bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased anti-inflammatory activity and enhanced phytochemical concentrations in superfine powders obtained by controlled differential sieving process from four medicinal plants
Authors: Soulimani Rachid , Dicko Amadou , Baudelaire Elie , Bouayed Jaouad
Published: November 2021

Abstract: Anti-inflammatory effect of Rosa canina, Salix alba, Scrophularia nodosa and Hedera helix were studied in LPS-stimulated primary peripheral blood mononuclear cells (PBMCs) from mice (n=18) by comparing homogeneous powders of small microparticles (50–100 μm, 100–180 μm and 180–315 μm) obtained from plants via a controlled differential sieving process (CDSp) versus total plant materials obtained via hydroethanolic (HE) extraction. Further, phytochemical composition of the fine powders and HE extracts was determined by LC-PDA-ESI/MS analyses. Results showed that a one-hour pretreatment of PBMCs with fine powders, particularly those with superfine particle sizes (i.e. 50–100 μm and 100–180 μm), significantly inhibited TNFα, IL-1β, IL-6 and NO production in LPS-stimulated PBMCs, by at least ca. 20% more than HE extracts (all, p<0.05). For each of the plants studied, their superfine powdered fractions were more concentrated in phenolic contents than their HE extracts. Overall, our results further confirm CDSp, as an environmentally friendly method, for improving the concentration of bioactive compounds as well as their biological activities.
Schmerz, Opioide und deren Krise: laute und leise Symptome
Authors: Schettle Markus , Blum David
Published: November 2021

Zusammenfassung. Schmerzen sind ein häufiger Konsultationsgrund in der Hausarztpraxis und in der Palliative Care. Der Artikel geht auf ein Update der WHO-Leitlinien und den Nutzen und die Nachteile von Opioiden in der Palliative Care ein. Neben dem «lauten Symptom» Schmerz können Fatigue, Depression und Angst auch als «stille Symptome» bezeichnet werden und gehen im schnelllebigen Praxisalltag leicht vergessen. Im Fall einer unzureichenden Symptomkontrolle sollte eine Mitbetreuung durch spezialisierte Palliative-Care-Dienste im ambulanten oder wenn nötig stationären Setting erfolgen. Darüber hinaus sollte auch psychosoziale und wenn erwünscht spirituelle Unterstützung unter Einbezug der Angehörigen angeboten werden.
Palliative Care For Patients with Advanced COPD in Primary Care
Authors: Fusi-Schmidhauser Tanja
Published: November 2021

Abstract. Patients with advanced COPD have a high symptom burden that is often multidimensional. Identification of patients who might benefit from palliative care through validated identification tools, multidimensional symptom management, and timely discussion of advance planning are elements of a palliative care approach for these patients and their families. Coordination among stakeholders providing care and support to these patients is central to ensuring high-quality care and meeting all of their needs.
Rock Size‐Frequency Distributions at the InSight Landing Site, Mars
Authors: Golombek M. P. , Trussell A. , Williams N. , Charalambous C. , Abarca H. , Warner N. H. , Deahn M. , Trautman M. , Crocco R. , Grant J. A. , Hauber E. , Deen R.
Published: November 2021

Rocks around the InSight lander were measured in lander orthoimages of the near field (<10 m), in panoramas of the far field (<40 m), and in a high‐resolution orbital image around the lander (1 km2). The cumulative fractional area versus diameter size‐frequency distributions for four areas in the near field fall on exponential model curves used for estimating hazards for landing spacecraft. The rock abundance varies in the near field from 0.6% for the sand and pebble‐rich area to the east within Homestead hollow to ∼3–5% for the progressively rockier areas to the south, north, and west. The rock abundance of the entire near field is just over 3%, which falls between that at the Phoenix (2%) and Spirit (5%) landing sites. Rocks in the far field (<40 m) that could be identified in both the surface panorama and a high‐resolution orbital image fall on the same exponential model curve as the average near‐field rocks. Rocks measured in a high‐resolution orbital image (27.5 cm/pixel) within ∼500 m of the lander that includes several rocky ejecta craters fall on 4–5% exponential model curves, similar to the northern and western near‐field areas. As a result, the rock abundances observed from orbit fall on the same exponential model rock abundance curves as those viewed from the surface. These rock abundance measurements around the lander are consistent with thermal imaging estimates over larger pixel areas as well as expectations from fragmentation theory of an impacted Amazonian/Hesperian lava flow.
Air Pollution Poses Inequitable Health Risks in Washington, D.C.
Authors: Scammell Alexandra
Published: November 2021

Certain health risks are greatest in neighborhoods with higher proportions of people of color and lower levels of income and education.
The Pamir Frontal Thrust Fault: Holocene Full‐Segment Ruptures and Implications for Complex Segment Interactions in a Continental Collision Zone
Authors: Patyniak M. , Landgraf A. , Dzhumabaeva A. , Baikulov S. , Williams A. M. , Weiss J.R. , Hilley G. E. , Preusser F. , Abdrakhmatov K. E. , Arrowsmith R. J , Strecker M. R.
Published: November 2021

The Pamir Frontal Thrust (PFT) of the Trans‐Alai Range in Central Asia is the principal active fault of the intracontinental convergence zone between the Pamir and Tien Shan. Its northward propagation is reflected by frequent seismic activity and ongoing crustal shortening. Recent and historic earthquakes exhibit complex rupture patterns within and across seismotectonic segments bounding the Trans Alai, challenging our understanding of fault interaction and seismogenic potential. We provide paleoseismic data from five trenches along the central PFT segment (cPFT) and interpret five and possibly six paleoearthquakes that have ruptured since ∼7 ka and 16 ka, respectively. Our results indicate that at least three major earthquakes ruptured the full‐segment length and possibly crossed segment boundaries with a recurrence interval of ∼1.9 kyr and potential magnitudes of up to Mw 7.4. We did not find evidence for great (i.e., Mw ≥8) earthquakes. However, discrepancies between slip and rupture extent during apparent partial segment ruptures in the western half of the cPFT, combined with significantly higher scarp offsets, indicate a more mature fault section with potential for future fault linkage. We estimate an average rate of horizontal motion for the cPFT of 4.1 ± 1.5 mm/yr during the past ∼5 kyr, which does not fully match the GNSS‐derived present‐day shortening rate of ∼10 mm/yr. This suggests a complex distribution of strain accumulation and potential slip partitioning between the cPFT and additional faults and folds within the Pamir that may be associated with a partially locked regional décollement.
High‐Spatial‐Resolution Mass Rates From GRACE and GRACE‐FO: Global and Ice Sheet Analyses
Authors: Loomis Bryant D. , Felikson Denis , Sabaka Terence J. , Medley Brooke
Published: November 2021

GRACE and GRACE‐FO gravimetry data are unique in its ability to observe global water mass variability and has frequently been applied for the determination of global mass rates to quantify the impacts of climate change and human activity on global freshwater availability and land ice evolution. However, its relatively coarse spatial resolution of ∼300‐500 km at monthly intervals precludes its direct use to measure mass changes in smaller drainage basins and individual glacier systems. We present a new global high‐resolution mascon product that improves spatial resolution and signal recovery by estimating trends directly from more than 16 years of Level 1B GRACE and GRACE‐FO data. We compare this product to independent gravimetry spherical harmonic trend estimates and to ice sheet mass rates derived from ICESat and ICESat‐2 laser altimetry. We demonstrate enhanced global signal recovery and improved agreement with ICESat/ICESat‐2 and discuss likely causes for the remaining discrepancies between the gravimetry and laser altimetry solutions.
Joint Estimation of Balanced Motions and Internal Tides From Future Wide‐Swath Altimetry
Authors: Le Guillou Florian , Lahaye Noé , Ubelmann Clément , Metref Sammy , Cosme Emmanuel , Ponte Aurélien , Le Sommer Julien , Blayo Eric , Vidard Arthur
Published: November 2021

Wide‐swath altimetry, for example, the Surface Water and Ocean Topography mission is expected to provide Sea Surface Height (SSH) measurements resolving scales of a few tens of kilometers. Over a large fraction of the globe, the SSH signal at these scales is essentially a superposition of a component due to balanced motions (BMs) and another component due to internal tides (ITs). Several oceanographic applications require the separation of these components and their mapping on regular grids. For that purpose, the paper introduces an alternating minimization algorithm that iteratively implements two data assimilation techniques, each specific to the mapping of one component: a quasi‐geostrophic model with Back‐and‐Forth Nudging for BMs, and a linear shallow‐water model with 4‐Dimensional Variational assimilation for ITs. The algorithm is tested with Observation System Simulation Experiments where the truth is provided by a primitive‐equation ocean model in an idealized configuration simulating a turbulent jet and mode‐one ITs. The algorithm reconstructs almost 80% of the variance of BMs and ITs, the remaining 20% being mostly due to dynamics that cannot be described by the simple models used. Importantly, in addition to the reconstruction of stationary ITs, the amplitude and phase of nonstationary ITs are reconstructed. Sensitivity experiments show that the quality of reconstruction significantly depends upon the timing of observations. Although idealized, this study represents a step forward towards the disentanglement of BMs and ITs signals from real wide‐swath altimetry data.
Crosstalk between circRNAs and the PI3K/AKT signaling pathway in cancer progression
Authors: Xue Chen , Li Ganglei , Lu Juan , Li Lanjuan
Published: November 2021

Circular RNAs (circRNAs), covalently closed noncoding RNAs, are widely expressed in eukaryotes and viruses. They can function by regulating target gene expression, linear RNA transcription and protein generation. The phosphoinositide 3-kinase (PI3K)/AKT signaling pathway plays key roles in many biological and cellular processes, such as cell proliferation, growth, invasion, migration, and angiogenesis. It also plays a pivotal role in cancer progression. Emerging data suggest that the circRNA/PI3K/AKT axis modulates the expression of cancer-associated genes and thus regulates tumor progression. Aberrant regulation of the expression of circRNAs in the circRNA/PI3K/AKT axis is significantly associated with clinicopathological characteristics and plays an important role in the regulation of biological functions. In this review, we summarized the expression and biological functions of PI3K-AKT-related circRNAs in vitro and in vivo and assessed their associations with clinicopathological characteristics. We also further discussed the important role of circRNAs in the diagnosis, prognostication, and treatment of cancers.
Transcriptional responses of Trichodesmium to natural inverse gradients of Fe and P availability
Authors: Cerdan-Garcia E , Baylay A , Polyviou D , Woodward E M S , Wrightson L , Mahaffey C , Lohan M C , Moore C M , Bibby T S , Robidart J C
Published: November 2021

The filamentous diazotrophic cyanobacterium Trichodesmium is responsible for a significant fraction of marine di-nitrogen (N2) fixation. Growth and distribution of Trichodesmium and other diazotrophs in the vast oligotrophic subtropical gyres is influenced by iron (Fe) and phosphorus (P) availability, while reciprocally influencing the biogeochemistry of these nutrients. Here we use observations across natural inverse gradients in Fe and P in the North Atlantic subtropical gyre (NASG) to demonstrate how Trichodesmium acclimates in situ to resource availability. Transcriptomic analysis identified progressive upregulation of known iron-stress biomarker genes with decreasing Fe availability, and progressive upregulation of genes involved in the acquisition of diverse P sources with decreasing P availability, while genes involved in N2 fixation were upregulated at the intersection under moderate Fe and P availability. Enhanced N2 fixation within the Fe and P co-stressed transition region was also associated with a distinct, consistent metabolic profile, including the expression of alternative photosynthetic pathways that potentially facilitate ATP generation required for N2 fixation with reduced net oxygen production. The observed response of Trichodesmium to availability of both Fe and P supports suggestions that these biogeochemically significant organisms employ unique molecular, and thus physiological responses as adaptations to specifically exploit the Fe and P co-limited niche they construct.
Pseudogene RPL32P3 regulates the blood–tumor barrier permeability via the YBX2/HNF4G axis
Authors: Ding Ye , Liu Xiaobai , Yang Chunqing , Ruan Xuelei , Wang Di , Liu Yunhui , Shang Xiuli , Liu Qianshuo , Shen Shuyuan , Zhu Lu , Xue Yixue
Published: November 2021

The existence of the blood–tumor barrier (BTB) severely hinders the transport of anti-tumor drugs to brain tumor tissues. Selectively opening BTB is of great significance to improve the chemotherapy effect of glioma. Pseudogenes have been recognized as important regulators in various biologic processes. In this study, we identified that ribosomal protein L32 pseudogene 3 (RPL32P3) was highly expressed in glioma-exposed endothelial cells (GECs). Knockdown of RPL32P3 decreased the expression of tight junction-related proteins (TJPs) and increased BTB permeability. Subsequent analysis of the underlying mechanism indicated that RPL32P3 recruited lysine methyltransferase 2 A (KMT2A) to the Y-box binding protein 2 (YBX2) promoter region and mediated H3K4me3 to promote YBX2 transcription. Highly expressed YBX2 bound and stabilized hepatocyte nuclear factor 4 gamma (HNF4G) mRNA. Highly expressed HNF4G directly bound to the promoters of TJPs ZO-1, occludin and claudin-5 to promote their transcriptional activities and regulated BTB permeability. The simultaneous knockdown of RPL32P3, YBX2, and HNF4G combined with doxorubicin (DOX) increased the apoptosis of glioma cells. In conclusion, the current study indicated that RPL32P3 knockdown increased BTB permeability through the YBX2/HNF4G pathway. These findings may provide new targets for the comprehensive treatment of glioma.
Dynamic transition of current-driven single-skyrmion motion in a room-temperature chiral-lattice magnet
Authors: Peng Licong , Karube Kosuke , Taguchi Yasujiro , Nagaosa Naoto , Tokura Yoshinori , Yu Xiuzhen
Published: November 2021

Driving and controlling single-skyrmion motion promises skyrmion-based spintronic applications. Recently progress has been made in moving skyrmionic bubbles in thin-film heterostructures and low-temperature chiral skyrmions in the FeGe helimagnet by electric current. Here, we report the motion tracking and control of a single skyrmion at room temperature in the chiral-lattice magnet Co9Zn9Mn2 using nanosecond current pulses. We have directly observed that the skyrmion Hall motion reverses its direction upon the reversal of skyrmion topological number using Lorentz transmission electron microscopy. Systematic measurements of the single-skyrmion trace as a function of electric current reveal a dynamic transition from the static pinned state to the linear flow motion via a creep event, in agreement with the theoretical prediction. We have clarified the role of skyrmion pinning and evaluated the intrinsic skyrmion Hall angle and the skyrmion velocity in the course of the dynamic transition. Our results pave a way to skyrmion applications in spintronic devices.
Bioinformatic and cell-based tools for pooled CRISPR knockout screening in mosquitos
Authors: Viswanatha Raghuvir , Mameli Enzo , Rodiger Jonathan , Merckaert Pierre , Feitosa-Suntheimer Fabiana , Colpitts Tonya M. , Mohr Stephanie E. , Hu Yanhui , Perrimon Norbert
Published: November 2021

Mosquito-borne diseases present a worldwide public health burden. Current efforts to understand and counteract them have been aided by the use of cultured mosquito cells. Moreover, application in mammalian cells of forward genetic approaches such as CRISPR screens have identified essential genes and genes required for host-pathogen interactions, and in general, aided in functional annotation of genes. An equivalent approach for genetic screening of mosquito cell lines has been lacking. To develop such an approach, we design a new bioinformatic portal for sgRNA library design in several mosquito genomes, engineer mosquito cell lines to express Cas9 and accept sgRNA at scale, and identify optimal promoters for sgRNA expression in several mosquito species. We then optimize a recombination-mediated cassette exchange system to deliver CRISPR sgRNA and perform pooled CRISPR screens in anAnophelescell line. Altogether, we provide a platform for high-throughput genome-scale screening in cell lines from disease vector species.
LSD1 inhibition sustains T cell invigoration with a durable response to PD-1 blockade
Authors: Liu Yi , Debo Brian , Li Mingfeng , Shi Zhennan , Sheng Wanqiang , Shi Yang
Published: November 2021

Exhausted CD8+ T cells are key targets of immune checkpoint blockade therapy and their ineffective reinvigoration limits the durable benefit in some cancer patients. Here, we demonstrate that histone demethylase LSD1 acts to enforce an epigenetic program in progenitor exhausted CD8+ T cells to antagonize the TCF1-mediated progenitor maintenance and to promote terminal differentiation. Consequently, genetic perturbation or small molecules targeting LSD1 increases the persistence of the progenitor exhausted CD8+ T cells, which provide a sustained source for the proliferative conversion to numerically larger terminally exhausted T cells with tumor-killing cytotoxicity, thereby leading to effective and durable responses to anti-PD1 therapy. Collectively, our findings provide important insights into epigenetic mechanisms that regulate T cell exhaustion and have important implications for durable immunotherapy.
Wolbachia cifB induces cytoplasmic incompatibility in the malaria mosquito vector
Authors: Adams Kelsey L. , Abernathy Daniel G. , Willett Bailey C. , Selland Emily K. , Itoe Maurice A. , Catteruccia Flaminia
Published: November 2021

Wolbachia, a maternally inherited intracellular bacterial species, can manipulate host insect reproduction by cytoplasmic incompatibility (CI), which results in embryo lethality in crosses between infected males and uninfected females. CI is encoded by two prophage genes, cifA and cifB. Wolbachia, coupled with the sterile insect technique, has been used in field trials to control populations of the dengue vector Aedes albopictus, but CI-inducing strains are not known to infect the malaria vector Anopheles gambiae. Here we show that cifA and cifB can induce conditional sterility in the malaria vector An. gambiae. We used transgenic expression of these Wolbachia-derived genes in the An. gambiae germline to show that cifB is sufficient to cause embryonic lethality and that cifB-induced sterility is rescued by cifA expression in females. When we co-expressed cifA and cifB in male mosquitoes, the CI phenotype was attenuated. In female mosquitoes, cifB impaired fertility, which was overcome by co-expression of cifA. Our findings pave the way towards using CI to control malaria mosquito vectors.
Incorporation mechanism of Fe and Al into bridgmanite in a subducting mid-ocean ridge basalt and its crystal chemistry
Authors: Nakatsuka Akihiko , Fukui Hiroshi , Kamada Seiji , Hirao Naohisa , Ohkawa Makio , Sugiyama Kazumasa , Yoshino Takashi
Published: November 2021

The compositional difference between subducting slabs and their surrounding lower-mantle can yield the difference in incorporation mechanism of Fe and Al into bridgmanite between both regions, which should cause heterogeneity in physical properties and rheology of the lower mantle. However, the precise cation-distribution has not been examined in bridgmanites with Fe- and Al-contents expected in a mid-ocean ridge basalt component of subducting slabs. Here we report on Mg0.662Fe0.338Si0.662Al0.338O3 bridgmanite single-crystal characterized by a combination of single-crystal X-ray diffraction, synchrotron 57Fe-Mössbauer spectroscopy and electron probe microanalysis. We find that the charge-coupled substitution AMg2+  + BSi4+  ↔ AFe3+(high-spin) + BAl3+ is predominant in the incorporation of Fe and Al into the practically eightfold-coordinated A-site and the sixfold-coordinated B-site in bridgmanite structure. The incorporation of both cations via this substitution enhances the structural distortion due to the tilting of BO6 octahedra, yielding the unusual expansion of mean  bond-length due to flexibility of A–O bonds for the structural distortion, in contrast to mean  bond-length depending reasonably on the ionic radius effect. Moreover, we imply the phase-transition behavior and the elasticity of bridgmanite in slabs subducting into deeper parts of the lower mantle, in terms of the relative compressibility of AO12 (practically AO8) and BO6 polyhedra.
First observation of radiolytic bubble formation in unstirred nano-powder sludges and a consistent model thereof
Authors: O’Leary Mel , Baidak Aliaksandr , Barnes Martyn , Donoclift Thomas , Emerson Christopher , Figueira Catarina , Fox Oliver , Kleppe Annette , McCulloch Aaron , Messer Darryl , Orr Robin , Currell Fred
Published: November 2021

Experiments involving the irradiation of water contained within magnesium hydroxide and alumina nanoparticle sludges were conducted and culminated in observations of an increased yield of molecular hydrogen when compared to the yield from the irradiation of bulk water. We show that there is a relationship linking this increased yield to the direct nanoscale ionization mechanism in the nanoparticles, indicating that electron emission from the nanoparticles drives new radiative pathways in the water. Because the chemical changes in these sludges are introduced by irradiation only, we have a genuinely unstirred system. This feature allows us to determine the diffusivity of the dissolved gas. Using the measured gas production rate, we have developed a method for modelling when hydrogen bubble formation will occur within the nanoparticle sludges. This model facilitates the determination of a consistent radiolytic consumption rate coinciding with the observations of bubble formation. Thus, we demonstrate a nanoscale radiation effect directly influencing the formation of molecular hydrogen.
Association of lockdowns with the protective role of ultraviolet-B (UVB) radiation in reducing COVID-19 deaths
Authors: Moozhipurath Rahul Kalippurayil , Kraft Lennart
Published: November 2021

Nations are imposing unprecedented measures at a large scale to contain the spread of the COVID-19 pandemic. While recent studies show that non-pharmaceutical intervention measures such as lockdowns may have mitigated the spread of COVID-19, those measures also lead to substantial economic and social costs, and might limit exposure to ultraviolet-B radiation (UVB). Emerging observational evidence indicates the protective role of UVB and vitamin D in reducing the severity and mortality of COVID-19 deaths. This observational study empirically outlines the protective roles of lockdown and UVB exposure as measured by the ultraviolet index (UVI). Specifically, we examine whether the severity of lockdown is associated with a reduction in the protective role of UVB exposure. We use a log-linear fixed-effects model on a panel dataset of secondary data of 155 countries from 22 January 2020 until 7 October 2020 (n = 29,327). We use the cumulative number of COVID-19 deaths as the dependent variable and isolate the mitigating influence of lockdown severity on the association between UVI and growth rates of COVID-19 deaths from time-constant country-specific and time-varying country-specific potentially confounding factors. After controlling for time-constant and time-varying factors, we find that a unit increase in UVI and lockdown severity are independently associated with − 0.85 percentage points (p.p) and − 4.7 p.p decline in COVID-19 deaths growth rate, indicating their respective protective roles. The change of UVI over time is typically large (e.g., on average, UVI in New York City increases up to 6 units between January until June), indicating that the protective role of UVI might be substantial. However, the widely utilized and least severe lockdown (governmental recommendation to not leave the house) is associated with the mitigation of the protective role of UVI by 81% (0.76 p.p), which indicates a downside risk associated with its widespread use. We find that lockdown severity and UVI are independently associated with a slowdown in the daily growth rates of cumulative COVID-19 deaths. However, we find evidence that an increase in lockdown severity is associated with significant mitigation in the protective role of UVI in reducing COVID-19 deaths. Our results suggest that lockdowns in conjunction with adequate exposure to UVB radiation might have even reduced the number of COVID-19 deaths more strongly than lockdowns alone. For example, we estimate that there would be 11% fewer deaths on average with sufficient UVB exposure during the period people were recommended not to leave their house. Therefore, our study outlines the importance of considering UVB exposure, especially while implementing lockdowns, and could inspire further clinical studies that may support policy decision-making in countries imposing such measures.
Correlates of neutralizing/SARS-CoV-2-S1-binding antibody response with adverse effects and immune kinetics in BNT162b2-vaccinated individuals
Authors: Maeda Kenji , Amano Masayuki , Uemura Yukari , Tsuchiya Kiyoto , Matsushima Tomoko , Noda Kenta , Shimizu Yosuke , Fujiwara Asuka , Takamatsu Yuki , Ichikawa Yasuko , Nishimura Hidehiro , Kinoshita Mari , Matsumoto Shota , Gatanaga Hiroyuki , Yoshimura Kazuhisa , Oka Shin-ichi , Mikami Ayako , Sugiura Wataru , Sato Toshiyuki , Yoshida Tomokazu , Shimada Shinya , Mitsuya Hiroaki
Published: November 2021

While mRNA vaccines against SARS-CoV-2 are exceedingly effective in preventing symptomatic infection, their immune response features remain to be clarified. In the present prospective study, 225 healthy individuals in Japan, who received two BNT162b2 doses, were enrolled. Correlates of BNT162b2-elicited SARS-CoV-2-neutralizing activity (50% neutralization titer: NT50; assessed using infectious virions) with various determinants were examined and the potency of sera against variants of concerns was determined. Significant rise in NT50s was seen in sera on day 28 post-1st dose. A moderate inverse correlation was seen between NT50s and ages, but no correlation seen between NT50s and adverse effects. NT50s and SARS-CoV-2-S1-binding-IgG levels on day 28 post-1st dose and pain scores following the 2nd dose were greater in women than in men. The average half-life of NT50s was ~ 68 days, and 23.6% (49 out of 208 individuals) failed to show detectable neutralizing activity on day 150. While sera from elite-responders (NT50s > 1,500: the top 4% among the participants) potently to moderately blocked all variants of concerns examined, some sera with low NT50s failed to block the B.1.351-beta strain. Since BNT162b2-elicited immunity against SARS-CoV-2 is short, an additional vaccine or other protective measures are needed.
An inducible rodent glaucoma model that exhibits gradual sustained increase in intraocular pressure with distinct inner retina and optic nerve inflammation
Authors: Mathew David J. , Livne-Bar Izhar , Sivak Jeremy M.
Published: November 2021

Glaucoma is a chronic and progressive neurodegenerative disease of the optic nerve resulting in loss of retinal ganglion cells (RGCs) and vision. The most prominent glaucoma risk factor is increased intraocular pressure (IOP), and most models focus on reproducing this aspect to study disease mechanisms and targets. Yet, current models result in IOP profiles that often do not resemble clinical glaucoma. Here we introduce a new model that results in a gradual and sustained IOP increase over time. This approach modifies a circumlimbal suture method, taking care to make the sutures ‘snug’ instead of tight, without inducing an initial IOP spike. This approach did not immediately affect IOPs, but generated gradual ocular hypertension (gOHT) as the sutures tighten over time, in comparison to loosely sutured control eyes (CON), resulting in an average 12.6 mmHg increase in IOP at 17 weeks (p < 0.001). Corresponding characterization revealed relevant retinal and optic nerve pathology, such as thinning of the retinal nerve fiber layer, decreased optokinetic response, RGC loss, and optic nerve head remodeling. Yet, angles remained open, with no evidence of inflammation. Corresponding biochemical profiling indicated significant increases in TGF-β2 and 3, and IL-1 family cytokines in gOHT optic nerve tissues compared to CON, with accompanying microglial reactivity, consistent with active tissue injury and repair mechanisms. Remarkably, this signature was absent from optic nerves following acute ocular hypertension (aOHT) associated with intentionally tightened sutures, although the resulting RGC loss was similar in both methods. These results suggest that the pattern of IOP change has an important impact on underlying pathophysiology.
A new experimental model for the investigation of sequential hermaphroditism
Authors: Goikoetxea A. , Muncaster S. , Todd E. V. , Lokman P. M. , Robertson H. A. , De Farias e Moraes C. E. , Damsteegt E. L. , Gemmell N. J.
Published: November 2021

The stunning sexual transformation commonly triggered by age, size or social context in some fishes is one of the best examples of phenotypic plasticity thus far described. To date our understanding of this process is dominated by studies on a handful of subtropical and tropical teleosts, often in wild settings. Here we have established the protogynous New Zealand spotty wrasse, Notolabruscelidotus, as a temperate model for the experimental investigation of sex change. Captive fish were induced to change sex using aromatase inhibition or manipulation of social groups. Complete female-to-male transition occurred over 60 days in both cases and time-series sampling was used to quantify changes in hormone production, gene expression and gonadal cellular anatomy. Early-stage decreases in plasma 17β-estradiol (E2) concentrations or gonadal aromatase (cyp19a1a) expression were not detected in spotty wrasse, despite these being commonly associated with the onset of sex change in subtropical and tropical protogynous (female-to-male) hermaphrodites. In contrast, expression of the masculinising factor amh (anti-Müllerian hormone) increased during early sex change, implying a potential role as a proximate trigger for masculinisation. Collectively, these data provide a foundation for the spotty wrasse as a temperate teleost model to study sex change and cell fate in vertebrates.
Tianeptine, but not fluoxetine, decreases avoidant behavior in a mouse model of early developmental exposure to fluoxetine
Authors: Pekarskaya Elizabeth A. , Holt Emma S. , Gingrich Jay A. , Ansorge Mark S. , Javitch Jonathan A. , Canetta Sarah E.
Published: November 2021

Depression and anxiety, two of the most common mental health disorders, share common symptoms and treatments. Most pharmacological agents available to treat these disorders target monoamine systems. Currently, finding the most effective treatment for an individual is a process of trial and error. To better understand how disease etiology may predict treatment response, we studied mice exposed developmentally to the selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX). These mice show the murine equivalent of anxiety- and depression-like symptoms in adulthood and here we report that these mice are also behaviorally resistant to the antidepressant-like effects of adult SSRI administration. We investigated whether tianeptine (TIA), which exerts its therapeutic effects through agonism of the mu-opioid receptor instead of targeting monoaminergic systems, would be more effective in this model. We found that C57BL/6J pups exposed to FLX from postnatal day 2 to 11 (PNFLX, the mouse equivalent in terms of brain development to the human third trimester) showed increased avoidant behaviors as adults that failed to improve, or were even exacerbated, by chronic SSRI treatment. By contrast, avoidant behaviors in these same mice were drastically improved following chronic treatment with TIA. Overall, this demonstrates that TIA may be a promising alternative treatment for patients that fail to respond to typical antidepressants, especially in patients whose serotonergic system has been altered by in utero exposure to SSRIs.
Single-cell DNA and RNA sequencing of circulating tumor cells
Authors: Kojima Masato , Harada Takanori , Fukazawa Takahiro , Kurihara Sho , Saeki Isamu , Takahashi Shinya , Hiyama Eiso
Published: November 2021

Single-cell sequencing of circulating tumor cells can precisely represent tumor heterogeneity and provide useful information for cancer treatment and research. After spiking TGW neuroblastoma cells into blood derived from healthy volunteer, the cells were isolated by fluorescence-activated cell sorting. DNA and mRNA were amplified by four different whole-genome amplifications (WGA) and three whole-transcriptome amplifications (WTA) methods, followed by single-cell DNA and RNA sequencing. Multiple displacement amplification (MDA)-based WGA methods showed higher amplification efficiency than other methods with a comparable depth of coverage as the bulk sample. The uniformity of coverage greatly differed among samples (12.5–89.2%), with some samples evaluated by the MDA-based WGA method using phi29 DNA polymerase and random primers showing a high (> 80%) uniformity of coverage. The MDA-based WTA method less effectively amplified mRNA and showed non-specific gene expression patterns. The PCR-based WTA using template switching with locked nucleic acid technology accurately amplified mRNA from a single cell. Taken together, our results present a more reliable and adaptable approach for CTC profiling at the single-cell level. Such molecular information on CTCs derived from clinical patients will promote cancer treatment and research.
Related health risk assessment of exposure to arsenic and some heavy metals in gold mines in Banmauk Township, Myanmar
Authors: Wongsasuluk Pokkate , Tun Aung Zaw , Chotpantarat Srilert , Siriwong Wattasit
Published: November 2021

Exposure to heavy metals in mining activities is a health issue among miners. This study was carried out at three small-scale gold mining sites situated in Banmauk Township, Myanmar and aims to assess the occupational health risks of small-scale gold miners who are exposed to arsenic (As), cadmium (Cd), mercury (Hg) and lead (Pb) in the soil through the dermal route. Soil samples were analyzed through atomic absorption spectroscopy (AAS). The concentrations of the heavy metals in soils found As, ranged 1.04 mg/kg to 22.17 mg/kg, 0.13 mg/kg to 3.07 mg/kg for Cd, 0.15 mg/kg to 77.44 mg/kg for Hg, and 7.67 mg/kg to 210.00 mg/kg for Pb. In this study, 79% of the participants did not use any form of personal protective equipment (PPE) while working in gold mining processes. Regarding noncancer risk assessment, the results found all hazard quotient were lower than acceptable level (HQ < 1). In addition, all hazard index (HI) was lover than 1, the highest HI was found as 5.66 × 10−1 in the amalgamation process. On the other hand, the result found cancer risk ranged from 8.02 × 10−8 to 1.75 × 10−6, and the estimated cancer risks for 9 years ranged from 4.78 × 10−7 to 1.04 × 10−5. Therefore, the cancer risks of the miners were greater than the United State Environmental Protection Agency (U.S. EPA) acceptable cancer risk level, 1 × 10−6, and the miners may be at risk of developing carcinogenic diseases. The suggestion is to educate miners about the health risks of heavy metals and to encourage the use of proper PPE all the time while working in gold mine.
Critical switching current density of magnetic tunnel junction with shape perpendicular magnetic anisotropy through the combination of spin-transfer and spin-orbit torques
Authors: Kang Doo Hyung , Shin Mincheol
Published: November 2021

Recently, magnetic tunnel junctions (MTJs) with shape perpendicular magnetic anisotropy (S-PMA) have been studied extensively because they ensure high thermal stability at junctions smaller than 20 nm. Furthermore, spin-transfer torque (STT) and spin-orbit torque (SOT) hybrid switching, which guarantees fast magnetization switching and deterministic switching, has recently been achieved in experiments. In this study, the critical switching current density of the MTJ with S-PMA through the interplay of STT and SOT was investigated using theoretical and numerical methods. As the current density inducing SOT ($$J_{\text {SOT}}$$

J
SOT

) increases, the critical switching current density inducing STT ($$J_{\text {STT,c}}$$

J
STT,c

) decreases. Furthermore, for a given $$J_{\text {SOT}}$$

J
SOT

, $$J_{\text {STT,c}}$$

J
STT,c

increases with increasing thickness, whereas $$J_{\text {STT,c}}$$

J
STT,c

decreases as the diameter increases. Moreover, $$J_{\text {STT,c}}$$

J
STT,c

in the plane of thickness and spin-orbit field-like torque ($$\beta$$
β
) was investigated for a fixed $$J_{\text {SOT}}$$

J
SOT

and diameter. Although $$J_{\text {STT,c}}$$

J
STT,c

decreases with increasing $$\beta$$
β
, $$J_{\text {STT,c}}$$

J
STT,c

slowly increases with increasing thickness and increasing $$\beta$$
β
. The power consumption was investigated as a function of thickness and diameter at the critical switching current density. Experimental confirmation of these results using existing experimental techniques is anticipated.
Palaeohistology reveals a slow pace of life for the dwarfed Sicilian elephant
Authors: Köhler Meike , Herridge Victoria , Nacarino-Meneses Carmen , Fortuny Josep , Moncunill-Solé Blanca , Rosso Antonietta , Sanfilippo Rossana , Palombo Maria Rita , Moyà-Solà Salvador
Published: November 2021

The 1-m-tall dwarf elephantPalaeoloxodon falconerifrom the Pleistocene of Sicily (Italy) is an extreme example of insular dwarfism and epitomizes the Island Rule. Based on scaling of life-history (LH) traits with body mass,P. falconeriis widely considered to be ‘r-selected’ by truncation of the growth period, associated with an early onset of reproduction and an abbreviated lifespan. These conjectures are, however, at odds with predictions from LH models for adaptive shifts in body size on islands. To settle the LH strategy ofP. falconeri, we used bone, molar, and tusk histology to infer growth rates, age at first reproduction, and longevity. Our results from all approaches are congruent and provide evidence that the insular dwarf elephant grew at very slow rates over an extended period; attained maturity at the age of 15 years; and had a minimum lifespan of 68 years. This surpasses not only the values predicted from body mass but even those of both its giant sister taxon (P. antiquus) and its large mainland cousin (L. africana). The suite of LH traits ofP. falconeriis consistent with the LH data hitherto inferred for other dwarfed insular mammals.P. falconeri, thus, not only epitomizes the Island Rule but it can also be viewed as a paradigm of evolutionary change towards a slow LH that accompanies the process of dwarfing in insular mammals.
High prevalence of multiple antibiotic resistance in clinical E. coli isolates from Bangladesh and prediction of molecular resistance determinants using WGS of an XDR isolate
Authors: Jain Preeti , Bepari Asim Kumar , Sen Prosengit Kumer , Rafe Tanzir , Imtiaz Rashed , Hossain Maqsud , Reza Hasan Mahmud
Published: November 2021

Multi-drug-resistance (MDR) is a severe public health concern worldwide, and its containment is more challenging in developing countries due to poor antimicrobial resistance (AMR) surveillance and irrational use of antibiotics. The current study investigated 100 clinical E. coli isolates and revealed that 98% of them were MDR. PCR analysis using 25 selected isolates showed the predominance of metallo-β-lactamase gene blaNDM (80%) and ESBL genes blaOXA (48%) and blaCTX-M-15 (32%). The AmpC gene was detected in 68% of the isolates, while 32% was tetC positive. Notably, 34% of the isolates were resistant to carbapenem. Whole genome sequence (WGS) analysis of an extensively drug-resistant (XDR) isolate (L16) revealed the presence of the notorious sequence type 131 responsible for multi-drug-resistant infections, multiple antibiotic resistance genes (ARGs), virulence genes, and mobile genetic elements that pose risks to environmental transmission. Our results indicate that MDR is alarmingly increasing in Bangladesh that critically limits the treatment option against infections and contributes to further aggravation to the prevailing situation of MDR worldwide. The findings of this study will be valuable in designing sustainable strategies to contain MDR in the region.
Neural networks for computing and denoising the continuous nonlinear Fourier spectrum in focusing nonlinear Schrödinger equation
Authors: Sedov Egor V. , Freire Pedro J. , Seredin Vladimir V. , Kolbasin Vladyslav A. , Kamalian-Kopae Morteza , Chekhovskoy Igor S. , Turitsyn Sergei K. , Prilepsky Jaroslaw E.
Published: November 2021

We combine the nonlinear Fourier transform (NFT) signal processing with machine learning methods for solving the direct spectral problem associated with the nonlinear Schrödinger equation. The latter is one of the core nonlinear science models emerging in a range of applications. Our focus is on the unexplored problem of computing the continuous nonlinear Fourier spectrum associated with decaying profiles, using a specially-structured deep neural network which we coined NFT-Net. The Bayesian optimisation is utilised to find the optimal neural network architecture. The benefits of using the NFT-Net as compared to the conventional numerical NFT methods becomes evident when we deal with noise-corrupted signals, where the neural networks-based processing results in effective noise suppression. This advantage becomes more pronounced when the noise level is sufficiently high, and we train the neural network on the noise-corrupted field profiles. The maximum restoration quality corresponds to the case where the signal-to-noise ratio of the training data coincides with that of the validation signals. Finally, we also demonstrate that the NFT b-coefficient important for optical communication applications can be recovered with high accuracy and denoised by the neural network with the same architecture.
Temperature dependence of amorphous magnesium carbonate structure studied by PDF and XAFS analyses
Authors: Yamamoto Gen-ichiro , Kyono Atsushi , Okada Satoru
Published: November 2021

Mineral trapping through the precipitation of carbonate minerals is a potential approach to reduce CO2accumulation in the atmosphere. The temperature dependence of amorphous magnesium carbonate (AMC), a precursor of crystalline magnesium carbonate hydrates, was investigated using synchrotron X-ray scattering experiments with atomic pair distribution function (PDF) and X-ray absorption fine structure analysis. PDF analysis revealed that there were no substantial structural differences among the AMC samples synthesized at 20, 60, and 80 °C. In addition, the medium-range order of all three AMC samples was very similar to that of hydromagnesite. Stirring in aqueous solution at room temperature caused the AMC sample to hydrate immediately and form a three-dimensional hydrogen-bonding network. Consequently, it crystallized with the long-range structural order of nesquehonite. The Mg K-edge X-ray absorption near-edge structure spectrum of AMC prepared at 20 °C was very similar to that of nesquehonite, implying that the electronic structure and coordination geometry of Mg atoms in AMC synthesized at 20 °C are highly similar to those in nesquehonite. Therefore, the short-range order (coordination environment) around the Mg atoms was slightly modified with temperature, but the medium-range order of AMC remained unchanged between 20 and 80 °C.
In silico evaluation of the interaction between ACE2 and SARS-CoV-2 Spike protein in a hyperglycemic environment
Authors: Sartore Giovanni , Bassani Davide , Ragazzi Eugenio , Traldi Pietro , Lapolla Annunziata , Moro Stefano
Published: November 2021

The worse outcome of COVID-19 in people with diabetes mellitus could be related to the non-enzymatic glycation of human ACE2, leading to a more susceptible interaction with virus Spike protein. We aimed to evaluate, through a computational approach, the interaction between human ACE2 receptor and SARS-CoV-2 Spike protein under different conditions of hyperglycemic environment. A computational analysis was performed, based on the X-ray crystallographic structure of the Spike Receptor-Binding Domain (RBD)-ACE2 system. The possible scenarios of lysine aminoacid residues on surface transformed by glycation were considered: (1) on ACE2 receptor; (2) on Spike protein; (3) on both ACE2 receptor and Spike protein. In comparison to the native condition, the number of polar bonds (comprising both hydrogen bonds and salt bridges) in the poses considered are 10, 6, 6, and 4 for the states ACE2/Spike both native, ACE2 native/Spike glycated, ACE2 glycated/Spike native, ACE2/Spike both glycated, respectively. The analysis highlighted also how the number of non-polar contacts (in this case, van der Waals and aromatic interactions) significantly decreases when the lysine aminoacid residues undergo glycation. Following non-enzymatic glycation, the number of interactions between human ACE2 receptor and SARS-CoV-2 Spike protein is decreased in comparison to the unmodified model. The reduced affinity of the Spike protein for ACE2 receptor in case of non-enzymatic glycation may shift the virus to multiple alternative entry routes.
Alteration of acute toxicity of inorganic and methyl mercury to Daphnia magna by dietary addition
Authors: Hylton Christopher A. , Tsui Martin Tsz-Ki
Published: November 2021

Acute toxicity of inorganic mercury [Hg(II)] and methylmercury (MeHg) to Daphnia magna was characterized using a 48-h static, non-renewal acute toxicity test, in which we compared the toxicity of Hg(II) and MeHg in the absence (water-only) and presence of diet [green alga (Raphidocelis subcapitata), yeast, Cerophyll, and trout chow (YCT), or both]. Overall, Hg(II) is more toxic to D. magna than MeHg, with 48-h median lethal concentrations (LC50s) being 4.3 µg/L (95% confidence interval: 4.1–4.5 µg/L) for Hg(II) and 14.3 µg/L (13.2–15.3 µg/L) for MeHg. For Hg(II), the addition of any diet would significantly increase its 48-h LC50, but the 48-h LC50 for MeHg decreased significantly to 7.1 µg/L (6.4–7.8 µg/L) with the algal addition. We also show that the addition of diets significantly influenced the levels and speciation (dissolved vs. particulate) of both Hg forms in the test solution. The bioaccumulation of Hg(II) and MeHg was impacted by the dietary addition, and it appears that the body residue level triggering mortality varied widely among treatments. The results suggest that standard short-term toxicity tests (water-only) should be supplemented with extra tests with dietary addition to provide a more environmentally relevant estimation of short-term toxicity of chemical compounds.