bluuebunny/crossref_metadata_2025 huggingface dataset:
Ferromagnetism and giant magnetoresistance in zinc-blende FeAs monolayers embedded in semiconductor structures
Authors: Anh Le Duc , Hayakawa Taiki , Nakagawa Yuji , Shinya Hikari , Fukushima Tetsuya , Kobayashi Masaki , Katayama-Yoshida Hiroshi , Iwasa Yoshihiro , Tanaka Masaaki
Published: July 2021

Material structures containing tetrahedral FeAs bonds, depending on their density and geometrical distribution, can host several competing quantum ground states ranging from superconductivity to ferromagnetism. Here we examine structures of quasi two-dimensional (2D) layers of tetrahedral Fe-As bonds embedded with a regular interval in a semiconductor InAs matrix, which resembles the crystal structure of Fe-based superconductors. Contrary to the case of Fe-based pnictides, these FeAs/InAs superlattices (SLs) exhibit ferromagnetism, whose Curie temperature (TC) increases rapidly with decreasing the InAs interval thickness tInAs (TC ∝ tInAs−3), and an extremely large magnetoresistance up to 500% that is tunable by a gate voltage. Our first principles calculations reveal the important role of disordered positions of Fe atoms in the establishment of ferromagnetism in these quasi-2D FeAs-based SLs. These unique features mark the FeAs/InAs SLs as promising structures for spintronic applications.
Hexosamine biosynthetic pathway and O-GlcNAc-processing enzymes regulate daily rhythms in protein O-GlcNAcylation
Authors: Liu Xianhui , Blaženović Ivana , Contreras Adam J. , Pham Thu M. , Tabuloc Christine A. , Li Ying H. , Ji Jian , Fiehn Oliver , Chiu Joanna C.
Published: July 2021

The integration of circadian and metabolic signals is essential for maintaining robust circadian rhythms and ensuring efficient metabolism and energy use. Using Drosophila as an animal model, we show that cellular protein O-GlcNAcylation exhibits robust 24-hour rhythm and represents a key post-translational mechanism that regulates circadian physiology. We observe strong correlation between protein O-GlcNAcylation rhythms and clock-controlled feeding-fasting cycles, suggesting that O-GlcNAcylation rhythms are primarily driven by nutrient input. Interestingly, daily O-GlcNAcylation rhythms are severely dampened when we subject flies to time-restricted feeding at unnatural feeding time. This suggests the presence of clock-regulated buffering mechanisms that prevent excessive O-GlcNAcylation at non-optimal times of the day-night cycle. We show that this buffering mechanism is mediated by the expression and activity of GFAT, OGT, and OGA, which are regulated through integration of circadian and metabolic signals. Finally, we generate a mathematical model to describe the key factors that regulate daily O-GlcNAcylation rhythm.
Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women
Authors: Adedokun Babatunde , Du Zhaohui , Gao Guimin , Ahearn Thomas U. , Lunetta Kathryn L. , Zirpoli Gary , Figueroa Jonine , John Esther M. , Bernstein Leslie , Zheng Wei , Hu Jennifer J. , Ziegler Regina G. , Nyante Sarah , Bandera Elisa V. , Ingles Sue A. , Press Michael F. , Deming-Halverson Sandra L. , Rodriguez-Gil Jorge L. , Yao Song , Ogundiran Temidayo O. , Ojengbede Oladosu , Blot William , Troester Melissa A. , Nathanson Katherine L. , Hennis Anselm , Nemesure Barbara , Ambs Stefan , Fiorica Peter N. , Sucheston-Campbell Lara E. , Bensen Jeannette T. , Kushi Lawrence H. , Torres-Mejia Gabriela , Hu Donglei , Fejerman Laura , Bolla Manjeet K. , Dennis Joe , Dunning Alison M. , Easton Douglas F. , Michailidou Kyriaki , Pharoah Paul D. P. , Wang Qin , Sandler Dale P. , Taylor Jack A. , O’Brien Katie M. , Kitahara Cari M. , Falusi Adeyinka G. , Babalola Chinedum , Yarney Joel , Awuah Baffour , Addai-Wiafe Beatrice ,   The GBHS Study Team, Chanock Stephen J. , Olshan Andrew F. , Ambrosone Christine B. , Conti David V. , Ziv Elad , Olopade Olufunmilayo I. , Garcia-Closas Montserrat , Palmer Julie R. , Haiman Christopher A. , Huo Dezheng
Published: July 2021

Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium. The approach identifies four loci for overall breast cancer risk [1p13.3, 5q31.1, 15q24 (two independent signals), and 15q26.3] and two loci for estrogen receptor-negative disease (1q41 and 7q11.23) at genome-wide significance. Four of the index single nucleotide polymorphisms (SNPs) lie within introns of genes (KCNK2, C5orf56, SCAMP2, and SIN3A) and the other index SNPs are located close to GSTM4, AMPD2, CASTOR2, and RP11-168G16.2. Here we present risk loci with consistent direction of associations in African and European descendants. The study suggests that replication across multiple ancestry populations can help improve the understanding of breast cancer genetics and identify causal variants.
Mariana-type ophiolites constrain the establishment of modern plate tectonic regime during Gondwana assembly
Authors: Yao Jinlong , Cawood Peter A. , Zhao Guochun , Han Yigui , Xia Xiaoping , Liu Qian , Wang Peng
Published: July 2021

Initiation of Mariana-type oceanic subduction zones requires rheologically strong oceanic lithosphere, which developed through secular cooling of Earth’s mantle. Here, we report a 518 Ma Mariana-type subduction initiation ophiolite from northern Tibet, which, along with compilation of similar ophiolites through Earth history, argues for the establishment of the modern plate tectonic regime by the early Cambrian. The ophiolite was formed during the subduction initiation of the Proto-Tethys Ocean that coincided with slab roll-back along the southern and western Gondwana margins at ca. 530-520 Ma. This global tectonic re-organization and the establishment of modern plate tectonic regime was likely controlled by secular cooling of the Earth, and facilitated by enhanced lubrication of subduction zones by sediments derived from widespread surface erosion of the extensive mountain ranges formed during Gondwana assembly. This time also corresponds to extreme events recorded in climate and surface proxies that herald formation of the contemporary Earth.
Orbital forcing of ice sheets during snowball Earth
Authors: Mitchell Ross N. , Gernon Thomas M. , Cox Grant M. , Nordsvan Adam R. , Kirscher Uwe , Xuan Chuang , Liu Yebo , Liu Xu , He Xiaofang
Published: July 2021

The snowball Earth hypothesis—that a runaway ice-albedo feedback can cause global glaciation—seeks to explain low-latitude glacial deposits, as well as geological anomalies including the re-emergence of banded iron formation and “cap” carbonates. One of the most significant challenges to snowball Earth has been sedimentological cyclicity that has been taken to imply more climate dynamics than expected when the ocean is completely covered in ice. However, recent climate models suggest that as atmospheric CO2 accumulates, the snowball climate system becomes sensitive to orbital forcing. Here we show the presence of nearly all Milankovitch (orbital) cycles preserved in stratified banded iron formation deposited during the Sturtian snowball Earth. These results provide evidence for orbitally forced cyclicity of global ice sheets that resulted in periodic oxidation of ferrous iron. Orbital glacial advance and retreat cycles provide a simple mechanism to reconcile both the sedimentary dynamics and the enigmatic survival of multicellular life during snowball Earth.
Generation of even and odd high harmonics in resonant metasurfaces using single and multiple ultra-intense laser pulses
Authors: Shcherbakov Maxim R. , Zhang Haizhong , Tripepi Michael , Sartorello Giovanni , Talisa Noah , AlShafey Abdallah , Fan Zhiyuan , Twardowski Justin , Krivitsky Leonid A. , Kuznetsov Arseniy I. , Chowdhury Enam , Shvets Gennady
Published: July 2021

High harmonic generation (HHG) opens a window on the fundamental science of strong-field light-mater interaction and serves as a key building block for attosecond optics and metrology. Resonantly enhanced HHG from hot spots in nanostructures is an attractive route to overcoming the well-known limitations of gases and bulk solids. Here, we demonstrate a nanoscale platform for highly efficient HHG driven by intense mid-infrared laser pulses: an ultra-thin resonant gallium phosphide (GaP) metasurface. The wide bandgap and the lack of inversion symmetry of the GaP crystal enable the generation of even and odd harmonics covering a wide range of photon energies between 1.3 and 3 eV with minimal reabsorption. The resonantly enhanced conversion efficiency facilitates single-shot measurements that avoid material damage and pave the way to study the controllable transition between perturbative and non-perturbative regimes of light-matter interactions at the nanoscale.
Asymmetric reconstruction of mammalian reovirus reveals interactions among RNA, transcriptional factor µ2 and capsid proteins
Authors: Pan Muchen , Alvarez-Cabrera Ana L. , Kang Joon S. , Wang Lihua , Fan Chunhai , Zhou Z. Hong
Published: July 2021

Mammalian reovirus (MRV) is the prototypical member of genus Orthoreovirus of family Reoviridae. However, lacking high-resolution structures of its RNA polymerase cofactor μ2 and infectious particle, limits understanding of molecular interactions among proteins and RNA, and their contributions to virion assembly and RNA transcription. Here, we report the 3.3 Å-resolution asymmetric reconstruction of transcribing MRV and in situ atomic models of its capsid proteins, the asymmetrically attached RNA-dependent RNA polymerase (RdRp) λ3, and RdRp-bound nucleoside triphosphatase μ2 with a unique RNA-binding domain. We reveal molecular interactions among virion proteins and genomic and messenger RNA. Polymerase complexes in three Spinoreovirinae subfamily members are organized with different pseudo-D3d symmetries to engage their highly diversified genomes. The above interactions and those between symmetry-mismatched receptor-binding σ1 trimers and RNA-capping λ2 pentamers balance competing needs of capsid assembly, external protein removal, and allosteric triggering of endogenous RNA transcription, before, during and after infection, respectively.
Engineering atomic-scale magnetic fields by dysprosium single atom magnets
Authors: Singha A. , Willke P. , Bilgeri T. , Zhang X. , Brune H. , Donati F. , Heinrich A. J. , Choi T.
Published: July 2021

Atomic scale engineering of magnetic fields is a key ingredient for miniaturizing quantum devices and precision control of quantum systems. This requires a unique combination of magnetic stability and spin-manipulation capabilities. Surface-supported single atom magnets offer such possibilities, where long temporal and thermal stability of the magnetic states can be achieved by maximizing the magnet/ic anisotropy energy (MAE) and by minimizing quantum tunnelling of the magnetization. Here, we show that dysprosium (Dy) atoms on magnesium oxide (MgO) have a giant MAE of 250 meV, currently the highest among all surface spins. Using a variety of scanning tunnelling microscopy (STM) techniques including single atom electron spin resonance (ESR), we confirm no spontaneous spin-switching in Dy over days at ≈ 1 K under low and even vanishing magnetic field. We utilize these robust Dy single atom magnets to engineer magnetic nanostructures, demonstrating unique control of magnetic fields with atomic scale tunability.
Flat band carrier confinement in magic-angle twisted bilayer graphene
Authors: Tilak Nikhil , Lai Xinyuan , Wu Shuang , Zhang Zhenyuan , Xu Mingyu , Ribeiro Raquel de Almeida , Canfield Paul C. , Andrei Eva Y.
Published: July 2021

Magic-angle twisted bilayer graphene has emerged as a powerful platform for studying strongly correlated electron physics, owing to its almost dispersionless low-energy bands and the ability to tune the band filling by electrostatic gating. Techniques to control the twist angle between graphene layers have led to rapid experimental progress but improving sample quality is essential for separating the delicate correlated electron physics from disorder effects. Owing to the 2D nature of the system and the relatively low carrier density, the samples are highly susceptible to small doping inhomogeneity which can drastically modify the local potential landscape. This potential disorder is distinct from the twist angle variation which has been studied elsewhere. Here, by using low temperature scanning tunneling spectroscopy and planar tunneling junction measurements, we demonstrate that flat bands in twisted bilayer graphene can amplify small doping inhomogeneity that surprisingly leads to carrier confinement, which in graphene could previously only be realized in the presence of a strong magnetic field.
GIGYF1 loss of function is associated with clonal mosaicism and adverse metabolic health
Authors: Zhao Yajie , Stankovic Stasa , Koprulu Mine , Wheeler Eleanor , Day Felix R. , Lango Allen Hana , Kerrison Nicola D. , Pietzner Maik , Loh Po-Ru , Wareham Nicholas J. , Langenberg Claudia , Ong Ken K. , Perry John R. B.
Published: July 2021

Mosaic loss of chromosome Y (LOY) in leukocytes is the most common form of clonal mosaicism, caused by dysregulation in cell-cycle and DNA damage response pathways. Previous genetic studies have focussed on identifying common variants associated with LOY, which we now extend to rarer, protein-coding variation using exome sequences from 82,277 male UK Biobank participants. We find that loss of function of two genes—CHEK2 and GIGYF1—reach exome-wide significance. Rare alleles in GIGYF1 have not previously been implicated in any complex trait, but here loss-of-function carriers exhibit six-fold higher susceptibility to LOY (OR = 5.99 [3.04–11.81], p = 1.3 × 10−10). These same alleles are also associated with adverse metabolic health, including higher susceptibility to Type 2 Diabetes (OR = 6.10 [3.51–10.61], p = 1.8 × 10−12), 4 kg higher fat mass (p = 1.3 × 10−4), 2.32 nmol/L lower serum IGF1 levels (p = 1.5 × 10−4) and 4.5 kg lower handgrip strength (p = 4.7 × 10−7) consistent with proposed GIGYF1 enhancement of insulin and IGF-1 receptor signalling. These associations are mirrored by a common variant nearby associated with the expression of GIGYF1. Our observations highlight a potential direct connection between clonal mosaicism and metabolic health.
NUDT15 polymorphism influences the metabolism and therapeutic effects of acyclovir and ganciclovir
Authors: Nishii Rina , Mizuno Takanori , Rehling Daniel , Smith Colton , Clark Brandi L. , Zhao Xujie , Brown Scott A. , Smart Brandon , Moriyama Takaya , Yamada Yuji , Ichinohe Tatsuo , Onizuka Makoto , Atsuta Yoshiko , Yang Lei , Yang Wenjian , Thomas Paul G. , Stenmark Pål , Kato Motohiro , Yang Jun J.
Published: July 2021

Nucleobase and nucleoside analogs (NNA) are widely used as anti-viral and anti-cancer agents, and NNA phosphorylation is essential for the activity of this class of drugs. Recently, diphosphatase NUDT15 was linked to thiopurine metabolism with NUDT15 polymorphism associated with drug toxicity in patients. Profiling NNA drugs, we identify acyclovir (ACV) and ganciclovir (GCV) as two new NNAs metabolized by NUDT15. NUDT15 hydrolyzes ACV and GCV triphosphate metabolites, reducing their effects against cytomegalovirus (CMV) in vitro. Loss of NUDT15 potentiates cytotoxicity of ACV and GCV in host cells. In hematopoietic stem cell transplant patients, the risk of CMV viremia following ACV prophylaxis is associated with NUDT15 genotype (P = 0.015). Donor NUDT15 deficiency is linked to graft failure in patients receiving CMV-seropositive stem cells (P = 0.047). In conclusion, NUDT15 is an important metabolizing enzyme for ACV and GCV, and NUDT15 variation contributes to inter-patient variability in their therapeutic effects.
TOMM40 ‘523’ poly-T repeat length is a determinant of longitudinal cognitive decline in Parkinson’s disease
Authors: Bakeberg Megan C. , Gorecki Anastazja M. , Pfaff Abigail L. , Hoes Madison E. , Kõks Sulev , Akkari P. Anthony , Mastaglia Frank L. , Anderton Ryan S.
Published: July 2021

The translocase of outer mitochondrial membrane 40 (TOMM40) ‘523’ polymorphism has previously been associated with age of Alzheimer’s disease onset and cognitive functioning in non-pathological ageing, but has not been explored as a candidate risk marker for cognitive decline in Parkinson’s disease (PD). Therefore, this longitudinal study investigated the role of the ‘523’ variant in cognitive decline in a patient cohort from the Parkinson’s Progression Markers Initiative. As such, a group of 368 people with PD were assessed annually for cognitive performance using multiple neuropsychological protocols, and were genotyped for the TOMM40 ‘523’ variant using whole-genome sequencing data. Covariate-adjusted generalised linear mixed models were utilised to examine the relationship between TOMM40 ‘523’ allele lengths and cognitive scores, while taking into account the APOE ε genotype. Cognitive scores declined over the 5-year study period and were lower in males than in females. When accounting for APOE ε4, the TOMM40 ‘523’ variant was not robustly associated with overall cognitive performance. However, in APOE ε3/ε3 carriers, who accounted for ~60% of the whole cohort, carriage of shorter ‘523’ alleles was associated with more severe cognitive decline in both sexes, while carriage of the longer alleles in females were associated with better preservation of global cognition and a number of cognitive sub-domains, and with a delay in progression to dementia. The findings indicate that when taken in conjunction with the APOE genotype, TOMM40 ‘523’ allele length is a significant independent determinant and marker for the trajectory of cognitive decline and risk of dementia in PD.
Historical contingency impacts on community assembly and ecosystem function in chemosynthetic marine ecosystems
Authors: Kalenitchenko Dimitri , Peru Erwan , Galand Pierre E.
Published: July 2021

Predicting ecosystem functioning requires an understanding of the mechanisms that drive microbial community assembly. Many studies have explored microbial diversity extensively and environmental factors are thought to be the principal drivers of community composition. Community assembly is, however, also influenced by past conditions that might affect present-day assemblages. Historical events, called legacy effects or historical contingencies, remain poorly studied in the sea and their impact on the functioning of the communities is not known. We tested the influence, if any, of historical contingencies on contemporary community assembly and functions in a marine ecosystem. To do so, we verified if different inoculum communities colonizing the same substrate led to communities with different compositions. We inoculated wood with sea water microbes from different marine environments that differ in ecological and evolutionary history. Using 16S rRNA and metagenomic sequencing, it was demonstrated that historical contingencies change the composition and potential metabolisms of contemporary communities. The effect of historical events was transient, dominated by environmental selection as, over time, species sorting was a more important driver of community assembly. Our study shows not only that historical contingencies affect marine ecosystems but takes the analysis a step further by characterizing this effect as strong but transient.
Human sample﻿ authentication in biomedical research: comparison of two platforms
Authors: Manjunath Harshitha Shobha , James Nicola , Mathew Rebecca , Al Hashmi Muna , Silcock Lee , Biunno Ida , De Blasio Pasquale , Manickam Chidambaram , Tomei Sara
Published: July 2021

Samples used in biomedical research are often collected over years, in some cases from subjects that may have died and thus cannot be retrieved in any way. The value of these samples is priceless. Sample misidentification or mix-up are unfortunately common problems in biomedical research and can eventually result in the publication of incorrect data. Here we have compared the Fluidigm SNPtrace and the Agena iPLEX Sample ID panels for the authentication of human genomic DNA samples. We have tested 14 pure samples and simulated their cross-contamination at different percentages (2%, 5%, 10%, 25% and 50%). For both panels, we report call rate, allele intensity/probability score, performance in distinguishing pure samples and contaminated samples at different percentages, and sex typing. We show that both panels are reliable and efficient methods for sample authentication and we highlight their advantages and disadvantages. We believe that the data provided here is useful for sample authentication especially in biorepositories and core facility settings.
Recent decadal enhancement of Meiyu–Baiu heavy rainfall over East Asia
Authors: Takahashi Hiroshi G. , Fujinami Hatsuki
Published: July 2021

East of Eurasia, moist air is transported poleward, forming the Meiyu–Baiu front over East Asia in late June and early July. Recently, unusually heavy rainfall may have increased, causing catastrophic flooding in East Asia. Here, unique 23-year precipitation satellite radar data confirm recent enhancement in Meiyu–Baiu heavy rainfall from eastern China to southwestern Japan, which is also evident from independent conventional observations. Decadal changes in rainfall have been physically consistent with enhanced transport of water vapour due to the intensified Pacific subtropical high associated with weakened tropical cyclone activity over the Northwest Pacific. Furthermore, the upper-tropospheric trough, associated with wave train along the subtropical jet, influenced Meiyu–Baiu precipitation over East Asia. Long-term and continuous satellite radar observations reveal that the frequency of heavy precipitation along the Meiyu–Baiu front has increased in the last 22 years. In particular, heavy precipitation (10 mm/h) increased by 24% between 1998–2008 and 2009–2019, and the abruptly-changed level likely induced recent meteorological disasters across East Asia. This trend may also explain the severity of the 2020 Meiyu–Baiu season. Over the last decade, this front has likely transitioned to a new climate state, which requires adaptation of disaster prevention approaches.
Influence of occlusal reduction on pain after endodontic treatment: a systematic review and meta-analysis
Authors: Chagas Carvalho Alves Nayane , Raiane Mamede Veloso Sirley , de Andrade Silva Silmara , de Almeida Andressa Cartaxo , Tavares Velozo Telles Christianne , Romeiro Kaline , de Melo Monteiro Gabriela Queiroz , de Albuquerque Diana Santana
Published: July 2021

The purpose of this systematic review was to analyze the influence of occlusal reduction on the postoperative pain levels after endodontic treatment (instrumentation and obturation of the root canal system). This review followed the PRISMA statement and was registered at PROSPERO (CRD42018107918). Two independent reviewers searched the Lilacs, Cochrane Library, PubMed (Medline), Web of Science, Scopus, Scielo, and ScienceDirect for articles published until April 2021. The research question was, "Does occlusal reduction decrease postoperative pain in endodontically treated teeth?". Only randomized clinical trials were included. The RevMan 5 program was used for meta-analysis, calculating the relative risk (RR) and 95% confidence interval (CI) of the dichotomous outcome (presence or absence of pain). The search strategies retrieved 4114 studies. Twelve studies were included for qualitative analysis and nine for quantitative analysis. The meta-analysis results did not reveal a significant difference in the reduction of postoperative pain levels for endodontic instrumentation at 6, 12, 24, 48 h and for endodontic obturation at 6 or 12 h after occlusal reduction. According to the GRADE tool, the analyzed outcome was classified as having a moderate level of certainty. It is concluded that occlusal reduction does not interfere with postoperative pain levels after endodontic treatment.
The first insight into the genetic structure of the population of modern Serbia
Authors: Drljaca Tamara , Zukic Branka , Kovacevic Vladimir , Gemovic Branislava , Klaassen-Ljubicic Kristel , Perovic Vladimir , Lazarevic Mladen , Pavlovic Sonja , Veljkovic Nevena
Published: July 2021

The complete understanding of the genomic contribution to complex traits, diseases, and response to treatments, as well as genomic medicine application to the well-being of all humans will be achieved through the global variome that encompasses fine-scale genetic diversity. Despite significant efforts in recent years, uneven representation still characterizes genomic resources and among the underrepresented European populations are the Western Balkans including the Serbian population. Our research addresses this gap and presents the first ever targeted sequencing dataset of variants in clinically relevant genes. By measuring population differentiation and applying the Principal Component and Admixture analysis we demonstrated that the Serbian population differs little from other European populations, yet we identified several novel and more frequent variants that appear as its unique genetic determinants. We explored thoroughly the functional impact of frequent variants and its correlation with the health burden of the population of Serbia based on a sample of 144 individuals. Our variants catalogue improves the understanding of genetics of modern Serbia, contributes to research on ancestry, and aids in improvements of well-being and health equity. In addition, this resource may also be applicable in neighboring regions and valuable in worldwide functional analyses of genetic variants in individuals of European descent.
Perception on aggregation induced multicolor emission and emission centers in carbon nanodots using successive dilution, anion exchange chromatography, and multi-way statistics
Authors: Kompany-Zareh Mohsen , Bagheri Saeed
Published: July 2021

Exploration in the way of understanding the optical behavior and structure of carbon nanodots has been increased due to their vast application. Their emission dependency on excitation wavelengths is the more prevalent and controversial subject. In this report we considered the optical structure of hydrothermally synthesized carbon nanodots using citric acid and 2,3-diaminopyridine as precursors. The presence of different emission centers experimented through anion exchange chromatography which resulted in fractions with more unique optical structures. The quantum confinement effect and energy exchange between different types of carbon nanodots, due to aggregation in higher concentration levels, was studied applying a stepwise dilution experiment. Analysis of the experimental data was done through the parallel factor analysis and the trajectory pattern recognition which resolved more about optical interactions and the presence of different emission centers in different particles. Results from infrared spectroscopy confirmed the dominating density of carboxyl functional groups on the nanodots with negative surface charges and higher influence of amine groups on dots with positive surface charges.
A structure–function based approach to floc hierarchy and evidence for the non-fractal nature of natural sediment flocs
Authors: Spencer Kate L. , Wheatland Jonathan A. T. , Bushby Andrew J. , Carr Simon J. , Droppo Ian G. , Manning Andrew J.
Published: July 2021

Natural sediment flocs are fragile, highly irregular, loosely bound aggregates comprising minerogenic and organic material. They contribute a major component of suspended sediment load and are critical for the fate and flux of sediment, carbon and pollutants in aquatic environments. Understanding their behaviour is essential to the sustainable management of waterways, fisheries and marine industries. For several decades, modelling approaches have utilised fractal mathematics and observations of two dimensional (2D) floc size distributions to infer levels of aggregation and predict their behaviour. Whilst this is a computationally simple solution, it is highly unlikely to reflect the complexity of natural sediment flocs and current models predicting fine sediment hydrodynamics are not efficient. Here, we show how new observations of fragile floc structures in three dimensions (3D) demonstrate unequivocally that natural flocs are non-fractal. We propose that floc hierarchy is based on observations of 3D structure and function rather than 2D size distribution. In contrast to fractal theory, our data indicate that flocs possess characteristics of emergent systems including non-linearity and scale-dependent feedbacks. These concepts and new data to quantify floc structures offer the opportunity to explore new emergence-based floc frameworks which better represent natural floc behaviour and could advance our predictive capacity.
Contrasting drivers and trends of ocean acidification in the subarctic Atlantic
Authors: Pérez Fiz F. , Olafsson Jon , Ólafsdóttir Solveig R. , Fontela Marcos , Takahashi Taro
Published: July 2021

The processes of warming, anthropogenic CO2 (Canth) accumulation, decreasing pHT (increasing [H+]T; concentration in total scale) and calcium carbonate saturation in the subarctic zone of the North Atlantic are unequivocal in the time-series measurements of the Iceland (IS-TS, 1985–2003) and Irminger Sea (IRM-TS, 1983–2013) stations. Both stations show high rates of Canth accumulation with different rates of warming, salinification and stratification linked to regional circulation and dynamics. At the IS-TS, advected and stratified waters of Arctic origin drive a strong increase in [H+]T, in the surface layer, which is nearly halved in the deep layer (44.7 ± 3.6 and 25.5 ± 1.0 pmol kg−1 yr−1, respectively). In contrast, the weak stratification at the IRM-TS allows warming, salinification and Canth uptake to reach the deep layer. The acidification trends are even stronger in the deep layer than in the surface layer (44.2 ± 1.0 pmol kg−1 yr−1 and 32.6 ± 3.4 pmol kg−1 yr−1 of [H+]T, respectively). The driver analysis detects that warming contributes up to 50% to the increase in [H+]T at the IRM-TS but has a small positive effect on calcium carbonate saturation. The Canth increase is the main driver of the observed acidification, but it is partially dampened by the northward advection of water with a relatively low natural CO2 content.
Investigating the association of testosterone with survival in men and women using a Mendelian randomization study in the UK Biobank
Authors: Schooling C. M. , Zhao J. V.
Published: July 2021

Life expectancy in the developed West is currently stagnated and remains shorter in men than women. Well-established evolutionary biology theory suggests lifespan trades-off against reproductive success, possibly sex-specifically. We examined whether a key driver of reproductive success, testosterone, affected survival using a Mendelian randomization longevity study in the UK Biobank to obtain unbiased estimates, along with control exposures. We applied published genetic instruments for testosterone to obtain inverse variance weighted estimates of associations with survival to (i.e., age at) recruitment, in 167,020 men and 194,174 women. We similarly obtained estimates for a positive control (smoking initiation), and a negative control (absorbate), a marker of vitamin C metabolism. Testosterone was associated with poorer survival (0.10 years younger at recruitment per effect size of testosterone, 95% confidence interval (CI) 0.004 to 0.20). As expected, smoking initiation was also associated with poorer survival (0.37 years younger, 95% CI 0.25 to 0.50), but not absorbate (0.01 years younger, 95% CI − 0.09 to 0.11). Several aspects of a healthy lifestyle (low animal fat diet) and several widely used medications (statins, metformin, dexamethasone and possibly aspirin) may modulate testosterone. Explicitly designing interventions sex-specifically based on these insights might help address stagnating life expectancy and sexual disparities.
Cholesterol-dependent plasma membrane order (Lo) is critical for antigen-specific clonal expansion of CD4+ T cells
Authors: Sengupta Soumini , Karsalia Ritesh , Morrissey Amanda , Bamezai Anil K.
Published: July 2021

Early “T cell activation” events are initiated within the lipid microenvironment of the plasma membrane. Role of lipid membrane order (Lo) in spatiotemporal signaling through the antigen receptor in T cells is posited but remains unclear. We have examined the role of membrane order (Lo)/disorder (Ld) in antigen specific CD4+T cell activation and clonal expansion by first creating membrane disorder, and then reconstituting membrane order by inserting cholesterol into the disordered plasma membrane. Significant revival of antigen specific CD4+T cell proliferative response was observed after reconstituting the disrupted membrane order with cholesterol. These reconstitution experiments illustrate Koch’s postulate by demonstrating that cholesterol-dependent membrane order (Lo) is critical for responses generated by CD4+T cells and point to the importance of membrane order and lipid microenvironment in signaling through T cell membrane antigen receptors.
Antibiotics modulate neoadjuvant therapy efficiency in patients with breast cancer: a pilot analysis
Authors: Zhang Xi , Yu Long , Shi Jiajie , Li Sainan , Yang Shiwei , Gao Wei , Yang Shan , Cheng Meng , Wang Haoqi , Guo Zhanjun , Geng Cuizhi
Published: July 2021

Mounting evidence suggests that microbiota dysbiosis caused by antibiotic administration is a risk factor for cancer, but few research reports focus on the relationships between antibiotics and chemotherapy efficiency. We evaluated the influence of antibiotic administration on neoadjuvant therapy efficacy in patients with breast cancer (BC) in the present study. BC patients were stratified into two groups: antibiotic-treated and control based on antibiotic administration within 30 days after neoadjuvant therapy initiation. Disease-free survival (DFS) and overall survival (OS) were assessed using the Kaplan–Meier method, and the Cox proportional hazards model was used for multivariate analyses. The pathologic complete response rate of the control group was significantly higher than that of the antibiotic-treated group (29.09% vs. 10.20%, p = 0.017). Further univariate analysis with Kaplan–Meier calculations demonstrated that antibiotic administration was strongly linked with both reduced DFS (p = 0.04) at significant statistical levels and OS (p = 0.088) at borderline statistical levels. Antibiotic administration was identified as a significant independent prognostic factor for DFS [hazard ratio (HR) 3.026, 95%, confidence interval (CI) 1.314–6.969, p = 0.009] and OS (HR 2.836, 95% CI 1.016–7.858, p = 0.047) by Cox proportional hazards model analysis. Antibiotics that initiated reduced efficiency of chemotherapy were more noticeable in the HER2-positive subgroup for both DFS (HR 5.51, 95% CI 1.77–17.2, p = 0.003) and OS (HR 7.0395% CI 1.94–25.53, p = 0.003), as well as in the T3-4 subgroup for both DFS (HR 20.36, 95% CI 2.41–172.07, p = 0.006) and OS (HR 13.45, 95% CI 1.39–130.08, p = 0.025) by stratified analysis. Antibiotic administration might be associated with reduced efficacy of neoadjuvant therapy and poor prognosis in BC patients. As a preliminary study, our research made preparations for further understanding and large-scale analyses of the impact of antibiotics on the efficacy of neoadjuvant therapy.
SoxD transcription factor deficiency in Schwann cells delays myelination in the developing peripheral nervous system
Authors: Ittner Ella , Hartwig Anna C. , Elsesser Olga , Wüst Hannah M. , Fröb Franziska , Wedel Miriam , Schimmel Margit , Tamm Ernst R. , Wegner Michael , Sock Elisabeth
Published: July 2021

The three SoxD proteins, Sox5, Sox6 and Sox13, represent closely related transcription factors with important roles during development. In the developing nervous system, SoxD proteins have so far been primarily studied in oligodendroglial cells and in interneurons of brain and spinal cord. In oligodendroglial cells, Sox5 and Sox6 jointly maintain the precursor state, interfere with terminal differentiation, and thereby ensure the proper timing of myelination in the central nervous system. Here we studied the role of SoxD proteins in Schwann cells, the functional counterpart of oligodendrocytes in the peripheral nervous system. We show that Schwann cells express Sox5 and Sox13 but not Sox6. Expression was transient and ceased with the onset of terminal differentiation. In mice with early Schwann cell-specific deletion of both Sox5 and Sox13, embryonic Schwann cell development was not substantially affected and progressed normally into the promyelinating stage. However, there was a mild and transient delay in the myelination of the peripheral nervous system of these mice. We therefore conclude that SoxD proteins—in stark contrast to their action in oligodendrocytes—promote differentiation and myelination in Schwann cells.
Modelling of crustal composition and Moho depths and their Implications toward seismogenesis in the Kumaon–Garhwal Himalaya
Authors: Mandal Prantik , Srinivas D. , Suresh G. , Srinagesh D.
Published: July 2021

We image the lateral variations in the Moho depths and average crustal composition across the Kumaon–Garhwal (KG) Himalaya, through the H–K stacking of 1400 radial PRFs from 42 three-component broadband stations. The modelled Moho depth, average crustal Vp/Vs, and Poisson’s ratio estimates vary from 28.3 to 52.9 km, 1.59 to 2.13 and 0.17 to 0.36, respectively, in the KG Himalaya. We map three NS to NNE trending transverse zones of significant thinning of mafic crust, which are interspaced by zones of thickening of felsic crust. These mapped transverse zones bend toward the north to form a NE dipping zone of maximum changes in Moho depths, below the region between Munsiari and Vaikrita thrusts. The 1991 Mw6.6 Uttarakashi and 1999 Mw6.4 Chamoli earthquakes have occurred on the main Himalayan thrust (MHT), lying just above the mapped zone of maximum changes in Moho depths. Modelled large values of average crustal Vp/Vs (> 1.85) could be attributed to the high fluid (metamorphic fluids) pressure associated with the mid-crustal MHT. Additionally, the serpentinization of the lowermost crust resulted from the continent–continent Himalayan collision process could also contribute to the increase of the average crustal Vp/Vs ratio in the region.
On the shape and structure of the murine pulmonary heart valve
Authors: Liu Yifei , Feng Xinzeng , Liu Hao , McComb David W. , Breuer Christopher K. , Sacks Michael S.
Published: July 2021

Murine animal models are an established standard in translational research and provides a potential platform for studying heart valve disease. To date, studies on heart valve disease using murine models have been hindered by a lack of appropriate methodologies due to their small scale. In the present study, we developed a multi-scale, imaging-based approach to extract the functional structure and geometry for the murine heart valve. We chose the pulmonary valve (PV) to study, due to its importance in congenital heart valve disease. Excised pulmonary outflow tracts from eleven 1-year old C57BL/6J mice were fixed at 10, 20, and 30 mmHg to simulate physiological loading. Micro-computed tomography was used to reconstruct the 3D organ-level PV geometry, which was then spatially correlated with serial en-face scanning electron microscopy imaging to quantify local collagen fiber distributions. From the acquired volume renderings, we obtained the geometric descriptors of the murine PV under increasing transvalvular pressures, which demonstrated remarkable consistency. Results to date suggest that the preferred collagen orientation was predominantly in the circumferential direction, as in larger mammalian valves. The present study represents a first step in establishing organ-level murine models for the study of heart valve disease.
Preoperative nomogram for microvascular invasion prediction based on clinical database in hepatocellular carcinoma
Authors: Mao Shuqi , Yu Xi , Yang Yong , Shan Yuying , Mugaanyi Joseph , Wu Shengdong , Lu Caide
Published: July 2021

The presence of microvascular invasion (MVI) is a critical determinant of early hepatocellular carcinoma (HCC) recurrence and prognosis. We developed a nomogram model integrating clinical laboratory examinations and radiological imaging results from our clinical database to predict microvascular invasion presence at preoperation in HCC patients. 242 patients with pathologically confirmed HCC at the Ningbo Medical Centre Lihuili Hospital from September 2015 to January 2021 were included in this study. Baseline clinical laboratory examinations and radiological imaging results were collected from our clinical database. LASSO regression analysis model was used to construct data dimensionality reduction and elements selection. Multivariate logistic regression analysis was performed to identify the independent risk factors associated with MVI and finally a nomogram for predicting MVI presence of HCC was established. Nomogram performance was assessed via internal validation and calibration curve statistics. Decision curve analysis (DCA) was conducted to determine the clinical usefulness of the nomogram model by quantifying the net benefits along with the increase in threshold probabilities. Survival analysis indicated that the probability of overall survival (OS) and recurrence-free survival (RFS) were significantly different between patients with MVI and without MVI (P < 0.05). Histopathologically identified MVI was found in 117 of 242 patients (48.3%). The preoperative factors associated with MVI were large tumor diameter (OR = 1.271, 95%CI: 1.137–1.420, P < 0.001), AFP level greater than 20 ng/mL (20–400 vs. ≤ 20, OR = 2.025, 95%CI: 1.056–3.885, P = 0.034; > 400 vs. ≤ 20, OR = 3.281, 95%CI: 1.661–6.480, P = 0.001), total bilirubin level greater than 23 umol/l (OR = 2.247, 95%CI: 1.037–4.868, P = 0.040). Incorporating tumor diameter, AFP and TB, the nomogram achieved a better concordance index of 0.725 (95%CI: 0.661–0.788) in predicting MVI presence. Nomogram analysis showed that the total factor score ranged from 0 to 160, and the corresponding risk rate ranged from 0.20 to 0.90. The DCA showed that if the threshold probability was > 5%, using the nomogram to diagnose MVI could acquire much more benefit. And the net benefit of the nomogram model was higher than single variable within 0.3–0.8 of threshold probability. In summary, the presence of MVI is an independent prognostic risk factor for RFS. The nomogram detailed here can preoperatively predict MVI presence in HCC patients. Using the nomogram model may constitute a usefully clinical tool to guide a rational and personalized subsequent therapeutic choice.
Molecular characterization and nutritional regulation of sodium-dependent glucose cotransporter 1 (Sglt1) in blunt snout bream (Megalobrama amblycephala)
Authors: Liang Hualiang , Ge Xianping , Ren Mingchun , Zhang Lu , Xia Dong , Ke Ji , Pan Liangkun
Published: July 2021

Fish has poor utilization capacity for glucose metabolism. The possible reasons are related to the core regulatory elements of glucose metabolism: transport proteins. Studies on the species and functions of Sglt1 in aquatic animals are scarce, therefore further studies are needed. In this study, the full length of blunt snout bream (Megalobrama amblycephala) sglt1 (Masglt1) was 2965 bp including 5′-UTR region of 168 bp and a 3′-UTR region of 820 bp. Masglt1 have a highest sequence homology in Cypriniformes fish. MaSglt1 protein was identified as a transmembrane protein with 14 α-helix structures locating plasma membrane by the methods of predicted tertiary structure and immunohistochemical staining. MaSglt1 protein has a hollow channel forms which could be specifically coupled with two Na+ ions to recognize glucose and carry out transmembrane transport. High sglt1 mRNA was found in the intestine and kidney. The mRNA levels of intestinal sglt1 had a positive correlation with dietary starch levels at 3 h after feeding, and the mRNA was significantly higher than that at 24 h, however, the mRNA levels of renal sglt1 presented results opposite to those of intestinal sglt1. The mRNA levels of renal sglt1 had a positive correlation with dietary starch levels at 24 h after feeding, and the expression was significantly higher than that at 3 h. These results confirmed that Masglt11 was mainly found in the intestine and kidney and was located in the cell membrane, playing a role in glucose homeostasis.
Three dimensional modeling of biologically relevant fluid shear stress in human renal tubule cells mimics in vivo transcriptional profiles
Authors: Ross Emily J. , Gordon Emily R. , Sothers Hanna , Darji Roshan , Baron Oakley , Haithcock Dustin , Prabhakarpandian Balabhaskar , Pant Kapil , Myers Richard M. , Cooper Sara J. , Cox Nancy J.
Published: July 2021

The kidney proximal tubule is the primary site for solute reabsorption, secretion and where kidney diseases can originate, including drug-induced toxicity. Two-dimensional cell culture systems of the human proximal tubule cells (hPTCs) are often used to study these processes. However, these systems fail to model the interplay between filtrate flow, fluid shear stress (FSS), and functionality essential for understanding renal diseases and drug toxicity. The impact of FSS exposure on gene expression and effects of FSS at differing rates on gene expression in hPTCs has not been thoroughly investigated. Here, we performed RNA-sequencing of human RPTEC/TERT1 cells in a microfluidic chip-based 3D model to determine transcriptomic changes. We measured transcriptional changes following treatment of cells in this device at three different fluidic shear stress. We observed that FSS changes the expression of PTC-specific genes and impacted genes previously associated with renal diseases in genome-wide association studies (GWAS). At a physiological FSS level, we observed cell morphology, enhanced polarization, presence of cilia, and transport functions using albumin reabsorption via endocytosis and efflux transport. Here, we present a dynamic view of hPTCs response to FSS with increasing fluidic shear stress conditions and provide insight into hPTCs cellular function under biologically relevant conditions.