bluuebunny/crossref_metadata_2025 huggingface dataset:
10 Science Insights for COP27
Authors: Rodrigues Meghie
Published: November 2022

As nations convene in Sharm El-Sheikh, Egypt, leading climate scientists share a new report to support more effective policy.
Does the Threshold of Sediment Motion Constrain the Width of an Incising Laboratory River?
Authors: Ashley T. C. , Strom K.
Published: November 2022

A physically rational model for river width is critical to predict macroscopic landscape evolution driven by fluvial sediment transport. Growing evidence suggests that rivers widen until the stress exerted by the fluid on the bed surface is close to the critical entrainment stress of the bank material. In this study, we test the limits of this model as a closure assumption in dynamically evolving river systems. We consider a simple laboratory channel with a fixed water discharge, monodisperse bed material, no sediment supply, and an initial relief that was sufficiently large to guarantee a finite transport capacity. Over time, the transport capacity approaches zero through changes in channel morphology. Concurrent measurements of width and sediment load illustrate how theory developed for equilibrium rivers fails to predict transient channel processes. Similarity to first order trends in natural rivers suggest that many rivers could be far from equilibrium.
Density Staircases Generated by Symmetric Instability in a Cross‐Equatorial Deep Western Boundary Current
Authors: Goldsworth F. W. , Johnson H. L. , Marshall D. P.
Published: November 2022

Density staircases are observed in an idealized model of a deep western boundary current upon crossing the equator. We propose that the staircases are generated by the excitement of symmetric instability as the current crosses the equator. The latitude at which symmetric instability is excited can be predicted using simple scaling arguments. Symmetric instability generates overturning cells which, in turn, cause the inhomogenous mixing of waters with different densities. The mixing barriers and well mixed regions in density profiles coincide, respectively, with the boundaries and centers of the overturning cells generated by the symmetric instability. This new mechanism for producing density staircases may require us to re‐evaluate the origins of some of the density staircases observed in the Tropical Atlantic.
Amplitude Scintillation Severity and Fading Profiles Under Alignment Between GPS Propagation Paths and Equatorial Plasma Bubbles
Authors: Sousasantos J. , Affonso B. J. , Moraes A. , Rodrigues F. S. , Abdu M. A. , Salles L. A. , Vani B. C.
Published: November 2022

Ionospheric scintillation and fading events over low‐latitude regions are often caused by severely depleted geomagnetic field‐aligned structures known as Equatorial Plasma Bubbles. These events are subject of interest to scientific investigations and concern to technological applications. Over the past several years, most of scintillation studies have focused on the dependence of these events on density gradients, location, local time, geomagnetic conditions, and so forth. This work presents a discussion about the role of the alignment between the signal propagation path and the depleted structures or, equivalently, the geomagnetic field lines, on the observed scintillation and deep fading characteristics. Data from three stations (dip latitudes: 16.13°S, 19.87°S, and 22.05°S) located around the Equatorial Ionization Anomaly (EIA) region were used to assess the amplitude scintillation severity and the deep fading events features under aligned and nonaligned conditions. The results show that the alignment condition plays a crucial role in the occurrence of strong scintillation. The study also revealed that, as stations far from the crests of the EIA are considered, the alignment influence seems to increase, and that a combination of strong plasma density fluctuation and increased aligned path is, presumably, the configuration under which the most severe scintillation and drastic deep fading events are observed. The results indicate that this conjunction is typically met in regions somewhat distinct from that with largest plasma density background over the Brazilian region, therefore, strongest scintillation and largest deep fading rates were observed by a station slightly off‐the EIA peak.
Polygenic risk scores for schizophrenia and major depression are associated with socio-economic indicators of adversity in two British community samples
Authors: Machlitt-Northen Sandra , Keers Robert , Munroe Patricia B. , Howard David M. , Pluess Michael
Published: November 2022

Schizophrenia (SCZ) and major depressive disorder (MDD) are complex psychiatric disorders which contribute substantially to the global burden of disease. Both psychopathologies are heritable with some genetic overlap between them. Importantly, SCZ and MDD have also been found to be associated with environmental risk factors. However, rather than being independent of genetic influences, exposure to environmental risk factors may be under genetic control, known as gene-environment correlation (rGE). In this study we investigated rGE in relation to polygenic risk scores for SCZ and MDD in adults, derived from large genome-wide association studies, across two different British community samples: Understanding Society (USoc) and the National Child Development Study (NCDS). We tested whether established environmental risk factors for SCZ and/or MDD are correlated with polygenic scores in adults and whether these associations differ between the two disorders and cohorts. Findings partially overlapped between disorders and cohorts. In NCDS, we identified a significant correlation between the genetic risk for MDD and an indicator of low socio-economic status, but no significant findings emerged for SCZ. In USoc, we replicated associations between indicators of low socio-economic status and the genetic propensity for MDD. In addition, we identified associations between the genetic susceptibility for SCZ and being single or divorced. Results across both studies provide further evidence that the genetic risk for SCZ and MDD were associated with common environmental risk factors, specifically MDD’s association with lower socio-economic status.
MiMIC analysis reveals an isoform specific role for Drosophila Musashi in follicle stem cell maintenance and escort cell function
Authors: Siddall Nicole A. , Casagranda Franca , Johanson Timothy M. , Dominado Nicole , Heaney James , Sutherland Jessie M. , McLaughlin Eileen A. , Hime Gary R.
Published: November 2022

The Drosophila ovary is regenerated from germline and somatic stem cell populations that have provided fundamental conceptual understanding on how adult stem cells are regulated within their niches. Recent ovarian transcriptomic studies have failed to identify mRNAs that are specific to follicle stem cells (FSCs), suggesting that their fate may be regulated post-transcriptionally. We have identified that the RNA-binding protein, Musashi (Msi) is required for maintaining the stem cell state of FSCs. Loss of msi function results in stem cell loss, due to a change in differentiation state, indicated by upregulation of Lamin C in the stem cell population. In msi mutant ovaries, Lamin C upregulation was also observed in posterior escort cells that interact with newly formed germ cell cysts. Mutant somatic cells within this region were dysfunctional, as evidenced by the presence of germline cyst collisions, fused egg chambers and an increase in germ cell cyst apoptosis. The msi locus produces two classes of mRNAs (long and short). We show that FSC maintenance and escort cell function specifically requires the long transcripts, thus providing the first evidence of isoform-specific regulation in a population of Drosophila epithelial cells. We further demonstrate that although male germline stem cells have previously been shown to require Msi function to prevent differentiation this is not the case for female germline stem cells, indicating that these similar stem cell types have different requirements for Msi, in addition to the differential use of Msi isoforms between soma and germline. In summary, we show that different isoforms of the Msi RNA-binding protein are expressed in specific cell populations of the ovarian stem cell niche where Msi regulates stem cell differentiation, niche cell function and subsequent germ cell survival and differentiation.
Causal deep learning reveals the comparative effectiveness of antihyperglycemic treatments in poorly controlled diabetes
Authors: Belthangady Chinmay , Giampanis Stefanos , Jankovic Ivana , Stedden Will , Alves Paula , Chong Stephanie , Knott Charlotte , Norgeot Beau
Published: November 2022

Type-2 diabetes is associated with severe health outcomes, the effects of which are responsible for approximately 1/4th of the total healthcare spending in the United States (US). Current treatment guidelines endorse a massive number of potential anti-hyperglycemic treatment options in various combinations. Strategies for optimizing treatment selection are lacking. Real-world data from a nationwide population of over one million high-risk diabetic patients (HbA1c ≥ 9%) in the US is analyzed to evaluate the comparative effectiveness for HbA1c reduction in this population of more than 80 different treatment strategies ranging from monotherapy up to combinations of five concomitant classes of drugs across each of 10 clinical cohorts defined by age, insulin dependence, and a number of other chronic conditions. A causal deep learning approach developed on such data allows for more personalized evaluation of treatment selection. An average confounder-adjusted reduction in HbA1c of 0.69% [−0.75, −0.65] is observed between patients receiving high vs low ranked treatments across cohorts for which the difference was significant. This method can be extended to explore treatment optimization for other chronic conditions.
Energy requirements and carbon emissions for a low-carbon energy transition
Authors: Slameršak Aljoša , Kallis Giorgos , O’Neill Daniel W.
Published: November 2022

Achieving the Paris Agreement will require massive deployment of low-carbon energy. However, constructing, operating, and maintaining a low-carbon energy system will itself require energy, with much of it derived from fossil fuels. This raises the concern that the transition may consume much of the energy available to society, and be a source of considerable emissions. Here we calculate the energy requirements and emissions associated with the global energy system in fourteen mitigation pathways compatible with 1.5 °C of warming. We find that the initial push for a transition is likely to cause a 10–34% decline in net energy available to society. Moreover, we find that the carbon emissions associated with the transition to a low-carbon energy system are substantial, ranging from 70 to 395 GtCO2 (with a cross-scenario average of 195 GtCO2). The share of carbon emissions for the energy system will increase from 10% today to 27% in 2050, and in some cases may take up all remaining emissions available to society under 1.5 °C pathways.
Altered glycolysis triggers impaired mitochondrial metabolism and mTORC1 activation in diabetic β-cells
Authors: Haythorne Elizabeth , Lloyd Matthew , Walsby-Tickle John , Tarasov Andrei I. , Sandbrink Jonas , Portillo Idoia , Exposito Raul Terron , Sachse Gregor , Cyranka Malgorzata , Rohm Maria , Rorsman Patrik , McCullagh James , Ashcroft Frances M.
Published: November 2022

Chronic hyperglycaemia causes a dramatic decrease in mitochondrial metabolism and insulin content in pancreatic β-cells. This underlies the progressive decline in β-cell function in diabetes. However, the molecular mechanisms by which hyperglycaemia produces these effects remain unresolved. Using isolated islets and INS-1 cells, we show here that one or more glycolytic metabolites downstream of phosphofructokinase and upstream of GAPDH mediates the effects of chronic hyperglycemia. This metabolite stimulates marked upregulation of mTORC1 and concomitant downregulation of AMPK. Increased mTORC1 activity causes inhibition of pyruvate dehydrogenase which reduces pyruvate entry into the tricarboxylic acid cycle and partially accounts for the hyperglycaemia-induced reduction in oxidative phosphorylation and insulin secretion. In addition, hyperglycaemia (or diabetes) dramatically inhibits GAPDH activity, thereby impairing glucose metabolism. Our data also reveal that restricting glucose metabolism during hyperglycaemia prevents these changes and thus may be of therapeutic benefit. In summary, we have identified a pathway by which chronic hyperglycaemia reduces β-cell function.
Cytoskeletal components can turn wall-less spherical bacteria into kinking helices
Authors: Lartigue Carole , Lambert Bastien , Rideau Fabien , Dahan Yorick , Decossas Marion , Hillion Mélanie , Douliez Jean-Paul , Hardouin Julie , Lambert Olivier , Blanchard Alain , Béven Laure
Published: November 2022

Bacterial cell shape is generally determined through an interplay between the peptidoglycan cell wall and cytoplasmic filaments made of polymerized MreB. Indeed, some bacteria (e.g., Mycoplasma) that lack both a cell wall and mreB genes consist of non-motile cells that are spherical or pleomorphic. However, other members of the same class Mollicutes (e.g., Spiroplasma, also lacking a cell wall) display a helical cell shape and kink-based motility, which is thought to rely on the presence of five MreB isoforms and a specific fibril protein. Here, we show that heterologous expression of Spiroplasma fibril and MreB proteins confers helical shape and kinking ability to Mycoplasma capricolum cells. Isoform MreB5 is sufficient to confer helicity and kink propagation to mycoplasma cells. Cryoelectron microscopy confirms the association of cytoplasmic MreB filaments with the plasma membrane, suggesting a direct effect on membrane curvature. However, in our experiments, the heterologous expression of MreBs and fibril did not result in efficient motility in culture broth, indicating that additional, unknown Spiroplasma components are required for swimming.
Adenine base editing efficiently restores the function of Fanconi anemia hematopoietic stem and progenitor cells
Authors: Siegner Sebastian M. , Ugalde Laura , Clemens Alexandra , Garcia-Garcia Laura , Bueren Juan A. , Rio Paula , Karasu Mehmet E. , Corn Jacob E.
Published: November 2022

Fanconi Anemia (FA) is a debilitating genetic disorder with a wide range of severe symptoms including bone marrow failure and predisposition to cancer. CRISPR-Cas genome editing manipulates genotypes by harnessing DNA repair and has been proposed as a potential cure for FA. But FA is caused by deficiencies in DNA repair itself, preventing the use of editing strategies such as homology directed repair. Recently developed base editing (BE) systems do not rely on double stranded DNA breaks and might be used to target mutations in FA genes, but this remains to be tested. Here we develop a proof of concept therapeutic base editing strategy to address two of the most prevalent FANCA mutations in patient hematopoietic stem and progenitor cells. We find that optimizing adenine base editor construct, vector type, guide RNA format, and delivery conditions leads to very effective genetic modification in multiple FA patient backgrounds. Optimized base editing restored FANCA expression, molecular function of the FA pathway, and phenotypic resistance to crosslinking agents. ABE8e mediated editing in primary hematopoietic stem and progenitor cells from FA patients was both genotypically effective and restored FA pathway function, indicating the potential of base editing strategies for future clinical application in FA.
Benefits of subsidence control for coastal flooding in China
Authors: Fang Jiayi , Nicholls Robert J. , Brown Sally , Lincke Daniel , Hinkel Jochen , Vafeidis Athanasios T. , Du Shiqiang , Zhao Qing , Liu Min , Shi Peijun
Published: November 2022

Land subsidence is impacting large populations in coastal Asia via relative sea-level rise (RSLR). Here we assesses these risks and possible response strategies for China, including estimates of present rates of RSLR, flood exposure and risk to 2050. In 2015, each Chinese coastal resident experienced on average RSLR of 11 to 20 mm/yr. This is 3 to 5 times higher than climate-induced SLR, reflecting that people are concentrated in subsiding locations. In 2050, assuming these subsidence rates continue, land area, population and assets exposed to the 100-year coastal flood event is 20%-39%, 17%-37% and 18%-39% higher than assuming climate change alone, respectively. Realistic subsidence control measures can avoid up to two thirds of this additional growth in exposure, with adaptation required to address the residual. This analysis emphasizes subsidence as a RSLR hazard in China that requires a broad-scale policy response, utilizing subsidence control combined with coastal adaptation.
4D printing of MXene hydrogels for high-efficiency pseudocapacitive energy storage
Authors: Li Ke , Zhao Juan , Zhussupbekova Ainur , Shuck Christopher E. , Hughes Lucia , Dong Yueyao , Barwich Sebastian , Vaesen Sebastien , Shvets Igor V. , Möbius Matthias , Schmitt Wolfgang , Gogotsi Yury , Nicolosi Valeria
Published: November 2022

2D material hydrogels have recently sparked tremendous interest owing to their potential in diverse applications. However, research on the emerging 2D MXene hydrogels is still in its infancy. Herein, we show a universal 4D printing technology for manufacturing MXene hydrogels with customizable geometries, which suits a family of MXenes such as Nb2CTx, Ti3C2Tx, and Mo2Ti2C3Tx. The obtained MXene hydrogels offer 3D porous architectures, large specific surface areas, high electrical conductivities, and satisfying mechanical properties. Consequently, ultrahigh capacitance (3.32 F cm−2 (10 mV s−1) and 233 F g−1 (10 V s−1)) and mass loading/thickness-independent rate capabilities are achieved. The further 4D-printed Ti3C2Tx hydrogel micro-supercapacitors showcase great low-temperature tolerance (down to –20 °C) and deliver high energy and power densities up to 93 μWh cm−2 and 7 mW cm−2, respectively, surpassing most state-of-the-art devices. This work brings new insights into MXene hydrogel manufacturing and expands the range of their potential applications.
High temperature methane emissions from Large Igneous Provinces as contributors to late Permian mass extinctions
Authors: Chen Chengsheng , Qin Shengfei , Wang Yunpeng , Holland Greg , Wynn Peter , Zhong Wanxu , Zhou Zheng
Published: November 2022

Methane (CH4) emissions induced by Large Igneous Provinces have the potential to contribute to global environmental changes that triggered mass extinctions in Earth’s history. Here, we explore the source of methane in gas samples from central Sichuan Basin, which is within the Emeishan Large Igneous Province (ELIP). We report evidence of high methane formation temperatures (between 249−17/+19 and 256−20/+22 °C) from clumped methane measurements and mantle-derived signatures of noble gases, which verify that oil-cracked CH4 and pyrobitumen are by-products within the reservoirs, associated with hydrothermal activity and enhanced heating by the ELIP. We estimate the volume of oil-cracked CH4 induced by the ELIP and argue that CH4 emissions would have been sufficient to initiate global warming prior to the end of the Permian. We also suggest that similar emissions from oil-cracked CH4 associated with the Siberian Traps Large Igneous Province may also have contributed to the end-Permian mass extinction significantly.
Ligand-enabled Ni-catalyzed hydroarylation and hydroalkenylation of internal alkenes with organoborons
Authors: Wang Dao-Ming , She Li-Qin , Wu Yichen , Zhu Chunyin , Wang Peng
Published: November 2022

The transition metal-catalyzed hydrofunctionalization of alkenes offers an efficient solution for the rapid construction of complex functional molecules, and significant progress has been made during last decades. However, the hydrofunctionalization of internal alkenes remains a significant challenge due to low reactivity and the difficulties of controlling the regioselectivity. Here, we report the hydroarylation and hydroalkenylation of internal alkenes lacking a directing group with aryl and alkenyl boronic acids in the presence of a nickel catalyst, featuring a broad substrate scope and wide functional group tolerance under redox-neutral conditions. The key to achieving this reaction is the identification of a bulky 1-adamantyl β-diketone ligand, which is capable of overcoming the low reactivity of internal 1,2-disubstituted alkenes. Preliminary mechanistic studies unveiled that this reaction undergoes an Ar-Ni(II)-H initiated hydroarylation process, which is generated by the oxidative addition of alcoholic solvent with Ni(0) species and sequential transmetalation. In addition, the oxidative addition of the alcoholic solvent proves to be the turnover-limiting step.
The prognostic and diagnostic value of intraleukocytic malaria pigment in patients with severe falciparum malaria
Authors: Srinamon Ketsanee , Watson James A. , Silamut Kamolrat , Intharabut Benjamas , Phu Nguyen Hoan , Diep Pham Thi , Lyke Kirsten E. , Fanello Caterina , von Seidlein Lorenz , Chotivanich Kesinee , Dondorp Arjen M. , Day Nicholas P. J. , White Nicholas J.
Published: November 2022

Severe falciparum malaria is a major cause of death in tropical countries, particularly in African children. Rapid and accurate diagnosis and prognostic assessment are critical to clinical management. In 6027 prospectively studied patients diagnosed with severe malaria we assess the prognostic value of peripheral blood film counts of malaria pigment containing polymorphonuclear leukocytes (PMNs) and monocytes. We combine these results with previously published data and show, in an individual patient data meta-analysis (n = 32,035), that the proportion of pigment containing PMNs is predictive of in-hospital mortality. In African children the proportion of pigment containing PMNs helps distinguish severe malaria from other life-threatening febrile illnesses, and it adds to the prognostic assessment from simple bedside examination, and to the conventional malaria parasite count. Microscopy assessment of pigment containing PMNs is simple and rapid, and should be performed in all patients hospitalised with suspected severe malaria.
Size-matched hydrogen bonded hydroxylammonium frameworks for regulation of energetic materials
Authors: Lai Qi , Pei Le , Fei Teng , Yin Ping , Pang Siping , Shreeve Jean’ne M.
Published: November 2022

Size matching molecular design utilizing host-guest chemistry is a general, promising strategy for seeking new functional materials. With the growing trend of multidisciplinary investigations, taming the metastable high-energy guest moiety in well-matched frameworks is a new pathway leading to innovative energetic materials. Presented is a selective encapsulation in hydrogen-bonded hydroxylammonium frameworks (HHF) by screening different sized nitrogen-rich azoles. The size-match between a sensitive high-energy guest and an HHF not only gives rise to higher energetic performance by dense packing, but also reinforces the layer-by-layer structure which can stabilize the resulting materials towards external mechanic stimuli. Preliminary assessment based on calculated detonation properties and mechanical sensitivity indicates that HHF competed well with the energetic performance and molecular stability (detonation velocity = 9286 m s−1, impact sensitivity = 50 J). This work highlights the size-matched phenomenon of HHF and may serve as an alternative strategy for exploring next generation advanced energetic materials.
Daylight saving time affects European mortality
patterns
Authors: Lévy Laurent , Robine Jean-Marie , Rey Grégoire , Méndez Turrubiates Raúl Fernando , Quijal-Zamorano Marcos , Achebak Hicham , Ballester Joan , Rodó Xavier , Herrmann François R.
Published: November 2022

Daylight saving time (DST) consists in a one-hour advancement of legal
time in spring offset by a backward transition of the same magnitude in fall. It
creates a minimal circadian misalignment that could disrupt sleep and homoeostasis
in susceptible individuals and lead to an increased incidence of pathologies and
accidents during the weeks immediately following both transitions. How this shift
affects mortality dynamics on a large population scale remains, however, unknown.
This study examines the impact of DST on all-cause mortality in 16 European
countries for the period 1998-2012. It shows that mortality decreases in spring and
increases in fall during the first two weeks following each DST transition.
Moreover, the alignment of time data around DST transition dates revealed a
septadian mortality pattern (lowest on Sundays, highest on Mondays) that persists
all-year round, irrespective of seasonal variations, in men and women aged above
40.
Hot-carrier tunable abnormal nonlinear absorption conversion in quasi-2D perovskite
Authors: Wang Gang , Liu Tanghao , Wang Bingzhe , Gu Hao , Wei Qi , Zhang Zhipeng , He Jun , Li Mingjie , Xing Guichuan
Published: November 2022

Controlling the high-power laser transmittance is built on the diverse manipulation of multiple nonlinear absorption (NLA) processes in the nonlinear optical (NLO) materials. According to standard saturable absorption (SA) and reverse saturable absorption (RSA) model adapted for traditional semiconductor materials, the coexistence of SA and RSA will result in SA induced transparency at low laser intensity, yet switch to RSA with pump fluence increasing. Here, we observed, in contrast, an unusual RSA to SA conversion in quasi-two-dimensional (2D) perovskite film with a low threshold around 2.6 GW cm−2. With ultrafast transient absorption (TA) spectra measurement, such abnormal NLA is attributed to the competition between excitonic absorption enhancement and non-thermalized carrier induced bleaching. TA singularity from non-thermalized “Fermi Sea” is observed in quasi-2D perovskite film, indicating an ultrafast carrier thermalization within 100 fs. Moreover, the comparative study between the 2D and 3D perovskites uncovers the crucial role of hot-carrier effect to tune the NLA response. The ultrafast carrier cooling of quasi-2D perovskite is pointed out as an important factor to realize such abnormal NLA conversion process. These results provide fresh insights into the NLA mechanisms in low-dimensional perovskites, which may pave a promising way to diversify the NLO material applications.
Inhibiting ACK1-mediated phosphorylation of C-terminal Src kinase counteracts prostate cancer immune checkpoint blockade resistance
Authors: Sridaran Dhivya , Chouhan Surbhi , Mahajan Kiran , Renganathan Arun , Weimholt Cody , Bhagwat Shambhavi , Reimers Melissa , Kim Eric H. , Thakur Manish K. , Saeed Muhammad A. , Pachynski Russell K. , Seeliger Markus A. , Miller W. Todd , Feng Felix Y. , Mahajan Nupam P.
Published: November 2022

Solid tumours are highly refractory to immune checkpoint blockade (ICB) therapies due to the functional impairment of effector T cells and their inefficient trafficking to tumours. T-cell activation is negatively regulated by C-terminal Src kinase (CSK); however, the exact mechanism remains unknown. Here we show that the conserved oncogenic tyrosine kinase Activated CDC42 kinase 1 (ACK1) is able to phosphorylate CSK at Tyrosine 18 (pY18), which enhances CSK function, constraining T-cell activation. Mice deficient in the Tnk2 gene encoding Ack1, are characterized by diminished CSK Y18-phosphorylation and spontaneous activation of CD8+ and CD4+ T cells, resulting in inhibited growth of transplanted ICB-resistant tumours. Furthermore, ICB treatment of castration-resistant prostate cancer (CRPC) patients results in re-activation of ACK1/pY18-CSK signalling, confirming the involvement of this pathway in ICB insensitivity. An ACK1 small-molecule inhibitor, (R)-9b, recapitulates inhibition of ICB-resistant tumours, which provides evidence for ACK1 enzymatic activity playing a pivotal role in generating ICB resistance. Overall, our study identifies an important mechanism of ICB resistance and holds potential for expanding the scope of ICB therapy to tumours that are currently unresponsive.
Coherent momentum control of forbidden excitons
Authors: Ma Xuezhi , Kudtarkar Kaushik , Chen Yixin , Cunha Preston , Ma Yuan , Watanabe Kenji , Taniguchi Takashi , Qian Xiaofeng , Hipwell M. Cynthia , Wong Zi Jing , Lan Shoufeng
Published: November 2022

A double-edged sword in two-dimensional material science and technology is optically forbidden dark exciton. On the one hand, it is fascinating for condensed matter physics, quantum information processing, and optoelectronics due to its long lifetime. On the other hand, it is notorious for being optically inaccessible from both excitation and detection standpoints. Here, we provide an efficient and low-loss solution to the dilemma by reintroducing photonics bound states in the continuum (BICs) to manipulate dark excitons in the momentum space. In a monolayer tungsten diselenide under normal incidence, we demonstrated a giant enhancement (~1400) for dark excitons enabled by transverse magnetic BICs with intrinsic out-of-plane electric fields. By further employing widely tunable Friedrich-Wintgen BICs, we demonstrated highly directional emission from the dark excitons with a divergence angle of merely 7°. We found that the directional emission is coherent at room temperature, unambiguously shown in polarization analyses and interference measurements. Therefore, the BICs reintroduced as a momentum-space photonic environment could be an intriguing platform to reshape and redefine light-matter interactions in nearby quantum materials, such as low-dimensional materials, otherwise challenging or even impossible to achieve.
Anti-infective therapy using species-specific activators of Staphylococcus aureus ClpP
Authors: Wei Bingyan , Zhang Tao , Wang Pengyu , Pan Yihui , Li Jiahui , Chen Weizhong , Zhang Min , Ji Quanjiang , Wu Wenjuan , Lan Lefu , Gan Jianhua , Yang Cai-Guang
Published: November 2022

The emergence of methicillin-resistant Staphylococcus aureus isolates highlights the urgent need to develop more antibiotics. ClpP is a highly conserved protease regulated by ATPases in bacteria and in mitochondria. Aberrant activation of  bacterial ClpP is an alternative method of discovering antibiotics, while it remains difficult to develop selective  Staphylococcus aureus ClpP activators that can avoid disturbing Homo sapiens ClpP functions. Here, we use a structure-based design to identify (R)- and (S)-ZG197 as highly selective Staphylococcus aureus ClpP activators. The key structural elements in Homo sapiens ClpP, particularly W146 and its joint action with the C-terminal motif, significantly contribute to the discrimination of the activators. Our selective activators display wide antibiotic properties towards an array of multidrug-resistant staphylococcal strains in vitro, and demonstrate promising antibiotic efficacy in zebrafish and murine skin infection models. Our findings indicate that the species-specific activators of Staphylococcus aureus ClpP are exciting therapeutic agents to treat staphylococcal infections.
Vertical depletion of ophiolitic mantle reflects melt focusing and interaction in sub-spreading-center asthenosphere
Authors: Xiong Qing , Dai Hong-Kun , Zheng Jian-Ping , Griffin William L. , Zheng Hong-Da , Wang Li , Reilly Suzanne Y. O’
Published: November 2022

Decompressional melting of asthenosphere under spreading centers has been accepted to produce oceanic lithospheric mantle with vertical compositional variations, but these gradients are much smaller than those observed from ophiolites, which clearly require additional causes. Here we conduct high-density sampling and whole-rock and mineral analyses of peridotites across a Tibetan ophiolitic mantle section (~2 km thick), which shows a primary upward depletion (~12% difference) and local more-depleted anomalies. Thermodynamic modeling demonstrates that these features cannot be produced by decompressional melting or proportional compression of residual mantle, but can be explained by melt-peridotite reaction with lateral melt/rock ratio variations in an upwelling asthenospheric column, producing stronger depletion in the melt-focusing center and local zones. This column splits symmetrically and flows to become the horizontal uppermost lithospheric mantle, characterized by upward depletion and local anomalies. This model provides insights into melt extraction and uppermost-mantle origin beneath spreading centers with high melt fluxes.
Cognitive training enhances growth mindset in children through plasticity of cortico-striatal circuits
Authors: Chen Lang , Chang Hyesang , Rudoler Jeremy , Arnardottir Eydis , Zhang Yuan , de los Angeles Carlo , Menon Vinod
Published: November 2022

Growth mindset, the belief that one’s abilities can improve through cognitive effort, is an important psychological construct with broad implications for enabling children to reach their highest potential. However, surprisingly little is known about malleability of growth mindset in response to cognitive interventions in children and its neurobiological underpinnings. Here we address critical gaps in our knowledge by investigating behavioral and brain changes in growth mindset associated with a four-week training program designed to enhance foundational, academically relevant, cognitive skills in 7–10-year-old children. Cognitive training significantly enhanced children’s growth mindset. Cross-lagged panel analysis of longitudinal pre- and post-training data revealed that growth mindset prior to training predicted cognitive abilities after training, providing support for the positive role of growth mindset in fostering academic achievement. We then examined training-induced changes in brain response and connectivity associated with problem solving in relation to changes in growth mindset. Children’s gains in growth mindset were associated with increased neural response and functional connectivity of the dorsal anterior cingulate cortex, striatum, and hippocampus, brain regions crucial for cognitive control, motivation, and memory. Plasticity of cortico-striatal circuitry emerged as the strongest predictor of growth mindset gains. Taken together, our study demonstrates that children’s growth mindset can be enhanced by cognitive training, and elucidates the potential neurobiological mechanisms underlying its malleability. Findings provide important insights into effective interventions that simultaneously promote growth mindset and learning during the early stages of cognitive development.
A potent, broadly protective vaccine against SARS-CoV-2 variants of concern
Authors: Wang Ziyan , An Jiao , Liu Kunpeng , Yu Pin , Fang Xin , Li Jiadai , Zhu Hua , Zhu Qianjun , Huang Chuanqi , Zhang Chao , Zhao Binbin , Bao Linlin , Song Yujiao , Cao Xiayao , Hu Dongdong , Jiang Yuanxiang , Shi Likang , Zhou Lingyun , Fan Jiang , Guan Wuxiang , Zhou Chenliang , Hu Zhongyu , Yuan Zhiming , Liu Jiangning , Shan Chao , Liu Ge
Published: November 2022

Since the first outbreak in December 2019, SARS-CoV-2 has been constantly evolving and five variants have been classified as Variant of Concern (VOC) by the World Health Organization (WHO). These VOCs were found to enhance transmission and/or decrease neutralization capabilities of monoclonal antibodies and vaccine-induced antibodies. Here, we successfully designed and produced a recombinant COVID-19 vaccine in CHO cells at a high yield. The vaccine antigen contains four hot spot substitutions, K417N, E484K, N501Y and D614G, based on a prefusion-stabilized spike trimer of SARS-CoV-2 (S-6P) and formulated with an Alum/CpG 7909 dual adjuvant system. Results of immunogenicity studies showed that the variant vaccine elicited robust cross-neutralizing antibody responses against SARS-CoV-2 prototype (Wuhan) strain and all 5 VOCs. It further, stimulated a TH1 (T Helper type 1) cytokine profile and substantial CD4+ T cell responses in BALB/c mice and rhesus macaques were recorded. Protective efficacy of the vaccine candidate was evaluated in hamster and rhesus macaque models of SARS-CoV-2. In Golden Syrian hamsters challenged with Beta or Delta strains, the vaccine candidate reduced the viral loads in nasal turbinates and lung tissues, accompanied by significant weight gain and relieved inflammation in the lungs. In rhesus macaque challenged with prototype SARS-CoV-2, the vaccine candidate decreased viral shedding in throat, anal, blood swabs over time, reduced viral loads of bronchus and lung tissue, and effectively relieved the lung pathological inflammatory response. Together, our data demonstrated the broadly neutralizing activity and efficacy of the variant vaccine against both prototype and current VOCs of SARS-CoV-2, justifying further clinical development.
Asymmetric emergence of low-to-no snow in the midlatitudes of the American Cordillera
Authors: Rhoades Alan M. , Hatchett Benjamin J. , Risser Mark D. , Collins William D. , Bambach Nicolas E. , Huning Laurie S. , McCrary Rachel , Siirila-Woodburn Erica R. , Ullrich Paul A. , Wehner Michael F. , Zarzycki Colin M. , Jones Andrew D.
Published: November 2022

Societies and ecosystems within and downstream of mountains rely on seasonal snowmelt to satisfy their water demands. Anthropogenic climate change has reduced mountain snowpacks worldwide, altering snowmelt magnitude and timing. Here the global warming level leading to widespread and persistent mountain snowpack decline, termed low-to-no snow, is estimated for the world’s most latitudinally contiguous mountain range, the American Cordillera. We show that a combination of dynamical, thermodynamical and hypsometric factors results in an asymmetric emergence of low-to-no-snow conditions within the midlatitudes of the American Cordillera. Low-to-no-snow emergence occurs approximately 20 years earlier in the southern hemisphere, at a third of the local warming level, and coincides with runoff efficiency declines (8% average) in both dry and wet years. The prevention of a low-to-no-snow future in either hemisphere requires the level of global warming to be held to, at most, +2.5 °C.
Fraser Island (K'gari) and initiation of the Great Barrier Reef linked by Middle Pleistocene sea-level change
Authors: Ellerton D. , Rittenour T. M. , Shulmeister J. , Roberts A. P. , Miot da Silva G. , Gontz A. , Hesp P. A. , Moss P. , Patton N. , Santini T. , Welsh K. , Zhao X.
Published: November 2022

The eastern Australia coastline is characterized by impressive coastal landforms and an extensive northward-moving longshore drift system that have been influenced by a stable, long-term tectonic history over the Quaternary period. However, the timing and drivers of the formation of two conspicuous landscape features—Fraser Island (K’gari) and the Great Barrier Reef—remain poorly understood. Here we use optically stimulated luminescence and palaeomagnetic dating to constrain the formation of the extensive dunes that make up Fraser Island, the world’s largest sand island, and adjacent Cooloola Sand Mass in southeastern Queensland. We find that both formed between 1.2 Ma and 0.7 Ma, during a global climate reconfiguration across the Middle Pleistocene transition. They formed as a direct result of increased amplitude of sea-level fluctuations associated with increasing global ice volume that redistributed previously stored sediment across the continental shelf. The development of Fraser Island dramatically reduced sediment supply to the continental shelf north of the island. This facilitated widespread coral reef formation in the southern and central Great Barrier Reef and was a necessary precondition for its development. This major reorganization of the coastal sedimentary system is probably not unique to eastern Australia and should be investigated in other passive-margin coastlines.
Identification of novel interferon responsive protein partners of human leukocyte antigen A (HLA-A) using cross-linking mass spectrometry (CLMS) approach
Authors: Singh Ashita , Padariya Monikaben , Faktor Jakub , Kote Sachin , Mikac Sara , Dziadosz Alicja , Lam Tak W. , Brydon Jack , Wear Martin A. , Ball Kathryn L. , Hupp Ted , Sznarkowska Alicja , Vojtesek Borek , Kalathiya Umesh
Published: November 2022

The interferon signalling system elicits a robust cytokine response against a wide range of environmental pathogenic and internal pathological signals, leading to induction of a subset of interferon-induced proteins. We applied DSS (disuccinimidyl suberate) mediated cross-linking mass spectrometry (CLMS) to capture novel protein–protein interactions within the realm of interferon induced proteins. In addition to the expected interferon-induced proteins, we identified novel inter- and intra-molecular cross-linked adducts for the canonical interferon induced proteins, such as MX1, USP18, OAS3, and STAT1. We focused on orthogonal validation of a cohort of novel interferon-induced protein networks formed by the HLA-A protein (H2BFS-HLA-A-HMGA1) using co-immunoprecipitation assay, and further investigated them by molecular dynamics simulation. Conformational dynamics of the simulated protein complexes revealed several interaction sites that mirrored the interactions identified in the CLMS findings. Together, we showcase a proof-of-principle CLMS study to identify novel interferon-induced signaling complexes and anticipate broader use of CLMS to identify novel protein interaction dynamics within the tumour microenvironment.
Specific tractography differences in autism compared to developmental coordination disorder
Authors: Kilroy Emily , Gerbella Marzio , Cao Lei , Molfese Peter , Butera Christiana , Harrison Laura , Jayashankar Aditya , Rizzolatti Giacomo , Aziz-Zadeh Lisa
Published: November 2022

About 85% of children with autism spectrum disorder (ASD) experience comorbid motor impairments, making it unclear whether white matter abnormalities previously found in ASD are related to social communication deficits, the hallmark of ASD, or instead related to comorbid motor impairment. Here we aim to understand specific white matter signatures of ASD beyond those related to comorbid motor impairment by comparing youth (aged 8–18) with ASD (n = 22), developmental coordination disorder (DCD; n = 16), and typically developing youth (TD; n = 22). Diffusion weighted imaging was collected and quantitative anisotropy, radial diffusivity, mean diffusivity, and axial diffusivity were compared between the three groups and correlated with social and motor measures. Compared to DCD and TD groups, diffusivity differences were found in the ASD group in the mid-cingulum longitudinal and u-fibers, the corpus callosum forceps minor/anterior commissure, and the left middle cerebellar peduncle. Compared to the TD group, the ASD group had diffusivity differences in the right inferior frontal occipital/extreme capsule and genu of the corpus callosum. These diffusion differences correlated with emotional deficits and/or autism severity. By contrast, children with DCD showed unique abnormality in the left cortico-spinal and cortico-pontine tracts.

Trial Registration All data are available on the National Institute of Mental Health Data Archive: https://nda.nih.gov/edit_collection.html?id=2254.
Prediction of severe pancreatitis in a population with low atmospheric oxygen pressure
Authors: Londoño-Ruiz Germán , Ramírez-Giraldo Camilo , Vesga-Rosas Andrés , Vargas-Barato Felipe
Published: November 2022

To establish the severity of pancreatitis, there are many scoring systems, the most used are the Marshall and APACHE II systems, each one has advantages and disadvantages; but with good relation regarding mortality and prediction of complications. In populations with low barometric pressures produced by a decrease in atmospheric pressure, there is a decrease in partial pressure of oxygen, in these cases scores which take arterial oxygen partial pressure as one of their variables, may be overestimated. A diagnostic trial study was designed to evaluate the performance of APACHE II, Marshall and BISAP in a city 2640 m above sea level. A ROC analysis was performed to estimate the AUC of each of the scores, to evaluate the performance in predicting unfavorable outcomes (defined as the need for percutaneous drainage, surgery, or mortality) and a non-parametric comparison was made between the AUC of each of the scores with the DeLong test. From January 2018 to December 2019, data from 424 patients living in Bogota, with a diagnosis of gallstone pancreatitis was collected consecutively in a hospital in Bogota, Colombia. The ROC analysis showed AUC for predicting adverse outcomes for APACHE II in 0.738 (95% CI 0.647–0.829), Marshall in 0.650 (95% CI 0.554–0.746), and BISAP in 0.744 (95% CI 0.654–0.835). The non-parametric comparison to assess whether there were differences between the different AUC of the different scores showed that there is a statistically significant difference between Marshall and BISAP AUC to predict unfavorable outcomes (p=0.032). The mortality in the group of patients studied was 5.8%. We suggest the use of BISAP to predict clinical outcomes in patients with a diagnosis of biliary pancreatitis in populations with decreased atmospheric pressure because it is an easy-to-use tool and does not require arterial oxygen partial pressure for its calculation.
Meta-analysis of the functional neuroimaging literature with probabilistic logic programming
Authors: Abdallah Majd , Iovene Valentin , Zanitti Gaston , Wassermann Demian
Published: November 2022

Inferring reliable brain-behavior associations requires synthesizing evidence from thousands of functional neuroimaging studies through meta-analysis. However, existing meta-analysis tools are limited to investigating simple neuroscience concepts and expressing a restricted range of questions. Here, we expand the scope of neuroimaging meta-analysis by designing NeuroLang: a domain-specific language to express and test hypotheses using probabilistic first-order logic programming. By leveraging formalisms found at the crossroads of artificial intelligence and knowledge representation, NeuroLang provides the expressivity to address a larger repertoire of hypotheses in a meta-analysis, while seamlessly modeling the uncertainty inherent to neuroimaging data. We demonstrate the language’s capabilities in conducting comprehensive neuroimaging meta-analysis through use-case examples that address questions of structure-function associations. Specifically, we infer the specific functional roles of three canonical brain networks, support the role of the visual word-form area in visuospatial attention, and investigate the heterogeneous organization of the frontoparietal control network.