bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning modelling of blood lipid biomarkers in familial hypercholesterolaemia versus polygenic/environmental dyslipidaemia
Authors: Correia Marta , Kagenaar Eva , van Schalkwijk Daniël Bernardus , Bourbon Mafalda , Gama-Carvalho Margarida 
Published: February 2021

AbstractFamilial hypercholesterolaemia increases circulating LDL-C levels and leads to premature cardiovascular disease when undiagnosed or untreated. Current guidelines support genetic testing in patients complying with clinical diagnostic criteria and cascade screening of their family members. However, most of hyperlipidaemic subjects do not present pathogenic variants in the known disease genes, and most likely suffer from polygenic hypercholesterolaemia, which translates into a relatively low yield of genetic screening programs. This study aims to identify new biomarkers and develop new approaches to improve the identification of individuals carrying monogenic causative variants. Using a machine-learning approach in a paediatric dataset of individuals, tested for disease causative genes and with an extended lipid profile, we developed new models able to classify familial hypercholesterolaemia patients with a much higher specificity than currently used methods. The best performing models incorporated parameters absent from the most common FH clinical criteria, namely apoB/apoA-I, TG/apoB and LDL1. These parameters were found to contribute to an improved identification of monogenic individuals. Furthermore, models using only TC and LDL-C levels presented a higher specificity of classification when compared to simple cut-offs. Our results can be applied towards the improvement of the yield of genetic screening programs and corresponding costs.
Common architectures in cyanobacteria Prochlorococcus cells visualized by X-ray diffraction imaging using X-ray free electron laser
Authors: Kobayashi Amane , Takayama Yuki , Hirakawa Takeshi , Okajima Koji , Oide Mao , Oroguchi Tomotaka , Inui Yayoi , Yamamoto Masaki , Matsunaga Sachihiro , Nakasako Masayoshi 
Published: February 2021

AbstractVisualization of intracellular structures and their spatial organization inside cells without any modification is essential to understand the mechanisms underlying the biological functions of cells. Here, we investigated the intracellular structure of cyanobacteriaProchlorococcusin the interphase by X-ray diffraction imaging using X-ray free-electron laser. A number of diffraction patterns from single cells smaller than 1 µm in size were collected with high signal-to-noise ratio with a resolution of up to 30 nm. From diffraction patterns, a set of electron density maps projected along the direction of the incident X-ray were retrieved with high reliability. The most characteristic structure found to be common among the cells was a C-shaped arrangement of 100-nm sized high-density spots, which surrounded a low-density area of 100 nm. Furthermore, a three-dimensional map reconstructed from the projection maps of individual cells was non-uniform, indicating the presence of common structures among cyanobacteria cells in the interphase. By referring to the fluorescent images for distributions of thylakoid membranes, nucleoids, and carboxysomes, we inferred and represented their spatial arrangements in the three-dimensional map. The arrangement allowed us to discuss the relevance of the intracellular organization to the biological functions of cyanobacteria.
Associations of early pregnancy BMI with adverse pregnancy outcomes and infant neurocognitive development
Authors: Chen Yu-Ting , Zhang Ting , Chen Chang , Xia Yin-Yin , Han Ting-Li , Chen Xu-Yang , He Xiao-Ling , Xu Ge , Zou Zhen , Qi Hong-Bo , Zhang Hua , Albert Benjamin B. , Colombo John , Baker Philip N. 
Published: February 2021

AbstractThe prevalence of overweight and obesity amongst reproductive women has been increasing worldwide. Our aim was to compare pregnancy outcomes and infant neurocognitive development by different BMI classifications and investigate whether early pregnancy BMI was associated with risks of adverse outcomes in a Southwest Chinese population. We analysed data from 1273 women enrolled in the Complex Lipids in Mothers and Babies (CLIMB) randomized controlled trial in Chongqing, China. Maternal BMI was classified as underweight, normal weight and overweight/obese according to the Chinese, WHO Asian, and WHO European standards. For the adverse pregnancy outcomes, after adjustment for potential confounders, an underweight BMI was associated with increased risk of small for gestational age (SGA) babies, and an overweight/obese BMI was associated with increased risk of maternal gestational diabetes mellitus (GDM), caesarean section (C-section), macrosomia and large for gestational age (LGA) babies. For infant neurocognitive development, 1017 mothers and their children participated; no significant differences were seen in the Mental Development Index (MDI) or the Psychomotor Development Index (PDI) between the three BMI groups. Our findings demonstrate that abnormal early pregnancy BMI were associated with increased risks of adverse pregnancy outcomes in Chinese women, while early pregnancy BMI had no significant influence on the infant neurocognitive development at 12 months of age.
Colorimetric detection of individual biothiols by tailor made reactions with silver nanoprisms
Authors: Li Pei , Lee Sang Mo , Kim Hyo Yong , Kim Soohyun , Park Steve , Park Ki Soo , Park Hyun Gyu 
Published: February 2021

AbstractWe herein described a rapid, sensitive, and selective colorimetric sensing platform for biothiols in human serum, which relies on the dual functions of biothiols as anti-etching and aggregating agent for silver nanoprisms (AgNPRs). In principle, the target biothiols that bind to the surface of AgNPRs through Ag–S covalent interactions protect the AgNPRs from being etched by chloride ion (Cl−) in human serum, thus exhibiting the blue/purple color that is indicative of AgNPRs. On the other hand, the color of AgNPRs turned to yellow in the absence of biothiols or the presence of non-sulfur-containing amino acids, indicating the formation of small silver nanoparticles (AgNPs). Importantly, we found that individual biothiols (Hcy, Cys, and GSH) exert not only the anti-etching effect, but also the aggregating effect on AgNPRs, which can be modulated by simply tuning the pH conditions, and this consequently allows for the discriminative detection of each biothiol. Based on this simple and cost-effective strategy, we successfully determined the Hcy, Cys, and GSH in human serum with high sensitivity and selectivity within 10 min, demonstrating the diagnostic capability and potential in practical applications.
Arginine glycosylation enhances methylglyoxal detoxification
Authors: El Qaidi Samir , Scott Nichollas E. , Hardwidge Philip R. 
Published: February 2021

AbstractType III secretion system effector proteins have primarily been characterized for their interactions with host cell proteins and their ability to disrupt host signaling pathways. We are testing the hypothesis that some effectors are active within the bacterium, where they modulate bacterial signal transduction and physiology. We previously determined that the Citrobacter rodentium effector NleB possesses an intra-bacterial glycosyltransferase activity that increases glutathione synthetase activity to protect the bacterium from oxidative stress. Here we investigated the potential intra-bacterial activities of NleB orthologs in Salmonella enterica and found that SseK1 and SseK3 mediate resistance to methylglyoxal. SseK1 glycosylates specific arginine residues on four proteins involved in methylglyoxal detoxification, namely GloA (R9), GloB (R190), GloC (R160), and YajL (R149). SseK1-mediated Arg-glycosylation of these four proteins significantly enhances their catalytic activity, thus providing another important example of the intra-bacterial activities of type three secretion system effector proteins. These data are also the first demonstration that a Salmonella T3SS effector is active within the bacterium.
Nonsurgical treatment outcomes for surgical candidates with lumbar disc herniation: a comprehensive cohort study
Authors: Kim Chi Heon , Choi Yunhee , Chung Chun Kee , Kim Ki-Jeong , Shin Dong Ah , Park Youn-Kwan , Kwon Woo-Keun , Yang Seung Heon , Lee Chang Hyun , Park Sung Bae , Kim Eun Sang , Hong Hyunsook , Cho Yongeun 
Published: February 2021

AbstractPhysicians often encounter surgical candidates with lumbar disc herniation (LDH) who request non-surgical management even though surgery is recommended. However, second opinions may differ among doctors. Therefore, a prospective comprehensive cohort study (CCS) was designed to assess outcomes of nonsurgical treatment for surgical candidates who were recommended to undergo surgery for LDH but requested a second opinion. The CCS includes both randomized and observational cohorts, comprising a nonsurgery cohort and surgery cohort, in a parallel fashion. Crossover between the nonsurgery and surgery cohorts was allowed at any time. The present study was an as-treated interim analysis of 128 cases (nonsurgery cohort, n = 71; surgery cohort, n = 57). Patient-reported outcomes included visual analogue scores for the back (VAS-B) and leg (VAS-L), the Oswestry Disability Index, the EuroQol 5-Dimension instrument, and the 36-Item Short-Form Health Survey (SF-36), which were evaluated at baseline and at 1, 3, 6, 12, and 24 months. At baseline, age and SF-36 physical function were significantly lower in the surgery cohort than in the nonsurgery cohort (p < 0.05). All adjusted outcomes significantly improved after both nonsurgical and surgical treatment (p < 0.05). The nonsurgery cohort showed less improvement of VAS-B and VAS-L scores at 1 month (p < 0.01), but no difference between cohorts was observed thereafter for 24 months (p > 0.01). Nonsurgical management may be a negotiable option even for surgical candidates in the shared decision-making process.
Citizen science for monitoring seasonal-scale beach erosion and behaviour with aerial drones
Authors: Pucino Nicolas , Kennedy David M. , Carvalho Rafael C. , Allan Blake , Ierodiaconou Daniel 
Published: February 2021

AbstractSandy beaches are highly dynamic systems which provide natural protection from the impact of waves to coastal communities. With coastal erosion hazards predicted to increase globally, data to inform decision making on erosion mitigation and adaptation strategies is becoming critical. However, multi-temporal topographic data over wide geographical areas is expensive and time consuming and often requires highly trained professionals. In this study we demonstrate a novel approach combining citizen science with low-cost unmanned aerial vehicles that reliably produces survey-grade morphological data able to model sediment dynamics from event to annual scales. The high-energy wave-dominated coast of south-eastern Australia, in Victoria, is used as a field laboratory to test the reliability of our protocol and develop a set of indices to study multi-scale erosional dynamics. We found that citizen scientists provide unbiased data as accurate as professional researchers. We then observed that open-ocean beaches mobilise three times as much sediment as embayed beaches and distinguished between slowed and accelerated erosional modes. The data was also able to assess the efficiency of sand nourishment for shore protection. Our citizen science protocol provides high quality monitoring capabilities, which although subject to important legislative preconditions, it is applicable in other parts of the world and transferable to other landscape systems where the understanding of sediment dynamics is critical for management of natural or anthropogenic processes.
Brain network motifs are markers of loss and recovery of consciousness
Authors: Duclos Catherine , Nadin Danielle , Mahdid Yacine , Tarnal Vijay , Picton Paul , Vanini Giancarlo , Golmirzaie Goodarz , Janke Ellen , Avidan Michael S. , Kelz Max B. , Mashour George A. , Blain-Moraes Stefanie 
Published: February 2021

AbstractMotifs are patterns of inter-connections between nodes of a network, and have been investigated as building blocks of directed networks. This study explored the re-organization of 3-node motifs during loss and recovery of consciousness. Nine healthy subjects underwent a 3-h anesthetic protocol while 128-channel electroencephalography (EEG) was recorded. In the alpha (8–13 Hz) band, 5-min epochs of EEG were extracted for: Baseline; Induction; Unconscious; 30-, 10- and 5-min pre-recovery of responsiveness; 30- and 180-min post-recovery of responsiveness. We constructed a functional brain network using the weighted and directed phase lag index, on which we calculated the frequency and topology of 3-node motifs. Three motifs (motifs 1, 2 and 5) were significantly present across participants and epochs, when compared to random networks (p < 0.05). The topology of motifs 1 and 5 changed significantly between responsive and unresponsive epochs (p-values < 0.01; Kendall’s W = 0.664 (motif 1) and 0.529 (motif 5)). Motif 1 was constituted of long-range chain-like connections, while motif 5 was constituted of short-range, loop-like connections. Our results suggest that anesthetic-induced unconsciousness is associated with a topological re-organization of network motifs. As motif topological re-organization may precede (motif 5) or accompany (motif 1) the return of responsiveness, motifs could contribute to the understanding of the neural correlates of consciousness.
Machine learning enables prompt prediction of hydration kinetics of multicomponent cementitious systems
Authors: Lapeyre Jonathan , Han Taihao , Wiles Brooke , Ma Hongyan , Huang Jie , Sant Gaurav , Kumar Aditya 
Published: February 2021

AbstractCarbonaceous (e.g., limestone) and aluminosilicate (e.g., calcined clay) mineral additives are routinely used to partially replace ordinary portland cement in concrete to alleviate its energy impact and carbon footprint. These mineral additives—depending on their physicochemical characteristics—alter the hydration behavior of cement; which, in turn, affects the evolution of microstructure of concrete, as well as the development of its properties (e.g., compressive strength). Numerical, reaction-kinetics models—e.g., phase boundary nucleation-and-growth models; which are based partly on theoretically-derived kinetic mechanisms, and partly on assumptions—are unable to produce a priori prediction of hydration kinetics of cement; especially in multicomponent systems, wherein chemical interactions among cement, water, and mineral additives occur concurrently. This paper introduces a machine learning-based methodology to enable prompt and high-fidelity prediction of time-dependent hydration kinetics of cement, both in plain and multicomponent (e.g., binary; and ternary) systems, using the system’s physicochemical characteristics as inputs. Based on a database comprising hydration kinetics profiles of 235 unique systems—encompassing 7 synthetic cements and three mineral additives with disparate physicochemical attributes—a random forests (RF) model was rigorously trained to establish the underlying composition-reactivity correlations. This training was subsequently leveraged by the RF model: to predict time-dependent hydration kinetics of cement in new, multicomponent systems; and to formulate optimal mixture designs that satisfy user-imposed kinetics criteria.
Amplified risk of spatially compounding droughts during co-occurrences of modes of natural ocean variability
Authors: Singh Jitendra , Ashfaq Moetasim , Skinner Christopher B. , Anderson Weston B. , Singh Deepti 
Published: February 2021

AbstractSpatially compounding droughts over multiple regions pose amplifying pressures on the global food system, the reinsurance industry, and the global economy. Using observations and climate model simulations, we analyze the influence of various natural Ocean variability modes on the likelihood, extent, and severity of compound droughts across ten regions that have similar precipitation seasonality and cover important breadbaskets and vulnerable populations. Although a majority of compound droughts are associated with El Niños, a positive Indian Ocean Dipole, and cold phases of the Atlantic Niño and Tropical North Atlantic (TNA) can substantially modulate their characteristics. Cold TNA conditions have the largest amplifying effect on El Niño-related compound droughts. While the probability of compound droughts is ~3 times higher during El Niño conditions relative to neutral conditions, it is ~7 times higher when cold TNA and El Niño conditions co-occur. The probability of widespread and severe compound droughts is also amplified by a factor of ~3 and ~2.5 during these co-occurring modes relative to El Niño conditions alone. Our analysis demonstrates that co-occurrences of these modes result in widespread precipitation deficits across the tropics by inducing anomalous subsidence, and reducing lower-level moisture convergence over the study regions. Our results emphasize the need for considering interactions within the larger climate system in characterizing compound drought risks rather than focusing on teleconnections from individual modes. Understanding the physical drivers and characteristics of compound droughts has important implications for predicting their occurrence and characterizing their impacts on interconnected societal systems.
Insulin-like 3 affects zebrafish spermatogenic cells directly and via Sertoli cells
Authors: Crespo Diego , Assis Luiz H. C. , Zhang Yu Ting , Safian Diego , Furmanek Tomasz , Skaftnesmo Kai Ove , Norberg Birgitta , Ge Wei , Choi Yung-Ching , den Broeder Marjo J. , Legler Juliette , Bogerd Jan , Schulz Rüdiger W. 
Published: February 2021

AbstractPituitary hormones can use local signaling molecules to regulate target tissue functions. In adult zebrafish testes, follicle-stimulating hormone (Fsh) strongly increases the production of insulin-like 3 (Insl3), a Leydig cell-derived growth factor found in all vertebrates. Little information is available regarding Insl3 function in adult spermatogenesis. The Insl3 receptors Rxfp2a and 2b were expressed by type A spermatogonia and Sertoli and myoid cells, respectively, in zebrafish testis tissue. Loss of insl3 increased germ cell apoptosis in males starting at 9 months of age, but spermatogenesis appeared normal in fully fertile, younger adults. Insl3 changed the expression of 409 testicular genes. Among others, retinoic acid (RA) signaling was up- and peroxisome proliferator-activated receptor gamma (Pparg) signaling was down-regulated. Follow-up studies showed that RA and Pparg signaling mediated Insl3 effects, resulting in the increased production of differentiating spermatogonia. This suggests that Insl3 recruits two locally active nuclear receptor pathways to implement pituitary (Fsh) stimulation of spermatogenesis.
Function of histone H2B monoubiquitination in transcriptional regulation of auxin biosynthesis in Arabidopsis
Authors: Zhang Li , Luo Pan , Bai Jie , Wu Lei , Di Dong-Wei , Liu Hai-Qing , Li Jing-Jing , Liu Ya-Li , Khaskheli Allah Jurio , Zhao Chang-Ming , Guo Guang-Qin 
Published: February 2021

AbstractThe auxin IAA is a vital plant hormone in controlling growth and development, but our knowledge about its complicated biosynthetic pathways and molecular regulation are still limited and fragmentary. cytokinin induced root waving 2 (ckrw2) was isolated as one of the auxin-deficient mutants in a large-scale forward genetic screen aiming to find more genes functioning in auxin homeostasis and/or its regulation. Here we show that CKRW2 is identical to Histone Monoubiquitination 1 (HUB1), a gene encoding an E3 ligase required for histone H2B monoubiquitination (H2Bub1) in Arabidopsis. In addition to pleiotropic defects in growth and development, loss of CKRW2/HUB1 function also led to typical auxin-deficient phenotypes in roots, which was associated with significantly lower expression levels of several functional auxin synthetic genes, namely TRP2/TSB1, WEI7/ASB1, YUC7 and AMI1. Corresponding defects in H2Bub1 were detected in the coding regions of these genes by chromatin immunoprecipitation (ChIP) analysis, indicating the involvement of H2Bub1 in regulating auxin biosynthesis. Importantly, application of exogenous cytokinin (CK) could stimulate CKRW2/HUB1 expression, providing an epigenetic avenue for CK to regulate the auxin homeostasis. Our results reveal a previously unknown mechanism for regulating auxin biosynthesis via HUB1/2-mediated H2Bub1 at the chromatin level.
1 °C warming increases spatial competition frequency and complexity in Antarctic marine macrofauna
Authors: Barnes David K. A. , Ashton Gail V. , Morley Simon A. , Peck Lloyd S. 
Published: February 2021

AbstractEnvironmental conditions of the Southern Ocean around Antarctica have varied little for >5 million years but are now changing. Here, we investigated how warming affects competition for space. Little considered in the polar regions, this is a critical component of biodiversity response. Change in competition in response to environment forcing might be detectable earlier than individual species presence/absence or performance measures (e.g. growth). Examination of fauna on artificial substrata in Antarctica’s shallows at ambient or warmed temperature found that, mid-century predicted 1°C warming (throughout the year or just summer-only), increased the probability of individuals encountering spatial competition, as well as density and complexity of such interactions. 2°C, late century predicted warming, increased variance in the probability and density of competition, but overall, competition did not significantly differ from ambient (control) levels. In summary only 1°C warming increased probability, density and complexity of spatial competition, which seems to be summer-only driven.
Silver-assisted gold-catalyzed formal synthesis of the anticoagulant Fondaparinux pentasaccharide
Authors: Walke Gulab , Kasdekar Niteshlal , Sutar Yogesh , Hotha Srinivas 
Published: February 2021

AbstractClinically approved anti-coagulant Fondaparinux is safe since it has zero contamination problems often associated with animal based heparins. Fondaparinux is a synthetic pentasaccharide based on the antithrombin-binding domain of Heparin sulfate and contains glucosamine, glucuronic acid and iduronic acid in its sequence. Here, we show the formal synthesis of Fondaparinux pentasaccharide by performing all glycosidations in a catalytic fashion for the first time to the best of our knowledge. Designer monosaccharides were synthesized avoiding harsh reaction conditions or reagents. Further, those were subjected to reciprocal donor-acceptor selectivity studies to guide [Au]/[Ag]-catalytic glycosidations for assembling the pentasaccharide in a highly convergent [3 + 2] or [3 + 1 + 1] manner. Catalytic and mild activation during glycosidations that produce desired glycosides exclusively, scalable route to the synthesis of unnatural and expensive iduronic acid, minimal number of steps and facile purifications, shared use of functionalized building blocks and excellent process efficiency are the salient features.