bluuebunny/crossref_metadata_2025 huggingface dataset:
Thouless pumping in disordered photonic systems
Authors: Cerjan Alexander , Wang Mohan , Huang Sheng , Chen Kevin P. , Rechtsman Mikael C.
Published: October 2020

Thouless charge pumping protocols provide a route for one-dimensional systems to realize topological transport. Here, using arrays of evanescently coupled optical waveguides, we experimentally demonstrate bulk Thouless pumping in the presence of disorder. The degree of pumping is quite tolerant to significant deviations from adiabaticity as well as the addition of system disorder until the disorder is sufficiently strong to reduce the bulk mobility gap of the system to be on the scale of the modulation frequency of the system. Moreover, we show that this approach realizes near-full-unit-cell transport per pump cycle for a physically relevant class of localized initial system excitations. Thus, temporally pumped systems can potentially be used as a design principle for a new class of modulated slow-light devices that are resistant to system disorder.
Common and distinct patterns of intrinsic brain activity alterations in major depression and bipolar disorder: voxel-based meta-analysis
Authors: Gong Jiaying , Wang Junjing , Qiu Shaojuan , Chen Pan , Luo Zhenye , Wang Jurong , Huang Li , Wang Ying
Published: October 2020

Identification of intrinsic brain activity differences and similarities between major depression (MDD) and bipolar disorder (BD) is necessary. However, results have not yet yielded consistent conclusions. A meta-analysis of whole-brain resting-state functional MRI (rs-fMRI) studies that explored differences in the amplitude of low-frequency fluctuation (ALFF) between patients (including MDD and BD) and healthy controls (HCs) was conducted using seed-based d mapping software. Systematic literature search identified 50 studies comparing 1399 MDD patients and 1332 HCs, and 15 studies comparing 494 BD patients and 593 HCs. MDD patients displayed increased ALFF in the right superior frontal gyrus (SFG) (including the medial orbitofrontal cortex, medial prefrontal cortex [mPFC], anterior cingulate cortex [ACC]), bilateral insula extending into the striatum and left supramarginal gyrus and decreased ALFF in the bilateral cerebellum, bilateral precuneus, and left occipital cortex compared with HCs. BD showed increased ALFF in the bilateral inferior frontal gyrus, bilateral insula extending into the striatum, right SFG, and right superior temporal gyrus (STG) and decreased ALFF in the bilateral precuneus, left cerebellum (extending to the occipital cortex), left ACC, and left STG. In addition, MDD displayed increased ALFF in the left lingual gyrus, left ACC, bilateral precuneus/posterior cingulate gyrus, and left STG and decreased ALFF in the right insula, right mPFC, right fusiform gyrus, and bilateral striatum relative to BD patients. Conjunction analysis showed increased ALFF in the bilateral insula, mPFC, and decreased ALFF in the left cerebellum in both disorders. Our comprehensive meta-analysis suggests that MDD and BD show a common pattern of aberrant regional intrinsic brain activity which predominantly includes the insula, mPFC, and cerebellum, while the limbic system and occipital cortex may be associated with spatially distinct patterns of brain function, which provide useful insights for understanding the underlying pathophysiology of brain dysfunction in affective disorders, and developing more targeted and efficacious treatment and intervention strategies.
A quantitative and qualitative study on the neuropsychiatric sequelae of acutely ill COVID-19 inpatients in isolation facilities
Authors: Hao Fengyi , Tam Wilson , Hu Xiaoyu , Tan Wanqiu , Jiang Li , Jiang Xiaojiang , Zhang Ling , Zhao Xinling , Zou Yiran , Hu Yirong , Luo Xi , McIntyre Roger S. , Quek Travis , Tran Bach Xuan , Zhang Zhisong , Pham Hai Quang , Ho Cyrus S. H. , Ho Roger C.M.
Published: October 2020

This study examined the neuropsychiatric sequelae of acutely ill patients with coronavirus disease 2019 (COVID-19) infection who received treatment in hospital isolation wards during the COVID-19 pandemic. Ten COVID-19 patients who received treatment in various hospitals in Chongqing, China; 10 age- and gender-matched psychiatric patients; and 10 healthy control participants residing in the same city were recruited. All participants completed a survey that collected information on demographic data, physical symptoms in the past 14 days and psychological parameters. Face-to-face interviews with COVID-19 patients were also performed using semi-structured questions. Among the COVID-19 patients, 40% had abnormal findings on the chest computed topography scan, 20% had dysosmia, 10% had dysgeusia, and 80% had repeated positivity on COVID-19 reverse-transcription polymerase chain reaction testing. COVID-19 and psychiatric patients were significantly more worried about their health than healthy controls (p = 0.019). A greater proportion of COVID-19 patients experienced impulsivity (p = 0.016) and insomnia (p = 0.039) than psychiatric patients and healthy controls. COVID-19 patients reported a higher psychological impact of the outbreak than psychiatric patients and healthy controls, with half of them having clinically significant symptoms of posttraumatic stress disorder. COVID-19 and psychiatric patients had higher levels of depression, anxiety and stress than healthy controls. Three themes emerged from the interviews with COVID-19 patients: (i) The emotions experienced by patients after COVID-19 infection (i.e., shock, fear, despair, hope, and boredom); (ii) the external factors that affected patients’ mood (i.e., discrimination, medical expenses, care by healthcare workers); and (iii) coping and self-help behavior (i.e., distraction, problem-solving and online support). The future direction in COVID-19 management involves the development of a holistic inpatient service to promote immune and psychological resilience.
Sex-dimorphic role of prefrontal oxytocin receptors in social-induced facilitation of extinction in juvenile rats
Authors: Maroun Mouna , Sarussi-Elyahu Amit , Yaseen Aseel , Hatoum O. A. , Kritman Milly
Published: October 2020

We previously reported that in the adult animal extinction in pairs resulted in enhanced extinction, showing that social presence can reduce previously acquired fear responses. Based on our findings that juvenile and adult animals differ in the mechanisms of extinction, here we address whether the social presence of a conspecific affects extinction in juvenile animals similarly to adults. We further address whether such presence has a different impact on juvenile males and females. To that end, we examined in our established experimental setting whether conditioned male and female animals extinguish contextual fear memory better while in pairs. Taking advantage of the role of oxytocin (OT) in the mediation of extinction memory and social interaction, we also study the effect of antagonizing the OT receptors (OTR) either systemically or in the prefrontal cortex on social interaction-induced effects of fear extinction. The results show that social presence accelerates extinction in males and females as compared to the single condition. Yet, we show differential and opposing effects of an OTR antagonist in both sexes. Whereas in females, the systemic application of an OTR antagonist is associated with impaired extinction, it is associated with enhanced extinction in males. In contrast, prefrontal OT is not engaged in extinction in juvenile males, while is it is critical in females. Previously reported differences in the levels of prefrontal OT between males and females might explain the differences in OT action. These results suggest that even during the juvenile period, critical mechanisms are differently involved in the regulation of fear in males and females.
Optimizing whole-genomic prediction for autotetraploid blueberry breeding
Authors: de Bem Oliveira Ivone , Amadeu Rodrigo Rampazo , Ferrão Luis Felipe Ventorim , Muñoz Patricio R.
Published: October 2020

Blueberry (Vacciniumspp.) is an important autopolyploid crop with significant benefits for human health. Apart from its genetic complexity, the feasibility of genomic prediction has been proven for blueberry, enabling a reduction in the breeding cycle time and increasing genetic gain. However, as for other polyploid crops, sequencing costs still hinder the implementation of genome-based breeding methods for blueberry. This motivated us to evaluate the effect of training population sizes and composition, as well as the impact of marker density and sequencing depth on phenotype prediction for the species. For this, data from a large real breeding population of 1804 individuals were used. Genotypic data from 86,930 markers and three traits with different genetic architecture (fruit firmness, fruit weight, and total yield) were evaluated. Herein, we suggested that marker density, sequencing depth, and training population size can be substantially reduced with no significant impact on model accuracy. Our results can help guide decisions toward resource allocation (e.g., genotyping and phenotyping) in order to maximize prediction accuracy. These findings have the potential to allow for a faster and more accurate release of varieties with a substantial reduction of resources for the application of genomic prediction in blueberry. We anticipate that the benefits and pipeline described in our study can be applied to optimize genomic prediction for other diploid and polyploid species.
The ultrafast onset of exciton formation in 2D semiconductors
Authors: Trovatello Chiara , Katsch Florian , Borys Nicholas J. , Selig Malte , Yao Kaiyuan , Borrego-Varillas Rocio , Scotognella Francesco , Kriegel Ilka , Yan Aiming , Zettl Alex , Schuck P. James , Knorr Andreas , Cerullo Giulio , Conte Stefano Dal
Published: October 2020

The equilibrium and non-equilibrium optical properties of single-layer transition metal dichalcogenides (TMDs) are determined by strongly bound excitons. Exciton relaxation dynamics in TMDs have been extensively studied by time-domain optical spectroscopies. However, the formation dynamics of excitons following non-resonant photoexcitation of free electron-hole pairs have been challenging to directly probe because of their inherently fast timescales. Here, we use extremely short optical pulses to non-resonantly excite an electron-hole plasma and show the formation of two-dimensional excitons in single-layer MoS2 on the timescale of 30 fs via the induced changes to photo-absorption. These formation dynamics are significantly faster than in conventional 2D quantum wells and are attributed to the intense Coulombic interactions present in 2D TMDs. A theoretical model of a coherent polarization that dephases and relaxes to an incoherent exciton population reproduces the experimental dynamics on the sub-100-fs timescale and sheds light into the underlying mechanism of how the lowest-energy excitons, which are the most important for optoelectronic applications, form from higher-energy excitations. Importantly, a phonon-mediated exciton cascade from higher energy states to the ground excitonic state is found to be the rate-limiting process. These results set an ultimate timescale of the exciton formation in TMDs and elucidate the exceptionally fast physical mechanism behind this process.
The structure of a red-shifted photosystem I reveals a red site in the core antenna
Authors: Toporik Hila , Khmelnitskiy Anton , Dobson Zachary , Riddle Reece , Williams Dewight , Lin Su , Jankowiak Ryszard , Mazor Yuval
Published: October 2020

Photosystem I coordinates more than 90 chlorophylls in its core antenna while achieving near perfect quantum efficiency. Low energy chlorophylls (also known as red chlorophylls) residing in the antenna are important for energy transfer dynamics and yield, however, their precise location remained elusive. Here, we construct a chimeric Photosystem I complex in Synechocystis PCC 6803 that shows enhanced absorption in the red spectral region. We combine Cryo-EM and spectroscopy to determine the structure−function relationship in this red-shifted Photosystem I complex. Determining the structure of this complex reveals the precise architecture of the low energy site as well as large scale structural heterogeneity which is probably universal to all trimeric Photosystem I complexes. Identifying the structural elements that constitute red sites can expand the absorption spectrum of oxygenic photosynthetic and potentially modulate light harvesting efficiency.
Detection of early stage pancreatic cancer using 5-hydroxymethylcytosine signatures in circulating cell free DNA
Authors: Guler Gulfem D. , Ning Yuhong , Ku Chin-Jen , Phillips Tierney , McCarthy Erin , Ellison Christopher K. , Bergamaschi Anna , Collin Francois , Lloyd Paul , Scott Aaron , Antoine Michael , Wang Wendy , Chau Kim , Ashworth Alan , Quake Stephen R. , Levy Samuel
Published: October 2020

Pancreatic cancer is often detected late, when curative therapies are no longer possible. Here, we present non-invasive detection of pancreatic ductal adenocarcinoma (PDAC) by 5-hydroxymethylcytosine (5hmC) changes in circulating cell free DNA from a PDAC cohort (n = 64) in comparison with a non-cancer cohort (n = 243). Differential hydroxymethylation is found in thousands of genes, most significantly in genes related to pancreas development or function (GATA4, GATA6, PROX1, ONECUT1, MEIS2), and cancer pathogenesis (YAP1, TEAD1, PROX1, IGF1). cfDNA hydroxymethylome in PDAC cohort is differentially enriched for genes that are commonly de-regulated in PDAC tumors upon activation of KRAS and inactivation of TP53. Regularized regression models built using 5hmC densities in genes perform with AUC of 0.92 (discovery dataset, n = 79) and 0.92–0.94 (two independent test sets, n = 228). Furthermore, tissue-derived 5hmC features can be used to classify PDAC cfDNA (AUC = 0.88). These findings suggest that 5hmC changes enable classification of PDAC even during early stage disease.
A pyridinic Fe-N4 macrocycle models the active sites in Fe/N-doped carbon electrocatalysts
Authors: Marshall-Roth Travis , Libretto Nicole J. , Wrobel Alexandra T. , Anderton Kevin J. , Pegis Michael L. , Ricke Nathan D. , Voorhis Troy Van , Miller Jeffrey T. , Surendranath Yogesh
Published: October 2020

Iron- and nitrogen-doped carbon (Fe-N-C) materials are leading candidates to replace platinum catalysts for the oxygen reduction reaction (ORR) in fuel cells; however, their active site structures remain poorly understood. A leading postulate is that the iron-containing active sites exist primarily in a pyridinic Fe-N4 ligation environment, yet, molecular model catalysts generally feature pyrrolic coordination. Herein, we report a molecular pyridinic hexaazacyclophane macrocycle, (phen2N2)Fe, and compare its spectroscopic, electrochemical, and catalytic properties for ORR to a typical Fe-N-C material and prototypical pyrrolic iron macrocycles. N 1s XPS and XAS signatures for (phen2N2)Fe are remarkably similar to those of Fe-N-C. Electrochemical studies reveal that (phen2N2)Fe has a relatively high Fe(III/II) potential with a correlated ORR onset potential within 150 mV of Fe-N-C. Unlike the pyrrolic macrocycles, (phen2N2)Fe displays excellent selectivity for four-electron ORR, comparable to Fe-N-C materials. The aggregate spectroscopic and electrochemical data demonstrate that (phen2N2)Fe is a more effective model of Fe-N-C active sites relative to the pyrrolic iron macrocycles, thereby establishing a new molecular platform that can aid understanding of this important class of catalytic materials.
Probing complex geophysical geometries with chattering dust
Authors: Pyrak-Nolte Laura J. , Braverman William , Nolte Nicholas J. , Wright Alan J. , Nolte David D.
Published: October 2020

The modern energy economy and environmental infrastructure rely on the flow of fluids through fractures in rock. Yet this flow cannot be imaged directly because rocks are opaque to most probes. Here we apply chattering dust, or chemically reactive grains of sucrose containing pockets of pressurized carbon dioxide, to study rock fractures. As a dust grain dissolves, the pockets burst and emit acoustic signals that are detected by distributed sets of external ultrasonic sensors that track the dust movement through fracture systems. The dust particles travel through locally varying fracture apertures with varying speeds and provide information about internal fracture geometry, flow paths and bottlenecks. Chattering dust particles have an advantage over chemical sensors because they do not need to be collected, and over passive tracers because the chattering dust delineates the transport path. The current laboratory work has potential to scale up to near-borehole applications in the field.
Author Correction: Superior Temperature-Dependent Mechanical Properties and Deformation Behavior of Equiatomic CoCrFeMnNi High-Entropy Alloy Additively Manufactured by Selective Laser Melting
Authors: Kim Young-Kyun , Yang Sangsun , Lee Kee-Ahn
Published: October 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Epigenetic regulation of gene expression improves Fusarium head blight resistance in durum wheat
Authors: Kumar Jitendra , Rai Krishan M. , Pirseyedi Seyedmostafa , Elias Elias M. , Xu Steven , Dill-Macky Ruth , Kianian Shahryar F.
Published: October 2020

Eight advanced durum-breeding lines were treated with 5-methyl-azacytidine to test the feasibility of generating sources of Fusarium head blight (FHB) resistance. Of the 800 treated seeds, 415 germinated and were advanced up to four (M4) generations by selfing. Thirty-two of the resulting 415 M4 lines were selected following preliminary screening and were further tested for FHB resistance for three years at two field locations, and in the greenhouse. Five of the 32 M4 lines showed less than 30% disease severity, as compared to the parental lines and susceptible checks. Fusarium-damaged kernels and deoxynivalenol analyses supported the findings of the field and greenhouse disease assessments. Two of the most resistant M4 lines were crossed to a susceptible parent, advanced to third generation (BC1:F3) and were tested for stability and inheritance of the resistance. About, one third of the BC1:F3 lines showed FHB resistance similar to their M4 parents. The overall methylation levels (%) were compared using FASTmC method, which did not show a significant difference between M4 and parental lines. However, transcriptome analysis of one M4 line revealed significant number of differentially expressed genes related to biosynthesis of secondary metabolites, MAPK signaling, photosynthesis, starch and sucrose metabolism, plant hormone signal transduction and plant-pathogen interaction pathways, which may have helped in improved FHB resistance.
A general theory of far-field optical microscopy image formation and resolution limit using double-sided Feynman diagrams
Authors: Fukutake Naoki
Published: October 2020

Optical resolution of far-field optical microscopy is limited by the diffraction of light, while diverse light-matter interactions are used to push the limit. The image resolution limit depends on the type of optical microscopy; however, the current theoretical frameworks provide oversimplified pictures of image formation and resolution that only address individual types of microscopy and light-matter interactions. To compare the fundamental optical resolutions of all types of microscopy and to codify a unified image-formation theory, a new method that describes the influence of light-matter interactions on the resolution limit is required. Here, we develop an intuitive technique using double-sided Feynman diagrams that depict light-matter interactions to provide a bird’s-eye view of microscopy classification. This diagrammatic methodology also allows for the optical resolution calculation of all types of microscopy. We show a guidepost for understanding the potential resolution and limitation of all optical microscopy. This principle opens the door to study unexplored theoretical questions and lead to new applications.
Evolutionary analysis of the Moringa oleifera genome reveals a recent burst of plastid to nucleus gene duplications
Authors: Ojeda-López José , Marczuk-Rojas Juan Pablo , Polushkina Oliver Aleksandrei , Purucker Darius , Salinas María , Carretero-Paulet Lorenzo
Published: October 2020

It is necessary to identify suitable alternative crops to ensure the nutritional demands of a growing global population. The genome of Moringa oleifera, a fast-growing drought-tolerant orphan crop with highly valuable agronomical, nutritional and pharmaceutical properties, has recently been reported. We model here gene family evolution in Moringa as compared with ten other flowering plant species. Despite the reduced number of genes in the compact Moringa genome, 101 gene families, grouping 957 genes, were found as significantly expanded. Expanded families were highly enriched for chloroplastidic and photosynthetic functions. Indeed, almost half of the genes belonging to Moringa expanded families grouped with their Arabidopsis thaliana plastid encoded orthologs. Microsynteny analysis together with modeling the distribution of synonymous substitutions rates, supported most plastid duplicated genes originated recently through a burst of simultaneous insertions of large regions of plastid DNA into the nuclear genome. These, together with abundant short insertions of plastid DNA, contributed to the occurrence of massive amounts of plastid DNA in the Moringa nuclear genome, representing 4.71%, the largest reported so far. Our study provides key genetic resources for future breeding programs and highlights the potential of plastid DNA to impact the structure and function of nuclear genes and genomes.
Quantitative characterization of Clostridioides difficile population in the gut microbiome of patients with C. difficile infection and their association with clinical factors
Authors: Kim Jieun , Cho Youna , Seo Mi-Ran , Bae Mi Hyun , Kim Bongyoung , Rho Mina , Pai Hyunjoo
Published: October 2020

Objective was to analyse bacterial composition and abundance of Clostridioides difficile in gut microbiome of patients with C. difficile infection (CDI) in association with clinical characteristics. Whole metagenome sequencing of gut microbiome of 26 CDI patients was performed, and the relative abundance of C. difficile and its toxin genes was measured. Clinical characteristics of the patients were obtained through medical records. A strong correlation between the abundance of C. difficile and tcdB genes in CDI patients was found. The relative abundance of C. difficile in the gut microbiome ranged from undetectable to 2.8% (median 0.089). Patients with fever exhibited low abundance of C. difficile in their gut, and patients with fewer C. difficile organisms required long-term anti-CDI treatment. Abundance of Bifidobacterium and Bacteroides negatively correlated with that of C. difficile at the genus level. CDI patients were clustered using the bacterial composition of the gut: one with high population of Enterococcus (cluster 1, n = 12) and another of Bacteroides or Lactobacillus (cluster 2, n = 14). Cluster1 showed significantly lower bacterial diversity and clinical cure at the end of treatment. Additionally, patients with CDI exhibited increased ARGs; notably, blaTEM, blaSHV and blaCTX-M were enriched. C. difficile existed in variable proportion of the gut microbiome in CDI patients. CDI patients with Enterococcus-rich microbiome in the gut had lower bacterial diversity and poorer clinical cure.
A multilevel analysis of financial institutions’ systemic exposure from local and system-wide information
Authors: Gandica Yérali , Béreau Sophie , Gnabo Jean-Yves
Published: October 2020

In the aftermath of the financial crisis of 2007–2009, the growing body of literature on financial networks has widely documented the predictive power of topological characteristics (e.g., degree centrality measures) to explain the systemic impact or systemic exposure of financial institutions. This study shows that considering alternative topological measures based on local sub-network environment improves our ability to identify systemic institutions. To provide empirical evidence, we apply a two-step procedure. First, we recover network communities (i.e., close-peer environment) on a spillover network of financial institutions. Second, we regress alternative measures of vulnerability (i.e. firm’s losses)on three levels of topological measures: the global level (i.e., firm topological characteristics computed over the whole system), local level (i.e., firm topological characteristics computed over the community to which it belongs), and aggregated level by averaging individual characteristics over the community. The sample includes 46 financial institutions (banks, broker-dealers, and insurance and real-estate companies) listed in the Standard & Poor’s 500 index. Our results confirm the informational content of topological metrics based on a close-peer environment. Such information is different from that embedded in traditional system-wide topological metrics and can help predict distress of financial institutions in times of crisis.
Large scale, robust, and accurate whole transcriptome profiling from clinical formalin-fixed paraffin-embedded samples
Authors: Newton Yulia , Sedgewick Andrew J. , Cisneros Luis , Golovato Justin , Johnson Mark , Szeto Christopher W. , Rabizadeh Shahrooz , Sanborn J. Zachary , Benz Stephen Charles , Vaske Charles
Published: October 2020

Transcriptome profiling can provide information of great value in clinical decision-making, yet RNA from readily available formalin-fixed paraffin-embedded (FFPE) tissue is often too degraded for quality sequencing. To assess the clinical utility of FFPE-derived RNA, we performed ribo-deplete RNA extractions on > 3200 FFPE slide samples; 25 of these had direct FFPE vs. fresh frozen (FF) replicates, 57 were sequenced in 2 different labs, 87 underwent multiple library analyses, and 16 had direct microdissected vs. macrodissected replicates. Poly-A versus ribo-depletion RNA extraction methods were compared using transcriptomes of TCGA cohort and 3116 FFPE samples. Compared to FF, FFPE transcripts coding for nuclear/cytoplasmic proteins involved in DNA packaging, replication, and protein synthesis were detected at lower rates and zinc finger family transcripts were of poorer quality. The greatest difference in extraction methods was in histone transcripts which typically lack poly-A tails. Encouragingly, the overall sequencing success rate was 81%. Exome coverage was highly concordant in direct FFPE and FF replicates, with 98% agreement in coding exon coverage and a median correlation of whole transcriptome profiles of 0.95. We provide strong rationale for clinical use of FFPE-derived RNA based on the robustness, reproducibility, and consistency of whole transcriptome profiling.
Forebrain delta opioid receptors regulate the response of delta agonist in models of migraine and opioid-induced hyperalgesia
Authors: Dripps Isaac J. , Bertels Zachariah , Moye Laura S. , Tipton Alycia F. , Siegersma Kendra , Baca Serapio M. , Kieffer Brigitte L. , Pradhan Amynah A.
Published: October 2020

Delta opioid receptor (DOR) agonists have been identified as a promising novel therapy for headache disorders. DORs are broadly expressed in several peripheral and central regions important for pain processing and mood regulation; and it is unclear which receptors regulate headache associated symptoms. In a model of chronic migraine-associated pain using the human migraine trigger, nitroglycerin, we observed increased expression of DOR in cortex, hippocampus, and striatum; suggesting a role for these forebrain regions in the regulation of migraine. To test this hypothesis, we used conditional knockout mice with DORs deleted from forebrain GABAergic neurons (Dlx-DOR), and investigated the outcome of this knockout on the effectiveness of the DOR agonist SNC80 in multiple headache models. In DOR loxP controls SNC80 blocked the development of acute and chronic cephalic allodynia in the chronic nitroglycerin model, an effect that was lost in Dlx-DOR mice. In addition, the anti-allodynic effects of SNC80 were lost in a model of opioid induced hyperalgesia/medication overuse headache in Dlx-DOR conditional knockouts. In a model reflecting negative affect associated with migraine, SNC80 was only effective in loxP controls and not Dlx-DOR mice. Similarly, SNC80 was ineffective in the cortical spreading depression model of migraine aura in conditional knockout mice. Taken together, these data indicate that forebrain DORs are necessary for the action of DOR agonists in relieving headache-related symptoms and suggest that forebrain regions may play an important role in migraine modulation.
Association of advanced glycation end products with sarcopenia and frailty in chronic kidney disease
Authors: Yabuuchi Junko , Ueda Seiji , Yamagishi Sho-ichi , Nohara Nao , Nagasawa Hajime , Wakabayashi Keiichi , Matsui Takanori , Yuichiro Higashimoto , Kadoguchi Tomoyasu , Otsuka Tomoyuki , Gohda Tomohito , Suzuki Yusuke
Published: October 2020

Prevalence of sarcopenia is high in patients with chronic kidney disease (CKD), especially in those with dialysis. Various pathological conditions related to CKD, such as chronic inflammation, insulin resistance, and endothelial dysfunction, are thought to be associated with the development and progression of sarcopenia. Advanced glycation end products (AGE), one of the representative uremic toxins, have been shown to contribute to various CKD-associated complications. This study investigated the role of AGE in frailty and sarcopenia in patients and animals with CKD, respectively. In patients undergoing dialysis, serum AGE levels were significantly increased according to the frailty status and inversely associated with physical performance and activity. AGE accumulated in the gastrocnemius muscle of 5/6 nephrectomy mice in association with morphological abnormalities, capillary rarefaction, and mitochondrial dysfunction, all of which were completely inhibited by DNA-aptamer raised against AGE. Our present findings may suggest the pathological role of AGE in sarcopenia and frailty in CKD.
Defective liver glycogen autophagy related to hyperinsulinemia in intrauterine growth-restricted newborn wistar rats
Authors: de Toro-Martín Juan , Fernández-Marcelo Tamara , González-Rodríguez Águeda , Escrivá Fernando , Valverde Ángela M. , Álvarez Carmen , Fernández-Millán Elisa
Published: October 2020

Maternal malnutrition plays a critical role in the developmental programming of later metabolic diseases susceptibility in the offspring, such as obesity and type 2 diabetes. Because the liver is the major organ that produces and supplies blood glucose, we aimed at defining the potential role of liver glycogen autophagy in the programming of glucose metabolism disturbances. To this end, newborns were obtained from pregnant Wistar rats fed ad libitum with a standard diet or 65% food-restricted during the last week of gestation. We found that newborns from undernourished mothers showed markedly high basal insulin levels whereas those of glucagon were decreased. This unbalance led to activation of the mTORC1 pathway and inhibition of hepatic autophagy compromising the adequate handling of glycogen in the very early hours of extrauterine life. Restoration of autophagy with rapamycin but not with glucagon, indicated no defect in autophagy machinery per se, but in signals triggered by glucagon. Taken together, these results support the notion that hyperinsulinemia is an important mechanism by which mobilization of liver glycogen by autophagy is defective in food-restricted animals. This early alteration in the hormonal control of liver glycogen autophagy may influence the risk of developing metabolic diseases later in life.
Finding disease modules for cancer and COVID-19 in gene co-expression networks with the Core&Peel method
Authors: Lucchetta Marta , Pellegrini Marco
Published: October 2020

Genes are organized in functional modules (or pathways), thus their action and their dysregulation in diseases may be better understood by the identification of the modules most affected by the disease (aka disease modules, or active subnetworks). We describe how an algorithm based on the Core&Peel method is used to detect disease modules in co-expression networks of genes. We first validate Core&Peel for the general task of functional module detection by comparison with 42 methods participating in the Disease Module Identification DREAM challenge. Next, we use four specific disease test cases (colorectal cancer, prostate cancer, asthma, and rheumatoid arthritis), four state-of-the-art algorithms (ModuleDiscoverer, Degas, KeyPathwayMiner, and ClustEx), and several pathway databases to validate the proposed algorithm. Core&Peel is the only method able to find significant associations of the predicted disease module with known validated relevant pathways for all four diseases. Moreover, for the two cancer datasets, Core&Peel detects further eight relevant pathways not discovered by the other methods used in the comparative analysis. Finally, we apply Core&Peel and other methods to explore the transcriptional response of human cells to SARS-CoV-2 infection, finding supporting evidence for drug repositioning efforts at a pre-clinical level.
Establishment of fast-growing serum-free immortalised cells from Chinese hamster lung tissues for biopharmaceutical production
Authors: Yamano-Adachi Noriko , Arishima Rintaro , Puriwat Sukwattananipaat , Omasa Takeshi
Published: October 2020

Chinese hamster (Cricetulus griseus) ovary-derived Chinese hamster ovary (CHO) cells are the most commonly used mammalian hosts for the industrial production of recombinant therapeutics because of their ability to fold, assemble, and perform post-translational modifications, such as glycosylation, on proteins. They are also valuable for their ability to grow in serum-free suspension cultures. In this study, we established a cell line derived from lung tissue of Chinese hamsters, named Chinese hamster lung (CHL)-YN cells. The biosafety of CHL-YN cells was confirmed by in vitro sterility testing, mycoplasma detection, and reverse transcriptase assays. One of the key characteristics of CHL-YN cells was their doubling time of 8.1 h in chemically defined culture medium; thus, they proliferate much faster than conventional CHO cells and general mammalian cells. Transgenes could be introduced into CHL-YN cells with high efficiency. Finally, between 50% to > 100% of the amount of glycosylated immunoglobulin G (IgG)1 produced by CHO-K1 cells was produced by CHL-YN cells over a shorter period of time. In summary, fast-growing CHL-YN cells are a unique cell line for producing recombinant proteins.
Altered amygdala-based functional connectivity in individuals with attenuated psychosis syndrome and first-episode schizophrenia
Authors: Kim Woo-Sung , Shen Guangfan , Liu Congcong , Kang Nam-In , Lee Keon-Hak , Sui Jing , Chung Young-Chul
Published: October 2020

Altered resting-state functional connectivity (FC) of the amygdala (AMY) has been demonstrated to be implicated in schizophrenia (SZ) and attenuated psychosis syndrome (APS). Specifically, no prior work has investigated FC in individuals with APS using subregions of the AMY as seed regions of interest. The present study examined AMY subregion-based FC in individuals with APS and first-episode schizophrenia (FES) and healthy controls (HCs). The resting state FC maps of the three AMY subregions were computed and compared across the three groups. Correlation analysis was also performed to examine the relationship between the Z-values of regions showing significant group differences and symptom rating scores. Individuals with APS showed hyperconnectivity between the right centromedial AMY (CMA) and left frontal pole cortex (FPC) and between the laterobasal AMY and brain stem and right inferior lateral occipital cortex compared to HCs. Patients with FES showed hyperconnectivity between the right superficial AMY and left occipital pole cortex and between the left CMA and left thalamus compared to the APS and HCs respectively. A negative relationship was observed between the connectivity strength of the CMA with the FPC and negative-others score of the Brief Core Schema Scales in the APS group. We observed different altered FC with subregions of the AMY in individuals with APS and FES compared to HCs. These results shed light on the pathogenetic mechanisms underpinning the development of APS and SZ.
Impact of heat generation/absorption of magnetohydrodynamics Oldroyd-B fluid impinging on an inclined stretching sheet with radiation
Authors: Mabood Fazle , Bognár Gabriella , Shafiq Anum
Published: October 2020

In this paper, we have investigated thermally stratified MHD flow of an Oldroyd-B fluid over an inclined stretching surface in the presence of heat generation/absorption. Similarity solutions for the transformed governing equations are obtained. The reduced equations are solved numerically using the Runge–Kutta Fehlberg method with shooting technique. The influences of various involved parameters on velocity profiles, temperature profiles, local skin friction, and local Nusselt number are discussed. Numerical values of local skin friction and local Nusselt number are computed. The significant outcomes of the study are that the velocity decreases when the radiation parameter $$R_{d}$$

R
d

is increased while the temperature profile is increased for higher values of radiation parameter $$R_{d}$$

R
d

in case of opposing flow, moreover, growth in Deborah number $$\beta_{2}$$

β
2

enhance the velocity and momentum boundary layer. The heat transfer rate is decrease due to magnetic strength but increase with the increased values of Prandtl and Deborah numbers. The results of this model are closely matched with the outputs available in the literature.
EEG microstate complexity for aiding early diagnosis of Alzheimer’s disease
Authors: Tait Luke , Tamagnini Francesco , Stothart George , Barvas Edoardo , Monaldini Chiara , Frusciante Roberto , Volpini Mirco , Guttmann Susanna , Coulthard Elizabeth , Brown Jon T. , Kazanina Nina , Goodfellow Marc
Published: October 2020

The dynamics of the resting brain exhibit transitions between a small number of discrete networks, each remaining stable for tens to hundreds of milliseconds. These functional microstates are thought to be the building blocks of spontaneous consciousness. The electroencephalogram (EEG) is a useful tool for imaging microstates, and EEG microstate analysis can potentially give insight into altered brain dynamics underpinning cognitive impairment in disorders such as Alzheimer’s disease (AD). Since EEG is non-invasive and relatively inexpensive, EEG microstates have the potential to be useful clinical tools for aiding early diagnosis of AD. In this study, EEG was collected from two independent cohorts of probable AD and cognitively healthy control participants, and a cohort of mild cognitive impairment (MCI) patients with four-year clinical follow-up. The microstate associated with the frontoparietal working-memory/attention network was altered in AD due to parietal inactivation. Using a novel measure of complexity, we found microstate transitioning was slower and less complex in AD. When combined with a spectral EEG measure, microstate complexity could classify AD with sensitivity and specificity > 80%, which was tested on an independent cohort, and could predict progression from MCI to AD in a small preliminary test cohort of 11 participants. EEG microstates therefore have potential to be a non-invasive functional biomarker of AD.
Quantifying the distribution of protein oligomerization degree reflects cellular information capacity
Authors: Danielli Lena , Li Ximing , Tuller Tamir , Daniel Ramez
Published: October 2020

The generation of information, energy and biomass in living cells involves integrated processes that optimally evolve into complex and robust cellular networks. Protein homo-oligomerization, which is correlated with cooperativity in biology, is one means of scaling the complexity of protein networks. It can play critical roles in determining the sensitivity of genetic regulatory circuits and metabolic pathways. Therefore, understanding the roles of oligomerization may lead to new approaches of probing biological functions. Here, we analyzed the frequency of protein oligomerization degree in the cell proteome of nine different organisms, and then, we asked whether there are design trade-offs between protein oligomerization, information precision and energy costs of protein synthesis. Our results indicate that there is an upper limit for the degree of protein oligomerization, possibly because of the trade-off between cellular resource limitations and the information precision involved in biochemical reaction networks. These findings can explain the principles of cellular architecture design and provide a quantitative tool to scale synthetic biological systems.
Utilization of emergency ophthalmology services in Taiwan: a nationwide population study
Authors: Hsu Min-Huei , Hsu Chia-An , Hsiao Sheng-Huang , Chu Dachen , Yen Ju-Chuan
Published: October 2020

The aim of this study was to conduct a nationwide survey of the use of emergency ophthalmology services using a sub-dataset of one million beneficiaries sampled from Taiwan’s National Health Insurance Research Database (NHIRD) for the years 2008 through 2012. By analyzing this population dataset, the study illustrates the disease landscape of emergency eye care services. The five-year, one-million-person NHIRD sub-dataset for 2008 through 2012 was used to explore emergency visits and ophthalmology specialty visits and to analyze the associated demographics and diagnosis codes based on the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM). Diagnoses were categorized into three groups: urgent, non-urgent, and intermediate. A total of 2454 emergency eye care visits were identified. The mean age of the patients who made these visits was 34.6 years old, and their sex ratio was 1.36 men to women. The percentages of urgent, non-urgent, and intermediate eye care visits in this study were 48.2%, 30.9%, and 20.9%, respectively. The leading diagnoses in the urgent category were corneal abrasions, foreign bodies in the eyes, eye burns, and blunt eye injuries. The leading diagnoses for the non-urgent visits were conjunctivitis, subconjunctival hemorrhages, trichiasis, and dry eye disease. Those for the intermediate category were superficial punctate keratitis, corneal opacity and degeneration, and lid, orbital, and lacrimal drainage infections. The urgent visit category accounted for nearly half of all the visits identified in this study. Compared to outpatient department visitors, the emergency ophthalmology service patients were younger and more predominantly male. These results were consistent with those of previous reports. Low copays have made emergency ophthalmology services highly accessible in Taiwan. However, future policies can be designed to more effectively allocate resources to urgent cases.
Syringa vulgaris leaves powder a novel low-cost adsorbent for methylene blue removal: isotherms, kinetics, thermodynamic and optimization by Taguchi method
Authors: Mosoarca Giannin , Vancea Cosmin , Popa Simona , Gheju Marius , Boran Sorina
Published: October 2020

In this study, the potential of a new low-cost adsorbent, Syringa vulgaris leaves powder, for methylene blue adsorption from aqueous solution was investigated. The adsorbent surface was examined using SEM and FTIR techniques. The experiments were conducted, in batch system, to find out the effect of pH, contact time, adsorbent dose, initial dye concentration, temperature and ionic strength on dye adsorption. The process is best described by Langmuir isotherm and the pseudo second order kinetic model. Maximum adsorption capacity, 188.2 (mg g−1), is better than other similar adsorbent materials. Thermodynamic parameters revealed a spontaneous and endothermic process, suggesting a physisorption mechanism. A Taguchi orthogonal array (L27) experimental design was used to determine the optimum conditions for the removal of dye. Various desorbing agents were used to investigate the regeneration possibility of used adsorbent. Results suggest that the adsorbent material is very effective for removal of methylene blue from aqueous solutions.
Predicting human health from biofluid-based metabolomics using machine learning
Authors: Evans Ethan D. , Duvallet Claire , Chu Nathaniel D. , Oberst Michael K. , Murphy Michael A. , Rockafellow Isaac , Sontag David , Alm Eric J.
Published: October 2020

Biofluid-based metabolomics has the potential to provide highly accurate, minimally invasive diagnostics. Metabolomics studies using mass spectrometry typically reduce the high-dimensional data to only a small number of statistically significant features, that are often chemically identified—where each feature corresponds to a mass-to-charge ratio, retention time, and intensity. This practice may remove a substantial amount of predictive signal. To test the utility of the complete feature set, we train machine learning models for health state-prediction in 35 human metabolomics studies, representing 148 individual data sets. Models trained with all features outperform those using only significant features and frequently provide high predictive performance across nine health state categories, despite disparate experimental and disease contexts. Using only non-significant features it is still often possible to train models and achieve high predictive performance, suggesting useful predictive signal. This work highlights the potential for health state diagnostics using all metabolomics features with data-driven analysis.
The constraints and driving forces of oasis development in arid region: a case study of the Hexi Corridor in northwest China
Authors: Bie Qiang , Xie Yaowen
Published: October 2020

The oasis, a special landscape with the integration of nature and humanity in the arid region, has undergone an enormous transformation during the past decades. To gain a better understanding of the tradeoff between economic growth and oases stability in the arid land, we took the oases in the Hexi Corridor as a case to explore the constraints of oases development and the driving factors of oases expansion. The dynamic changes and spatial distribution patterns underwent by the oases were examined using multispectral remote sensing imagery. The constraints of oasis development in arid land were investigated by the grid-transformed model, as well as the index system of driving forces was analyzed using the grey incidence model based on the data from statistics yearbooks. The oasis area in the Hexi Corridor had tremendous changes expanded 40% from 1986 to 2015, the stable oasis area was 9062 km2, while the maximum area reached 16,374 km2. The constraints for oases of topography, hydrology and heat condition are as follow: The elevation of oasis ranged from 1000 to 1800 m, peaked in 1500 m; the slope of oasis distribution was flatter than 3 degrees; the aspect of oases on slope land concentrated in northeast and north, accounting for more than 60%. The main driving forces of oasis spatial expansion in the arid region were population, water resource, economy, policies, and other factors. These results are expected to (1) improve the rationality of oasis development, and (2) promote the sustainable planning and management of oases in the arid land.