bluuebunny/crossref_metadata_2025 huggingface dataset:
Inter- and intra-tumor heterogeneity of metastatic prostate cancer determined by digital spatial gene expression profiling
Authors: Brady Lauren , Kriner Michelle , Coleman Ilsa , Morrissey Colm , Roudier Martine , True Lawrence D. , Gulati Roman , Plymate Stephen R. , Zhou Zoey , Birditt Brian , Meredith Rhonda , Geiss Gary , Hoang Margaret , Beechem Joseph , Nelson Peter S.
Published: March 2021

Metastatic prostate cancer (mPC) comprises a spectrum of diverse phenotypes. However, the extent of inter- and intra-tumor heterogeneity is not established. Here we use digital spatial profiling (DSP) technology to quantitate transcript and protein abundance in spatially-distinct regions of mPCs. By assessing multiple discrete areas across multiple metastases, we find a high level of intra-patient homogeneity with respect to tumor phenotype. However, there are notable exceptions including tumors comprised of regions with high and low androgen receptor (AR) and neuroendocrine activity. While the vast majority of metastases examined are devoid of significant inflammatory infiltrates and lack PD1, PD-L1 and CTLA4, the B7-H3/CD276 immune checkpoint protein is highly expressed, particularly in mPCs with high AR activity. Our results demonstrate the utility of DSP for accurately classifying tumor phenotype, assessing tumor heterogeneity, and identifying aspects of tumor biology involving the immunological composition of metastases.
Reconfigurable photonics with on-chip single-photon detectors
Authors: Gyger Samuel , Zichi Julien , Schweickert Lucas , Elshaari Ali W. , Steinhauer Stephan , Covre da Silva Saimon F. , Rastelli Armando , Zwiller Val , Jöns Klaus D. , Errando-Herranz Carlos
Published: March 2021

Integrated quantum photonics offers a promising path to scale up quantum optics experiments by miniaturizing and stabilizing complex laboratory setups. Central elements of quantum integrated photonics are quantum emitters, memories, detectors, and reconfigurable photonic circuits. In particular, integrated detectors not only offer optical readout but, when interfaced with reconfigurable circuits, allow feedback and adaptive control, crucial for deterministic quantum teleportation, training of neural networks, and stabilization of complex circuits. However, the heat generated by thermally reconfigurable photonics is incompatible with heat-sensitive superconducting single-photon detectors, and thus their on-chip co-integration remains elusive. Here we show low-power microelectromechanical reconfiguration of integrated photonic circuits interfaced with superconducting single-photon detectors on the same chip. We demonstrate three key functionalities for photonic quantum technologies: 28 dB high-extinction routing of classical and quantum light, 90 dB high-dynamic range single-photon detection, and stabilization of optical excitation over 12 dB power variation. Our platform enables heat-load free reconfigurable linear optics and adaptive control, critical for quantum state preparation and quantum logic in large-scale quantum photonics applications.
Germ granule dysfunction is a hallmark and mirror of Piwi mutant sterility
Authors: Spichal Maya , Heestand Bree , Billmyre Katherine Kretovich , Frenk Stephen , Mello Craig C. , Ahmed Shawn
Published: March 2021

In several species, Piwi/piRNA genome silencing defects cause immediate sterility that correlates with transposon expression and transposon-induced genomic instability. In C. elegans, mutations in the Piwi-related gene (prg-1) and other piRNA deficient mutants cause a transgenerational decline in fertility over a period of several generations. Here we show that the sterility of late generation piRNA mutants correlates poorly with increases in DNA damage signaling. Instead, sterile individuals consistently exhibit altered perinuclear germ granules. We show that disruption of germ granules does not activate transposon expression but induces multiple phenotypes found in sterile prg-1 pathway mutants. Furthermore, loss of the germ granule component pgl-1 enhances prg-1 mutant infertility. Environmental restoration of germ granule function for sterile pgl-1 mutants restores their fertility. We propose that Piwi mutant sterility is a reproductive arrest phenotype that is characterized by perturbed germ granule structure and is phenocopied by germ granule dysfunction, independent of genomic instability.
A critical period of neuronal activity results in aberrant neurogenesis rewiring hippocampal circuitry in a mouse model of epilepsy
Authors: Lybrand Zane R. , Goswami Sonal , Zhu Jingfei , Jarzabek Veronica , Merlock Nikolas , Aktar Mahafuza , Smith Courtney , Zhang Ling , Varma Parul , Cho Kyung-Ok , Ge Shaoyu , Hsieh Jenny
Published: March 2021

In the mammalian hippocampus, adult-born granule cells (abGCs) contribute to the function of the dentate gyrus (DG). Disruption of the DG circuitry causes spontaneous recurrent seizures (SRS), which can lead to epilepsy. Although abGCs contribute to local inhibitory feedback circuitry, whether they are involved in epileptogenesis remains elusive. Here, we identify a critical window of activity associated with the aberrant maturation of abGCs characterized by abnormal dendrite morphology, ectopic migration, and SRS. Importantly, in a mouse model of temporal lobe epilepsy, silencing aberrant abGCs during this critical period reduces abnormal dendrite morphology, cell migration, and SRS. Using mono-synaptic tracers, we show silencing aberrant abGCs decreases recurrent CA3 back-projections and restores proper cortical connections to the hippocampus. Furthermore, we show that GABA-mediated amplification of intracellular calcium regulates the early critical period of activity. Our results demonstrate that aberrant neurogenesis rewires hippocampal circuitry aggravating epilepsy in mice.
A multiplexed, next generation sequencing platform for high-throughput detection of SARS-CoV-2
Authors: Aynaud Marie-Ming , Hernandez J. Javier , Barutcu Seda , Braunschweig Ulrich , Chan Kin , Pearson Joel D. , Trcka Daniel , Prosser Suzanna L. , Kim Jaeyoun , Barrios-Rodiles Miriam , Jen Mark , Song Siyuan , Shen Jess , Bruce Christine , Hazlett Bryn , Poutanen Susan , Attisano Liliana , Bremner Rod , Blencowe Benjamin J. , Mazzulli Tony , Han Hong , Pelletier Laurence , Wrana Jeffrey L.
Published: March 2021

Population scale sweeps of viral pathogens, such as SARS-CoV-2, require high intensity testing for effective management. Here, we describe “Systematic Parallel Analysis of RNA coupled to Sequencing for Covid-19 screening” (C19-SPAR-Seq), a multiplexed, scalable, readily automated platform for SARS-CoV-2 detection that is capable of analyzing tens of thousands of patient samples in a single run. To address strict requirements for control of assay parameters and output demanded by clinical diagnostics, we employ a control-based Precision-Recall and Receiver Operator Characteristics (coPR) analysis to assign run-specific quality control metrics. C19-SPAR-Seq coupled to coPR on a trial cohort of several hundred patients performs with a specificity of 100% and sensitivity of 91% on samples with low viral loads, and a sensitivity of >95% on high viral loads associated with disease onset and peak transmissibility. This study establishes the feasibility of employing C19-SPAR-Seq for the large-scale monitoring of SARS-CoV-2 and other pathogens.
Reversible thermal regulation for bifunctional dynamic control of gene expression in Escherichia coli
Authors: Wang Xuan , Han Jia-Ning , Zhang Xu , Ma Yue-Yuan , Lin Yina , Wang Huan , Li Dian-Jie , Zheng Tao-Ran , Wu Fu-Qing , Ye Jian-Wen , Chen Guo-Qiang
Published: March 2021

Genetically programmed circuits allowing bifunctional dynamic regulation of enzyme expression have far-reaching significances for various bio-manufactural purposes. However, building a bio-switch with a post log-phase response and reversibility during scale-up bioprocesses is still a challenge in metabolic engineering due to the lack of robustness. Here, we report a robust thermosensitive bio-switch that enables stringent bidirectional control of gene expression over time and levels in living cells. Based on the bio-switch, we obtain tree ring-like colonies with spatially distributed patterns and transformer cells shifting among spherical-, rod- and fiber-shapes of the engineered Escherichia coli. Moreover, fed-batch fermentations of recombinant E. coli are conducted to obtain ordered assembly of tailor-made biopolymers polyhydroxyalkanoates including diblock- and random-copolymer, composed of 3-hydroxybutyrate and 4-hydroxybutyrate with controllable monomer molar fraction. This study demonstrates the possibility of well-organized, chemosynthesis-like block polymerization on a molecular scale by reprogrammed microbes, exemplifying the versatility of thermo-response control for various practical uses.
Millimeter wave photonics with terahertz semiconductor lasers
Authors: Pistore Valentino , Nong Hanond , Vigneron Pierre-Baptiste , Garrasi Katia , Houver Sarah , Li Lianhe , Giles Davies A. , Linfield Edmund H. , Tignon Jerome , Mangeney Juliette , Colombelli Raffaele , Vitiello Miriam S. , Dhillon Sukhdeep S.
Published: March 2021

Millimeter wave (mmWave) generation using photonic techniques has so far been limited to the use of near-infrared lasers that are down-converted to the mmWave region. However, such methodologies do not currently benefit from a monolithic architecture and suffer from the quantum defect i.e. the difference in photon energies between the near-infrared and mmWave region, which can ultimately limit the conversion efficiency. Miniaturized terahertz (THz) quantum cascade lasers (QCLs) have inherent advantages in this respect: their low energy photons, ultrafast gain relaxation and high nonlinearities open up the possibility of innovatively integrating both laser action and mmWave generation in a single device. Here, we demonstrate intracavity mmWave generation within THz QCLs over the unprecedented range of 25 GHz to 500 GHz. Through ultrafast time resolved techniques, we highlight the importance of modal phases and that the process is a result of a giant second-order nonlinearity combined with a phase matched process between the THz and mmWave emission. Importantly, this work opens up the possibility of compact, low noise mmWave generation using modelocked THz frequency combs.
Current-induced switching of proximity-induced ferromagnetic surface states in a topological insulator
Authors: Mogi Masataka , Yasuda Kenji , Fujimura Reika , Yoshimi Ryutaro , Ogawa Naoki , Tsukazaki Atsushi , Kawamura Minoru , Takahashi Kei S. , Kawasaki Masashi , Tokura Yoshinori
Published: March 2021

Electrical manipulation of magnetization could be an essential function for energy-efficient spintronics technology. A magnetic topological insulator, possessing a magnetically gapped surface state with spin-polarized electrons, not only exhibits exotic topological phases relevant to the quantum anomalous Hall state but also enables the electrical control of its magnetic state at the surface. Here, we demonstrate efficient current-induced switching of the surface ferromagnetism in hetero-bilayers consisting of the topological insulator (Bi1-xSbx)2Te3 and the ferromagnetic insulator Cr2Ge2Te6, where the proximity-induced ferromagnetic surface states play two roles: efficient charge-to-spin current conversion and emergence of large anomalous Hall effect. The sign reversal of the surface ferromagnetic states with current injection is clearly observed, accompanying the nearly full magnetization reversal in the adjacent insulating Cr2Ge2Te6 layer of an optimal thickness range. The present results may facilitate an electrical control of dissipationless topological-current circuits.
Textured ferroelectric ceramics with high electromechanical coupling factors over a broad temperature range
Authors: Yang Shuai , Li Jinglei , Liu Yao , Wang Mingwen , Qiao Liao , Gao Xiangyu , Chang Yunfei , Du Hongliang , Xu Zhuo , Zhang Shujun , Li Fei
Published: March 2021

The figure-of-merits of ferroelectrics for transducer applications are their electromechanical coupling factor and the operable temperature range. Relaxor-PbTiO3ferroelectric crystals show a much improved electromechanical coupling factork33(88~93%) compared to their ceramic counterparts (65~78%) by taking advantage of the strong anisotropy of crystals. However, only a few relaxor-PbTiO3systems, for example Pb(In1/2Nb1/2)O3-Pb(Mg1/3Nb2/3)O3-PbTiO3, can be grown into single crystals, whose operable temperature range is limited by their rhombohedral-tetragonal phase transition temperatures (Trt: 60~120 °C). Here, we develop a templated grain-growth approach to fabricate <001>-textured Pb(In1/2Nb1/2)O3-Pb(Sc1/2Nb1/2)O3-PbTiO3(PIN-PSN-PT) ceramics that contain a large amount of the refractory component Sc2O3, which has the ability to increase theTrtof the system. The highk33of 85~89% and the greatly increasedTrtof 160~200 °C are simultaneously achieved in the textured PIN-PSN-PT ceramics. The above merits will make textured PIN-PSN-PT ceramics an alternative to single crystals, benefiting the development of numerous advanced piezoelectric devices.
Lipid regulation of hERG1 channel function
Authors: Miranda Williams E. , Guo Jiqing , Mesa-Galloso Haydee , Corradi Valentina , Lees-Miller James P. , Tieleman D. Peter , Duff Henry J. , Noskov Sergei Yu.
Published: March 2021

The lipid regulation of mammalian ion channel function has emerged as a fundamental mechanism in the control of electrical signalling and transport specificity in various cell types. In this work, we combine molecular dynamics simulations, mutagenesis, and electrophysiology to provide mechanistic insights into how lipophilic molecules (ceramide-sphingolipid probe) alter gating kinetics and K+ currents of hERG1. We show that the sphingolipid probe induced a significant left shift of activation voltage, faster deactivation rates, and current blockade comparable to traditional hERG1 blockers. Microseconds-long MD simulations followed by experimental mutagenesis elucidated ceramide specific binding locations at the interface between the pore and voltage sensing domains. This region constitutes a unique crevice present in mammalian channels with a non-swapped topology. The combined experimental and simulation data provide evidence for ceramide-induced allosteric modulation of the channel by a conformational selection mechanism.
Global profiling of distinct cysteine redox forms reveals wide-ranging redox regulation in C. elegans
Authors: Meng Jin , Fu Ling , Liu Keke , Tian Caiping , Wu Ziyun , Jung Youngeun , Ferreira Renan B. , Carroll Kate S. , Blackwell T. Keith , Yang Jing
Published: March 2021

Post-translational changes in the redox state of cysteine residues can rapidly and reversibly alter protein functions, thereby modulating biological processes. The nematode C. elegans is an ideal model organism for studying cysteine-mediated redox signaling at a network level. Here we present a comprehensive, quantitative, and site-specific profile of the intrinsic reactivity of the cysteinome in wild-type C. elegans. We also describe a global characterization of the C. elegans redoxome in which we measured changes in three major cysteine redox forms after H2O2 treatment. Our data revealed redox-sensitive events in translation, growth signaling, and stress response pathways, and identified redox-regulated cysteines that are important for signaling through the p38 MAP kinase (MAPK) pathway. Our in-depth proteomic dataset provides a molecular basis for understanding redox signaling in vivo, and will serve as a valuable and rich resource for the field of redox biology.
Pharmacological rescue in patient iPSC and mouse models with a rare DISC1 mutation
Authors: Kim Nam-Shik , Wen Zhexing , Liu Jing , Zhou Ying , Guo Ziyuan , Xu Chongchong , Lin Yu-Ting , Yoon Ki-Jun , Park Junhyun , Cho Michelle , Kim Minji , Wang Xinyuan , Yu Huimei , Sakamuru Srilatha , Christian Kimberly M. , Hsu Kuei-sen , Xia Menghang , Li Weidong , Ross Christopher A. , Margolis Russell L. , Lu Xin-Yun , Song Hongjun , Ming Guo-li
Published: March 2021

We previously identified a causal link between a rare patient mutation in DISC1 (disrupted-in-schizophrenia 1) and synaptic deficits in cortical neurons differentiated from isogenic patient-derived induced pluripotent stem cells (iPSCs). Here we find that transcripts related to phosphodiesterase 4 (PDE4) signaling are significantly elevated in human cortical neurons differentiated from iPSCs with the DISC1 mutation and that inhibition of PDE4 or activation of the cAMP signaling pathway functionally rescues synaptic deficits. We further generated a knock-in mouse line harboring the same patient mutation in the Disc1 gene. Heterozygous Disc1 mutant mice exhibit elevated levels of PDE4s and synaptic abnormalities in the brain, and social and cognitive behavioral deficits. Pharmacological inhibition of the PDE4 signaling pathway rescues these synaptic, social and cognitive behavioral abnormalities. Our study shows that patient-derived isogenic iPSC and humanized mouse disease models are integral and complementary for translational studies with a better understanding of underlying molecular mechanisms.
Momentarily trapped exciton polaron in two-dimensional lead halide perovskites
Authors: Tao Weijian , Zhang Chi , Zhou Qiaohui , Zhao Yida , Zhu Haiming
Published: March 2021

Two-dimensional (2D) lead halide perovskites with distinct excitonic feature have shown exciting potential for optoelectronic applications. Compared to their three-dimensional counterparts with large polaron character, how the interplay between long- and short- range exciton-phonon interaction due to polar and soft lattice define the excitons in 2D perovskites is yet to be revealed. Here, we seek to understand the nature of excitons in 2D CsPbBr3 perovskites by static and time-resolved spectroscopy which is further rationalized with Urbach-Martienssen rule. We show quantitatively an intermediate exciton-phonon coupling in 2D CsPbBr3 where exciton polarons are momentarily self-trapped by lattice vibrations. The 0.25 ps ultrafast interconversion between free and self-trapped exciton polaron with a barrier of ~ 34 meV gives rise to intrinsic asymmetric photoluminescence with a low energy tail at room temperature. This study reveals a complex and dynamic picture of exciton polarons in 2D perovskites and emphasizes the importance to regulate exciton-phonon coupling.
Practical verification protocols for analog quantum simulators
Authors: Shaffer Ryan , Megidish Eli , Broz Joseph , Chen Wei-Ting , Häffner Hartmut
Published: March 2021

Analog quantum simulation is expected to be a significant application of near-term quantum devices. Verification of these devices without comparison to known simulation results will be an important task as the system size grows beyond the regime that can be simulated classically. We introduce a set of experimentally-motivated verification protocols for analog quantum simulators, discussing their sensitivity to a variety of error sources and their scalability to larger system sizes. We demonstrate these protocols experimentally using a two-qubit trapped-ion analog quantum simulator and numerically using models of up to five qubits.
The quantum Hall effect in the absence of disorder
Authors: Kim Kyung-Su , Kivelson Steven A.
Published: March 2021

It is widely held that disorder is essential to the existence of a finite interval of magnetic field in which the Hall conductance is quantized, i.e., for the existence of “plateaus” in the quantum Hall effect. Here, we show that the existence of a quasi-particle Wigner crystal (QPWC) results in the persistence of plateaus of finite extent even in the limit of vanishing disorder. Several experimentally detectable features that characterize the behavior in the zero disorder limit are also explored.
Combined analysis of gestational diabetes and maternal weight status from pre-pregnancy through post-delivery in future development of type 2 diabetes
Authors: Chen Ling-Wei , Soh Shu E , Tint Mya-Thway , Loy See Ling , Yap Fabian , Tan Kok Hian , Lee Yung Seng , Shek Lynette Pei-Chi , Godfrey Keith M. , Gluckman Peter D. , Eriksson Johan G. , Chong Yap-Seng , Chan Shiao-Yng
Published: March 2021

We examined the associations of gestational diabetes mellitus (GDM) and women’s weight status from pre-pregnancy through post-delivery with the risk of developing dysglycaemia [impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes (T2D)] 4–6 years post-delivery. Using Poisson regression with confounder adjustments, we assessed associations of standard categorisations of prospectively ascertained pre-pregnancy overweight and obesity (OWOB), gestational weight gain (GWG) and substantial post-delivery weight retention (PDWR) with post-delivery dysglycaemia (n = 692). Women with GDM had a higher risk of later T2D [relative risk (95% CI) 12.07 (4.55, 32.02)] and dysglycaemia [3.02 (2.19, 4.16)] compared with non-GDM women. Independent of GDM, women with pre-pregnancy OWOB also had a higher risk of post-delivery dysglycaemia. Women with GDM who were OWOB pre-pregnancy and had subsequent PDWR (≥ 5 kg) had 2.38 times (1.29, 4.41) the risk of post-delivery dysglycaemia compared with pre-pregnancy lean GDM women without PDWR. No consistent associations were observed between GWG and later dysglycaemia risk. In conclusion, women with GDM have a higher risk of T2D 4–6 years after the index pregnancy. Pre-pregnancy OWOB and PDWR exacerbate the risk of post-delivery dysglycaemia. Weight management during preconception and post-delivery represent early windows of opportunity for improving long-term health, especially in those with GDM.
LINC00665 promotes the progression of acute myeloid leukemia by regulating the miR-4458/DOCK1 pathway
Authors: Yang Xiaoyu , Wang Yan , Pang Sulei , Li Xiaojie , Wang Panpan , Ma Ruojin , Ma Yunyun , Song Chunge
Published: March 2021

This study aimed to explore the role of LINC00665, miR-4458 and DOCK1 and their interactions in the development of acute myeloid leukemia (AML). The relative expression of LINC00665, miR-4458 and DOCK1 in AML samples was measured using qRT-PCR, and the protein level of DOCK1 in AML cell lines was examined using western blot. CCK8, BrdU, transwell, cell adhesion, and caspase-3 activity assays were carried out to evaluate the viability, proliferation, migration, adhesion, and apoptosis of AML cells, respectively. Luciferase reporter, RIP, and RNA pull-down assays were also performed to confirm the target relationship among LINC00665, miR-4458 and DOCK1. Findings revealed that LINC00665 and DOCK1 were aberrantly overexpressed in AML tissues and that the expression of miR-4458 was low in AML tissues. Silencing LINC00665 or DOCK1 presented significant restriction to the proliferation, migration and adhesion of AML cells. Apart from that, it was found that inhibiting miR-4458 could enhance the proliferation, migration and adhesion of AML cells but suppress the apoptosis of AML cells. Experimental results also indicated that LINC00665 exerted its positive function on AML cells by sponging miR-4458 and that miR-4458 influenced the progression of AML cells by targeting DOCK1 directly. Overall, this finding not only provided a novel molecular pathway for the diagnosis and treatment of AML but also showed that LINC00665 could enhance the progression of AML by regulating the miR-4458/DOCK1 pathway.
Quantitative conversion of biomass in giant DNA virus infection
Authors: Kördel Mikael , Svenda Martin , Reddy Hemanth K. N. , Fogelqvist Emelie , Arsana Komang G. Y. , Hamawandi Bejan , Toprak Muhammet S. , Hertz Hans M. , Sellberg Jonas A.
Published: March 2021

Bioconversion of organic materials is the foundation of many applications in chemical engineering, microbiology and biochemistry. Herein, we introduce a new methodology to quantitatively determine conversion of biomass in viral infections while simultaneously imaging morphological changes of the host cell. As proof of concept, the viral replication of an unidentified giant DNA virus and the cellular response of an amoebal host are studied using soft X-ray microscopy, titration dilution measurements and thermal gravimetric analysis. We find that virions produced inside the cell are visible from 18 h post infection and their numbers increase gradually to a burst size of 280–660 virions. Due to the large size of the virion and its strong X-ray absorption contrast, we estimate that the burst size corresponds to a conversion of 6–12% of carbonaceous biomass from amoebal host to virus. The occurrence of virion production correlates with the appearance of a possible viral factory and morphological changes in the phagosomes and contractile vacuole complex of the amoeba, whereas the nucleus and nucleolus appear unaffected throughout most of the replication cycle.
COVID-19: a simple statistical model for predicting intensive care unit load in exponential phases of the disease
Authors: Ritter Matthias , Ott Derek V. M. , Paul Friedemann , Haynes John-Dylan , Ritter Kerstin
Published: March 2021

One major bottleneck in the ongoing COVID-19 pandemic is the limited number of critical care beds. Due to the dynamic development of infections and the time lag between when patients are infected and when a proportion of them enters an intensive care unit (ICU), the need for future intensive care can easily be underestimated. To infer future ICU load from reported infections, we suggest a simple statistical model that (1) accounts for time lags and (2) allows for making predictions depending on different future growth of infections. We have evaluated our model for three heavily affected regions in Europe, namely Berlin (Germany), Lombardy (Italy), and Madrid (Spain). Before extensive containment measures made an impact, we first estimate the region-specific model parameters, namely ICU rate, time lag between infection, and ICU admission as well as length of stay in ICU. Whereas for Berlin, an ICU rate of 6%, a time lag of 6 days, and a stay of 12 days in ICU provide the best fit of the data, for Lombardy and Madrid the ICU rate was higher (18% and 15%) and the time lag (0 and 3 days) and the stay in ICU (3 and 8 days) shorter. The region-specific models are then used to predict future ICU load assuming either a continued exponential phase with varying growth rates (0–15%) or linear growth. By keeping the growth rates flexible, this model allows for taking into account the potential effect of diverse containment measures. Thus, the model can help to predict a potential exceedance of ICU capacity depending on future growth. A sensitivity analysis for an extended time period shows that the proposed model is particularly useful for exponential phases of the disease.
Habitat generalist species constrain the diversity of mimicry rings in heterogeneous habitats
Authors: Birskis-Barros Irina , Freitas André V. L. , Guimarães Paulo R.
Published: March 2021

How evolution creates and maintains trait patterns in species-rich communities is still an unsolved topic in evolutionary ecology. One classical example of community-level pattern is the unexpected coexistence of different mimicry rings, each of which is a group of mimetic species with the same warning signal. The coexistence of different mimicry rings in a community seems paradoxical because selection among unpalatable species should favor convergence to a single warning pattern. We combined mathematical modeling based on network theory and numerical simulations to explore how different types of selection, such as mimetic and environmental selections, and habitat use by mimetic species influence the formation of coexisting rings. We show that when habitat and mimicry are strong sources of selection, the formation of multiple rings takes longer due to conflicting selective pressures. Moreover, habitat generalist species decrease the distinctiveness of different mimicry rings’ patterns and a few habitat generalist species can generate a “small-world effect”, preventing the formation of multiple mimicry rings. These results may explain why the coexistence of mimicry rings is more common in groups of animals that tend towards habitat specialism, such as butterflies.
Clustering of cardio-metabolic risk factors and pre-diabetes among U.S. adolescents
Authors: Liu Chibo , Wu Susu , Pan Xiao
Published: March 2021

Few studies have assessed the association between clustering of cardio-metabolic risk factors (CMRFs) and pre-diabetes in children or adolescents. We aimed to examine the association between clustering of CMRFs and pre-diabetes among U.S. adolescents. Data were available for 5,633 U.S. adolescents aged 12–19 years from the National Health and Nutrition Examination Surveys 1999–2014. Pre-diabetes was defined as impaired fasting glucose (IFG) (fasting plasma glucose 100–125 mg/dL), impaired glucose tolerance (IGT) (2-h plasma glucose 140–199 mg/dL) or elevated hemoglobin A1c (HbA1c) (HbA1c 5.7–6.4%). The individual CMRFs considered in the present study were as follows: waist-to-height ratio, blood pressure, triglycerides, and high-density lipoprotein cholesterol. CMRFs were defined based on the modified National Cholesterol Education Program (NCEP) criteria or the modified International Diabetes Federation (IDF) criteria. Logistic regression analysis was used to examine the association between clustering of CMRFs and pre-diabetes with adjustment for potential covariates. Among 5633 adolescents, 11.4% had IFG, 4.7% had IGT, 4.5% had elevated HbA1c and 16.1% had pre-diabetes. Compared with adolescents with no CMRFs, the odds ratios (ORs) with 95% confidence intervals (CIs) for pre-diabetes across the clustering of CMRFs (i.e., 1, 2, 3, and 4) were 1.32 (1.03–1.68), 2.07 (1.55–2.76), 2.52 (1.69–3.76), and 5.41 (3.14–9.32), respectively, based on the modified NCEP criteria. The corresponding ORs with 95% CIs were 1.16 (0.89–1.51), 1.78 (1.35–2.36), 3.07 (1.89–4.98) and 12.20 (3.93–37.89), respectively, based on the modified IDF criteria. The present study suggests that the clustering of CMRFs is associated with increased pre-diabetes among U.S. adolescents. It might be necessary for effective strategies and measures targeting adolescents with clustering of CMRFs, including those with less than 3 risk factors.
Supramolecular assemblies of carbon nanocoils and tetraphenylporphyrin derivatives for sensing of catechol and hydroquinone in aqueous solution
Authors: Bukhari Syeda Aqsa Batool , Nasir Habib , Pan Lujun , Tasawar Mehroz , Sohail Manzar , Shahbaz Muhammad , Gul Fareha , Sitara Effat
Published: March 2021

Non-enzymatic electrochemical detection of catechol (CC) and hydroquinone (HQ), the xenobiotic pollutants, was carried out at the surface of novel carbon nanocoils/zinc-tetraphenylporphyrin (CNCs/Zn-TPP) nanocomposite supported on glassy carbon electrode. The synergistic effect of chemoresponsive activity of Zn-TPP and a large surface area and electron transfer ability of CNCs lead to efficient detection of CC and HQ. The nanocomposite was characterized by using FT-IR, UV/vis. spectrophotometer, SEM and energy dispersive X-ray spectroscopy (EDS). Cyclic voltammetry, differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy were used for the electrochemical studies. CNCs/Zn-TPP/GCE nanosensor displayed a limit of detection (LOD), limit of quantification (LOQ) and sensitivity for catechol as 0.9 µM, 3.1 µM and 0.48 µA µM−1 cm−2, respectively in a concentration range of 25–1500 µM. Similarly, a linear trend in the concentration of hydroquinone detection was observed between 25 and 1500 µM with an LOD, LOQ and sensitivity of 1.5 µM, 5.1 µM and 0.35 µA µM−1 cm−2, respectively. DPV of binary mixture pictured well resolved peaks with anodic peak potential difference, ∆Epa(CC-HQ),of 110 mV showing efficient sensing of CC and HQ. The developed nanosensor exhibits stability for up to 30 days, better selectivity and good repeatability for eight measurements (4.5% for CC and 5.4% for HQ).
Targeted peripheral focused ultrasound stimulation attenuates obesity-induced metabolic and inflammatory dysfunctions
Authors: Huerta Tomás S. , Devarajan Alex , Tsaava Tea , Rishi Arvind , Cotero Victoria , Puleo Christopher , Ashe Jeffrey , Coleman Thomas R. , Chang Eric H. , Tracey Kevin J. , Chavan Sangeeta S.
Published: March 2021

Obesity, a growing health concern, is associated with an increased risk of morbidity and mortality. Chronic low-grade inflammation is implicated in obesity-driven metabolic complications. Peripheral focused ultrasound stimulation (pFUS) is an emerging non-invasive technology that modulates inflammation. Here, we reasoned that focused ultrasound stimulation of the liver may alleviate obesity-related inflammation and other comorbidities. After 8 weeks on a high-fat high-carbohydrate “Western” diet, C57BL/6J mice were subjected to either sham stimulation or focused ultrasound stimulation at the porta hepatis. Daily liver-focused ultrasound stimulation for 8 weeks significantly decreased body weight, circulating lipids and mitigated dysregulation of adipokines. In addition, liver-focused ultrasound stimulation significantly reduced hepatic cytokine levels and leukocyte infiltration. Our findings demonstrate the efficacy of hepatic focused ultrasound for alleviating obesity and obesity-associated complications in mice. These findings suggest a previously unrecognized potential of hepatic focused ultrasound as a possible novel noninvasive approach in the context of obesity.
Composite of bentonite and cyclodextrin as an efficient catalyst for promoting chemical transformations in aqueous media
Authors: Koohestani Fatemeh , Sadjadi Samahe , Heravi Majid
Published: March 2021

Combining the encapsulating capability of cyclodextrin and instinctive features of bentonite clay, a versatile metal free catalyst has been developed that could promote various chemical reactions such as Knoevenagel condensation, synthesis of xanthan and octahydroquinazolinones in aqueous media under ultrasonic irradiation. To prepare the catalyst, bentonite was Cl-functionalized and then reacted with isatin and guanidine successively to furnish amino functionalized bentonite. The latter then reacted with tosylated cyclodextrin. The resultant catalytic composite was characterized via XRD, SEM, EDS, BET, elemental mapping analysis, TGA and FTIR. The catalytic activity tests approved excellent activity of the catalyst as well as broad substrate scope. Notably, the catalyst could be simply recovered and reused for several reaction runs. Moreover, the activity of the composite was superior to that of its components.
Photocrosslinking and photopatterning of magneto-optical nanocomposite sol–gel thin film under deep-UV irradiation
Authors: Bidaud C. , Berling D. , Jamon D. , Gamet E. , Neveu S. , Royer F. , Soppera O.
Published: March 2021

This paper is aimed at investigating the process of photocrosslinking under Deep-UV irradiation of nanocomposite thin films doped with cobalt ferrite magnetic nanoparticles (MNPs). This material is composed of a hybrid sol–gel matrix in which MNP can be introduced with high concentrations up to 20 vol%. Deep-UV (193 nm) is not only interesting for high-resolution patterning but we also show an efficient photopolymerization pathway even in the presence of high concentration of MNPs. In this study, we demonstrate that the photocrosslinking is based on the free radical polymerization of the methacrylate functions of the hybrid precursor. This process is initiated by Titanium-oxo clusters. The impact of the nanoparticles on the photopolymerization kinetic and photopatterning is investigated. We finally show that the photosensitive nanocomposite is suitable to obtain micropatterns with sub-micron resolution, with a simple and versatile process, which opens many opportunities for fabrication of miniaturized magneto-optical devices for photonic applications.
Initiating an epilepsy surgery program with limited resources in Indonesia
Authors: Thohar Arifin Muhamad , Hanaya Ryosuke , Bakhtiar Yuriz , Bintoro Aris Catur , Iida Koji , Kurisu Kaoru , Arita Kazunori , Bunyamin Jacob , Askoro Rofat , Brilliantika Surya Pratama , Khairunnisa Novita Ikbar , Muttaqin Zainal
Published: March 2021

To share the experiences of organizing the epilepsy surgery program in Indonesia. This study was divided into two periods based on the presurgical evaluation method: the first period (1999–2004), when interictal electroencephalogram (EEG) and magnetic resonance imaging (MRI) were used mainly for confirmation, and the second period (2005–2017), when long-term non-invasive and invasive video-EEG was involved in the evaluation. Long-term outcomes were recorded up to December 2019 based on the Engel scale. All 65 surgical recruits in the first period possessed temporal lobe epilepsy (TLE), while 524 patients were treated in the second period. In the first period, 76.8%, 16.1%, and 7.1% of patients with TLE achieved Classes I, II, and III, respectively, and in the second period, 89.4%, 5.5%, and 4.9% achieved Classes I, II, and III, respectively, alongside Class IV, at 0.3%. The overall median survival times for patients with focal impaired awareness seizures (FIAS), focal to bilateral tonic–clonic seizures and generalized tonic–clonic seizures were 9, 11 and 11 years (95% CI: 8.170–9.830, 10.170–11.830, and 7.265–14.735), respectively, with p = 0.04. The utilization of stringent and selective criteria to reserve surgeries is important for a successful epilepsy program with limited resources.
Variability of the nutrient stream near Kuroshio's origin
Authors: Chen Chen-Tung Arthur , Huang Ting-Hsuan , Wu Chi-Hsuan , Yang Haiyan , Guo Xinyu
Published: March 2021

The Kuroshio—literally “the Black Stream”—is the most substantial current in the Pacific Ocean. It was called the Black Stream because this oligotrophic current is so nutrient-poor in its euphotic zone that the water appears black without the influence of phytoplankton and the associated, often colored dissolved organic matter. Yet, below the euphotic layer, nutrient concentrations increase with depth while current speed declines. Consequently, a core of maximum nutrient flux, the so-called nutrient stream, develops at a depth of roughly between 200 and 800 m. This poorly studied nutrient stream transports nutrients to and supports high productivity and fisheries on the East China Sea continental shelf; it also transports nutrients to and promotes increased productivity and fisheries in the Kuroshio Extension and the subarctic Pacific Ocean. Three modes of the Kuroshio nutrient stream are detected off SE Taiwan for the first time: one has a single-core; one has two cores that are apparently separated by the ridge at 120.6–122° E, and one has two cores that are separated by a southward flow above the ridge. More importantly, northward nutrient transports seem to have been increasing since 2015 as a result of a 30% increase in subsurface water transport, which began in 2013. Such a nutrient stream supports the Kuroshio's high productivity, such as on the East China Sea continental shelf and in the Kuroshio Extension SE of Japan.
The role of volcanic-derived clays in the preservation of Ediacaran biota from the Itajaí Basin (ca. 563 Ma, Brazil)
Authors: Becker-Kerber Bruno , El Albani Abderrazak , Konhauser Kurt , Abd Elmola Ahmed , Fontaine Claude , Paim Paulo S. G. , Mazurier Arnaud , Prado Gustavo M. E. M. , Galante Douglas , Kerber Pedro B. , da Rosa Ana L. Z. , Fairchild Thomas R. , Meunier Alain , Pacheco Mírian L. A. F.
Published: March 2021

The early evolution of metazoans has been reconstructed by studies on exceptionally preserved molds in siliciclastic rocks from the Ediacaran Period. However, there remains considerable controversy regarding the formation mechanisms of this unusual ‘Ediacaran-style’ preservation. Proposed hypotheses usually include early authigenesis of minerals, but evidence for this is scarce. In a recently discovered deposit of Ediacaran biota in Brazil, we show that the classic moldic preservation is related to clay mineral authigenesis. Specifically, these clays originated from the alteration of original pyroclastic sediments, likely enhanced by microbial activity, leading to early illitization and morphological templating of the fossiliferous surfaces at a micrometric scale. Such high-fidelity preservation was made possible by rapid burial during volcanic events and the in-situ templating of tissue by clays via microbially-mediated mineralization. This newly described Lagerstätte demonstrates that a number of minerals can facilitate preservation, and that perhaps ‘Ediacaran-style’ preservation result from different processes leading to the same broad style of preservation.
Author Correction: Associations of mortality with own blood pressure using son’s blood pressure as an instrumental variable
Authors: Carslake David , Fraser Abigail , May Margaret T. , Palmer Tom , Silventoinen Karri , Tynelius Per , Lawlor Debbie A. , Davey Smith George
Published: March 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Mycobacterium abscessus biofilms have viscoelastic properties which may contribute to their recalcitrance in chronic pulmonary infections
Authors: Gloag Erin S. , Wozniak Daniel J. , Stoodley Paul , Hall-Stoodley Luanne
Published: March 2021

Mycobacterium abscessus is emerging as a cause of recalcitrant chronic pulmonary infections, particularly in people with cystic fibrosis (CF). Biofilm formation has been implicated in the pathology of this organism, however the role of biofilm formation in infection is unclear. Two colony-variants of M. abscessus are routinely isolated from CF samples, smooth (MaSm) and rough (MaRg). These two variants display distinct colony morphologies due to the presence (MaSm) or absence (MaRg) of cell wall glycopeptidolipids (GPLs). We hypothesized that MaSm and MaRg variant biofilms might have different mechanical properties. To test this hypothesis, we performed uniaxial mechanical indentation, and shear rheometry on MaSm and MaRg colony-biofilms. We identified that MaRg biofilms were significantly stiffer than MaSm under a normal force, while MaSm biofilms were more pliant compared to MaRg, under both normal and shear forces. Furthermore, using theoretical indices of mucociliary and cough clearance, we identified that M. abscessus biofilms may be more resistant to mechanical forms of clearance from the lung, compared to another common pulmonary pathogen, Pseudomonas aeruginosa. Thus, the mechanical properties of M. abscessus biofilms may contribute to the persistent nature of pulmonary infections caused by this organism.
Network structure-based decorated CPA@CuO hybrid nanocomposite for methyl orange environmental remediation
Authors: Katowah Dina F. , Saleh Sayed M. , Alqarni Sara A. , Ali Reham , Mohammed Gharam I. , Hussein Mahmoud A.
Published: March 2021

A unique network core–shell hybrid design-based cross-linked polyaniline (CPA), which was coated with CuO nanoparticles (NPs) and decorated with nitrogen-doped SWCNT/GO/cellulose N-SWCNTS-GO-CE, has been fabricated using the oxidative polymerization technique. This hybrid nanocomposite shows excellent photocatalytic degradation and an acceptable adsorption capability for Methyl Orange (MO) dye in aqueous solutions with a very slight effect for the N-SWCNTS-GO-CE CuO component. The prepared nanocomposites were used for the removal of a carcinogenic and noxious dye, Methyl Orange, from aqueous samples under various adsorption conditions. Approximately 100% degradation of 10 mg/L of Methylene orange dye was observed within 100 min at pH 6.0 using 50 mg/L CPA/N-SWCNTS-GO-CE/CuO nanocomposite under UV radiation. Additionally, significant factors were investigated on the degradation process including the contact time, MO initial concentration (Ci), solution pH, and dosage of the CuO nanocomposite. All investigated experiments were performed under UV radiation, which provided significant data for the MO degradation process. Furthermore, the recovery of the nanocomposite was studied based on the photocatalytic process efficiency. The obtained data provide the high opportunity of reusing CPA/N-SWCNTS-GO-CE/CuO nanocomposite for numerous photocatalytic processes. The CPA/N-SWCNTS-GO-CE/CuO nanocomposite was prepared via chemical oxidative copolymerization of polyaniline (PANI) with p-phenylenediamine (PPDA) and triphenylamine (TPA) in the presence of N-SWCNTS-GO-CE and CuO NPs. The morphology, structure and thermal properties of the CPA/N-SWCNTS-GO-CE/CuO nanocomposite were investigated using various techniques, including FTIR, XRD, RAMAN, SEM, MAP, EDX, TEM, TGA and DTG. Therefore, CPA/N-SWCNTS-GO-CE/CuO nanocomposite can be effectively used as a convenient and reusable adsorbent to remove hazardous dye from wastewater.
Reduced expression of innate immunity-related genes in lymph node metastases of luminal breast cancer patients
Authors: Popeda Marta , Markiewicz Aleksandra , Stokowy Tomasz , Szade Jolanta , Niemira Magdalena , Kretowski Adam , Bednarz-Knoll Natalia , Zaczek Anna J.
Published: March 2021

Immune system plays a dual role in cancer by either targeting or supporting neoplastic cells at various stages of disease, including metastasis. Yet, the exact immune-related transcriptome profiles of primary tumours (PT) and lymph node metastases (LNM) and their evolution during luminal breast cancer (BCa) dissemination remain undiscovered. In order to identify the immune-related transcriptome changes that accompany lymphatic spread, we analysed PT-LNM pairs of luminal BCa using NanoString technology. Decrease in complement C3—one of the top-downregulated genes, in LNM was validated at the protein level using immunohistochemistry. Thirty-three of 360 analysed genes were downregulated (9%), whereas only 3 (0.8%) upregulated in LNM when compared to the corresponding PT. In LNM, reduced expression was observed in genes related to innate immunity, particularly to the complement system (C1QB,C1S,C1R,C4B,CFB,C3,SERPING1andC3AR1). In validation cohort, complement C3 protein was less frequently expressed in LNM than in PT and it was associated with worse prognosis. To conclude, local expression of the complement system components declines during lymphatic spread of non-metastatic luminal BCa, whilst further reduction of tumoral complement C3 in LNM is indicative for poor survival. This points to context-dependent role of complement C3 in BCa dissemination.
Human molecular evolutionary rate, time dependency and transient polymorphism effects viewed through ancient and modern mitochondrial DNA genomes
Authors: Cabrera Vicente M.
Published: March 2021

Human evolutionary genetics gives a chronological framework to interpret the human history. It is based on the molecular clock hypothesis that suppose a straightforward relationship between the mutation rate and the substitution rate with independence of other factors as demography dynamics. Analyzing ancient and modern human complete mitochondrial genomes we show here that, along the time, the substitution rate can be significantly slower or faster than the average germline mutation rate confirming a time dependence effect mainly attributable to changes in the effective population size of the human populations, with an exponential growth in recent times. We also detect that transient polymorphisms play a slowdown role in the evolutionary rate deduced from haplogroup intraspecific trees. Finally, we propose the use of the most divergent lineages within haplogroups as a practical approach to correct these molecular clock mismatches.