bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting global numbers of teleomorphic ascomycetes
Authors: Senanayake Indunil C. , Pem Dhandevi , Rathnayaka Achala R. , Wijesinghe Subodini N. , Tibpromma Saowaluck , Wanasinghe Dhanushka N. , Phookamsak Rungtiwa , Kularathnage Nuwan D. , Gomdola Deecksha , Harishchandra Dulanjalee , Dissanayake Lakmali S. , Xiang Mei-mei , Ekanayaka Anusha H. , McKenzie Eric H. C. , Hyde Kevin D. , Zhang Hao-xing , Xie Ning
Published: February 2022

Sexual reproduction is the basic way to form high genetic diversity and it is beneficial in evolution and speciation of fungi. The global diversity of teleomorphic species in Ascomycota has not been estimated. This paper estimates the species number for sexual ascomycetes based on five different estimation approaches, viz. by numbers of described fungi, by fungus:substrate ratio, by ecological distribution, by meta-DNA barcoding or culture-independent studies and by previous estimates of species in Ascomycota. The assumptions were made with the currently most accepted, “2.2–3.8 million” species estimate and results of previous studies concluding that 90% of the described ascomycetes reproduce sexually. The Catalogue of Life, Species Fungorum and published research were used for data procurement. The average value of teleomorphic species in Ascomycota from all methods is 1.86 million, ranging from 1.37 to 2.56 million. However, only around 83,000 teleomorphic species have been described in Ascomycota and deposited in data repositories. The ratio between described teleomorphic ascomycetes to predicted teleomorphic ascomycetes is 1:22. Therefore, where are the undiscovered teleomorphic ascomycetes? The undescribed species are no doubt to be found in biodiversity hot spots, poorly-studied areas and species complexes. Other poorly studied niches include extremophiles, lichenicolous fungi, human pathogens, marine fungi, and fungicolous fungi. Undescribed species are present in unexamined collections in specimen repositories or incompletely described earlier species. Nomenclatural issues, such as the use of separate names for teleomorph and anamorphs, synonyms, conspecific names, illegitimate and invalid names also affect the number of described species. Interspecies introgression results in new species, while species numbers are reduced by extinctions.
A New Termitophilous Genus of Paederinae Rove Beetles (Coleoptera, Staphylinidae) from the Neotropics and Its Phylogenetic Position
Authors: Żyła Dagmara , Bogri Amalia , Hansen Aslak Kappel , Jenkins Shaw Josh , Kypke Janina , Solodovnikov Alexey
Published: February 2022

We describe a new genus and species of Paederinae rove beetles, Ruptor cordatus gen. et sp. nov., which lives in the arboreal nests of the termite Labiotermes labralis (Holmgren, 1906) in the Amazon lowlands of Peru. The morphology of Ruptor gen. nov. is highly derived, apparently due to its close association with the termite host, and thus, morphologically, the genus cannot be classified further than Lathrobiini incertae sedis. In order to address the sister-group relationships of Ruptor gen. nov., we conducted a molecular phylogenetic analysis based on seven gene fragments. The analysis indeed resolved the genus as a member of the tribe Lathrobiini and placed it nested within the informal clade of ‘Medonina and allied taxa’. We provide a morphological comparison of the new genus with all known myrmeco- and termitophilous representatives of the subfamily, and to the extent possible, we illustrate other relevant and poorly known Neotropical Paederinae inquilines.
A Call-to-Action for Clinicians to Implement Evidence-Based Best Practices When Caring for Women with Uterine Fibroids
Authors: Leyland Nicholas , Leonardi Mathew , Murji Ally , Singh Sukhbir S. , Al-Hendy Ayman , Bradley Linda
Published: February 2022

Uterine fibroids are common benign tumors that occur in up to 80% of women. Approximately half of the women affected experience considerable physical, psychological, and economic burdens and impact on quality of life due to symptoms such as heavy menstrual bleeding, pelvic pain, and infertility. Several medical and surgical options are available to treat uterine fibroids; however, healthcare providers may benefit from practical guidance in the development of individualized treatment plans based on a personalized approach. Medical treatments and minimally invasive procedures are generally preferred by most patients before considering more invasive, higher risk surgical interventions. In general, patient-centered, uterine-preserving procedures may be prioritized based on the patient’s goals and the clinical scenario. Occasionally, hysterectomy may be the preferred treatment option for some patients who require definitive treatment. This call-to-action highlights recent challenges to patient care, including radical shifts in physician–patient interactions due to the COVID-19 pandemic and recent changes to evidence-based, clinically approved therapies. This report also reviews contemporary recommendations for women’s health providers in the diagnosis and medical and surgical management of uterine fibroids. This call-to-action aims to empower healthcare providers to optimize the quality of care for women with uterine fibroids utilizing the best available evidence and best practices.
Absorption and Theatricality
Authors: Carville Conor
Published: February 2022

Samuel Beckett's 1976 Television play Ghost Trio is one of his most beautiful and mysterious works. It is also the play that most clearly demonstrates Beckett's imaginative and aesthetic engagement with the visual arts and the history of painting in particular. Drawing on the work of Stanley Cavell and Michael Fried, On Ghost Trio demonstrates Beckett's exploration of the relationship between theatricality, absorption and objecthood, and shows how his work anticipates the development of video and installation art. In doing so Conor Carville develops a new and highly original reading of Beckett's art, rooted in both archival sources and philosophical aesthetics.
Monetary Policy and Central Banking in Korea
Authors: Moon Woosik
Published: February 2022

This study is among the first to examine the theory and practice of monetary policy in South Korea. Woosik Moon provides a detailed analysis of the central bank of South Korea, one of the most successful and important economies in Asia. He covers everything from monetary policy to inflation targeting and macroprudential regulation, explaining how these policy tools were used to deal with the aftermath of the 2007-2011 financial crisis. He then brings his study into our current moment, speculating as to how the use of these policies will change in order to deal with the fallout of the Covid-19 pandemic. This book offers in-depth investigations and the provision of the most up-to-date information about the Bank of Korea's monetary and financial actions, serving as essential reading for central bankers and professionals of financial markets around the world, as well as anyone interested in monetary policy-making.
Trade Links
Authors: Bacchus James
Published: February 2022

The World Trade Organization is undergoing an existential crisis. Trade links the world not only through the flow of international commerce in goods, services, and ideas; but also through its economic, environmental, and social impacts. Trade links are supported by a WTO trading system founded on rules established in the 20th century which do not account for all the modern changes in the global economy. James Bacchus, a founder of the WTO, posits that this global organization can survive and continue to succeed only if the trade links among WTO members are revitalized and reimagined. He explains how to bring the WTO into the twenty-first century, exploring the ways it can be utilized to combat future pandemics and climate change and advance sustainable development, all while continuing to foster free trade. This book is among the first to comprehensively explain the new trade rules needed for our new world.
Stability of waves on fluid of infinite depth with constant vorticity
Authors: Blyth M.G. , Părău E.I.
Published: February 2022

The stability of periodic travelling waves on fluid of infinite depth is examined in the presence of a constant background shear field. The effects of gravity and surface tension are ignored. The base waves are described by an exact solution that was discovered recently by Hur and Wheeler (J. Fluid Mech., vol. 896, 2020). Linear growth rates are calculated using both an asymptotic approach valid for small-amplitude waves and a numerical approach based on a collocation method. Both superharmonic and subharmonic perturbations are considered. Instability is shown to occur for any non-zero amplitude wave.
Interaction between biological parameters of Panonychus citri (Acari: Tetranychidae) and some phytochemical metabolites in different citrus species
Authors: Shirinbeik Mohajer Sheila , Golizadeh Ali , Hassanpour Mahdi , Fathi Seyed Ali Asghar , Sedaratian-Jahromi Amin , Abedi Zahra
Published: February 2022

The citrus red mite, Panonychus citri McGregor, is a key pest of different citrus species in various parts of the world. Considering the key role of resistant host plants in integrated pest management strategies, we evaluated the effects of five citrus species including grapefruit (Citrus paradisi), lime (Citrus aurantifolia), tangerine (Citrus reticulata), orange (Citrus sinensis), and sour orange (Citrus aurantium) on life table parameters of P. citri under laboratory conditions (25 ± 1°C, 65 ± 5% RH, 16:8 L:D). In addition, biochemical traits of the citrus plant species were evaluated in order to understand any possible relationship between important life history parameters with biochemical metabolites of citrus plant leaves. Phytochemicals were determined in leaf extract of citrus plant species. Various citrus species had significant effects on life history and demographical parameters of P. citri. The longest pre-adult time was observed on grapefruit (16.52 ± 0.43 days). Higher fecundity rate was on orange (15.05 ± 2.41 eggs) and tangerine (14.60 ± 3.07 eggs) and the lowest was on grapefruit (7.21 ± 2.00 eggs). The highest intrinsic rate of increase (r) was recorded as 0.071 (day−1) on tangerine, and the lowest value of this parameter was obtained on grapefruit (0.016 day−1). Significant correlations were observed between life history parameters with biochemical metabolites (carbohydrate, phenolic compounds, anthocyanin, and flavonoid). The results revealed that grapefruit was a relatively resistant host plant and tangerine was the most suitable host plant for feeding of P. citri. Our findings could be helpful for sustainable management of P. citri in citrus orchards.
FromThe Good EarthtoMother India: esthetic circulations of peasant womanhood between India and China
Authors: Grewal Anup
Published: February 2022

The mid-1920s to the 1950s witnessed the uneasy imbrication of the rural, the peasantry, and women as symbols and subjects of the nation in the era of anti colonial and socialist movements in both India and China. This essay examines this rural/peasant/woman nexus within conflicting representations of the peasant woman as embodiment of the nation's past, present and future, to map a range of connected global political-aesthetic imaginations of Indian and Chinese nationhood. A close analysis of the convergence of three texts – Pearl Buck's novel,The Good Earth(1931), Katherine Mayo's polemic,Mother India(1927), and Indian director Mehboob Khan's re-staging and transformation of both in his 1957 film,Mother India– opens up to a wider set of entangled Indian and Chinese co-texts within an expanded space of global aesthetic circulation. Together, these texts reveal a contested history of representations of the rural, the peasantry, and women in projections of Indian and Chinese national becoming that, in the end, cannot be easily recuperated or consolidated within singular nation-state narratives.
Inter‐Annual Variability of the Along‐Shore Lagrangian Transport Success in the Southern Benguela Current Upwelling System
Authors: Ragoasha Moagabo Natalie , Herbette Steven , Veitch Jennifer , Cambon Gildas , Reason Chris J. C. , Roy Claude
Published: February 2022

A 3‐km resolution regional ocean model is used to investigate the role of wind‐driven coastal circulation and mesoscale variability on the inter‐annual variability of transport success in the southern Benguela between Cape Point (34°S) and St Helena Bay (32°S) from 1992 to 2011. Lagrangian particles are released within the top 100 m of the water column along an across‐shore transect off Cape Point. Transport success is given by the ratio of the number of particles that reach St Helena Bay over the total number of particles released. The analysis of transport success anomalies and their relationship with the local circulation and wind forcing reveal that there is no single driver of the inter‐annual variability. The transport success variability of particles released on the shelf (depths <300 m) mainly depends on their capacity to remain embedded within the coastal Benguela Jet. Nevertheless, peaks in offshore Ekman transport and episodic occurrence of a poleward inner‐shelf counter‐current contribute to negative anomalies. For particles released on the outer shelf edge (depths >500 m), across‐shore transports induced by mesoscale eddies are the main contributors to transport success variability. Rare passage of Agulhas rings near the shelf edge can induce strong offshore advection of particles into the open ocean. In contrast, shelf‐edge cyclonic eddies favor the onshore transport of particles originating from the outer shelf edge and thus contribute to increasing transport success.
Improved Representation of Extratropical Cyclone Structure in HighResMIP Models
Authors: Priestley Matthew D. K. , Catto Jennifer L.
Published: February 2022

General circulation models are broadly able to capture the shape and structure of extratropical cyclones. Increased atmospheric resolution has been shown to improve the representation of cyclone structure. However, the intensity of cyclones, and the strength of their winds, are commonly underestimated in models. Using a cyclone compositing technique applied to the new generation HighResMIP and CMIP6 models, the representation of cyclone wind speeds and airstreams is quantified. CMIP6 models are able to capture the structure of cyclones, however winds associated with various airstreams within the cyclones are too weak. HighResMIP models show considerable improvements, with a majority of cyclone‐scale biases present in the CMIP6 models reduced in both winter and summer seasons in the Northern and Southern hemispheres. HighResMIP and CMIP6 models have similar biases on the large‐scale, with both struggling to represent the width of the upper‐level jet.
Validation of Ocean Model Predictions of Mean Dynamic Topography in Shallow, Tidally Dominated Regions Using Observations of Overtides
Authors: Renkl C. , Thompson K. R.
Published: February 2022

In shallow, tidally dominated regions, overtides and the mean state of the ocean are coupled through their simultaneous generation by nonlinear processes. We present a new method that uses observed overtides (e.g., M4) and mean currents to independently assess the accuracy of mean dynamic topography (MDT) predicted by ocean models. This is useful in regions where no sufficiently long, geodetically referenced sea level records are available for validation of the predicted MDT. We apply the new method to a regional model of the Gulf of Maine/Scotian Shelf region (GoMSS) and a barotropic, higher resolution model focused on the upper Bay of Fundy (UBoF). We first show that the tides and mean circulation predicted by UBoF are in good agreement with observations and a significant improvement over GoMSS. Next, we use UBoF to demonstrate that observed overtides are useful in selecting the optimal bathymetry and constraining parameters of an ocean model. An accurate bathymetry is critical for capturing the dominant nonlinear processes that generate overtides and control the form of MDT in shallow, tidally dominated regions. Finally, we use the observed overtides to argue that the MDT predicted by UBoF is more realistic than the prediction by GoMSS. In the vicinity of headlands, both horizontal advection and bottom friction in UBoF generate harmonics of the tidal flow and local setdowns of coastal MDT of (10 cm). The prediction of such features, validated by observed overtides, can provide guidance in future deployments of tide gauges in support of geoid and ocean model validation.
Characterizing the Response of Vegetation Cover to Water Limitation in Africa Using Geostationary Satellites
Authors: Küçük Çağlar , Koirala Sujan , Carvalhais Nuno , Miralles Diego G. , Reichstein Markus , Jung Martin
Published: February 2022

Hydrological interactions between vegetation, soil, and topography are complex, and heterogeneous in semi‐arid landscapes. This along with data scarcity poses challenges for large‐scale modeling of vegetation‐water interactions. Here, we exploit metrics derived from daily Meteosat data over Africa at ca. 5 km spatial resolution for ecohydrological analysis. Their spatial patterns are based on Fractional Vegetation Cover (FVC) time series and emphasize limiting conditions of the seasonal wet to dry transition: the minimum and maximum FVC of temporal record, the FVC decay rate and the FVC integral over the decay period. We investigate the relevance of these metrics for large scale ecohydrological studies by assessing their co‐variation with soil moisture, and with topographic, soil, and vegetation factors. Consistent with our initial hypothesis, FVC minimum and maximum increase with soil moisture, while the FVC integral and decay rate peak at intermediate soil moisture. We find evidence for the relevance of topographic moisture variations in arid regions, which, counter‐intuitively, is detectable in the maximum but not in the minimum FVC. We find no clear evidence for wide‐spread occurrence of the “inverse texture effect” on FVC. The FVC integral over the decay period correlates with independent data sets of plant water storage capacity or rooting depth while correlations increase with aridity. In arid regions, the FVC decay rate decreases with canopy height and tree cover fraction as expected for ecosystems with a more conservative water‐use strategy. Thus, our observation‐based products have large potential for better understanding complex vegetation‐water interactions from regional to continental scales.
Sowing Storms: How Model Timestep Can Control Tropical Cyclone Frequency in a GCM
Authors: Zarzycki Colin M.
Published: February 2022

With general circulation models (GCMs) being increasingly used to explore extreme events over short temporal and small spatial scales, understanding how design choices in model configuration impact simulation results is critical. This research shows that the number of spontaneously generated tropical cyclones (TCs) in a version of the Community Atmosphere Model can be controlled by changing the coupling frequency between the dynamical core and physical parameterizations. More frequent coupling (i.e., shorter physics timesteps), even in the presence of an otherwise identical model, leads to large increases in TC activity. It is suggested that this arises due to competition within moist physics subroutines. Simulations with reduced physics timesteps preferentially eliminate instantaneous atmospheric instability via grid‐scale motions, even while producing mean climates similar to those with longer timesteps. These small‐scale variability increases lead to more tropical “seeds,” which are converted to full‐fledged TCs. This behavior is confirmed through a set of sensitivity experiments and highlights the caution needed in studying and generalizing phenomena that depend on both resolved and sub‐grid scales in GCMs and the need for targeting physics‐dynamics coupling as a model improvement strategy.
Exposure to Low Levels of Air Pollution Increases COVID-19 Risk
Authors: Hornyak Tim
Published: February 2022

Although causality has yet to be established, an Italian case study found that an increase in annual average exposure to PM2.5 was associated with a jump in the rate of COVID-19.
Reduced expression of TAZ inhibits primary cilium formation in renal glomeruli
Authors: Jun Jae Hee , Lee Eun Ji , Park Minah , Ko Je Yeong , Park Jong Hoon
Published: February 2022

Renal primary cilia are antenna-like organelles that maintain cellular homeostasis via multiple receptors clustered along their membranes. Recent studies have revealed that YAP/TAZ, key paralogous effectors of the Hippo pathway, are involved in ciliogenesis; however, their independent roles need to be further investigated. Here, we analyzed the renal phenotypes of kidney-specific TAZ knockout mice and observed ciliary defects only in glomeruli where mild cysts were formed. This finding prompted us to verify the role of TAZ specifically in renal tubule ciliary regulation. Therefore, we investigated the effects of TAZ silencing and compared them to those of YAP knockdown using three different types of renal tubular cells. We found that the absence of TAZ prevented proper cilia formation in glomerular cells, whereas it had a negligible effect in collecting duct and proximal tubule cells. IFT and NPHP protein levels were altered because of TAZ deficiency, accompanied by ciliary defects in glomerular cells, and ciliary recovery was identified by regulating some NPHP proteins. Although our study focused on TAZ, ciliogenesis, and other ciliary genes, the results suggest the very distinct roles of YAP and TAZ in kidneys, specifically in terms of ciliary regulation.
Wearable multimode sensor with a seamless integrated structure for recognition of different joint motion states with the assistance of a deep learning algorithm
Authors: Wen Lei , Nie Meng , Chen Pengfan , Zhao Yu-na , Shen Jingcheng , Wang Chongqing , Xiong Yuwei , Yin Kuibo , Sun Litao
Published: February 2022

Accurate motion feature extraction and recognition provide critical information for many scientific problems. Herein, a new paradigm for a wearable seamless multimode sensor with the ability to decouple pressure and strain stimuli and recognize the different joint motion states is reported. This wearable sensor is integrated into a unique seamless structure consisting of two main parts (a resistive component and a capacitive component) to decouple the different stimuli by an independent resistance-capacitance sensing mechanism. The sensor exhibits both high strain sensitivity (GF = 7.62, 0–140% strain) under the resistance mechanism and high linear pressure sensitivity (S = 3.4 kPa−1, 0–14 kPa) under the capacitive mechanism. The sensor can differentiate the motion characteristics of the positions and states of different joints with precise recognition (97.13%) with the assistance of machine learning algorithms. The unique integrated seamless structure is achieved by developing a layer-by-layer casting process that is suitable for large-scale manufacturing. The proposed wearable seamless multimode sensor and the convenient process are expected to contribute significantly to developing essential components in various emerging research fields, including soft robotics, electronic skin, health care, and innovative sports systems applications.
Nanog mediated by FAO/ACLY signaling induces cellular dormancy in colorectal cancer cells
Authors: Zhang Meng , Peng Ruyi , Wang Haizhou , Yang Zhenwei , Zhang Hailin , Zhang Yangyang , Wang Meng , Wang Hongling , Lin Jun , Zhao Qiu , Liu Jing
Published: February 2022

Dormant cancer cells drive recurrence and drug resistance, which lead to poor prognosis in colorectal cancer (CRC). The mechanisms that regulate the entry of cancer cells into dormancy remain to be extensively studied. Nanog is a master transcription factor to maintain the self-renewal and pluripotency of stem cells. Since dormant cancer cells are similar to quiescent cancer stem cells, the correlation between dormant state and Nanog in CRC is worth to be explored. Serum deprivation is a common method to establish experimental cellular dormancy model. Here, we verified that serum deprivation-induced CRC cells to enter a cellular dormancy state, characterized by no proliferation, no death, no senescence, resistance to chemotherapy, high expression of dormant markers, metabolic suppression, and recovery to active status. Interestingly, we further identified that Nanog was upregulated in dormant CRC cells. Nanog knockdown could destroy the dormant state of serum-deprived CRC cells while Nanog overexpression could induce dormancy in CRC cells. Mechanistically, Nanog was regulated through a fatty acid oxidation (FAO)/ATP citrate lyase (ACLY)-dependent pathway. FAO increased ACLY expression to promote the synthesis of acetyl-CoA, which was transferred by P300 to accelerate H3K27 acetylation of Nanog promoter. Then, Nanog upregulation increased the transcription of P21 and P27, which promoted the dormancy of CRC cells. Our findings revealed that Nanog could induce cellular dormancy in CRC cells and unlocked a specific mechanism to govern the process.
Oxeiptosis: a novel pathway of melanocytes death in response to oxidative stress in vitiligo
Authors: Kang Pan , Chen Jianru , Zhang Weigang , Guo Ningning , Yi Xiuli , Cui Tingting , Chen Jiaxi , Yang Yuqi , Wang Yinghan , Du Pengran , Ye Zhubiao , Li Baizhang , Li Chunying , Li Shuli
Published: February 2022

Vitiligo is a cutaneous depigmenting autoimmune disease caused by the extensive destruction of epidermal melanocytes. Convincing data has defined a critical role for oxidative stress in the pathogenesis of vitiligo. Oxeiptosis is a caspase-independent cell death modality that was reportedly triggered by oxidative stress and operative in pathogen clearance. However, whether oxeiptosis exists in oxidative stress-induced melanocytes demise in vitiligo remains undetermined. In the present study, we initially found that other cell death modalities might exist in addition to the well-recognized apoptosis and necroptosis in H2O2-treated melanocytes. Furthermore, AIFM1 was found to be dephosphorylated at Ser116 in oxidative stress-induced melanocytes death, which was specific to oxeiptosis. Moreover, KEAP1 and PGAM5, upstream of the AIFM1 in oxeiptosis, were found to operate in melanocytic death. Subsequently, the KEAP1-PGAM5-AIFM1 signaling pathway was proved to be involved in oxidative stress-triggered melanocytes demise through the depletion of KEAP1 and PGAM5. Altogether, our study indicated that oxeiptosis might occur in melanocytes death under oxidative stress and contribute to the pathogenesis of vitiligo.
Mitochondrial homeostasis regulates definitive endoderm differentiation of human pluripotent stem cells
Authors: Lv Jing , Yi Ying , Qi Yan , Yan Chenchao , Jin Wenwen , Meng Liming , Zhang Donghui , Jiang Wei
Published: February 2022

Cellular organelles play fundamental roles in almost all cell behaviors. Mitochondria have been reported to be functionally linked to various biological processes, including reprogramming and pluripotency maintenance. However, very little about the role of mitochondria has been revealed in human early development and lineage specification. Here, we reported the characteristics and function of mitochondria during human definitive endoderm differentiation. Using a well-established differentiation system, we first investigated the change of mitochondrial morphology by comparing undifferentiated pluripotent stem cells, the intermediate mesendoderm cells, and differentiated endoderm cells, and found that mitochondria were gradually elongated and matured along differentiation. We further analyzed the expression pattern of mitochondria-related genes by RNA-seq, indicating that mitochondria became active during differentiation. Supporting this notion, the production of adenosine triphosphate (ATP) and reactive oxygen species (ROS) was increased as well. Functionally, we utilized chemicals and genome editing techniques, which could interfere with mitochondrial homeostasis, to determine the role of mitochondria in human endoderm differentiation. Treatment with mitochondrial inhibitors, or genetic depletion of mitochondrial transcription factor A (TFAM), significantly reduced the differentiation efficiency of definitive endoderm. In addition, the defect in endoderm differentiation due to dysfunctional mitochondria could be restored to some extent by the addition of ATP. Moreover, the clearance of excessive ROS due to dysfunctional mitochondria by N-acetylcysteine (NAC) improved the differentiation as well. We further found that ATP and NAC could partially replace the growth factor activin A for definitive endoderm differentiation. Our study illustrates the essential role of mitochondria during human endoderm differentiation through providing ATP and regulating ROS levels, which may provide new insight for metabolic regulation of cell fate determination.
Nanoscale rules governing the organization of glutamate receptors in spine synapses are subunit specific
Authors: Hruska Martin , Cain Rachel E. , Dalva Matthew B.
Published: February 2022

Heterotetrameric glutamate receptors are essential for the development, function, and plasticity of spine synapses but how they are organized to achieve this is not known. Here we show that the nanoscale organization of glutamate receptors containing specific subunits define distinct subsynaptic features. Glutamate receptors containing GluA2 or GluN1 subunits establish nanomodular elements precisely positioned relative to Synaptotagmin-1 positive presynaptic release sites that scale with spine size. Glutamate receptors containing GluA1 or GluN2B specify features that exhibit flexibility: GluA1-subunit containing AMPARs are found in larger spines, while GluN2B-subunit containing NMDARs are enriched in the smallest spines with neither following a strict modular organization. Given that the precise positioning of distinct classes of glutamate receptors is linked to diverse events including cell death and synaptic plasticity, this unexpectedly robust synaptic nanoarchitecture provides a resilient system, where nanopositioned glutamate receptor heterotetramers define specific subsynaptic regions of individual spine synapses.
Observational evidence of ring current in the magnetosphere of Mercury
Authors: Zhao J.-T. , Zong Q.-G. , Yue C. , Sun W.-J. , Zhang H. , Zhou X.-Z. , Le G. , Rankin R. , Slavin J. A. , Raines J. M. , Liu Y. , Wei Y.
Published: February 2022

The magnetic gradient and curvature drift of energetic ions can form a longitudinal electric current around a planet known as the ring current, that has been observed in the intrinsic magnetospheres of Earth, Jupiter, and Saturn. However, there is still a lack of observational evidence of ring current in Mercury’s magnetosphere, which has a significantly weaker dipole magnetic field. Under such conditions, charged particles are thought to be efficiently lost through magnetopause shadowing and/or directly impact the planetary surface. Here, we present the observational evidence of Mercury’s ring current by analysing particle measurements from MErcury Surface, Space Environment, GEochemistry, and Ranging (MESSENGER) spacecraft. The ring current is bifurcated because of the dayside off-equatorial magnetic minima. Test-particle simulation with Mercury’s dynamic magnetospheric magnetic field model (KT17 model) validates this morphology. The ring current energy exceeds $$5\times {10}^{10}$$
5
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 J during active times, indicating that magnetic storms may also occur on Mercury.
Structure units oriented approach towards collective synthesis of sarpagine-ajmaline-koumine type alkaloids
Authors: Chen Wen , Ma Yonghui , He Wenyan , Wu Yinxia , Huang Yuancheng , Zhang Yipeng , Tian Hongchang , Wei Kai , Yang Xiaodong , Zhang Hongbin
Published: February 2022

Sarpagine-Ajmaline-Koumine type monoterpenoid indole alkaloids represent a fascinating class of natural products with polycyclic and cage-like structures, interesting biological activities, and related biosynthetic origins. Herein we report a unified approach towards the asymmetric synthesis of these three types of alkaloids, leading to a collective synthesis of 14 natural alkaloids. Among them, akuammidine, 19-Z-akuammidine, vincamedine, vincarine, quebrachidine, vincamajine, alstiphylianine J, and dihydrokoumine are accomplished for the first time. Features of our synthesis are a new Mannich-type cyclization to construct the key indole-fused azabicyclo[3.3.1]nonane common intermediate, a SmI2 mediated coupling to fuse the aza-bridged E-ring, stereoselective olefinations to install either the 19-E or 19-Z terminal alkenes presented in the natural alkaloids, and an efficient iodo-induced cyclization to establish the two vicinal all-carbon quaternary centers in the Koumine-type alkaloids.
Filling the gap between topological insulator nanomaterials and triboelectric nanogenerators
Authors: Li Mengjiao , Lu Hong-Wei , Wang Shu-Wei , Li Rei-Ping , Chen Jiann-Yeu , Chuang Wen-Shuo , Yang Feng-Shou , Lin Yen-Fu , Chen Chih-Yen , Lai Ying-Chih
Published: February 2022

Reliable energy modules and higher-sensitivity, higher-density, lower-powered sensing systems are constantly required to develop wearable electronics and the Internet of Things technology. As an emerging technology, triboelectric nanogenerators have been potentially guiding the landscape of sustainable power units and energy-efficient sensors. However, the existing triboelectric series is primarily populated by polymers and rubbers, limiting triboelectric sensing plasticity to some extent owing to their stiff surface electronic structures. To enrich the current triboelectric group, we explore the triboelectric properties of the topological insulator nanofilm by Kelvin probe force microscopy and reveal its relatively positive electrification charging performance. Both the larger surface potential difference and the conductive surface states of the nanofilms synergistically improve the charge transfer behavior between the selected triboelectric media, endowing the topological insulator-based triboelectric nanogenerator with considerable output performance. Besides serving as a wearable power source, the ultra-compact device array demonstrates innovative system-level sensing capabilities, including precise monitoring of dynamic objects and real-time signal control at the human-machine interface. This work fills the blank between topological quantum matters and triboelectric nanogenerators and, more importantly, exploits the significant potential of topological insulator nanofilms for self-powered flexible/wearable electronics and scalable sensing technologies.
ASPP2 maintains the integrity of mechanically stressed pseudostratified epithelia during morphogenesis
Authors: Royer Christophe , Sandham Elizabeth , Slee Elizabeth , Schneider Falk , Lagerholm Christoffer B. , Godwin Jonathan , Veits Nisha , Hathrell Holly , Zhou Felix , Leonavicius Karolis , Garratt Jemma , Narendra Tanaya , Vincent Anna , Jones Celine , Child Tim , Coward Kevin , Graham Chris , Fritzsche Marco , Lu Xin , Srinivas Shankar
Published: February 2022

During development, pseudostratified epithelia undergo large scale morphogenetic events associated with increased mechanical stress. Using a variety of genetic and imaging approaches, we uncover that in the mouse E6.5 epiblast, where apical tension is highest, ASPP2 safeguards tissue integrity. It achieves this by preventing the most apical daughter cells from delaminating apically following division events. In this context, ASPP2 maintains the integrity and organisation of the filamentous actin cytoskeleton at apical junctions. ASPP2 is also essential during gastrulation in the primitive streak, in somites and in the head fold region, suggesting that it is required across a wide range of pseudostratified epithelia during morphogenetic events that are accompanied by intense tissue remodelling. Finally, our study also suggests that the interaction between ASPP2 and PP1 is essential to the tumour suppressor function of ASPP2, which may be particularly relevant in the context of tissues that are subject to increased mechanical stress.
Hypoxia-induced macropinocytosis represents a metabolic route for liver cancer
Authors: Zhang Misty Shuo , Cui Jane Di , Lee Derek , Yuen Vincent Wai-Hin , Chiu David Kung-Chun , Goh Chi Ching , Cheu Jacinth Wing-Sum , Tse Aki Pui-Wah , Bao Macus Hao-Ran , Wong Bowie Po Yee , Chen Carrie Yiling , Wong Chun-Ming , Ng Irene Oi-Lin , Wong Carmen Chak-Lui
Published: February 2022

Hepatocellular carcinoma (HCC) invariably exhibits inadequate O2 (hypoxia) and nutrient supply. Hypoxia-inducible factor (HIF) mediates cascades of molecular events that enable cancer cells to adapt and propagate. Macropinocytosis is an endocytic process initiated by membrane ruffling, causing the engulfment of extracellular fluids (proteins), protein digestion and subsequent incorporation into the biomass. We show that macropinocytosis occurs universally in HCC under hypoxia. HIF-1 activates the transcription of a membrane ruffling protein, EH domain-containing protein 2 (EHD2), to initiate macropinocytosis. Knockout of HIF-1 or EHD2 represses hypoxia-induced macropinocytosis and prevents hypoxic HCC cells from scavenging protein that support cell growth. Germline or somatic deletion of Ehd2 suppresses macropinocytosis and HCC development in mice. Intriguingly, EHD2 is overexpressed in HCC. Consistently, HIF-1 or macropinocytosis inhibitor suppresses macropinocytosis and HCC development. Thus, we show that hypoxia induces macropinocytosis through the HIF/EHD2 pathway in HCC cells, harnessing extracellular protein as a nutrient to survive.
Stratification of hospitalized COVID-19 patients into clinical severity progression groups by immuno-phenotyping and machine learning
Authors: Mueller Yvonne M. , Schrama Thijs J. , Ruijten Rik , Schreurs Marco W. J. , Grashof Dwin G. B. , van de Werken Harmen J. G. , Lasinio Giovanna Jona , Álvarez-Sierra Daniel , Kiernan Caoimhe H. , Castro Eiro Melisa D. , van Meurs Marjan , Brouwers-Haspels Inge , Zhao Manzhi , Li Ling , de Wit Harm , Ouzounis Christos A. , Wilmsen Merel E. P. , Alofs Tessa M. , Laport Danique A. , van Wees Tamara , Kraker Geoffrey , Jaimes Maria C. , Van Bockstael Sebastiaan , Hernández-González Manuel , Rokx Casper , Rijnders Bart J. A. , Pujol-Borrell Ricardo , Katsikis Peter D.
Published: February 2022

Quantitative or qualitative differences in immunity may drive clinical severity in COVID-19. Although longitudinal studies to record the course of immunological changes are ample, they do not necessarily predict clinical progression at the time of hospital admission. Here we show, by a machine learning approach using serum pro-inflammatory, anti-inflammatory and anti-viral cytokine and anti-SARS-CoV-2 antibody measurements as input data, that COVID-19 patients cluster into three distinct immune phenotype groups. These immune-types, determined by unsupervised hierarchical clustering that is agnostic to severity, predict clinical course. The identified immune-types do not associate with disease duration at hospital admittance, but rather reflect variations in the nature and kinetics of individual patient’s immune response. Thus, our work provides an immune-type based scheme to stratify COVID-19 patients at hospital admittance into high and low risk clinical categories with distinct cytokine and antibody profiles that may guide personalized therapy.
The histone demethylase Kdm6b regulates subtype diversification of mouse spinal motor neurons during development
Authors: Wang Wenxian , Cho Hyeyoung , Lee Jae W. , Lee Soo-Kyung
Published: February 2022

How a single neuronal population diversifies into subtypes with distinct synaptic targets is a fundamental topic in neuroscience whose underlying mechanisms are unclear. Here, we show that the histone H3-lysine 27 demethylase Kdm6b regulates the diversification of motor neurons to distinct subtypes innervating different muscle targets during spinal cord development. In mouse embryonic motor neurons, Kdm6b promotes the medial motor column (MMC) and hypaxial motor column (HMC) fates while inhibiting the lateral motor column (LMC) and preganglionic motor column (PGC) identities. Our single-cell RNA-sequencing analyses reveal the heterogeneity of PGC, LMC, and MMC motor neurons. Further, our single-cell RNA-sequencing data, combined with mouse model studies, demonstrates that Kdm6b acquires cell fate specificity together with the transcription factor complex Isl1-Lhx3. Our study provides mechanistic insight into the gene regulatory network regulating neuronal cell-type diversification and defines a regulatory role of Kdm6b in the generation of motor neuron subtypes in the mouse spinal cord.
Programming cell-free biosensors with DNA strand displacement circuits
Authors: Jung Jaeyoung K. , Archuleta Chloé M. , Alam Khalid K. , Lucks Julius B.
Published: February 2022

Cell-free biosensors are powerful platforms for monitoring human and environmental health. Here, we expand their capabilities by interfacing them with toehold-mediated strand displacement circuits, a dynamic DNA nanotechnology that enables molecular computation through programmable interactions between nucleic acid strands. We develop design rules for interfacing a small molecule sensing platform called ROSALIND with toehold-mediated strand displacement to construct hybrid RNA–DNA circuits that allow fine-tuning of reaction kinetics. We use these design rules to build 12 different circuits that implement a range of logic functions (NOT, OR, AND, IMPLY, NOR, NIMPLY, NAND). Finally, we demonstrate a circuit that acts like an analog-to-digital converter to create a series of binary outputs that encode the concentration range of the molecule being detected. We believe this work establishes a pathway to create ‘smart’ diagnostics that use molecular computations to enhance the speed and utility of biosensors.
A human tau seeded neuronal cell model recapitulates molecular responses associated with Alzheimer’s disease
Authors: Ficulle Elena , Kananathan Sarubini , Airey David , Gharbi Severine I. , Humphryes-Kirilov Neil , Scherschel James , Dunbar Charlotte , Eastwood Brian J. , Laing Emma , Collier David A. , Bose Suchira
Published: February 2022

Cellular models recapitulating features of tauopathies are useful tools to investigate the causes and consequences of tau aggregation and the identification of novel treatments. We seeded rat primary cortical neurons with tau isolated from Alzheimer’s disease brains to induce a time-dependent increase in endogenous tau inclusions. Transcriptomics of seeded and control cells identified 1075 differentially expressed genes (including 26 altered at two time points). These were enriched for lipid/steroid metabolism and neuronal/glial cell development genes. 50 genes were correlated with tau inclusion formation at both transcriptomic and proteomic levels, including several microtubule and cytoskeleton-related proteins such as Tubb2a, Tubb4a, Nefl and Snca. Several genes (such as Fyn kinase and PTBP1, a tau exon 10 repressor) interact directly with or regulate tau. We conclude that this neuronal model may be a suitable platform for high-throughput screens for target or hit compound identification and validation.
The burden of stroke and its attributable risk factors in the Middle East and North Africa region, 1990–2019
Authors: Jaberinezhad Mehran , Farhoudi Mehdi , Nejadghaderi Seyed Aria , Alizadeh Mahasti , Sullman Mark J. M. , Carson-Chahhoud Kristin , Collins Gary S. , Safiri Saeid
Published: February 2022

Stroke is one of the leading causes of mortality and morbidity across the globe. Providing comprehensive data on the burden of stroke in the Middle East and North Africa (MENA) could be useful for health policy makers in the region. Therefore, this article reported the burden of stroke and its attributable risk factors between 1990 and 2019 by age, sex, type of stroke, and socio-demographic index. Data on the point prevalence, death, and disability-adjusted life-years (DALYs), due to stroke, were retrieved from the Global Burden of Disease study 2019 for the 21 countries located in the MENA region from 1990 to 2019. The counts and age-standardised rates (per 100,000) were presented, along with their corresponding 95% uncertainty intervals (UIs). In 2019, the regional age-standardised point prevalence and death rates of stroke were 1537.5 (95% UI: 1421.9–1659.9) and 87.7 (78.2–97.6) per 100,000, which represent a 0.5% (− 2.3 to 1.1) and 27.8% (− 35.4 to − 16) decrease since 1990, respectively. Moreover, the regional age-standardised DALY rate in 2019 was 1826.2 (1635.3–2026.2) per 100,000, a 32.0% (− 39.1 to − 23.3) decrease since 1990. In 2019, Afghanistan [3498.2 (2508.8–4500.4)] and Lebanon [752.9 (593.3–935.9)] had the highest and lowest age-standardised DALY rates, respectively. Regionally, the total number of stroke cases were highest in the 60–64 age group and was more prevalent in women in all age groups. In addition, there was a general negative association between SDI and the burden of stoke from 1990 to 2019. Also, in 2019, high systolic blood pressure [53.5%], high body mass index [39.4%] and ambient particulate air pollution [27.1%] made the three largest contributions to the burden of stroke in the MENA region. The stroke burden has decreased in the MENA region over the last three decades, although there are large inter-country differences. Preventive programs should be implemented which focus on metabolic risk factors, especially among older females in low SDI countries.
Characterization of the canine CD20 as a therapeutic target for comparative passive immunotherapy
Authors: Dias Joana N. R. , Almeida André , André Ana S. , Aguiar Sandra I. , Bule Pedro , Nogueira Sara , Oliveira Soraia S. , Carrapiço Belmira , Gil Solange , Tavares Luís , Aires-da-Silva Frederico
Published: February 2022

Anti-CD20 therapies have revolutionized the treatment of B-cell malignancies. Despite these advances, relapsed and refractory disease remains a major treatment challenge. The optimization of CD20-targeted immunotherapies is considered a promising strategy to improve current therapies. However, research has been limited by the scarcity of preclinical models that recapitulate the complex interaction between the immune system and cancers. The addition of the canine lymphoma (cNHL) model in the development of anti-CD20 therapies may provide a clinically relevant approach for the translation of improved immunotherapies. Still, an anti-CD20 therapy for cNHL has not been established stressing the need of a comprehensive target characterization. Herein, we performed an in-depth characterization on canine CD20 mRNA transcript and protein expression in a cNHL biobank and demonstrated a canine CD20 overexpression in B-cell lymphoma samples. Moreover, CD20 gene sequencing analysis identified six amino acid differences in patient samples (C77Y, L147F, I159M, L198V, A201T and G273E). Finally, we reported the use of a novel strategy for the generation of anti-CD20 mAbs, with human and canine cross-reactivity, by exploring our rabbit derived single-domain antibody platform. Overall, these results support the rationale of using CD20 as a target for veterinary settings and the development of novel therapeutics and immunodiagnostics.