bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of PM2.5 and its constituents on hemoglobin during the third trimester in pregnant women
Authors: Xie Guilan , Yue Jie , Yang Wenfang , Yang Liren , Xu Mengmeng , Sun Landi , Zhang Boxing , Guo Leqian , Chung Mei Chun
Published: January 2022

Anemia has been a public health issue evoking global concern, and the low hemoglobin (Hb) concentration links to adverse pregnancy outcomes. However, the associations of PM2.5 and its constituents with Hb and anemia in pregnant women remain unclear. In this retrospective birth cohort study, 7932 pregnant women who delivered in the First Affiliated Hospital of Xi’an Jiaotong University from 2015 to 2018 were included. The Hb during the third trimester in pregnant women was assessed before delivery. PM2.5 and its constituents (BC, NH4+, NO3−, OM, SO42−, and Dust) during pregnancy were retrieved from the V4.CH.03 product constructed by the Atmospheric Composition Analysis Group. Generalized linear regression model was applied to investigate the effects of PM2.5 and its constituents on Hb and anemia during the third trimester in pregnant women. The means and standard deviations of PM2.5, BC, NH4+, NO3−, OM, SO42−, and Dust were 69.56 (15.24), 10.02 (2.72), 8.11 (1.77), 14.96 (5.42), 15.36 (4.11), 10.08 (1.20), and 10.98 (1.85) μg/m3, respectively. Per IQR increase (μg/m3) of PM2.5, BC, NO3−, and OM linked to − 0.75 (− 1.50, − 0.01), − 0.85 (− 1.65, − 0.04), − 0.79 (− 1.56, − 0.03), and − 0.73 (− 1.44, − 0.03) g/L decrease of Hb during the third trimester in multiparous pregnant women, but not for NH4+, SO42−, Dust, and primiparous pregnant women. PM2.5 and its constituents had no significant association with anemia, except for Dust (OR: 0.90, 95% CI: 0.82, 0.99, per IQR increase) in primiparous pregnant women. Besides, SO42− was of lag effects on Hb and anemia in multiparous pregnant women. Moreover, non-linear associations were found among PM2.5 and its constituents, Hb, and anemia. Therefore, exposure to PM2.5 and some constituents of PM2.5 was associated with reduced Hb level during the third trimester in multiparous pregnant women. Related departments and pregnant women should take targeted actions to eliminate the detrimental effects of PM2.5 and its constituents on pregnancy outcomes.
SOX2 knockdown with siRNA reverses cisplatin resistance in NSCLC by regulating APE1 signaling
Authors: Chen Tai-yu , Zhou Ji , Li Peng-cheng , Tang Chun-han , Xu Ke , Li Tao , Ren Tao
Published: January 2022

SOX2 is related to drug resistance in many types of cancer, including lung cancer. Herein, we investigated the role of SOX2 and its regulatory signaling in cisplatin-treated non-small-cell lung cancer (NSCLC). The effects of SOX2 on cell viability, proliferation, and apoptosis were evaluated in vitro. Western blotting, real-time quantitative PCR, immunohistochemistry, and luciferase reporter assays were used to investigate the underlying mechanism. Kaplan–Meier survival analysis and the log-rank test were used to assess the relationship between SOX2 expression and patient survival. A549/CDDP cells had marked resistance to cisplatin and stronger colony formation ability than A549 cells. The expression of SOX2 protein or mRNA in A549/CDDP was higher than that in A549. Knockdown of SOX2 in A549/CDDP-induced apoptosis by inhibiting colony formation and decreasing viability, but overexpression of SOX2 reversed these effects. Interestingly, Genomatix software predicted that the APE1 promoter has some SOX2 binding sites, while the SOX2 promoter has no APE1 binding sites. Furthermore, luciferase reporter assays proved that SOX2 could bind the promoter of APE1 in 293T cells. We further verified that SOX2 expression was not affected by shAPE1 in A549/CDDP. As expected, colony formation was obviously inhibited and apoptosis was strongly enhanced in A549/CDDP treated with SOX2 siSOX2 alone or combined with CDDP compared with control cells. Meaningfully, patients with low expression of SOX2, and even including its regulating APE1, survived longer than those with high expression of SOX2, and APE1. siSOX2 overcomes cisplatin resistance by regulating APE1 signaling, providing a new target for overcoming cisplatin resistance in NSCLC.
Non-clinical Pharmacology of YTX-7739: a Clinical Stage Stearoyl-CoA Desaturase Inhibitor Being Developed for Parkinson’s Disease
Authors: Tardiff Daniel F. , Lucas Matthew , Wrona Iwona , Chang Belle , Chung Chee Yeun , Le Bourdonnec Bertrand , Rhodes Kenneth J. , Scannevin Robert H.
Published: January 2022

Stearoyl-CoA desaturase (SCD) is a potential therapeutic target for Parkinson’s and related neurodegenerative diseases. SCD inhibition ameliorates neuronal toxicity caused by aberrant α-synuclein, a lipid-binding protein implicated in Parkinson’s disease. Its inhibition depletes monounsaturated fatty acids, which may modulate α-synuclein conformations and membrane interactions. Herein, we characterize the pharmacokinetic and pharmacodynamic properties of YTX-7739, a clinical-stage SCD inhibitor. Administration of YTX-7739 to rats and monkeys for 15 days caused a dose-dependent increase in YTX-7739 concentrations that were well-tolerated and associated with concentration-dependent reductions in the fatty acid desaturation index (FADI), the ratio of monounsaturated to saturated fatty acids. An approximate 50% maximal reduction in the carbon-16 desaturation index was observed in the brain, with comparable responses in the plasma and skin. A study with a diet supplemented in SCD products indicates that changes in brain C16 desaturation were due to local SCD inhibition, rather than to changes in systemic fatty acids that reach the brain. Assessment of pharmacodynamic response onset and reversibility kinetics indicated that approximately 7 days of dosing were required to achieve maximal responses, which persisted for at least 2 days after cessation of dosing. YTX-7739 thus achieved sufficient concentrations in the brain to inhibit SCD and produce pharmacodynamic responses that were well-tolerated in rats and monkeys. These results provide a framework for evaluating YTX-7739 pharmacology clinically as a disease-modifying therapy to treat synucleinopathies.
The contribution of fisheries and aquaculture to the global protein supply
Authors: Boyd Claude E. , McNevin Aaron A. , Davis Robert P.
Published: January 2022

The contribution of aquatic animal protein to the global, animal-source protein supply and the relative importance of aquaculture to capture fisheries in supplying this protein is relevant in assessments and decisions related to the future of aquatic food production and its security. Meat of terrestrial animals, milk, and eggs resulted in 76,966 Kt crude protein compared with 13,950 Kt or 15.3% from aquatic animals in 2018.While aquaculture produced a greater tonnage of aquatic animals, capture fisheries resulted in 7,135 Kt crude protein while aquaculture yielded 6,815 Kt. Capture fisheries production has not increased in the past two decades, and aquaculture production must increase to assure the growing demand for fisheries products by a larger and more affluent population. We estimated based onstatus quoconsumption, that aquaculture production would need to increase from 82,087 Kt in 2018 to 129,000 Kt by 2050 to meet the demand of the greater population. About two-thirds of finfish and crustacean production by aquaculture is feed-based, and feeds for these species include fishmeal and fish oil as ingredients. Aquaculture feeds require a major portion of the global supply of fishmeal and fish oil. An estimated 71.0% of fishmeal and 73.9% of fish oil are made from the catch with the rest coming from aquatic animal processing waste. The catch of small, pelagic fish from the ocean is not predicted to increase in the future. Aquaculture should reduce its fishmeal and oil use to lessen its dependency on small wild fish important to the integrity of marine food webs and food security for the poor in many coastal areas. Fishmeal and fish oil shortages for use in aquaculture feed will result in a limit on production in the future if goals to lessen their use in feeds are not met.
Novel Dithiolene Nickel Complex Catalysts for Electrochemical Hydrogen Evolution Reaction for Hydrogen Production in Nonaqueous and Aqueous Solutions
Authors: Niu Zhicheng , Yang Lemin , Xiao Yongxin , Xue Min , Zhou Jiarong , Zhang Lei , Zhang Jiujun , Wilkinson David P. , Ni Chunlin
Published: January 2022

Three molecular catalysts based on mononuclear nickel(II) complexes with square planar geometries, [BzPy]2[Ni(mnt)2] (1), [BzPy]2[Ni(i-mnt)2] (2), and [BzPy]2[Ni(tdas)2] (3) (BzPy = benzyl pyridinium) are synthesized by the reaction of NiCl2∙6H2O, [BzPy]Br, and Na2(mnt)/Na2(i-mnt)/Na2(tdas) (mnt = 1,2-dicyanoethylene-1,2-dithiolate for (1), i-mnt = 2,2-dicyanoethylene-1,1-dithiolate for (2), and tdas = 1,2,5-thiadiazole-3,4-dithiolate for (3)), respectively. The structures and compositions of these three catalysts are characterized by XRD, elemental analysis, FT-IR, and ESI-MS. The electrochemical properties and the corresponding catalytic activities of these three catalysts are studied by cyclic voltammetry. The controlled-potential electrolysis with gas chromatography analysis confirms the hydrogen production with a turnover frequency (TOF) of 116.89, 165.51, and 189.16 moles of H2per mole of catalyst per hour at a potential of − 0.99 V (versus SHE) in acetonitrile solutions containing the catalysts, respectively. In a neutral buffer solution, these three molecular catalysts exhibit a TOF of 411.85, 488.76, and 555.06 mol of H2per mole of catalyst per hour at a potential of − 0.49 V (versus SHE), respectively, indicating that Complex3constitutes the better active catalyst than Complexes1and2. For fundamental understanding, a catalytic HER mechanism is also proposed.

Graphical abstract
Evidence of glucose absorption in a neoformed intestine
Authors: Tuveri Massimiliano , Paiella Salvatore , Boschi Federico , Luchini Claudio , Perri Giampaolo , Gasparini Clizia , Aresta Alex , Scarpa Aldo , Salvia Roberto , Bassi Claudio
Published: January 2022

Recent advances in the field of tissue regeneration are offering promising therapeutic options for the treatment of short bowel syndrome. This study aimed to evaluate the glucose absorptive capacity of a neoformed intestine obtained from a biological scaffold in a rodent model and the steadiness of the engrafted segment area. Twenty-four male Sprague–Dawley rats were used for this study. Under anesthesia, a patch of biological material (2.2 × 1.5 cm) was engrafted in the anti-mesenteric border of the small bowels of 12 rats. Twelve rats were sham-operated. Animals were studied at 4, 8, and 10 months postengraftment. Functional and histological analyses were performed. The functional analysis was performed using an 18F-FDG analog as a probe and the results were acquired with an optical imager. The intensity of the fluorescent signal emitted by the neointestine was comparable with that emitted by the native intestine in all animals and was visible after injection in the preserved mesentery. The mean intestinal volume at time of engraftment and after 10 months was 4.08 cm3 (95% CI [3.58–4.58]) and 3.26 cm3 (CI 95% [3.23–3.29]), respectively, with a mean shrinkage of 17.3% (range 10.6–23.8%), without any evidence of stenosis. Morphological analysis revealed the progression of the biological material toward a neoformed intestine similar to the native intestine, especially at 8 and 10 months. In a rodent model, we demonstrated that a neointestine, obtained from a biological scaffold showed glucose absorption and a durable increase in diameter.
Antisocial Personality
Authors: Howard Richard , Duggan Conor
Published: January 2022

It remains something of a mystery why some individuals behave in persistently malevolent and destructive ways towards their fellows, causing untold harm both to themselves and their victims. This book argues that to understand the roots of antisocial behaviour, one first has to understand what motivates the majority of people to behave prosocially - to think, feel and act in non-malevolent ways. All people are motivated to seek emotion goals - to feel thrilled and excited, to feel safe from the threats of others, to feel a sense of justice, and to feel gratified. However some individuals seek these emotion goals in antisocial ways due to an excess of emotions such as distrust, boredom, greed, vengeance and insecurity. The authors outline interpersonal and neurobiological correlates of antisocial personality, its developmental antecedents, its frequency and pattern across different societies and cultures, and different approaches to its treatment and rehabilitation.
Postwar Industrial Media Culture in Sweden, 1945–1960
Authors: Björkin Mats
Published: January 2022

During the 1950s, companies aiming for international markets demanded new theories and methods of communication. Ideas regarding cybernetics, systems analysis, new accounting practices, and budgetary principles, as well as theories of information, communication, marketing, public relations, and organization were discussed at conferences, seminars, and courses, and in articles and books. At the same time, new technologies changed corporate communication, from a loose-leaf accounting system to mechanical and electronic business machines, from written texts and oral presentations to slide shows, audio tapes, films, television, and flannelgraphs. By looking at a vast array of objects and relations related to uses of media technologies in Swedish industry from the end of World War II to the breakthrough of television, this book shows what happened in the glitches between mass communication and interaction, and how Swedish postwar industry worked to disrupt established understandings of communication.
What Exactly is it that the Taiwan Greens Want? Extracting “Taiwan Subjectivity” from the Liberty Times Newspaper
Authors: Lynch Daniel C. , Yau Cody Wai-kwok
Published: January 2022

One source of the idea that Taiwan independence would be politically desirable is belief in the concept of “Taiwan subjectivity,” which indicates that Taiwan is not an appendage of China but instead an autonomous actor charting its own course – or trying to do so in the face of huge difficulties. The ruling (since 2016) Democratic Progressive Party (DPP) pledges fealty to the goal of ultimately realizing subjectivity but cannot aggressively pursue the agenda because of opposition from the People's Republic of China (PRC), the United States, and some in Taiwan itself. What might that agenda be? Using a Structural Topic Model, we excavate the subjectivity discourse as it developed from 2008 to 2020 in the mainstream DPP-supporting newspaper, the Liberty Times. We find fourteen topics associated with the concept, the most prevalent of which in recent years warn of threats to subjectivity's realization in the political and sociocultural spheres.
Doctors as Appointed Fiduciaries: A Supplemental Model for Medical Decision-Making
Authors: Davies Ben , Parker Joshua
Published: January 2022

How should we respond to patients who do not wish to take on the responsibility and burdens of making decisions about their own care? In this paper, we argue that existing models of decision-making in modern healthcare are ill-equipped to cope with such patients and should be supplemented by an “appointed fiduciary” model where decision-making authority is formally transferred to a medical professional. Healthcare decisions are often complex and for patients can come at time of vulnerability. While this does not undermine their capacity, it can be excessively burdensome. Most existing models of decision-making mandate that patients with capacity must retain ultimate responsibility for decisions. An appointed fiduciary model provides a formalized mechanism through which those few patients who wish to defer responsibility can hand over decision-making authority. By providing a formal structure for deferring to an appointed fiduciary, the confusions and risks of the informal transfers that can occur in practice are avoided. Finally, we note how appropriate governance and law can provide safeguards against risks to the welfare of patients and medical professionals.
Your reserves may be best estimate, but are they valid?
Authors: Diffey William , Hobern Laura , Lauder Al , Cleugh Malcolm , Wu Mark , Mukherjee Satraajeet , Dan Apollos , Dharamshi Param , Atwal Rav , Vijay Arun , Dolan Fergal , Grewal Amo , Harrison Ed
Published: January 2022

This paper outlines frameworks to use for reserving validation and gives the reader an overview of current techniques being employed. In the experience of the authors, many companies lack an embedded reserve validation framework and reserve validation can appear piecemeal and unstructured. The paper outlines a case study demonstrating how successful machine learning techniques will become and then goes on to discuss the implications of machine learning to the future of reserving departments, processes, data and validation techniques. Reserving validation can take many forms, from simple checks to full independent reviews to add value to the reserving process, enhance governance and increase confidence in and reliability in results. This paper discusses covers common weaknesses and their solutions and suggestions of a framework in which to apply validation tools. The impacts of the COVID-19 pandemic on reserving validation is also covered as are early warning indicators and the topic of IFRS 17 from the standpoint of reserving validation. The paper looks at the future for reserving validation and discusses the data challenges that need overcoming on the path to embedded reserving process validation.
Cross-language interactions during novel word learning: The contribution of form similarity and participant characteristics
Authors: Elias Mariana , Degani Tamar
Published: January 2022

The study examined whether false-cognates, overlapping in form but not meaning across languages, are easier to learn due to form overlap, or more difficult to learn due to meaning competition, compared to unambiguous control and cognate words. Fifty-four native Hebrew speakers learned 14 cognates, 14 false-cognates, and 28 control Arabic words in one session. Cognates were learned better than control items. There was no overall difference in learning false-cognates relative to controls, but individuals with higher phonological short-term memory, or with lower L1 verbal fluency, did exhibit a false-cognate learning-advantage. For these individuals, form overlap was more influential than meaning competition. Lexical decisions to Hebrew words following Arabic learning were slower for false-cognates than controls, indicative of backward influences. The findings reveal the influence of prior knowledge on learning and processing, and highlight the importance of jointly considering item-based and learner-based characteristics during the initial stages of vocabulary learning.
Mechanisms of glyphosate resistance in common ragweed (Ambrosia artemisiifolia): patterns of absorption, translocation, and metabolism
Authors: Byker Holly P. , Soltani Nadar , Nissen Scott J. , Gaines Todd A. , Westra Philip E. , Martin Sara L. , Tardif François J. , Robinson Darren E. , Lawton Mark B. , Sikkema Peter H.
Published: January 2022

Glyphosate’s efficacy is influenced by the amount absorbed and translocated throughout the plant to inhibit 5-enolpyruvyl shikimate-3-phosphate synthase (EPSPS). Glyphosate resistance can be due to target-site (TS) or non–target site (NTS) resistance mechanisms. TS resistance includes an altered target site and gene overexpression, while NTS resistance includes reduced absorption, reduced translocation, enhanced metabolism, and exclusion/sequestration. The goal of this research was to elucidate the mechanism(s) of glyphosate resistance in common ragweed (Ambrosia artemisiifolia L.) from Ontario, Canada. The resistance factor for this glyphosate-resistant (GR) A. artemisiifolia biotype is 5.1. No amino acid substitutions were found at positions 102 or 106 of the EPSPS enzyme in this A. artemisiifolia biotype. Based on [14C]glyphosate studies, there was no difference in glyphosate absorption or translocation between glyphosate-susceptible (GS) and GR A. artemisiifolia biotypes. Radio-labeled glyphosate metabolites were similar for GS and GR A. artemisiifolia 96 h after application. Glyphosate resistance in this A. artemisiifolia biotype is not due to an altered target site due to amino acid substitutions at positions 102 and 106 in the EPSPS and is not due to the NTS mechanisms of reduced absorption, reduced translocation, or enhanced metabolism.
Thiobencarb resistance mechanism is distinct from CYP81A-based cross-resistance in late watergrass (Echinochloa phyllopogon)
Authors: Dimaano Niña Gracel , Tominaga Tohru , Iwakami Satoshi
Published: January 2022

The genetic and molecular basis of resistance evolution in weeds to multiple herbicides remains unclear despite being a great threat to agriculture. A population of late watergrass [Echinochloa phyllopogon(Stapf.) Koso-Pol.] was reported to exhibit resistance to ≥15 herbicides from six sites of action, including thiobencarb (TB). While previous studies disclosed that the resistance to a majority of herbicides such as acetolactate synthase (ALS) and acetyl-CoA carboxylase inhibitors is caused by the overexpression of herbicide-metabolizing cytochrome P450s (CYP81A12andCYP81A21), the resistance mechanisms to some herbicides remain unknown. Here, we analyzed the resistance segregation in the progenies between resistant and sensitive populations and performed a transgenic plant sensitivity assay to resolve whether TB resistance is endowed by the sameCYP81A12/21-based cross-resistance mechanism or other unknown multiple-resistance mechanisms. In the F6progenies, resistance to the ALS inhibitor bensulfuron-methyl cosegregated with the resistances to many other herbicides under theCYP81A12/21-based cross-resistance mechanism; however, TB resistance segregated independently. Furthermore,CYP81A12/21failed to confer TB resistance in transgenicArabidopsis thalianaL. Heynh, thus confirming that TB resistance in resistantE. phyllopogonis not endowed by the two P450s that are responsible for the metabolism-based cross-resistance. This study provides evidence that resistance inE. phyllopogonto herbicides with multiple sites of action is endowed by both P450-based and other uncharacterized non–target site based mechanisms. Our findings add another layer in the understanding of resistance evolution to multiple herbicides inE. phyllopogon. Identification of the key genes endowing TB resistance will be the future direction of this research.
Bulk Aerosol Trace Element Concentrations and Deposition Fluxes During the U.S. GEOTRACES GP15 Pacific Meridional Transect
Authors: Marsay Chris M. , Kadko David , Landing William M. , Buck Clifton S.
Published: January 2022

Atmospheric deposition of aerosols transported from the continents is an important source of nutrient and pollutant trace elements (TEs) to the surface ocean. During the U.S. GEOTRACES GP15 Pacific Meridional Transect between Alaska and Tahiti (September–November 2018), aerosol samples were collected over the North Pacific and equatorial Pacific and analyzed for a suite of TEs, including Al, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, and Pb. Sampling coincided with the annual minimum in dust transport from Asia, providing an opportunity to quantify aerosol TE concentrations and deposition during the low dust season. Nevertheless, peak concentrations of “crustal” TEs measured at ∼40–50°N (∼145 pmol/m3 Fe) were associated with transport from northern Asia, with lower concentrations (36 ± 14 pmol/m3 Fe) over the equatorial Pacific. Relative to crustal abundances, equatorial Pacific aerosols typically had higher TE enrichment factors than North Pacific aerosols. In contrast, aerosol V was more enriched over the North Pacific, presumably due to greater supply to this region from oil combustion products. Bulk deposition velocity (Vbulk) was calculated along the transect using the surface ocean decay inventory of the naturally occurring radionuclide, 7Be, and aerosol 7Be activity. Deposition velocities were significantly higher (4,570 ± 1,146 m/d) within the Intertropical Convergence Zone than elsewhere (1,764 ± 261 m/d) due to aerosol scavenging by intense rainfall. Daily deposition fluxes to the central Pacific during the low dust season were calculated using Vbulk and aerosol TE concentration data, with Fe fluxes ranging from 19 to 258 nmol/m2/d.
Rheology of Metasedimentary Rocks at the Base of the Subduction Seismogenic Zone
Authors: Condit Cailey B. , French Melodie E. , Hayles Justin A. , Yeung Laurence Y. , Chin Emily J. , Lee Cin‐Ty A.
Published: January 2022

The Arosa Zone, Central Alps, represents a Cretaceous to Paleogene fossil subduction interface from paleodepths of 10 to >35 km. Metasedimentary schists directly below a preserved seismogenic zone exhibit viscous (foliations, folds, and lineations) and brittle (crack‐seal quartz ± calcite veins) deformation features. Si‐in‐phengite barometry and published temperature estimates yield deformation and metamorphism conditions of 0.8–0.9 GPa and 300–350°C for an albite‐rich pelitic schist and 0.9 GPa and 420°C for a quartz and calcite‐rich calcareous schist. Petrography, microprobe element maps, and electron backscattered diffraction data constrain the modal mineralogies, microtextures, and active deformation mechanisms of these schists. There is evidence of minor crystal plasticity of quartz in both rocks and calcite in the calcareous schist. However, the most prominent deformation microstructures formed during pressure solution creep of quartz and albite. Pressure solution creep was activated due to pinning by ubiquitous fine grained phengite. Rheologic modeling indicates that pressure solution of quartz and albite can accommodate tectonic strain rates at stresses of <30 of MPa and is weaker than dislocation creep at these same conditions; results that are consistent with our microstructural observations. However, to accommodate slow slip strain rates by either pressure solution or dislocation creep, stresses would need to be >>100 MPa. Triple oxygen isotope data from veins in these rocks combined with published data suggest a metamorphic mafic source for these vein filling and pressure solution accommodating fluids, indicating that dehydration from subducting oceanic lithosphere likely provided the fluids that facilitated viscous deformation in these rocks.
Stratosphere‐Troposphere Coupling Leading to Extended Seasonal Predictability of Summer North Atlantic Oscillation and Boreal Climate
Authors: Wang Lei , Ting Mingfang
Published: January 2022

The boreal summer climate is of significant societal importance and is trending toward increased risks of extreme climate events such as heatwaves. The summer North Atlantic Oscillation, as the primary mode of atmospheric variability in the northern hemisphere, has been long considered lacking predictability on seasonal time scales. Here we show that the summer North Atlantic Oscillation is predictable with a 2‐month lead for the recent decades. The primary predictor is the March North Atlantic jet strength, which is correlated with the summer North Atlantic Oscillation index at a correlation coefficient of 0.66 over 1979–2018. Spring stratosphere‐troposphere coupling plays a critical role in this extended predictability from spring to summer, in contrast to the common knowledge that this dynamical coupling is relatively inactive outside the winter season. These results may bring sound prospects for summer seasonal prediction of boreal climate that benefits the energy and public health sectors.
PGK1 represses autophagy-mediated cell death to promote the proliferation of liver cancer cells by phosphorylating PRAS40
Authors: Zhang Tianhua , Wang Yuzhen , Yu Hongjiu , Zhang Ting , Guo Lianying , Xu Jie , Wei Xiaoqing , Wang Ning , Wu Yingjie , Wang Xiuli , Huang Lin
Published: January 2022

Autophagy predominantly promotes cell survival by recycling cell components, while it kills cells in specific contexts. Cell death related to autophagy plays important roles in multiple physiological and pathological situations including tumorigenesis, and the mechanism needs to be defined further. PRAS40 was found to be crucial in various cancers, and phosphorylation was reported to be involved in autophagy inhibition in monocytes. However, the detailed role of PRAS40 in autophagy and the relationship to tumorigenesis remain largely unknown. Herein we screened the binding partners of PRAS40, and found that PRAS40 interacted with Phosphoglycerate kinase 1 (PGK1). PGK1 phosphorylated PRAS40 at Threonine 246, which could be inhibited by blocking the interaction. Both in vitro and in vivo results revealed that PRAS40 mediated PGK1-induced cell growth. By tracing the mechanism, we found that PGK1 suppressed autophagy-mediated cell death, in which PRAS40 was crucial. Thus PGK1 phosphorylates PRAS40 to repress autophagy-mediated cell death under normoxia, promoting cellular proliferation. The binding of PGK1 to PRAS40 was transferred to Beclin1 under hypoxia, resulting in the increase of Beclin1 phosphorylation. These results suggest a novel model of tumorigenesis, in which PGK1 switches between repressing autophagy-mediated cell death via PRAS40 and inducing autophagy through Beclin1 according to the environmental oxygen level. Our study is anticipated to be able to offer novel insights in understanding PGK1/PRAS40 signaling hyperactivated cancers.
Magnetite layer formation in the Bushveld Complex of South Africa
Authors: Yao Zhuosen , Mungall James E.
Published: January 2022

The great economic significance of layered mafic-ultramafic intrusions like the Bushveld Complex of South Africa results from the existence within them of some layers highly concentrated in valuable elements. Here we address the origins of the Main Magnetite Layer, a globally important resource of Fe-Ti-V-rich magnetite. Previous models of in situ fractional magnetite crystallization require frequent ad hoc adjustments to the boundary conditions. An alternative model incorporating compositional convection near the top of the pile and infiltration of the pile from beneath by migrating intercumulus melt fits observations without any adjustments. Lateral variations in Cr concentration formerly held as indisputable evidence for in situ crystallization can be accommodated better by models of reactive melt infiltration from below. The choice of models has pivotal ramifications for understanding of the fundamental processes by which crystals accumulate and layers form in layered intrusions.
Phonons as a platform for non-Abelian braiding and its manifestation in layered silicates
Authors: Peng Bo , Bouhon Adrien , Monserrat Bartomeu , Slager Robert-Jan
Published: January 2022

Topological phases of matter have revolutionised the fundamental understanding of band theory and hold great promise for next-generation technologies such as low-power electronics or quantum computers. Single-gap topologies have been extensively explored, and a large number of materials have been theoretically proposed and experimentally observed. These ideas have recently been extended to multi-gap topologies with band nodes that carry non-Abelian charges, characterised by invariants that arise by the momentum space braiding of such nodes. However, the constraints placed by the Fermi-Dirac distribution to electronic systems have so far prevented the experimental observation of multi-gap topologies in real materials. Here, we show that multi-gap topologies and the accompanying phase transitions driven by braiding processes can be readily observed in the bosonic phonon spectra of known monolayer silicates. The associated braiding process can be controlled by means of an electric field and epitaxial strain, and involves, for the first time, more than three bands. Finally, we propose that the band inversion processes at the Γ point can be tracked by following the evolution of the Raman spectrum, providing a clear signature for the experimental verification of the band inversion accompanied by the braiding process.
A structural basis for the diverse linkage specificities within the ZUFSP deubiquitinase family
Authors: Hermanns Thomas , Pichlo Christian , Baumann Ulrich , Hofmann Kay
Published: January 2022

Eukaryotic deubiquitinases are important regulators of ubiquitin signaling and can be subdivided into several structurally distinct classes. The ZUFSP family, with ZUP1 as its sole human member, has a modular architecture with a core catalytic domain highly active against the ubiquitin-derived peptide RLRGG, but not against ubiquitin itself. Ubiquitin recognition is conferred by additional non-catalytic domains, making full-length ZUP1 active against long K63-linked chains. However, non-mammalian ZUFSP family members contain different ubiquitin-binding domains in their N-terminal regions, despite their high conservation within the catalytic domain. Here, by working with representative ZUFSP family members from insects, fungi and plants, we show that different N-terminal domains are associated with different linkage preferences. Biochemical and structural studies suggest that the acquisition of two family-specific proximal domains have changed the default K48 preference of the ZUFSP family to the K63 preference observed in ZUP1 and its insect homolog. Additional N-terminal zinc finger domains promote chain cleavage without changing linkage-specificity.
Correction of a Factor VIII genomic inversion with designer-recombinases
Authors: Lansing Felix , Mukhametzyanova Liliya , Rojo-Romanos Teresa , Iwasawa Kentaro , Kimura Masaki , Paszkowski-Rogacz Maciej , Karpinski Janet , Grass Tobias , Sonntag Jan , Schneider Paul Martin , Günes Ceren , Hoersten Jenna , Schmitt Lukas Theo , Rodriguez-Muela Natalia , Knöfler Ralf , Takebe Takanori , Buchholz Frank
Published: January 2022

Despite advances in nuclease-based genome editing technologies, correcting human disease-causing genomic inversions remains a challenge. Here, we describe the potential use of a recombinase-based system to correct the 140 kb inversion of the F8 gene frequently found in patients diagnosed with severe Hemophilia A. Employing substrate-linked directed molecular evolution, we develop a coupled heterodimeric recombinase system (RecF8) achieving 30% inversion of the target sequence in human tissue culture cells. Transient RecF8 treatment of endothelial cells, differentiated from patient-derived induced pluripotent stem cells (iPSCs) of a hemophilic donor, results in 12% correction of the inversion and restores Factor VIII mRNA expression. In this work, we present designer-recombinases as an efficient and specific means towards treatment of monogenic diseases caused by large gene inversions.
Insertion of ammonia into alkenes to build aromatic N-heterocycles
Authors: Liu Shuai , Cheng Xu
Published: January 2022

Ammonia is one of the most abundant and simple nitrogen sources with decent stability and reactivity. Direct insertion of ammonia into a carbon skeleton is an ideal approach to building valuable N-heterocycles for extensive applications with unprecedented atom and step economy. Here, we show an electrochemical dehydrogenative method in which ammonia is inserted directly into alkenes to build aromatic N-heterocycles in a single step without the use of any external oxidant. This new approach achieves 98–99.2% atom economy with hydrogen as the only byproduct. Quinoline and pyridine with diverse substitutions are readily available. In this work, electrochemistry was used to drive a 4-electron oxidation reaction that is hard to access by other protocols, providing a parallel pathway to nitrene chemistry. In a tandem transformation that included three distinct electrochemical processes, the insertion of ammonia further showcased the tremendous potential to manipulate heterocycles derived from Hantzsch ester to diazine via pyridine and pyrrole.
High neutrophil-to-lymphocyte ratio predicts short survival in multiple system atrophy
Authors: Zhang LingYu , Cao Bei , Hou Yanbing , Wei Qianqian , Ou RuWei , Zhao Bi , Shang Huifang
Published: January 2022

The neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, can predict the prognosis of neurodegenerative diseases. However, the significance of NLR for the prognosis of multiple system atrophy (MSA) has not been reported. We aimed to examine the prognostic significance of NLR in MSA. A total of 169 MSA patients and 163 matched healthy controls (HCs) were enrolled. MSA patients were divided into three groups according to the tertiles of their NLR. Kaplan–Meier survival analysis and Cox regression model were used to assessing the effect of NLR on survival. An independent validation cohort of 56 consecutive patients with probable MSA who met the inclusion criteria was included. The NLR was significantly higher in patients with MSA than that in HCs. The survival duration in patients with MSA in group 3 was shorter than that in patients in the other two groups (P = 0.013). In the multivariable Cox regression model, a higher NLR increased the risk of mortality in patients with MSA after adjusting for confounding factors (HR = 1.922, P = 0.035). Additionally, a higher NLR increased the risk of mortality in MSA with predominant cerebellar ataxia (MSA-C) (HR = 2.398, P = 0.033) and in men (HR = 3.483, P = 0.027). The concordance index for the multivariate Cox regression model was more than 0.7 both in the primary cohort and external validation cohort. Patients with MSA had a higher NLR than did HCs. A high NLR increased the risk of mortality with MSA, especially in MSA-C and in men.
Fourteen years of continuous soil moisture records from plant and biocrust-dominated microsites
Authors: Moreno Joaquín , Asensio Sergio , Berdugo Miguel , Gozalo Beatriz , Ochoa Victoria , Pescador David S. , Benito Blas M. , Maestre Fernando T.
Published: January 2022

Drylands cover ~41% of the terrestrial surface. In these water-limited ecosystems, soil moisture contributes to multiple hydrological processes and is a crucial determinant of the activity and performance of above- and belowground organisms and of the ecosystem processes that rely on them. Thus, an accurate characterisation of the temporal dynamics of soil moisture is critical to improve our understanding of how dryland ecosystems function and are responding to ongoing climate change. Furthermore, it may help improve climatic forecasts and drought monitoring. Here we present the MOISCRUST dataset, a long-term (2006–2020) soil moisture dataset at a sub-daily resolution from five different microsites (vascular plants and biocrusts) in a Mediterranean semiarid dryland located in Central Spain. MOISCRUST is a unique dataset for improving our understanding on how both vascular plants and biocrusts determine soil water dynamics in drylands, and thus to better assess their hydrological impacts and responses to ongoing climate change.
ICEO, a biological ontology for representing and analyzing bacterial integrative and conjugative elements
Authors: Liu Meng , Liu Jialin , Liu Guitian , Wang Hui , Wang Xiaoli , Deng Zixin , He Yongqun , Ou Hong-Yu
Published: January 2022

Bacterial integrative and conjugative elements (ICEs) are highly modular mobile genetic elements critical to the horizontal transfer of antibiotic resistance and virulence factor genes. To better understand and analyze the ongoing increase of ICEs, we developed an Integrative and Conjugative Element Ontology (ICEO) to represent the gene components, functional modules, and other information of experimentally verified ICEs. ICEO is aligned with the upper-level Basic Formal Ontology and reuses existing reliable ontologies. There are 31,081 terms, including 26,814 classes from 14 ontologies and 4128 ICEO-specific classes, representing the information of 271 known experimentally verified ICEs from 235 bacterial strains in ICEO currently and 311 predicted ICEs of 272 completely sequenced Klebsiella pneumoniae strains. Three ICEO use cases were illustrated to investigate complex joins of ICEs and their harboring antibiotic resistance or virulence factor genes by using SPARQL or DL query. ICEO has been approved as an Open Biomedical Ontology library ontology. It may be dedicated to facilitating systematical ICE knowledge representation, integration, and computer-assisted queries.
Trilled /r/ is associated with roughness, linking sound and touch across spoken languages
Authors: Winter Bodo , Sóskuthy Márton , Perlman Marcus , Dingemanse Mark
Published: January 2022

Cross-modal integration between sound and texture is important to perception and action. Here we show this has repercussions for the structure of spoken languages. We present a new statistical universal linking speech with the evolutionarily ancient sense of touch. Words that express roughness—the primary perceptual dimension of texture—are highly likely to feature a trilled /r/, the most commonly occurring rhotic consonant. In four studies, we show the pattern to be extremely robust, being the first widespread pattern of iconicity documented not just across a large, diverse sample of the world’s spoken languages, but also across numerous sensory words within languages. Our deep analysis of Indo-European languages and Proto-Indo-European roots indicates remarkable historical stability of the pattern, which appears to date back at least 6000 years.
Motor cortex plasticity response to acute cardiorespiratory exercise and intermittent theta-burst stimulation is attenuated in premanifest and early Huntington’s disease
Authors: Andrews Sophie C. , Curtin Dylan , Coxon James P. , Stout Julie C.
Published: January 2022

Huntington’s disease (HD) mouse models suggest that cardiovascular exercise may enhance neuroplasticity and delay disease signs, however, the effects of exercise on neuroplasticity in people with HD are unknown. Using a repeated-measures experimental design, we compared the effects of a single bout of high-intensity exercise, moderate-intensity exercise, or rest, on motor cortex synaptic plasticity in 14 HD CAG-expanded participants (9 premanifest and 5 early manifest) and 20 CAG-healthy control participants, using transcranial magnetic stimulation. Measures of cortico-motor excitability, short-interval intracortical inhibition and intracortical facilitation were obtained before and after a 20-min bout of either high-intensity interval exercise, moderate-intensity continuous exercise, or rest, and again after intermittent theta burst stimulation (iTBS). HD participants showed less inhibition at baseline compared to controls. Whereas the control group showed increased excitability and facilitation following high-intensity exercise and iTBS, the HD group showed no differences in neuroplasticity responses following either exercise intensity or rest, with follow-up Bayesian analyses providing consistent evidence that these effects were absent in the HD group. These findings indicate that exercise-induced synaptic plasticity mechanisms in response to acute exercise may be attenuated in HD, and demonstrate the need for future research to further investigate exercise and plasticity mechanisms in people with HD.
Application of ensemble machine learning algorithms on lifestyle factors and wearables for cardiovascular risk prediction
Authors: Huang Weiting , Ying Tan Wei , Chin Woon Loong Calvin , Baskaran Lohendran , Marcus Ong Eng Hock , Yeo Khung Keong , Kiong Ng See
Published: January 2022

This study looked at novel data sources for cardiovascular risk prediction including detailed lifestyle questionnaire and continuous blood pressure monitoring, using ensemble machine learning algorithms (MLAs). The reference conventional risk score compared against was the Framingham Risk Score (FRS). The outcome variables were low or high risk based on calcium score 0 or calcium score 100 and above. Ensemble MLAs were built based on naive bayes, random forest and support vector classifier for low risk and generalized linear regression, support vector regressor and stochastic gradient descent regressor for high risk categories. MLAs were trained on 600 Southeast Asians aged 21 to 69 years free of cardiovascular disease. All MLAs outperformed the FRS for low and high-risk categories. MLA based on lifestyle questionnaire only achieved AUC of 0.715 (95% CI 0.681, 0.750) and 0.710 (95% CI 0.653, 0.766) for low and high risk respectively. Combining all groups of risk factors (lifestyle survey questionnaires, clinical blood tests, 24-h ambulatory blood pressure and heart rate monitoring) along with feature selection, prediction of low and high CVD risk groups were further enhanced to 0.791 (95% CI 0.759, 0.822) and 0.790 (95% CI 0.745, 0.836). Besides conventional predictors, self-reported physical activity, average daily heart rate, awake blood pressure variability and percentage time in diastolic hypertension were important contributors to CVD risk classification.
Comparative assessment and novel strategy on methods for imputing proteomics data
Authors: Shen Minjie , Chang Yi-Tan , Wu Chiung-Ting , Parker Sarah J. , Saylor Georgia , Wang Yizhi , Yu Guoqiang , Van Eyk Jennifer E. , Clarke Robert , Herrington David M. , Wang Yue
Published: January 2022

Missing values are a major issue in quantitative proteomics analysis. While many methods have been developed for imputing missing values in high-throughput proteomics data, a comparative assessment of imputation accuracy remains inconclusive, mainly because mechanisms contributing to true missing values are complex and existing evaluation methodologies are imperfect. Moreover, few studies have provided an outlook of future methodological development. We first re-evaluate the performance of eight representative methods targeting three typical missing mechanisms. These methods are compared on both simulated and masked missing values embedded within real proteomics datasets, and performance is evaluated using three quantitative measures. We then introduce fused regularization matrix factorization, a low-rank global matrix factorization framework, capable of integrating local similarity derived from additional data types. We also explore a biologically-inspired latent variable modeling strategy—convex analysis of mixtures—for missing value imputation and present preliminary experimental results. While some winners emerged from our comparative assessment, the evaluation is intrinsically imperfect because performance is evaluated indirectly on artificial missing or masked values not authentic missing values. Nevertheless, we show that our fused regularization matrix factorization provides a novel incorporation of external and local information, and the exploratory implementation of convex analysis of mixtures presents a biologically plausible new approach.