunition development, and deep-earth protection engineering.
Role of dual specificity phosphatases (DUSPs) in melanoma cellular plasticity and drug resistance
Authors: Singh Mithalesh K. , Altameemi Sarah , Lares Marcos , Newton Michael A. , Setaluri Vijayasaradhi
Published: August 2022

Melanoma cells exhibit phenotypic plasticity that allows transition from a proliferative and differentiated phenotype to a more invasive and undifferentiated or transdifferentiated phenotype often associated with drug resistance. The mechanisms that control melanoma phenotype plasticity and its role in drug resistance are not fully understood. We previously demonstrated that emergence of MAPK inhibitor (MAPKi)-resistance phenotype is associated with decreased expression of stem cell proliferation genes and increased expression of MAPK inactivation genes, including dual specificity phosphatases (DUSPs). Several members of the DUSP family genes, specifically DUSP1, -3, -8 and -9, are expressed in primary and metastatic melanoma cell lines and pre-and post BRAFi treated melanoma cells. Here, we show that knockdown of DUSP1 or DUSP8 or treatment with BCI, a pharmacological inhibitor of DUSP1/6 decrease the survival of MAPKi-resistant cells and sensitizes them to BRAFi and MEKi. Pharmacological inhibition of DUSP1/6 upregulated nestin, a neural crest stem cell marker, in both MAPKi-sensitive cells and cells with acquired MAPKi-resistance. In contrast, treatment with BCI resulted in upregulation of MAP2, a neuronal differentiation marker, only in MAPKi-sensitive cells but caused downregulation of both MAP2 and GFAP, a glial marker, in all MAPKi-resistant cell lines. These data suggest that DUSP proteins are involved in the regulation of cellular plasticity cells and melanoma drug resistance and are potential targets for treatment of MAPKi-resistant melanoma.
Stone tools differences across three capuchin monkey populations: food’s physical properties, ecology, and culture
Authors: Falótico Tiago , Valença Tatiane , Verderane Michele P. , Fogaça Mariana D.
Published: August 2022

Robust capuchin monkeys (Sapajus) are known for processing mechanically challenging foods, having morphological adaptations to do so. However, several populations go beyond body limitations by using stone tools to expand their food range. Those populations use stones in a variety of ways, goals, and with different frequencies. Stone tool size correlates with the food’s resistance within some populations. However, we have no detailed comparisons to identify if this correlation is the same across populations. This study described and compared stone raw material availability, food’s physical properties (hardness and elasticity), and stone tool weight in three populations of bearded capuchin monkeys (Sapajus libidinosus), including a newly described site (Chapada dos Veadeiros National Park, CVNP). The differences we observed regarding stone tool weight selection among sites were not correlated to the food’s physical properties we analyzed. Lithic resource availability could partly explain some differences in the stone tools used. However, the tool weight differences are larger than the raw material variance across sites, meaning some distinctions are possible behavioral traditions, such as the same fruit (Hymenaea) being processed with bigger than needed tools in CVNP than in the other two sites. Capuchin monkey behavioral variability in stone tool use can be caused by several interacting factors, from ecological to cultural.