bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors predicting 10-year seizure freedom after temporal lobe resection
Authors: Schmitt Friedhelm C. , Meencke H.‑Joachim
Published: January 2020

Background

Resective surgery is an established and evidence-based treatment approach in pharmacoresistant temporal lobe epilepsy (TLE). Extra-long-term follow-up data are important to allow for good patient counseling. So far, only few trials provide prospective or retrospective data exceeding 5 years.

Objective

This study aimed to present data of continuous seizure outcome over an extended time period, with a particular focus on patients who remained seizure free for 10 years.

Methods

We analyzed seizure outcome after epilepsy surgery for TLE in 46 consecutive patients, who were seen on an annual basis for 10 years in a single center (Epilepsy Center Berlin Brandenburg). Factors for remaining seizure free for 10 years were determined by univariate analysis.

Results

The class I outcome changed each year by 74–78%. Of the patients, 63% remained continuously in Engel class I (48% Engel Class IA for 10 years) for 10 years. Six patients were never seizure free (12.5%). After 10 years, 35% of the patients were cured (i.e., seizure-free without medication). A higher number of antiepileptic drugs and seizures before surgery as well as the indication for invasive presurgical monitoring were associated with “unsuccessful surgery.”

Conclusion

With almost half of the patients completely seizure free and more than a third “cured,” epilepsy surgery remains the mainstay of therapy for TLE patients. Analysis in larger cohorts with extra-long-term follow-up is needed to assess good prognostic factors and other postsurgical outcome issues such as neuropsychological, psychiatric, and psychosocial outcomes.
Genome-wide association analysis of stripe rust resistance loci in wheat accessions from southwestern China
Authors: Cheng Bin , Gao Xu , Cao Ning , Ding Yanqing , Gao Yu , Chen Tianqing , Xin Zhihai , Zhang Liyi
Published: January 2020

Wheat stripe rust can cause considerable yield losses, and genetic resistance is the most effective approach for controlling the disease. To identify the genomic regions responsible for Puccinia striiformis f. sp. tritici (Pst) resistance in a set of winter wheat strains mainly from southwestern China, and to identify DNA markers in these regions, we carried out a genome-wide association study (GWAS) of 120 China winter wheat accessions using single nucleotide polymorphism (SNP) markers from 90K wheat SNP arrays. In total, 16 SNP loci were significantly associated with wheat stripe rust in field and greenhouse trials. Of these, three distinctive SNPs on chromosomes 1B, 4A, and 6A were identified at a site in Mianyang in 2014, where the most prevalent wheat stripe rust races since 2009 have been V26 (G22-9, G22-14). This suggests that the three SNP loci were linked to the new quantitative trait loci (QTL)/genes resistant to the V26 races. Germplasm with immunity to Pst is a good source of stripe rust resistance for breeding, and after further validation, SNPs closely linked to resistance QTLs/genes could be converted into user-friendly markers and facilitate marker-assisted selection to improve wheat stripe rust resistance.
Comparative study of dust acoustic solitons in two-temperature ion homogeneous and inhomogeneous plasmas
Authors: Srivastava Rashmi , Malik Hitendra K. , Singh Devi
Published: January 2020

The dust acoustic solitary waves are theoretically investigated in dusty plasmas for different cases of with and without density gradients. These low-frequency solitary waves are studied using appropriate Korteweg–de Vries equations obtained using relevant stretched coordinates. The soliton solutions in homogeneous plasma, weakly inhomogeneous plasma and strongly inhomogeneous plasma, are thoroughly investigated for studying the effect of different parameters like dust charge and density of all the plasma species on the soliton profiles. The combination of the dust charge with its number density changes the dynamics of the solitons and that is further affected by the number density of the hot ion with respect to the cold ions.
Emotion Recognition from Multimodal Physiological Signals for Emotion Aware Healthcare Systems
Authors: Ayata Değer , Yaslan Yusuf , Kamasak Mustafa E.
Published: January 2020

Purpose

The purpose of this paper is to propose a novel emotion recognition algorithm from multimodal physiological signals for emotion aware healthcare systems. In this work, physiological signals are collected from a respiratory belt (RB), photoplethysmography (PPG), and fingertip temperature (FTT) sensors. These signals are used as their collection becomes easy with the advance in ergonomic wearable technologies.

Methods

Arousal and valence levels are recognized from the fused physiological signals using the relationship between physiological signals and emotions. This recognition is performed using various machine learning methods such as random forest, support vector machine and logistic regression. The performance of these methods is studied.

Results

Using decision level fusion, the accuracy improved from 69.86 to 73.08% for arousal, and from 69.53 to 72.18% for valence. Results indicate that using multiple sources of physiological signals and their fusion increases the accuracy rate of emotion recognition.

Conclusion

This study demonstrated a framework for emotion recognition using multimodal physiological signals from respiratory belt, photo plethysmography and fingertip temperature. It is shown that decision level fusion from multiple classifiers (one per signal source) improved the accuracy rate of emotion recognition both for arousal and valence dimensions.
In-Fiber Structured Particles and Filament Arrays from the Perspective of Fluid Instabilities
Authors: Xu Bingrui , Ma Shuqi , Xiang Yuanzhuo , Zhang Jing , Zhu Meifang , Wei Lei , Tao Guangming , Deng Daosheng
Published: January 2020

In-fiber structured particles and filament array have been recently emerging, providing unique advantages of feasible fabrication, diverse structures and sophisticated functionalities. This review will focus on the progress of this topic mainly from the perspective of fluid instabilities. By suppressing the capillary instability, the uniform layered structures down to nanometers are attained with the suitable materials selection. On the other hand, by utilizing capillary instability via post-drawing thermal treatment, the unprecedent structured particles can be designed with multimaterials for multifunctional fiber devices. Moreover, an interesting filamentation instability of a stretching viscous sheet has been identified during thermal drawing, resulting in an array of filaments. This review may inspire more future work to produce versatile devices for fiber electronics, either at a single fiber level or in large-scale fabrics and textiles, simply by manipulating and controlling fluid instabilities.
Perception of Labial Size and Objective Measurements-Is There a Correlation? A Cross-Sectional Study in a Cohort Not Seeking Labiaplasty
Authors: Widschwendter Andreas , Riedl David , Freidhager Katharina , Abdel Azim Samira , Jerabek-Klestil Susanne , D'Costa Elisabeth , Fessler Siegfried , Ciresa-König Alexandra , Marth Christian , Böttcher Bettina
Published: January 2020

Introduction

Poor genital self-image is a common phenomenon leading to an increasing interest in female genital surgery over the last years.

Aim

The aim was to correlate objective measurements of the labia minora with the individual subjective perception of the labial size.

Methods

In a cross-sectional study with 200 premenopausal women (median age 33.5 years) presenting for gynecological issues other than vulvar diseases, labial width and length were measured, and psychological and physical complaints were assessed. Multivariable logistic regression analyses were performed to identify factors that influenced self-reported complaints and subjective perception of labia size.

Main Outcome Measure

The main outcome measure was labial appearance (width and length in mm, color), subjective perception of the labial size, and complaints.

Results

The median width of the labia minora was 19.0 mm (interquartile range = 12.6–27.5), and the median length was 35.5 mm (interquartile range = 27.8–48.9). The objective size of the labia was significantly associated with womens' subjective perception of the labial size, but not with self-reported complaints. Nearly one-third of the women (n = 53, 27%) reported complaints of their labia minora which were mainly physical (n = 41, 77%) or a combination of physical and psychological problems (n = 9, 17%), while only a small group reported experiencing only psychological complaints (n = 3, 6%). Predictors of complaints were previous cosmetic surgery and the subjective perception of the labia size. The latter was significantly associated with discomfort during intercourse and when visiting a sauna and by labia minora that protruded over the labia majora.

Clinical Implications

Cutoff values to define labial hypertrophy and to justify labial reduction surgery should be avoided.

Strength & Limitations

This is a large sample of labial measurements in women not seeking labiaplasty. Standardized and validated questions regarding quality of life, sexuality, and body image could have provided more insight into psychological aspects.

Conclusion

These data demonstrate the variability of labial anatomy and its perception.
A new method for improving the inductively coupled data transmission rate of mooring buoy based on carrier signal frequency selection
Authors: Du Rong , Li Xingfei , Yang Shaobo , Li Hongyu
Published: January 2020

In the inductively coupled data transmission system of the mooring buoy, the carrier signal frequency of the transmission channel is limited due to the inherent characteristics of the system, resulting in limited channel bandwidth. The limited channel bandwidth limits the increase in inductively coupled data transmission rate. In order to improve the inductively coupled data transmission rate of mooring buoy as much as possible without damaging the data transmission performance, a new method was proposed in this paper. The method is proposed to improve the data transmission rate by selecting the appropriate carrier signal frequencies based on the principle of maximizing the amplitude value of amplitude-frequency characteristic curve of the system. Research has been done according to this method as follows. Firstly, according to the inductively coupled transmission mooring buoy structure, the inductively coupled data transmission circuit model was established. The binary frequency shift keying (2FSK) digital signal modulation mode was selected. Through theoretical analysis, the relation between the carrier signal frequency and the data transmission performance, the relation between the carrier signal frequency and the 2FSK signal bandwidth were obtained. Secondly, the performance and the bandwidth of the signal transmission were studied for the inherent characteristics of the actual inductively coupled data transmission system. The amplitude-frequency characteristic of the system was analyzed by experiments. By selecting the appropriate carrier signal frequency parameters, an excellent data transmission performance was guaranteed and a large 2FSK signal bandwidth was obtained. Finally, an inductively coupled data transmission rate optimization experiment and a bit error rate analysis experiment were designed and carried out. The results show that the high-speed and reliable data transmission of the system was realized and the rate can reach 100 kbps.
Moment-to-moment dynamics between auditory verbal hallucinations and negative affect and the role of beliefs about voices
Authors: So Suzanne Ho-wai , Chung Lawrence Kin-hei , Tse Chun-Yu , Chan Sandra Sau-man , Chong George Heung-chuen , Hung Karen Shee-yueng , Sommer Iris E. C.
Published: January 2020

Background

Negative affect (NA) has been suggested to be both an antecedent and a consequence of auditory verbal hallucinations (AVH). Furthermore, negative appraisals of voices have been theorized to contribute to the maintenance of AVH. Using the experience sampling method (ESM), this study examined the bi-directional relationship between NA and AVH, and the moderating effect of negative beliefs about voices.

Methods

Forty-seven patients diagnosed with schizophrenia spectrum disorders with frequent AVH completed a clinical interview, followed by ESM for 10 times a day over 6 days on an electronic device. Time-lagged analyses were conducted using multilevel regression modeling. Beliefs about voices were assessed at baseline.

Results

A total of 1654 data points were obtained. NA predicted an increase in AVH in the subsequent moment, and AVH predicted an increase in NA in the subsequent moment. Baseline beliefs about voices as malevolent and omnipotent significantly strengthened the association between NA and AVH within the same moment. In addition, the belief of omnipotence was associated with more hallucinatory experiences in the moment following NA. However, beliefs about voices were not associated directly with momentary levels of NA or AVH.

Conclusions

Experiences of NA and AVH drove each other, forming a feedback loop that maintained the voices. The associations between NA and AVH, either within the same moment or across moments, were exacerbated by negative beliefs about voices. Our results suggest that affect-improving interventions may stop the feedback loop and reduce AVH frequency.
Abnormal reward valuation and event-related connectivity in unmedicated major depressive disorder
Authors: Rupprechter S. , Stankevicius A. , Huys Q. J. M. , Series P. , Steele J. D.
Published: January 2020

Background

Experience of emotion is closely linked to valuation. Mood can be viewed as a bias to experience positive or negative emotions and abnormally biased subjective reward valuation and cognitions are core characteristics of major depression.

Methods

Thirty-four unmedicated subjects with major depressive disorder and controls estimated the probability that fractal stimuli were associated with reward, based on passive observations, so they could subsequently choose the higher of either their estimated fractal value or an explicitly presented reward probability. Using model-based functional magnetic resonance imaging, we estimated each subject's internal value estimation, with psychophysiological interaction analysis used to examine event-related connectivity, testing hypotheses of abnormal reward valuation and cingulate connectivity in depression.

Results

Reward value encoding in the hippocampus and rostral anterior cingulate was abnormal in depression. In addition, abnormal decision-making in depression was associated with increased anterior mid-cingulate activity and a signal in this region encoded the difference between the values of the two options. This localised decision-making and its impairment to the anterior mid-cingulate cortex (aMCC) consistent with theories of cognitive control. Notably, subjects with depression had significantly decreased event-related connectivity between the aMCC and rostral cingulate regions during decision-making, implying impaired communication between the neural substrates of expected value estimation and decision-making in depression.

Conclusions

Our findings support the theory that abnormal neural reward valuation plays a central role in major depressive disorder (MDD). To the extent that emotion reflects valuation, abnormal valuation could explain abnormal emotional experience in MDD, reflect a core pathophysiological process and be a target of treatment.
Marketing hospitality
Authors: Chen Lindsey N.
Published: January 2020

Store image is an important factor in the consumer's decision-making process (Nevin & Houston, 1980). As a cue to a store's image, a store sign and its visual design and content form (which may include the name of the store or brand) serve as vital elements that can immediately attract potential customers. In particular, a store's name can be used as an extrinsic signal to suggest and maintain quality perceptions. With a well chosen, memorable name, retailers can establish trust and a loyal following, which in turn means repeated business. For those who understand how store signs can influence patronage decisions and improve competitiveness in the marketplace, therefore, much effort is exerted to create advertising and marketing strategies designed to attract and retain customers.
Powder X-ray diffraction of flucytosine, C4H4FN3O
Authors: Patel Nilan V. , Golab Joseph T. , Kaduk James A. , Gindhart Amy M. , Blanton Thomas N.
Published: January 2020

Flucytosine, CAS #2022-85-7, crystallizes in the tetragonal space group P41212 (#94) with a = 6.643768(27), c = 23.89009(10) Å, V = 1054.500(7) Å3, and Z = 8. In this work, the sample was obtained from the United States Pharmacopeial Convention (USP) Lot #R03100 and analyzed as-received. The room temperature (295 K) crystal structure was refined using synchrotron (λ = 0.412826 Å) powder diffraction data and optimized using the density functional theory (DFT). When looking down the a-axis, the crystal structure consists of multiple ribbon-like structures stacked into columns. The powder X-ray diffraction pattern of the compound has been submitted to ICDD® for inclusion in the Powder Diffraction File™ (PDF®). The agreement of the Rietveld-refined and DFT-optimized structures is good, with the largest difference in the external amine group with an overall root mean displacement of 0.056 Å. There is also evidence of unit cell expansion at higher temperatures, as the volume of the unit cell at 298 K was 1.6–1.9% greater than the two unit cells obtained at 150 K. A N–H⋯O hydrogen bond exists in the inter-ribbon region between the flucytosine molecules, resulting in a 3D hydrogen bond network.
Joseph Johnson's Lost Gamuts: Native Hymnody, Materials of Exchange, and the Colonialist Archive
Authors: GOODMAN GLENDA
Published: January 2020

In the winter of 1772–1773, Joseph Johnson (Mohegan/Brothertown) copied musical notation into eight books for Christian Native Americans in Farmington, Connecticut, a town established by English settler colonists on the land known as Tunxis Sepus. Johnson did so because, as he wrote in his diary, “The indians are all desireous of haveing Gamuts.” Johnson's “gamuts” have not survived, but their erstwhile existence reveals hymnody's important role within the Native community in Farmington as well as cross-culturally with the English settler colonists. In order to reconstruct the missing music books and assess their sociocultural significance, this article proposes a surrogate bibliography, gathering a constellation of sources among which Johnson's books would have circulated and gained meaning for Native American Christians and English colonists (including other printed and manuscript music, wampum, and legal documents pertaining to land transfer). By bringing together this multi-modal network of materials, this essay seeks to redress the material and epistemological effects of a colonialist archive. On one level, this is a case study that focuses on a short period of time in order to document the impact on sacred music of conversion, literacy, shifting intercultural relations, and a drive to preserve sovereignty. On another, this article presents a methodological intervention for dealing with lost materials and colonialist archives without recourse to discourses of recovery or discovery, the latter of which is considered through the framework of what I term “archival orientalism.”
Teratogenic effects ofBocconia frutescensL.
Authors: Lunagómez L. S. , Santiago-Roque I. , Gheno-Heredia Y. A. , Corona-Morales A. A. , Bolado-García V. E.
Published: January 2020

It is estimated that 80% of the world population trusts traditional medicine. A large number of Americans use infusions ofBocconia frutescensL. leaves to treat cough and gastrointestinal disorders. However, phytochemical studies reveal that this plant contains alkaloids and other potentially harmful substances. This study aimed to evaluate the teratogenic effects ofB. frutescensL. in an experimental model. Pregnant Wistar rats were administered lyophilizedB. frutescensL. extract at 300 mg/kg/day or vehicle by orogastric route during the organogenesis period (gestation days 7–13), and external and internal congenital malformations were analyzed on the progeny on gestational day 20.Bocconia frutescensL. produced a significant increase in the number of different malformations, relative to the control group. We conclude that the consumption ofB. frutescensL. during pregnancy at a dose equivalent to that consumed by humans increases the risk of teratogenic effects.
Commensal Hafnia alvei strain reduces food intake and fat mass in obese mice—a new potential probiotic for appetite and body weight management
Authors: Legrand Romain , Lucas Nicolas , Dominique Manon , Azhar Saida , Deroissart Camille , Le Solliec Marie-Anne , Rondeaux Julie , Nobis Séverine , Guérin Charlène , Léon Fatima , do Rego Jean-Claude , Pons Nicolas , Le Chatelier Emmanuelle , Ehrlich S. Dusko , Lambert Gregory , Déchelotte Pierre , Fetissov Sergueï O.
Published: January 2020

Background/objectives

Based on the recent identification of E.coli heat shock protein ClpB as a mimetic of the anorexigenic α-melanocyte stimulating hormone (α-MSH), the objective of this study was to preclinically validate Hafnia alvei, a ClpB-producing commensal bacterium as a potential probiotic for appetite and body weight management in overweight and obesity.

Methods

The involvement of enterobacterial ClpB in the putative anti-obesity effects was studied using ClpB-deficient E.coli. A food-grade H. alvei HA4597 strain synthetizing the ClpB protein with an α-MSH-like motif was selected as a candidate probiotic to be tested in ob/ob and high-fat diet (HFD)-fed obese and overweight mice. The relevance of the enterobacterial ClpB gene to human obesity was studied by in silico analysis of fecal metagenomes of 569 healthy individuals from the “MetaHIT” database.

Results

Chronic per os administration of native but not ClpB-deficient E.coli strain reduced body weight gain (p < 0.05) and daily meal frequency (p < 0.001) in ob/ob mice. Oral gavage of H.alvei for 18 and 46 days in ob/ob and HFD-fed obese mice, respectively, was well tolerated, reduced body weight gain and fat mass in both obesity models (p < 0.05) and decreased food intake in hyperphagic ob/ob mice (p < 0.001). Elevated fat tissue levels of phosphorylated hormone-sensitive lipase were detected in H.alvei -treated ob/ob mice (p < 0.01). Enterobacterial ClpB gene richness was lower in obese vs. non-obese humans (p < 0.0001) and correlated negatively with BMI in genera of Enterobacter, Klebsiella and Hafnia.

Conclusions

H.alvei HA4597 strain reduces food intake, body weight and fat mass gain in hyperphagic and obese mice. These data combined with low enterobacterial ClpB gene abundance in the microbiota of obese humans provide the rationale for using H.alvei as a probiotic for appetite and body weight management in overweight and obesity.
Neonatal abstinence syndrome management in California birth hospitals: results of a statewide survey
Authors: Clemans-Cope Lisa , Holla Nikhil , Lee Henry C. , Cong Allison Shufei , Castro Robert , Chyi Lisa , Huang Angela , Taylor Kimá Joy , Kenney Genevieve M.
Published: January 2020

Objective

Assess management of neonatal abstinence syndrome (NAS) in California hospitals to identify potential opportunities to expand the use of best practices.

Study design

We fielded an internet-based survey of 37 questions to medical directors or nurse managers at 145 birth hospitals in California.

Results

Seventy-five participants (52%) responded. Most respondents reported having at least one written protocol for managing NAS, but gaps included protocols for pharmacologic management. Newer tools for assessing NAS severity were not commonly used. About half reported usually or always using nonpharmacologic strategies; there is scope for increasing breastfeeding when recommended, skin-to-skin care, and rooming-in.

Conclusions

We found systematic gaps in care for infants with NAS in a sample of California birth hospitals, as well as opportunities to spread best practices. Adoption of new approaches will vary across hospitals. A concerted statewide effort to facilitate such implementation has strong potential to increase access to evidence-based treatment for infants and mothers.
Microstructural constraints on magmatic mushes under Kīlauea Volcano, Hawaiʻi
Authors: Wieser Penny E. , Edmonds Marie , Maclennan John , Wheeler John
Published: January 2020

Distorted olivines of enigmatic origin are ubiquitous in erupted products from a wide range of volcanic systems (e.g., Hawaiʻi, Iceland, Andes). Investigation of these features at Kīlauea Volcano, Hawaiʻi, using an integrative crystallographic and chemical approach places quantitative constraints on mush pile thicknesses. Electron backscatter diffraction (EBSD) reveals that the microstructural features of distorted olivines, whose chemical composition is distinct from undistorted olivines, are remarkably similar to olivines within deformed mantle peridotites, but inconsistent with an origin from dendritic growth. This, alongside the spatial distribution of distorted grains and the absence of adcumulate textures, suggests that olivines were deformed within melt-rich mush piles accumulating within the summit reservoir. Quantitative analysis of subgrain geometry reveals that olivines experienced differential stresses of ∼3–12 MPa, consistent with their storage in mush piles with thicknesses of a few hundred metres. Overall, our microstructural analysis of erupted crystals provides novel insights into mush-rich magmatic systems.
TGF-β induces ST2 and programs ILC2 development
Authors: Wang Li , Tang Jun , Yang Xia , Zanvit Peter , Cui Kairong , Ku Wai Lim , Jin Wenwen , Zhang Dunfang , Goldberg Nathan , Cain Alexander , Ni Bing , Zhao Keji , Wu Yuzhang , Chen WanJun
Published: January 2020

The molecular pathways underlying the development of innate lymphoid cells (ILCs) are mostly unknown. Here we show that TGF-β signaling programs the development of ILC2s from their progenitors. Specifically, the deficiency of TGF-β receptor II in bone marrow progenitors results in inefficient development of ILC2s, but not ILC1s or ILC3s. Mechanistically, TGF-β signaling is required for the generation and maintenance of ILC2 progenitors (ILC2p). In addition, TGF-β upregulates the expression of the IL-33 receptor gene Il1rl1 (encoding IL-1 receptor-like 1, also known as ST2) in ILC2p and common helper-like innate lymphoid progenitors (CHILP), at least partially through the MEK-dependent pathway. These findings identify a function of TGF-β in the development of ILC2s from their progenitors.
Heritability estimates for 361 blood metabolites across 40 genome-wide association studies
Authors: Hagenbeek Fiona A. , Pool René , van Dongen Jenny , Draisma Harmen H. M. , Jan Hottenga Jouke , Willemsen Gonneke , Abdellaoui Abdel , Fedko Iryna O. , den Braber Anouk , Visser Pieter Jelle , de Geus Eco J. C. N. , Willems van Dijk Ko , Verhoeven Aswin , Suchiman H. Eka , Beekman Marian , Slagboom P. Eline , van Duijn Cornelia M. ,   BBMRI Metabolomics Consortium, Barkey Wolf J. J. H. , Cats D. , Amin N. , Beulens J. W. , van der Bom J. A. , Bomer N. , Demirkan A. , van Hilten J. A. , Meessen J. M. T. A. , Moed M. H. , Fu J. , Onderwater G. L. J. , Rutters F. , So-Osman C. , van der Flier W. M. , van der Heijden A. A. W. A. , van der Spek A. , Asselbergs F. W. , Boersma E. , Elders P. M. , Geleijnse J. M. , Ikram M. A. , Kloppenburg M. , Meulenbelt I. , Mooijaart S. P. , Nelissen R. G. H. H. , Netea M. G. , Penninx B. W. J. H. , Stehouwer C. D. A. , Teunissen C. E. , Terwindt G. M. , ‘t Hart L. M. , van den Maagdenberg A. M. J. M. , van der Harst P. , van der Horst I. C. C. , van der Kallen C. J. H. , van Greevenbroek M. M. J. , van Spil W. E. , Wijmenga C. , Zwinderman A. H. , Zhernikova A. , Jukema J. W. , Mei H. , Slofstra M. , Swertz M. , van den Akker E. B. , Deelen J. , Reinders M. J. T. , Harms Amy C. , Hankemeier Thomas , Bartels Meike , Nivard Michel G. , Boomsma Dorret I.
Published: January 2020

Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2total), and the proportion of heritability captured by known metabolite loci (h2Metabolite-hits) for 309 lipids and 52 organic acids. Our study reveals significant differences in h2Metabolite-hitsamong different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h2Metabolite-hitsestimates than phosphatidylcholines with low degrees of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes.
Quantitative earthquake-like statistical properties of the flow of soft materials below yield stress
Authors: Bera P. K. , Majumdar S. , Ouillon G. , Sornette D. , Sood A. K.
Published: January 2020

The flow behavior of soft materials below the yield stress can be rich and is not fully understood. Here, we report shear-stress-induced reorganization of three-dimensional solid-like soft materials formed by closely packed nematic domains of surfactant micelles and a repulsive Wigner glass formed by anisotropic clay nano-discs having ionic interactions. The creep response of both the systems below the yield stress results in angular velocity fluctuations of the shearing plate showing large temporal burst-like events that resemble seismic foreshocks-aftershocks data measuring the ground motion during earthquake avalanches. We find that the statistical properties of the quake events inside such a burst map on to the scaling relations for magnitude and frequency distribution of earthquakes, given by Gutenberg-Richter and Omori laws, and follow a power-law distribution of the inter-occurrence waiting time. In situ polarized optical microscopy reveals that during these events the system self-organizes to a much stronger solid-like state.
Microparticle traction force microscopy reveals subcellular force exertion patterns in immune cell–target interactions
Authors: Vorselen Daan , Wang Yifan , de Jesus Miguel M. , Shah Pavak K. , Footer Matthew J. , Huse Morgan , Cai Wei , Theriot Julie A.
Published: January 2020

Force exertion is an integral part of cellular behavior. Traction force microscopy (TFM) has been instrumental for studying such forces, providing spatial force measurements at subcellular resolution. However, the applications of classical TFM are restricted by the typical planar geometry. Here, we develop a particle-based force sensing strategy for studying cellular interactions. We establish a straightforward batch approach for synthesizing uniform, deformable and tuneable hydrogel particles, which can also be easily derivatized. The 3D shape of such particles can be resolved with superresolution (<50 nm) accuracy using conventional confocal microscopy. We introduce a reference-free computational method allowing inference of traction forces with high sensitivity directly from the particle shape. We illustrate the potential of this approach by revealing subcellular force patterns throughout phagocytic engulfment and force dynamics in the cytotoxic T-cell immunological synapse. This strategy can readily be adapted for studying cellular forces in a wide range of applications.
Electrooxidation enables highly regioselective dearomative annulation of indole and benzofuran derivatives
Authors: Liu Kun , Song Wenxu , Deng Yuqi , Yang Huiyue , Song Chunlan , Abdelilah Takfaoui , Wang Shengchun , Cong Hengjiang , Tang Shan , Lei Aiwen
Published: January 2020

The dearomatization of arenes represents a powerful synthetic methodology to provide three-dimensional chemicals of high added value. Here we report a general and practical protocol for regioselective dearomative annulation of indole and benzofuran derivatives in an electrochemical way. Under undivided electrolytic conditions, a series of highly functionalized five to eight-membered heterocycle-2,3-fused indolines and dihydrobenzofurans, which are typically unattainable under thermal conditions, can be successfully accessed in high yield with excellent regio- and stereo-selectivity. This transformation can also tolerate a wide range of functional groups and achieve good efficiency in large-scale synthesis under oxidant-free conditions. In addition, cyclic voltammetry, electron paramagnetic resonance (EPR) and kinetic studies indicate that the dehydrogenative dearomatization annulations arise from the anodic oxidation of indole into indole radical cation, and this process is the rate-determining step.
The Mouse Gut Microbial Biobank expands the coverage of cultured bacteria
Authors: Liu Chang , Zhou Nan , Du Meng-Xuan , Sun Yu-Tong , Wang Kai , Wang Yu-Jing , Li Dan-Hua , Yu Hai-Ying , Song Yuqin , Bai Bing-Bing , Xin Yuhua , Wu Linhuan , Jiang Cheng-Ying , Feng Jie , Xiang Hua , Zhou Yuguang , Ma Juncai , Wang Jun , Liu Hong-Wei , Liu Shuang-Jiang
Published: January 2020

Mice are widely used as experimental models for gut microbiome (GM) studies, yet the majority of mouse GM members remain uncharacterized. Here, we report the construction of a mouse gut microbial biobank (mGMB) that contains 126 species, represented by 244 strains that have been deposited in the China General Microorganism Culture Collection. We sequence and phenotypically characterize 77 potential new species and propose their nomenclatures. The mGMB includes 22 and 17 species that are significantly enriched in ob/ob and wild-type C57BL/6J mouse cecal samples, respectively. The genomes of the 126 species in the mGMB cover 52% of the metagenomic nonredundant gene catalog (sequence identity ≥ 60%) and represent 93–95% of the KEGG-Orthology-annotated functions of the sampled mouse GMs. The microbial and genome data assembled in the mGMB enlarges the taxonomic characterization of mouse GMs and represents a useful resource for studies of host-microbe interactions and of GM functions associated with host health and diseases.
Quantitative live cell imaging reveals influenza virus manipulation of Rab11A transport through reduced dynein association
Authors: Bhagwat Amar R. , Le Sage Valerie , Nturibi Eric , Kulej Katarzyna , Jones Jennifer , Guo Min , Tae Kim Eui , Garcia Benjamin A. , Weitzman Matthew D. , Shroff Hari , Lakdawala Seema S.
Published: January 2020

Assembly of infectious influenza A viruses (IAV) is a complex process involving transport from the nucleus to the plasma membrane. Rab11A-containing recycling endosomes have been identified as a platform for intracellular transport of viral RNA (vRNA). Here, using high spatiotemporal resolution light-sheet microscopy (~1.4 volumes/second, 330 nm isotropic resolution), we quantify Rab11A and vRNA movement in live cells during IAV infection and report that IAV infection decreases speed and increases arrest of Rab11A. Unexpectedly, infection with respiratory syncytial virus alters Rab11A motion in a manner opposite to IAV, suggesting that Rab11A is a common host component that is differentially manipulated by respiratory RNA viruses. Using two-color imaging we demonstrate co-transport of Rab11A and IAV vRNA in infected cells and provide direct evidence that vRNA-associated Rab11A have altered transport. The mechanism of altered Rab11A movement is likely related to a decrease in dynein motors bound to Rab11A vesicles during IAV infection.
BCL9 provides multi-cellular communication properties in colorectal cancer by interacting with paraspeckle proteins
Authors: Jiang Meng , Kang Yue , Sewastianik Tomasz , Wang Jiao , Tanton Helen , Alder Keith , Dennis Peter , Xin Yu , Wang Zhongqiu , Liu Ruiyang , Zhang Mengyun , Huang Ying , Loda Massimo , Srivastava Amitabh , Chen Runsheng , Liu Ming , Carrasco Ruben D.
Published: January 2020

Colorectal cancer (CRC) is the third most commonly diagnosed cancer, which despite recent advances in treatment, remains incurable due to molecular heterogeneity of tumor cells. The B-cell lymphoma 9 (BCL9) oncogene functions as a transcriptional co-activator of the Wnt/β-catenin pathway, which plays critical roles in CRC pathogenesis. Here we have identified a β-catenin-independent function of BCL9 in a poor-prognosis subtype of CRC tumors characterized by expression of stromal and neural associated genes. In response to spontaneous calcium transients or cellular stress, BCL9 is recruited adjacent to the interchromosomal regions, where it stabilizes the mRNA of calcium signaling and neural associated genes by interacting with paraspeckle proteins. BCL9 subsequently promotes tumor progression and remodeling of the tumor microenvironment (TME) by sustaining the calcium transients and neurotransmitter-dependent communication among CRC cells. These data provide additional insights into the role of BCL9 in tumor pathogenesis and point towards additional avenues for therapeutic intervention.
Imaging of fluorescence anisotropy during photoswitching provides a simple readout for protein self-association
Authors: Ojha Namrata , Rainey Kristin H. , Patterson George H.
Published: January 2020

Monitoring of protein oligomerization has benefited greatly from Förster Resonance Energy Transfer (FRET) measurements. Although donors and acceptors are typically fluorescent molecules with different spectra, homo-FRET can occur between fluorescent molecules of the same type if the emission spectrum overlaps with the absorption spectrum. Here, we describe homo-FRET measurements by monitoring anisotropy changes in photoswitchable fluorescent proteins while photoswitching to the off state. These offer the capability to estimate anisotropy in the same specimen during homo-FRET as well as non-FRET conditions. We demonstrate photoswitching anisotropy FRET (psAFRET) with a number of test chimeras and example oligomeric complexes inside living cells. We also present an equation derived from FRET and anisotropy equations which converts anisotropy changes into a factor we call delta r FRET (drFRET). This is analogous to an energy transfer efficiency and allows experiments performed on a given homo-FRET pair to be more easily compared across different optical configurations.
Different ways to transport ammonia in human and Mycobacterium tuberculosis NAD+ synthetases
Authors: Chuenchor Watchalee , Doukov Tzanko I. , Chang Kai-Ti , Resto Melissa , Yun Chang-Soo , Gerratana Barbara
Published: January 2020

NAD+ synthetase is an essential enzyme of de novo and recycling pathways of NAD+ biosynthesis in Mycobacterium tuberculosis but not in humans. This bifunctional enzyme couples the NAD+ synthetase and glutaminase activities through an ammonia tunnel but free ammonia is also a substrate. Here we show that the Homo sapiens NAD+ synthetase (hsNadE) lacks substrate specificity for glutamine over ammonia and displays a modest activation of the glutaminase domain compared to tbNadE. We report the crystal structures of hsNadE and NAD+ synthetase from M. tuberculosis (tbNadE) with synthetase intermediate analogues. Based on the observed exclusive arrangements of the domains and of the intra- or inter-subunit tunnels we propose a model for the inter-domain communication mechanism for the regulation of glutamine-dependent activity and NH3 transport. The structural and mechanistic comparison herein reported between hsNadE and tbNadE provides also a starting point for future efforts in the development of anti-TB drugs.
Enabling remote quantum emission in 2D semiconductors via porous metallic networks
Authors: Fonseca Jose J. , Yeats Andrew L. , Blue Brandon , Zalalutdinov Maxim K. , Brintlinger Todd , Simpkins Blake S. , Ratchford Daniel C. , Culbertson James C. , Grim Joel Q. , Carter Samuel G. , Ishigami Masa , Stroud Rhonda M. , Cress Cory D. , Robinson Jeremy T.
Published: January 2020

Here we report how two-dimensional crystal (2DC) overlayers influence the recrystallization of relatively thick metal films and the subsequent synergetic benefits this provides for coupling surface plasmon-polaritons (SPPs) to photon emission in 2D semiconductors. We show that annealing 2DC/Au films on SiO2 results in a reverse epitaxial process where initially nanocrystalline Au films gain texture, crystallographically orient with the 2D crystal overlayer, and form an oriented porous metallic network (OPEN) structure in which the 2DC can suspend above or coat the inside of the metal pores. Both laser excitation and exciton recombination in the 2DC semiconductor launch propagating SPPs in the OPEN film. Energy in-/out- coupling occurs at metal pore sites, alleviating the need for dielectric spacers between the metal and 2DC layer. At low temperatures, single-photon emitters (SPEs) are present across an OPEN-WSe2 film, and we demonstrate remote SPP-mediated excitation of SPEs at a distance of 17 μm.
Single-cell analysis based dissection of clonality in myelofibrosis
Authors: Mylonas Elena , Yoshida Kenichi , Frick Mareike , Hoyer Kaja , Christen Friederike , Kaeda Jaspal , Obenaus Matthias , Noerenberg Daniel , Hennch Cornelius , Chan Willy , Ochi Yotaro , Shiraishi Yuichi , Shiozawa Yusuke , Zenz Thorsten , Oakes Christopher C. , Sawitzki Birgit , Schwarz Michaela , Bullinger Lars , le Coutre Philipp , Rose-Zerilli Matthew J. J. , Ogawa Seishi , Damm Frederik
Published: January 2020

Cancer development is an evolutionary genomic process with parallels to Darwinian selection. It requires acquisition of multiple somatic mutations that collectively cause a malignant phenotype and continuous clonal evolution is often linked to tumor progression. Here, we show the clonal evolution structure in 15 myelofibrosis (MF) patients while receiving treatment with JAK inhibitors (mean follow-up 3.9 years). Whole-exome sequencing at multiple time points reveal acquisition of somatic mutations and copy number aberrations over time. While JAK inhibition therapy does not seem to create a clear evolutionary bottleneck, we observe a more complex clonal architecture over time, and appearance of unrelated clones. Disease progression associates with increased genetic heterogeneity and gain of RAS/RTK pathway mutations. Clonal diversity results in clone-specific expansion within different myeloid cell lineages. Single-cell genotyping of circulating CD34 + progenitor cells allows the reconstruction of MF phylogeny demonstrating loss of heterozygosity and parallel evolution as recurrent events.
Fungal community assembly in drought-stressed sorghum shows stochasticity, selection, and universal ecological dynamics
Authors: Gao Cheng , Montoya Liliam , Xu Ling , Madera Mary , Hollingsworth Joy , Purdom Elizabeth , Singan Vasanth , Vogel John , Hutmacher Robert B. , Dahlberg Jeffery A. , Coleman-Derr Devin , Lemaux Peggy G. , Taylor John W.
Published: January 2020

Community assembly of crop-associated fungi is thought to be strongly influenced by deterministic selection exerted by the plant host, rather than stochastic processes. Here we use a simple, sorghum system with abundant sampling to show that stochastic forces (drift or stochastic dispersal) act on fungal community assembly in leaves and roots early in host development and when sorghum is drought stressed, conditions when mycobiomes are small. Unexpectedly, we find no signal for stochasticity when drought stress is relieved, likely due to renewed selection by the host. In our experimental system, the host compartment exerts the strongest effects on mycobiome assembly, followed by the timing of plant development and lastly by plant genotype. Using a dissimilarity-overlap approach, we find a universality in the forces of community assembly of the mycobiomes of the different sorghum compartments and in functional guilds of fungi.
Hand-foot-and-mouth disease virus receptor KREMEN1 binds the canyon of Coxsackie Virus A10
Authors: Zhao Yuguang , Zhou Daming , Ni Tao , Karia Dimple , Kotecha Abhay , Wang Xiangxi , Rao Zihe , Jones E. Yvonne , Fry Elizabeth E. , Ren Jingshan , Stuart David I.
Published: January 2020

Coxsackievirus A10 (CV-A10) is responsible for an escalating number of severe infections in children, but no prophylactics or therapeutics are currently available. KREMEN1 (KRM1) is the entry receptor for the largest receptor-group of hand-foot-and-mouth disease causing viruses, which includes CV-A10. We report here structures of CV-A10 mature virus alone and in complex with KRM1 as well as of the CV-A10 A-particle. The receptor spans the viral canyon with a large footprint on the virus surface. The footprint has some overlap with that seen for the neonatal Fc receptor complexed with enterovirus E6 but is larger and distinct from that of another enterovirus receptor SCARB2. Reduced occupancy of a particle-stabilising pocket factor in the complexed virus and the presence of both unbound and expanded virus particles suggests receptor binding initiates a cascade of conformational changes that produces expanded particles primed for viral uncoating.
High-density information storage in an absolutely defined aperiodic sequence of monodisperse copolyester
Authors: Lee Jung Min , Koo Mo Beom , Lee Seul Woo , Lee Heelim , Kwon Junho , Shim Yul Hui , Kim So Youn , Kim Kyoung Taek
Published: January 2020

Synthesis of a polymer composed of a large discrete number of chemically distinct monomers in an absolutely defined aperiodic sequence remains a challenge in polymer chemistry. The synthesis has largely been limited to oligomers having a limited number of repeating units due to the difficulties associated with the step-by-step addition of individual monomers to achieve high molecular weights. Here we report the copolymers of α-hydroxy acids, poly(phenyllactic-co-lactic acid) (PcL) built via the cross-convergent method from four dyads of monomers as constituent units. Our proposed method allows scalable synthesis of sequence-defined PcL in a minimal number of coupling steps from reagents in stoichiometric amounts. Digital information can be stored in an aperiodic sequence of PcL, which can be fully retrieved as binary code by mass spectrometry sequencing. The information storage density (bit/Da) of PcL is 50% higher than DNA, and the storage capacity of PcL can also be increased by adjusting the molecular weight (~38 kDa).