bluuebunny/crossref_metadata_2025 huggingface dataset:
Auxin-mediated protein depletion for metabolic engineering in terpene-producing yeast
Authors: Lu Zeyu , Peng Bingyin , Ebert Birgitta E. , Dumsday Geoff , Vickers Claudia E.
Published: February 2021

In metabolic engineering, loss-of-function experiments are used to understand and optimise metabolism. A conditional gene inactivation tool is required when gene deletion is lethal or detrimental to growth. Here, we exploit auxin-inducible protein degradation as a metabolic engineering approach in yeast. We demonstrate its effectiveness using terpenoid production. First, we target an essential prenyl-pyrophosphate metabolism protein, farnesyl pyrophosphate synthase (Erg20p). Degradation successfully redirects metabolic flux toward monoterpene (C10) production. Second, depleting hexokinase-2, a key protein in glucose signalling transduction, lifts glucose repression and boosts production of sesquiterpene (C15) nerolidol to 3.5 g L−1 in flask cultivation. Third, depleting acetyl-CoA carboxylase (Acc1p), another essential protein, delivers growth arrest without diminishing production capacity in nerolidol-producing yeast, providing a strategy to decouple growth and production. These studies demonstrate auxin-mediated protein degradation as an advanced tool for metabolic engineering. It also has potential for broader metabolic perturbation studies to better understand metabolism.
Analysis of metagenome-assembled viral genomes from the human gut reveals diverse putative CrAss-like phages with unique genomic features
Authors: Yutin Natalya , Benler Sean , Shmakov Sergei A. , Wolf Yuri I. , Tolstoy Igor , Rayko Mike , Antipov Dmitry , Pevzner Pavel A. , Koonin Eugene V.
Published: February 2021

CrAssphage is the most abundant human-associated virus and the founding member of a large group of bacteriophages, discovered in animal-associated and environmental metagenomes, that infect bacteria of the phylum Bacteroidetes. We analyze 4907 Circular Metagenome Assembled Genomes (cMAGs) of putative viruses from human gut microbiomes and identify nearly 600 genomes of crAss-like phages that account for nearly 87% of the DNA reads mapped to these cMAGs. Phylogenetic analysis of conserved genes demonstrates the monophyly of crAss-like phages, a putative virus order, and of 5 branches, potential families within that order, two of which have not been identified previously. The phage genomes in one of these families are almost twofold larger than the crAssphage genome (145-192 kilobases), with high density of self-splicing introns and inteins. Many crAss-like phages encode suppressor tRNAs that enable read-through of UGA or UAG stop-codons, mostly, in late phage genes. A distinct feature of the crAss-like phages is the recurrent switch of the phage DNA polymerase type between A and B families. Thus, comparative genomic analysis of the expanded assemblage of crAss-like phages reveals aspects of genome architecture and expression as well as phage biology that were not apparent from the previous work on phage genomics.
Observed Antarctic sea ice expansion reproduced in a climate model after correcting biases in sea ice drift velocity
Authors: Sun Shantong , Eisenman Ian
Published: February 2021

The Antarctic sea ice area expanded significantly during 1979–2015. This is at odds with state-of-the-art climate models, which typically simulate a receding Antarctic sea ice cover in response to increasing greenhouse forcing. Here, we investigate the hypothesis that this discrepancy between models and observations occurs due to simulation biases in the sea ice drift velocity. As a control we use the Community Earth System Model (CESM) Large Ensemble, which has 40 realizations of past and future climate change that all undergo Antarctic sea ice retreat during recent decades. We modify CESM to replace the simulated sea ice velocity field with a satellite-derived estimate of the observed sea ice motion, and we simulate 3 realizations of recent climate change. We find that the Antarctic sea ice expands in all 3 of these realizations, with the simulated spatial structure of the expansion bearing resemblance to observations. The results suggest that the reason CESM has failed to capture the observed Antarctic sea ice expansion is due to simulation biases in the sea ice drift velocity, implying that an improved representation of sea ice motion is crucial for more accurate sea ice projections.
Author Correction: Crossover between the adiabatic and nonadiabatic electron transfer limits in the Landau-Zener model
Authors: Zhu Guang Yuan , Qin Yi , Meng Miao , Mallick Suman , Gao Hang , Chen Xiaoli , Cheng Tao , Tan Ying Ning , Xiao Xuan , Han Mei Juan , Sun Mei Fang , Liu Chun Y.
Published: February 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21530-8
Author Correction: Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder
Authors: Demontis Ditte , Walters Raymond K. , Rajagopal Veera M. , Waldman Irwin D. , Grove Jakob , Als Thomas D. , Dalsgaard Søren , Ribasés Marta , Bybjerg-Grauholm Jonas , Bækvad-Hansen Maria , Werge Thomas , Nordentoft Merete , Mors Ole , Mortensen Preben Bo ,   ADHD Working Group of the Psychiatric Genomics Consortium (PGC), Andreassen Ole A. , Arranz Maria Jesús , Banaschewski Tobias , Bau Claiton , Bellgrove Mark , Biederman Joseph , Brikell Isabell , Buitelaar Jan K. , Burton Christie L. , Casas Miguel , Crosbie Jennifer , Doyle Alysa E. , Ebstein Richard P. , Elia Josephine , Elizabeth Corfield C. , Grevet Eugenio , Grizenko Natalie , Havdahl Alexandra , Hawi Ziarih , Hebebrand Johannes , Hervas Amaia , Hohmann Sarah , Haavik Jan , Joober Ridha , Kent Lindsey , Kuntsi Jonna , Langley Kate , Larsson Henrik , Lesch Klaus-Peter , Leung Patrick W. L. , Liao Calwing , Loo Sandra K. , Martin Joanna , Martin Nicholas G. , Medland Sarah E. , Miranda Ana , Mota Nina Roth , Oades Robert D. , Ramos-Quiroga Josep Antoni , Reif Andreas , Rietschel Marcella , Roeyers Herbert , Rohde Luis Augusto , Rothenberger Aribert , Rovira Paula , Sánchez-Mora Cristina , Schachar Russell James , Sengupta Sarojini , Artigas Maria Soler , Steinhausen Hans-Christoph , Thapar Anita , Witt Stephanie H. , Yang Li , Zayats Tetyana , Zhang-James Yanli , Cormand Bru , Hougaard David M. , Neale Benjamin M. , Franke Barbara , Faraone Stephen V. , Børglum Anders D.
Published: February 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21566-w
“Hot cross bun” is a potential imaging marker for the severity of cerebellar ataxia in MSA-C
Authors: Zhu Shuzhen , Deng Bin , Huang Zifeng , Chang Zihan , Li Hualin , Liu Hui , Huang Yanjun , Pan Ying , Wang Yanping , Chao Yin-Xia , Chan Ling-Ling , Wu Yih-Ru , Tan Eng-King , Wang Qing
Published: February 2021

To evaluate the correlation between “hot cross bun” sign (HCBs) and disease severity in multiple system atrophy (MSA). We recruited patients with probable and possible MSA with parkinsonism (MSA-P) or the cerebellar ataxia (MSA-C) subtypes. Clinical and imaging characteristics were collected and comparison was performed between MSA-C and MSA-P cases. Spearman test was used to evaluate the correlation between HCBs and other variables. Curve estimate and general linear regression was performed to evaluate the relationship between HCBs and the Scale for Assessment and Rating of Ataxia (SARA). Unified Multiple System Atrophy Rating Scale (UMSARS) IV was used to assess the severity of disease. Multinomial ordered logistic regression was used to confirm the increased likelihood of disability for the disease. Eighty-one MSA with HCBs comprising of 50 MSA-C and 31 MSA-P were recruited. We demonstrated that the severity of HCBs showed a positive linear correlation with SARA scores in MSA-C. Multinomial ordered logistic regression test revealed that the increase in the HCBs grade may be associated with an increased likelihood of disability for the disease severity in MSA, especially in those with cerebellar ataxia subtype. We demonstrated that HCBs is a potential imaging marker for the severity of cerebellar ataxia. The increase in the HCBs grade may be associated with an increased likelihood of disability in MSA-C, but not MSA-P cases, suggesting that it may be a useful imaging indicator for disease progression in Chinese patients with MSA-C.
Anneal-path correction in flux qubits
Authors: Khezri Mostafa , Grover Jeffrey A. , Basham James I. , Disseler Steven M. , Chen Huo , Novikov Sergey , Zick Kenneth M. , Lidar Daniel A.
Published: February 2021

Quantum annealers require accurate control and optimized operation schemes to reduce noise levels, in order to eventually demonstrate a computational advantage over classical algorithms. We study a high coherence four-junction capacitively shunted flux qubit (CSFQ), using dispersive measurements to extract system parameters and model the device. Josephson junction asymmetry inherent to the device causes a deleterious nonlinear cross-talk when annealing the qubit. We implement a nonlinear annealing path to correct the asymmetry in situ, resulting in a substantial increase in the probability of the qubit being in the correct state given an applied flux bias. We also confirm the multi-level structure of our CSFQ circuit model by annealing it through small spectral gaps and observing quantum signatures of energy level crossings. Our results demonstrate an anneal-path correction scheme designed and implemented to improve control accuracy for high-coherence and high-control quantum annealers, which leads to an enhancement of success probability in annealing protocols.
Mapping drug-target interactions and synergy in multi-molecular therapeutics for pressure-overload cardiac hypertrophy
Authors: Rai Aparna , Kumar Vikas , Jerath Gaurav , Kartha C. C. , Ramakrishnan Vibin
Published: February 2021

Advancements in systems biology have resulted in the development of network pharmacology, leading to a paradigm shift from “one-target, one-drug” to “target-network, multi-component therapeutics”. We employ a chimeric approach involving in-vivo assays, gene expression analysis, cheminformatics, and network biology to deduce the regulatory actions of a multi-constituent Ayurvedic concoction, Amalaki Rasayana (AR) in animal models for its effect in pressure-overload cardiac hypertrophy. The proteomics analysis of in-vivo assays for Aorta Constricted and Biologically Aged rat models identify proteins expressed under each condition. Network analysis mapping protein–protein interactions and synergistic actions of AR using multi-component networks reveal drug targets such as ACADM, COX4I1, COX6B1, HBB, MYH14, and SLC25A4, as potential pharmacological co-targets for cardiac hypertrophy. Further, five out of eighteen AR constituents potentially target these proteins. We propose a distinct prospective strategy for the discovery of network pharmacological therapies and repositioning of existing drug molecules for treating pressure-overload cardiac hypertrophy.
Data centre water consumption
Authors: Mytton David
Published: February 2021

The information communication technology sector will experience huge growth over the coming years, with 29.3 billion devices expected online by 2030, up from 18.4 billion in 2018. To reliably support the online services used by these billions of users, data centres have been built around the world to provide the millions of servers they contain with access to power, cooling and internet connectivity. Whilst the energy consumption of these facilities regularly receives mainstream and academic coverage, analysis of their water consumption is scarce. Data centres consume water directly for cooling, in some cases 57% sourced from potable water, and indirectly through the water requirements of non-renewable electricity generation. Although in the USA, data centre water consumption (1.7 billion litres/day) is small compared to total water consumption (1218 billion litres/day), there are issues of transparency with less than a third of data centre operators measuring water consumption. This paper examines the water consumption of data centres, the measurement of that consumption, highlights the lack of data available to assess water efficiency, and discusses and where the industry is going in attempts to reduce future consumption.
Monitoring socio-climatic interactions to prioritise drinking water interventions in rural Africa
Authors: Armstrong Andrew , Hope Robert , Munday Callum
Published: February 2021

Rainfall variability and socioeconomic shocks pose a revenue risk for drinking water services in rural Africa. We examine the year-on-year and seasonal relationship between rainfall and remotely monitored water usage from rural piped schemes in four sub-Saharan countries to identify patterns that warn of a threat to operational sustainability. Continuous monitoring of socio-climatic interactions can reveal distributions and magnitudes of risk and guide policy action to safeguard rural water services.
Total Ortholog Median Matrix as an alternative unsupervised approach for phylogenomics based on evolutionary distance between protein coding genes
Authors: Maruyama Sandra Regina , Rogerio Luana Aparecida , Freitas Patricia Domingues , Teixeira Marta Maria Geraldes , Ribeiro José Marcos Chaves
Published: February 2021

The increasing number of available genomic data allowed the development of phylogenomic analytical tools. Current methods compile information from single gene phylogenies, whether based on topologies or multiple sequence alignments. Generally, phylogenomic analyses elect gene families or genomic regions to construct phylogenomic trees. Here, we presented an alternative approach for Phylogenomics, named TOMM (Total Ortholog Median Matrix), to construct a representative phylogram composed by amino acid distance measures of all pairwise ortholog protein sequence pairs from desired species inside a group of organisms. The procedure is divided two main steps, (1) ortholog detection and (2) creation of a matrix with the median amino acid distance measures of all pairwise orthologous sequences. We tested this approach within three different group of organisms: Kinetoplastida protozoa, hematophagous Diptera vectors and Primates. Our approach was robust and efficacious to reconstruct the phylogenetic relationships for the three groups. Moreover, novel branch topologies could be achieved, providing insights about some phylogenetic relationships between some taxa.
High throughput error correction in information reconciliation for semiconductor superlattice secure key distribution
Authors: Xie Jianguo , Wu Han , Xia Chao , Ding Peng , Song Helun , Xu Liwei , Chen Xiaoming
Published: February 2021

Semiconductor superlattice secure key distribution (SSL-SKD) has been experimentally demonstrated to be a novel scheme to generate and agree on the identical key in unconditional security just by public channel. The error correction in the information reconciliation procedure is introduced to eliminate the inevitable differences of analog systems in SSL-SKD. Nevertheless, the error correction has been proved to be the performance bottleneck of information reconciliation for high computational complexity. Hence, it determines the final secure key throughput of SSL-SKD. In this paper, different frequently-used error correction codes, including BCH codes, LDPC codes, and Polar codes, are optimized separately to raise the performance, making them usable in practice. Firstly, we perform multi-threading to support multi-codeword decoding for BCH codes and Polar codes and updated value calculation for LDPC codes. Additionally, we construct lookup tables to reduce redundant calculations, such as logarithmic table and antilogarithmic table for finite field computation. Our experimental results reveal that our proposed optimization methods can significantly promote the efficiency of SSL-SKD, and three error correction codes can reach the throughput of Mbps and provide a minimum secure key rate of 99%.
The miRNA199a/SIRT1/P300/Yy1/sST2 signaling axis regulates adverse cardiac remodeling following MI
Authors: Asensio-Lopez Maria Carmen , Sassi Yassine , Soler Fernando , Fernandez del Palacio Maria Josefa , Pascual-Figal Domingo , Lax Antonio
Published: February 2021

Left ventricular remodeling following myocardial infarction (MI) is related to adverse outcome. It has been shown that an up-regulation of plasma soluble ST2 (sST2) levels are associated with lower pre-discharge left ventricular (LV) ejection fraction, adverse cardiovascular outcomes and mortality outcome after MI. The mechanisms involved in its modulation are unknown and there is not specific treatment capable of lowering plasma sST2 levels in acute-stage HF. We recently identified Yin-yang 1 (Yy1) as a transcription factor related to circulating soluble ST2 isoform (sST2) expression in infarcted myocardium. However, the underlying mechanisms involved in this process have not been thoroughly elucidated. This study aimed to evaluate the pathophysiological implication of miR-199a-5p in cardiac remodeling and the expression of the soluble ST2 isoform. Myocardial infarction (MI) was induced by permanent ligation of the left anterior coronary artery in C57BL6/J mice that randomly received antimiR199a therapy, antimiR-Ctrl or saline. A model of biomechanical stretching was also used to characterize the underlying mechanisms involved in the activation of Yy1/sST2 axis. Our results show that the significant upregulation of miR-199a-5p after myocardial infarction increases pathological cardiac hypertrophy by upregulating circulating soluble sST2 levels. AntimiR199a therapy up-regulates Sirt1 and inactivates the co-activator P300 protein, thus leading to Yy1 inhibition which decreases both expression and release of circulating sST2 by cardiomyocytes after myocardial infarction. Pharmacological inhibition of miR-199a rescues cardiac hypertrophy and heart failure in mice, offering a potential therapeutic approach for cardiac failure.
Effects of long-acting, broad spectra anthelmintic treatments on the rumen microbial community compositions of grazing sheep
Authors: Moon Christina D. , Carvalho Luis , Kirk Michelle R. , McCulloch Alan F. , Kittelmann Sandra , Young Wayne , Janssen Peter H. , Leathwick Dave M.
Published: February 2021

Anthelmintic treatment of adult ewes is widely practiced to remove parasite burdens in the expectation of increased ruminant productivity. However, the broad activity spectra of many anthelmintic compounds raises the possibility of impacts on the rumen microbiota. To investigate this, 300 grazing ewes were allocated to treatment groups that included a 100-day controlled release capsule (CRC) containing albendazole and abamectin, a long-acting moxidectin injection (LAI), and a non-treated control group (CON). Rumen bacterial, archaeal and protozoal communities at day 0 were analysed to identify 36 sheep per treatment with similar starting compositions. Microbiota profiles, including those for the rumen fungi, were then generated for the selected sheep at days 0, 35 and 77. The CRC treatment significantly impacted the archaeal community, and was associated with increased relative abundances of Methanobrevibacter ruminantium, Methanosphaera sp. ISO3-F5, and Methanomassiliicoccaceae Group 12 sp. ISO4-H5 compared to the control group. In contrast, the LAI treatment increased the relative abundances of members of the Veillonellaceae and resulted in minor changes to the bacterial and fungal communities by day 77. Overall, the anthelmintic treatments resulted in few, but highly significant, changes to the rumen microbiota composition.
Regulation of shrimp prophenoloxidase activating system by lva-miR-4850 during bacterial infection
Authors: Boonchuen Pakpoom , Jaree Phattarunda , Somboonviwat Kulwadee , Somboonwiwat Kunlaya
Published: February 2021

MicroRNAs (miRNAs) suppress gene expression and regulate biological processes. Following small RNA sequencing, shrimp hemocytes miRNAs differentially expressed in response to acute hepatopancreatic necrosis disease (AHPND) caused by Vibrio parahaemolyticus (VPAHPND) were discovered and some were confirmed by qRT-PCR. VPAHPND-responsive miRNAs were predicted to target several genes in various immune pathways. Among them, lva-miR-4850 is of interest because its predicted target mRNAs are two important genes of the proPO system; proPO2 (PO2) and proPO activating factor 2 (PPAF2). The expression of lva-miR-4850 was significantly decreased after VPAHPND infection, whereas those of the target mRNAs, PO2 and PPAF2, and PO activity were significantly upregulated. Introducing the lva-miR-4850 mimic into VPAHPND-infected shrimps caused a reduction in the PO2 and PPAF2 transcript levels and the PO activity, but significantly increased the number of bacteria in the VPAHPND targeted tissues. This result inferred that lva-miR-4850 plays a crucial role in regulating the proPO system via suppressing expression of PPAF2 and PO2. To fight against VPAHPND infection, shrimp downregulated lva-miR-4850 expression resulted in proPO activation.
Probing the structure–function relationship with neural networks constructed by solving a system of linear equations
Authors: Mininni Camilo J. , Zanutto B. Silvano
Published: February 2021

Neural network models are an invaluable tool to understand brain function since they allow us to connect the cellular and circuit levels with behaviour. Neural networks usually comprise a huge number of parameters, which must be chosen carefully such that networks reproduce anatomical, behavioural, and neurophysiological data. These parameters are usually fitted with off-the-shelf optimization algorithms that iteratively change network parameters and simulate the network to evaluate its performance and improve fitting. Here we propose to invert the fitting process by proceeding from the network dynamics towards network parameters. Firing state transitions are chosen according to the transition graph associated with the solution of a task. Then, a system of linear equations is constructed from the network firing states and membrane potentials, in a way that guarantees the consistency of the system. This allows us to uncouple the dynamical features of the model, like its neurons firing rate and correlation, from the structural features, and the task-solving algorithm implemented by the network. We employed our method to probe the structure–function relationship in a sequence memory task. The networks obtained showed connectivity and firing statistics that recapitulated experimental observations. We argue that the proposed method is a complementary and needed alternative to the way neural networks are constructed to model brain function.
ABCC6 deficiency promotes dyslipidemia and atherosclerosis
Authors: Brampton Christopher , Pomozi Viola , Chen Li-Hsieh , Apana Ailea , McCurdy Sara , Zoll Janna , Boisvert William A. , Lambert Gilles , Henrion Daniel , Blanchard Simon , Kuo Sheree , Leftheriotis Georges , Martin Ludovic , Le Saux Olivier
Published: February 2021

ABCC6 deficiency promotes ectopic calcification; however, circumstantial evidence suggested that ABCC6 may also influence atherosclerosis. The present study addressed the role of ABCC6 in atherosclerosis using Ldlr−/− mice and pseudoxanthoma elasticum (PXE) patients. Mice lacking the Abcc6 and Ldlr genes were fed an atherogenic diet for 16 weeks before intimal calcification, aortic plaque formation and lipoprotein profile were evaluated. Cholesterol efflux and the expression of several inflammation, atherosclerosis and cholesterol homeostasis-related genes were also determined in murine liver and bone marrow-derived macrophages. Furthermore, we examined plasma lipoproteins, vascular calcification, carotid intima-media thickness and atherosclerosis in a cohort of PXE patients with ABCC6 mutations and compared results to dysmetabolic subjects with increased cardiovascular risk. We found that ABCC6 deficiency causes changes in lipoproteins, with decreased HDL cholesterol in both mice and humans, and induces atherosclerosis. However, we found that the absence of ABCC6 does not influence overall vascular mineralization induced with atherosclerosis. Decreased cholesterol efflux from macrophage cells and other molecular changes such as increased pro-inflammation seen in both humans and mice are likely contributors for the phenotype. However, it is likely that other cellular and/or molecular mechanisms are involved. Our study showed a novel physiological role for ABCC6, influencing plasma lipoproteins and atherosclerosis in a haploinsufficient manner, with significant penetrance.
Embossed topographic depolarisation maps of biological tissues with different morphological structures
Authors: Ushenko Volodimir A. , Hogan Benjamin T. , Dubolazov Alexander , Grechina Anastasiia V. , Boronikhina Tatiana V. , Gorsky Mikhailo , Ushenko Alexander G. , Ushenko Yurii O. , Bykov Alexander , Meglinski Igor
Published: February 2021

Layered topographic maps of the depolarisation due to diffuse biological tissues are produced using a polarisation-holographic Mueller matrix method approach. Histological sections of myocardial tissue with a spatially structured optically anisotropic fibrillar network, and parenchymal liver tissue with a polycrystalline island structure are successfully mapped. The topography of the myocardium maps relates to the scattering multiplicity within the volume and the specific morphological structures of the biological crystallite networks. The overall depolarisation map is a convolution of the effects of these two factors. Parenchymal liver tissues behave broadly similarly, but the different biological structures present cause the degree of scattering multiplicity to increase more rapidly with increasing phase. Through statistical analysis, the dependences of the magnitudes of the first to fourth order statistical moments are determined. These moments characterise the changing distributions of the depolarisation values through the volume of biological tissues with different morphological structures. Parenchymal liver tissue depolarisation maps are characterised by larger mean and variance, and less skewness and kurtosis, compared to the distributions for the myocardium. This work demonstrates that a polarisation-holographic Mueller matrix method can be applied to the assessment of the 3D morphology of biological tissues, with applications in disease diagnosis.
Retraction Note: Electrochemical Sensor for Detection of miRs Based on the Differential Effect of Competitive Structures in The p19 Function
Authors: Ghazizadeh E. , Oskuee R. K. , Jaafari M. R. , Hosseinkhani S.
Published: February 2021

Editor's Note: this Article has been retracted; the Retraction Note is available at https://doi.org/10.1038/s41598-021-83097-0.
De novo assembly and characterization of the first draft genome of quince (Cydonia oblonga Mill.)
Authors: Soyturk Aysenur , Sen Fatima , Uncu Ali Tevfik , Celik Ibrahim , Uncu Ayse Ozgur
Published: February 2021

Quince (Cydonia oblonga Mill.) is the sole member of the genus Cydonia in the Rosacea family and closely related to the major pome fruits, apple (Malus domestica Borkh.) and pear (Pyrus communis L.). In the present work, whole genome shotgun paired-end sequencing was employed in order to assemble the first draft genome of quince. A genome assembly that spans 488.4 Mb of sequence corresponding to 71.2% of the estimated genome size (686 Mb) was produced in the study. Gene predictions via ab initio and homology-based sequence annotation strategies resulted in the identification of 25,428 and 30,684 unique putative protein coding genes, respectively. 97.4 and 95.6% of putative homologs of Arabidopsis and rice transcription factors were identified in the ab initio predicted genic sequences. Different machine learning algorithms were tested for classifying pre-miRNA (precursor microRNA) coding sequences, identifying Support Vector Machine (SVM) as the best performing classifier. SVM classification predicted 600 putative pre-miRNA coding loci. Repetitive DNA content of the assembly was also characterized. The first draft assembly of the quince genome produced in this work would constitute a foundation for functional genomic research in quince toward dissecting the genetic basis of important traits and performing genomics-assisted breeding.
Depot medroxyprogesterone acetate (DMPA) enhances susceptibility and increases the window of vulnerability to HIV-1 in humanized mice
Authors: Wessels Jocelyn M. , Nguyen Philip V. , Vitali Danielle , Mueller Kristen , Vahedi Fatemeh , Felker Allison M. , Dupont Haley A. , Bagri Puja , Verschoor Chris P. , Deshiere Alexandre , Mazzulli Tony , Tremblay Michel J. , Ashkar Ali A. , Kaushic Charu
Published: February 2021

The progestin-based hormonal contraceptive Depot Medroxyprogesterone Acetate (DMPA) is widely used in sub-Saharan Africa, where HIV-1 is endemic. Meta-analyses have shown that women using DMPA are 40% more likely than women not using hormonal contraceptives to acquire Human Immunodeficiency Virus (HIV-1). Therefore understanding how DMPA increases susceptibility to HIV-1 is an important public health issue. Using C57BL/6 mice and our previously optimized humanized mouse model (NOD-Rag1tm1Mom Il2rgtm1Wjl transplanted with hCD34-enriched hematopoietic stem cells; Hu-mice) where peripheral blood and tissues are reconstituted by human immune cells, we assessed how DMPA affected mucosal barrier function, HIV-1 susceptibility, viral titres, and target cells compared to mice in the diestrus phase of the estrous cycle, when endogenous progesterone is highest. We found that DMPA enhanced FITC-dextran dye leakage from the vaginal tract into the systemic circulation, enhanced target cells (hCD68+ macrophages, hCD4+ T cells) in the vaginal tract and peripheral blood (hCD45+hCD3+hCD4+hCCR5+ T cells), increased the rate of intravaginal HIV-1 infection, extended the window of vulnerability, and lowered vaginal viral titres following infection. These findings suggest DMPA may enhance susceptibility to HIV-1 in Hu-mice by impairing the vaginal epithelial barrier, increasing vaginal target cells (including macrophages), and extending the period of time during which Hu-mice are susceptible to infection; mechanisms that might also affect HIV-1 susceptibility in women.
Movement behavior of a solitary large carnivore within a hotspot of human-wildlife conflicts in India
Authors: Naha Dipanjan , Dash Suraj Kumar , Kupferman Caitlin , Beasley James C. , Sathyakumar Sambandam
Published: February 2021

With a rise in human induced changes to natural habitats, large predators are forced to share space and resources with people to coexist within multiple-use landscapes. Within such shared landscapes, co-occurrence of humans and predators often leads to human-carnivore conflicts and pose a substantial challenge for biodiversity conservation. To better elucidate large carnivore space use within a hotspot of human-wildlife conflicts, we used GPS data for leopards (N = 6) to identify behavioral states and document spatial patterns of resource selection in response to season and human activity periods within a fragmented landscape of North Bengal, eastern India. We identified two major behavioral states (i.e. resting and travelling). From the resource selection models, we found leopards selected habitats with dense to moderate vegetation cover and proximity to water while resting and travelling within the landscape. During the dry season, when risk of human-leopard conflicts is highest, leopards selected tea plantations, forest patches but avoided protected areas. These results suggest a potential for increase in human-carnivore conflicts and a strategy to conserve large predators within multiple-use landscapes of South Asia.
Non-invasive diffuse optical neuromonitoring during cardiopulmonary resuscitation predicts return of spontaneous circulation
Authors: Ko Tiffany S. , Mavroudis Constantine D. , Morgan Ryan W. , Baker Wesley B. , Marquez Alexandra M. , Boorady Timothy W. , Devarajan Mahima , Lin Yuxi , Roberts Anna L. , Landis William P. , Mensah-Brown Kobina , Nadkarni Vinay M. , Berg Robert A. , Sutton Robert M. , Yodh Arjun G. , Licht Daniel J. , Guo Wensheng , Kilbaugh Todd J.
Published: February 2021

Neurologic injury is a leading cause of morbidity and mortality following pediatric cardiac arrest. In this study, we assess the feasibility of quantitative, non-invasive, frequency-domain diffuse optical spectroscopy (FD-DOS) neuromonitoring during cardiopulmonary resuscitation (CPR), and its predictive utility for return of spontaneous circulation (ROSC) in an established pediatric swine model of cardiac arrest. Cerebral tissue optical properties, oxy- and deoxy-hemoglobin concentration ([HbO2], [Hb]), oxygen saturation (StO2) and total hemoglobin concentration (THC) were measured by a FD-DOS probe placed on the forehead in 1-month-old swine (8–11 kg; n = 52) during seven minutes of asphyxiation followed by twenty minutes of CPR. ROSC prediction and time-dependent performance of prediction throughout early CPR (< 10 min), were assessed by the weighted Youden index (Jw, w = 0.1) with tenfold cross-validation. FD-DOS CPR data was successfully acquired in 48/52 animals; 37/48 achieved ROSC. Changes in scattering coefficient (785 nm), [HbO2], StO2 and THC from baseline were significantly different in ROSC versus No-ROSC subjects (p < 0.01) after 10 min of CPR. Change in [HbO2] of + 1.3 µmol/L from 1-min of CPR achieved the highest weighted Youden index (0.96) for ROSC prediction. We demonstrate feasibility of quantitative, non-invasive FD-DOS neuromonitoring, and stable, specific, early ROSC prediction from the third minute of CPR.
Disturbance of cellular homeostasis as a molecular risk evaluation of human endothelial cells exposed to nanoparticles
Authors: Wigner Paulina , Zielinski Krzysztof , Michlewska Sylwia , Danielska Paulina , Marczak Agnieszka , Ricci Eduardo Junior , Santos-Oliveira Ralph , Szwed Marzena
Published: February 2021

Even though application of nanoparticles in medicine seems to provide unique solutions for drug delivery and diagnosis diseases, understanding interactions between nanoscale materials and biological systems is imperative. Therefore, this study determined the effect of different types of nanoparticles (NPs) on human endothelial cells and examined the types of toxicity responses they can induce. Four different types of NPs were tested (PLA/MMT/TRASTUZUMAB, PLA/EDTMP, PLGA/MDP, and Pluronic F127 MICELLES), representing three putative areas of application: anticancer therapy, scintigraphy, and cosmetology. The experiments were performed on immortalized human umbilical vein endothelial cells (HUVEC-STs). Light contrast phase microscopy as well as cell viability assays showed that only Pluronic F127 MICELLES decreased the number of HUVEC-STs in contrast to PLA/MMT/TRASTUZUMAB, PLA/EDTMP, and PLGA/MDP NPs, which altered cell morphology, but not their confluency. The tested NPs induced not only DNA strand-breaks and alkali-labile sites, but also internucleosomal DNA fragmentation, visualized as a DNA ladder pattern typical of apoptosis. Moreover, generation of free radicals and subsequent mitochondrial membrane potential collapse showed the significance of free radical production during interactions between NPs and endothelial cells. High concentrations of NPs had different degrees of toxicity in human endothelial cells and affected cell proliferation, redox homeostasis, and triggered mitochondrial dysfunction.
Post-weaning stroking stimuli induce affiliative behavior toward humans and influence brain activity in female rats
Authors: Okabe Shota , Takayanagi Yuki , Yoshida Masahide , Onaka Tatsushi
Published: February 2021

Gentle touch contributes to affiliative interactions. We investigated the effects of gentle stroking in female rats on the development of affiliative behaviors toward humans and we exploratively examined brain regions in which activity was influenced by stroking. Rats that had received stroking stimuli repeatedly after weaning emitted 50-kHz calls, an index of positive emotion, and showed affiliative behaviors toward the experimenter. Hypothalamic paraventricular oxytocin neurons were activated in the rats after stroking. The septohypothalamic nucleus (SHy) in the post-weaningly stroked rats showed decreased activity in response to stroking stimuli compared with that in the non-stroked control group. There were negative correlations of neural activity in hypothalamic regions including the SHy with the number of 50-kHz calls. These findings revealed that post-weaning stroking induces an affiliative relationship between female rats and humans, possibly via activation of oxytocin neurons and suppression of the activity of hypothalamic neurons.
Optimizing machine learning models for granular NdFeB magnets by very fast simulated annealing
Authors: Park Hyeon-Kyu , Lee Jae-Hyeok , Lee Jehyun , Kim Sang-Koog
Published: February 2021

The macroscopic properties of permanent magnets and the resultant performance required for real implementations are determined by the magnets’ microscopic features. However, earlier micromagnetic simulations and experimental studies required relatively a lot of work to gain any complete and comprehensive understanding of the relationships between magnets’ macroscopic properties and their microstructures. Here, by means of supervised learning, we predict reliable values of coercivity (μ0Hc) and maximum magnetic energy product (BHmax) of granular NdFeB magnets according to their microstructural attributes (e.g. inter-grain decoupling, average grain size, and misalignment of easy axes) based on numerical datasets obtained from micromagnetic simulations. We conducted several tests of a variety of supervised machine learning (ML) models including kernel ridge regression (KRR), support vector regression (SVR), and artificial neural network (ANN) regression. The hyper-parameters of these models were optimized by a very fast simulated annealing (VFSA) algorithm with an adaptive cooling schedule. In our datasets of randomly generated 1,000 polycrystalline NdFeB cuboids with different microstructural attributes, all of the models yielded similar results in predicting both μ0Hc and BHmax. Furthermore, some outliers, which deteriorated the normality of residuals in the prediction of BHmax, were detected and further analyzed. Based on all of our results, we can conclude that our ML approach combined with micromagnetic simulations provides a robust framework for optimal design of microstructures for high-performance NdFeB magnets.
Higher maternal autonomy is associated with reduced child stunting in Malawi
Authors: Chilinda Zizwani Brian , Wahlqvist Mark L. , Lee Meei-Shyuan , Huang Yi-Chen
Published: February 2021

Child undernutrition is a major health problem in Malawi. We assessed the association between maternal autonomy and child stunting in Malawi. We utilized nationally representative pooled cross-sectional data from the 2010 and 2015/16 Malawi Demographic and Health Surveys (MDHS), which included 7348 mother (28.1 ± 6.8 years, range 15–49 years)—child (27.6 ± 16.7 months, range 0–59 months) pairs. Maternal autonomy composite scores captured decision-making power, tolerance of domestic violence, and financial independence. The nutritional outcome measure was stunting (height-for-age z score < – 2). Logistic regression assessed associations between maternal autonomy and stunting, and dominance analysis evaluated the relative importance of the associated factors. From the two surveys combined, 39.2% were stunted. Stunting decreased from 45.0% in 2010 to 34.6% in 2015/16; concurrently, maternal autonomy improved and was evidently associated with stunting (aOR = 0.81, 95% CI = 0.71, 0.93; p = 0.002). However, this association was probably mediated by other factors associated with improved child nutrition, including maternal education and family wealth, which, along with child age, were associated with stunting in the dominance analysis. Concurrent interventional programs may also have contributed to the decrease in stunting between the surveys, thus moderating the effect of maternal autonomy.
Synthesis, characterization and heavy metal removal efficiency of nickel ferrite nanoparticles (NFN’s)
Authors: Khoso Waheed Ali , Haleem Noor , Baig Muhammad Anwar , Jamal Yousuf
Published: February 2021

The heavy metals, such as Cr(VI), Pb(II) and Cd(II), in aqueous solutions are toxic even at trace levels and have caused adverse health impacts on human beings. Hence the removal of these heavy metals from the aqueous environment is important to protect biodiversity, hydrosphere ecosystems, and human beings. In this study, magnetic Nickel-Ferrite Nanoparticles (NFNs) were synthesized by co-precipitation method and characterized using X-Ray Diffraction (XRD), Energy Dispersive Spectroscopy (EDS) and Field Emission Scanning Electronic Microscopy (FE-SEM) techniques in order to confirm the crystalline structure, composition and morphology of the NFN’s, these were then used as adsorbent for the removal of Cr(VI), Pb(II) and Cd(II) from wastewater. The adsorption parameters under study were pH, dose and contact time. The values for optimum removal through batch-adsorption were investigated at different parameters (pH 3–7, dose: 10, 20, 30, 40 and 50 mg and contact time: 30, 60, 90, and 120 min). Removal efficiencies of Cr(VI), Pb(II) and Cd(II) were obtained 89%, 79% and 87% respectively under optimal conditions. It was found that the kinetics followed the pseudo second order model for the removal of heavy metals using Nickel ferrite nanoparticles.
Soil mite communities (Acari: Mesostigmata) as indicators of urban ecosystems in Bucharest, Romania
Authors: Manu M. , Băncilă R. I. , Bîrsan C. C. , Mountford O. , Onete M.
Published: February 2021

The aim of the present study was to establish the effect of management type and of environmental variables on the structure, abundance and species richness of soil mites (Acari: Mesostigmata) in twelve urban green areas in Bucharest-Romania. Three categories of ecosystem based upon management type were investigated: protected area, managed (metropolitan, municipal and district parks) and unmanaged urban areas. The environmental variables which were analysed were: soil and air temperature, soil moisture and atmospheric humidity, soil pH and soil penetration resistance. In June 2017, 480 soil samples were taken, using MacFadyen soil core. The same number of measures was made for quantification of environmental variables. Considering these, we observed that soil temperature, air temperature, air humidity and soil penetration resistance differed significantly between all three types of managed urban green area. All investigated environmental variables, especially soil pH, were significantly related to community assemblage. Analysing the entire Mesostigmata community, 68 species were identified, with 790 individuals and 49 immatures. In order to highlight the response of the soil mite communities to the urban conditions, Shannon, dominance, equitability and soil maturity indices were quantified. With one exception (numerical abundance), these indices recorded higher values in unmanaged green areas compared to managed ecosystems. The same trend was observed between different types of managed green areas, with metropolitan parks having a richer acarological fauna than the municipal or district parks.
Efficacy of KNO3, SiO2 and SA priming for improving emergence, seedling growth and antioxidant enzymes of rice (Oryza sativa), under drought
Authors: Ali Lawan Gana , Nulit Rosimah , Ibrahim Mohd Hafiz , Yien Christina Yong Seok
Published: February 2021

Rice is an important staple crop produced and consumed worldwide. However, poor seed emergence is one of the main impediments to obtaining higher yield of rice especially in hot and dry ecosystems of the world that are ravaged by drought. Therefore, this study was carried out to evaluate the effects of potassium nitrate (KNO3), salicylic acid (SA) and silicon dioxide (SiO2) priming in improving emergence, seedling growth, biochemical attributes and antioxidant activities of FARO44 rice under drought conditions. Rice seedlings primed with 2.5% and 5% KNO3, 3% and 3.5% SiO2, and 1 mM and 2.5 mM SA were subjected to three drought levels of low, moderate and severe under the greenhouse. Seed emergence, seedling growth, biochemical attributes and antioxidant activities were thereafter evaluated. Seed priming experiments were laid in a completely randomized design with five replicates per treatment. The results found that rice seedlings responded differently to different priming treatments. However, all primed rice seedlings had significantly (P ≤ 0.05) improved emergence percentage (72–92%), seedling growth, seedling vigor, seedling fresh and dry biomass and shorter emergence time compared with controls. Likewise, total soluble protein content, activities of catalase, ascorbate peroxidase and superoxide dismutase, carbohydrate, soluble sugar and total chlorophyll contents of rice seedlings were increased by more than two-folds by seed priming compared with control. Salicylic acid showed less effect in increasing emergence, seedling growth, antioxidant activities and biochemical attributes of rice. Thus, this study established that seed priming with KNO3 (2.5% and 5%) and SiO2 (3% and 3.5%) were more effective in improving emergence, seedling growth, biochemical attributes and antioxidant activities of FARO44. Thus, priming of FARO44 rice with this chemical is recommended for fast emergence, seedling growth and drought resistance in dry ecosystems.
Online and offline effects of transcranial alternating current stimulation of the primary motor cortex
Authors: Pozdniakov Ivan , Vorobiova Alicia Nunez , Galli Giulia , Rossi Simone , Feurra Matteo
Published: February 2021

Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation technique that allows interaction with endogenous cortical oscillatory rhythms by means of external sinusoidal potentials. The physiological mechanisms underlying tACS effects are still under debate. Whereas online (e.g., ongoing) tACS over the motor cortex induces robust state-, phase- and frequency-dependent effects on cortical excitability, the offline effects (i.e. after-effects) of tACS are less clear. Here, we explored online and offline effects of tACS in two single-blind, sham-controlled experiments. In both experiments we used neuronavigated transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) as a probe to index changes of cortical excitability and delivered M1 tACS at 10 Hz (alpha), 20 Hz (beta) and sham (30 s of low-frequency transcranial random noise stimulation; tRNS). Corticospinal excitability was measured by single pulse TMS-induced motor evoked potentials (MEPs). tACS was delivered online in Experiment 1 and offline in Experiment 2. In Experiment 1, the increase of MEPs size was maximal with the 20 Hz stimulation, however in Experiment 2 neither the 10 Hz nor the 20 Hz stimulation induced tACS offline effects. These findings support the idea that tACS affects cortical excitability only during online application, at least when delivered on the scalp overlying M1, thereby contributing to the development of effective protocols that can be applied to clinical populations.