bluuebunny/crossref_metadata_2025 huggingface dataset:
Coronavirus vaccination rates in cultural areas in Germany
Authors: Spahn Claudia , Hipp Anna Maria , Richter Bernhard , Nusseck Manfred
Published: January 2022

Vaccination is a significant preventive measure to contain the coronavirus disease-2019 (COVID-19) pandemic. Vaccination rates can provide useful information on the potential spread of infection in a given population. In this study, vaccination rates and attitudes towards vaccination in cultural sectors, specifically the music sector, have been investigated. In total, 4341 persons in four different areas, including visitors to performances of classical music and musicals, as well as professional and amateur musicians, have participated in this survey. Results show rates of 86% recovered from the COVID-19 virus or vaccinated at least once, with 54.5% fully vaccinated. These vaccination rates were considerably higher compared to the general population. An attitude of hesitation towards vaccination found in 6.4% of those sampled was half that of the general population. These findings drawn from a large sample indicate that in the field of music a high vaccination rate is to be found, as well as a low rejection rate of vaccination on the part of the audience and performers. The results can be used to provide insights into the vaccination status to be found at cultural events and, importantly, to assist in consideration of whether cultural events should be permitted to continue under pandemic circumstances.
Noonan syndrome and pregnancy outcomes
Authors: Chow Christopher A. , Campbell Katherine H. , Chou Josephine C. , Elder Robert W.
Published: January 2022

Background:

Noonan syndrome is a genetic disorder with high prevalence of congenital heart defects, such as pulmonary stenosis, atrial septal defect and hypertrophic cardiomyopathy. Scarce data exists regarding the safety of pregnancy in patients with Noonan syndrome, particularly in the context of maternal cardiac disease.

Study design:

We performed a retrospective chart review of patients at Yale-New Haven Hospital from 2012 to 2020 with diagnoses of Noonan syndrome and pregnancy. We analysed medical records for pregnancy details and cardiac health, including echocardiograms to quantify maternal cardiac dysfunction through measurements of pulmonary valve peak gradient, structural heart defects and interventricular septal thickness.

Results:

We identified five women with Noonan syndrome (10 pregnancies). Three of five patients had pulmonary valve stenosis at the time of pregnancy, two of which had undergone cardiac procedures. 50% of pregnancies (5/10) resulted in pre-term birth. 80% (8/10) of all deliveries were converted to caesarean section after a trial of labour. One pregnancy resulted in intra-uterine fetal demise while nine pregnancies resulted in the birth of a living infant. 60% (6/10) of livebirths required care in the neonatal intensive care unit. One infant passed away at 5 weeks of age.

Conclusions:

The majority of mothers had pre-existing, though mild, heart disease. We found high rates of prematurity, conversion to caesarean section, and elevated level of care. No maternal complications resulted in long-term morbidity. Our study suggests that women with Noonan syndrome and low-risk cardiac lesions can become pregnant and deliver a healthy infant with counselling and risk evaluation.
Wrangle with hypertension: lowered salt intake may not compromise iodine status among tribes of Central India
Authors: Chakma Tapas , Shrivastava Suyesh , Kavishwar Arvind
Published: January 2022

Objectives:

The most important risk factor of cardiovascular disease is hypertension and high salt intake contributes to high blood pressure. However, to prevent iodine deficiency disorders, the iodisation of salt is a proven strategy. So, on one hand, we suggest people reduced salt consumption but on the other hand, we also fear an increase in the prevalence of iodine deficiency disorders. In the present study, we investigated the possibility of salt intake at WHO recommended levels resulting in higher or lower iodine status in India by assessing the urinary iodine status and its relation with blood pressure.

Design:

It was a cross-sectional study.

Setting:

It was a community-based study.

Participants:

We collected 24-hour urine samples for estimation of iodine concentrations in urine from 411 adult hypertensives in the Mandla district of central India. Urinary iodine was estimated using Thermo ORION make ion-selective electrodes.

Results:

The median urinary iodine excretion was 162·6 mcg/l. Interestingly 371 (90·26 %) subjects were observed with > 200 mcg/l urinary iodine concentration level indicating iodine sufficiency. Individuals with high urine Na significantly had high blood pressure as compared with individuals with low urinary Na excretion (P < 0·01). There is a higher probability of high urine iodine levels among individuals with higher urine Na levels.

Conclusion:

The study revealed that 90 % of the population were excreting excessive iodine in urine, which is more than adequate iodine uptake. This excess uptake enables a scope for reduction in salt intake to control hypertension.
The performance of mid-upper arm circumference for identifying children and adolescents with overweight and obesity: a systematic review and meta-analysis
Authors: Sisay Binyam Girma , Hassen Hamid Yimam , Jima Beshada Rago , Atlantis Evan , Gebreyesus Seifu Hagos
Published: January 2022

Objective:

This study aimed to synthesise the existing evidence on the performance of mid-upper arm circumference (MUAC) to identify children and adolescents with overweight and obesity.

Design:

Systematic review and meta-analysis.

Setting:

We searched PubMed, EMBASE, SCOPUS, Cochrane Library, Web of Science, CINAHL and Google scholar databases from their inception to December 10, 2021, for relevant studies. There were no restrictions regarding the language of publication. Studies reporting measures for the diagnostic performance of MUAC compared with a reference standard for diagnosing overweight and obesity in children and adolescents aged 2–19 years were included.

Participants:

A total of 54 381 children and adolescents from twenty-one studies were reviewed; ten studies contributed to meta-analyses.

Results:

In boys, MUAC showed a pooled AUC of 0·92 (95 % CI 0·89, 0·94), sensitivity of 84·4 (95 % CI 84·6, 90·8) and a specificity of 86·0 (95 % CI 79·2, 90·8), when compared against BMI z-score, defined overweight and obesity. As for girls, MUAC showed a pooled AUC of 0·93 (95 % CI 0·90, 0·95), sensitivity of 86·4 (95 % CI 79·8, 91·0), specificity of 86·6 (95 % CI 82·2, 90·1) when compared against overweight and obesity defined using BMI z-scores.

Conclusion:

In comparison with BMI, MUAC has an excellent performance to identify overweight and obesity in children and adolescents. However, no sufficient evidence on the performance of MUAC compared with gold standard measures of adiposity. Future research should compare performance of MUAC to the ‘golden standard’ measure of excess adiposity.
Church of Nigeria (Anglican Communion) and the Challenges of Missionary Diocese
Authors: Asadu George C.
Published: January 2022

For some years now the Anglican Church in Nigeria has been contending with the problems arising from the creation of missionary dioceses. Many retreats for the bishops in the missionary dioceses have been held from late 2000 to date, in an effort to find solutions to the problems, yet the problems have continued unabated. The situation provokes concern and interest in public discourse and intellectual circles. This study examines critically the problems of missionary dioceses and the effects of such problems on the workers and their families therein using a historical approach and both primary and secondary sources. The findings show that some of the missionary dioceses were created with poor funding and facilities as there was no adequate preparation for their creation. The study therefore recommends that the Church of Nigeria should support the missionary dioceses to stabilize.
Variability of Jupiter's Main Auroral Emission and Satellite Footprints Observed With HST During the Galileo Era
Authors: Vogt Marissa F. , Rutala Matthew , Bonfond Bertrand , Clarke John T. , Moore Luke , Nichols Jonathan D.
Published: January 2022

Hubble Space Telescope images of Jupiter's UV aurora show that the main emission occasionally contracts or expands, shifting toward or away from the magnetic pole by several degrees in response to changes in the solar wind dynamic pressure and Io's volcanic activity. When the auroral footprints of the Galilean satellites move with the main emission this indicates a change in the stretched field line configuration that shifts the ionospheric mapping of a given radial distance at the equator. However, in some cases, the main emission shifts independently from the satellite footprints, indicating that the variability stems from some other part of the corotation enforcement current system that produces Jupiter's main auroral emissions. Here, we analyze HST images from the Galileo era (1996–2003) and compare latitudinal shifts of the Ganymede footprint and the main auroral emission. We focus on images with overlapping Galileo measurements because concurrent measurements are available of the current sheet strength, which indicates the amount of field line stretching and can influence both the main emission and satellite footprints. We show that the Ganymede footprint and main auroral emission typically, but do not always, move together. Additionally, we find that the auroral shifts are only weakly linked to changes in the current sheet strength measured by Galileo. We discuss implications of the observed auroral shifts in terms of the magnetospheric mapping. Finally, we establish how the statistical reference main emission contours vary with central meridian longitude and show that the dependence results from magnetospheric local time asymmetries.
The independent association between vitamin B12 and insomnia in Chinese patients with type 2 diabetes mellitus: a cross-sectional study
Authors: Xiong Shuyuan , Liu Zhiping , Yao Ning , Zhang Xiaoru , Ge Qian
Published: January 2022

Background/objectives

Insomnia is highly prevalent in patients with type 2 diabetes mellitus (T2DM). This study therefore evaluated the associations between various micronutrients and insomnia in patients with T2DM.

Subjects/methods

Between January 2018 and December 2020, a total of 418 T2DM patients with or without insomnia were recruited. Clinical and biochemical parameters, as well as micronutrient levels, were measured in each participant. Insomnia and sleep quality were assessed using the Athens Insomnia Scale and Pittsburgh Sleep Quality Index, respectively.

Results

Insomnia was found in 24.16% of patients with T2DM. Compared with T2DM patients without insomnia, patients with insomnia had significantly higher levels of vitamin B12 (VitB12). Increased VitB12 was an independent risk factor for insomnia (OR 1.61 [1.06–2.45], P = 0.03). A cut-off value of 517.50 pg/ml VitB12 (P = 0.01, AUC 0.61, standard error 0.04) predicted insomnia risk. Moreover, increased VitB12 levels in patients with insomnia were closely correlated with the use of mecobalamin.

Conclusions

This study suggests that elevated serum VitB12 level is independently associated with the incidence of insomnia and predicts increased insomnia risk in Chinese patients with T2DM.
Neurobehavioral abnormalities following prenatal psychosocial stress are differentially modulated by maternal environment
Authors: Zoubovsky Sandra P. , Williams Michael T. , Hoseus Sarah , Tumukuntala Shivani , Riesenberg Amy , Schulkin Jay , Vorhees Charles V. , Campbell Kenneth , Lim Hee-Woong , Muglia Louis J.
Published: January 2022

Prenatal stress (PS) is associated with increased vulnerability to affective disorders. Transplacental glucocorticoid passage and stress-induced maternal environment alterations are recognized as potential routes of transmission that can fundamentally alter neurodevelopment. However, molecular mechanisms underlying aberrant emotional outcomes or the individual contributions intrauterine stress versus maternal environment play in shaping these mechanisms remain unknown. Here, we report anxiogenic behaviors, anhedonia, and female hypothalamic-pituitary-adrenal axis hyperactivity as a consequence of psychosocial PS in mice. Evidence of fetal amygdala programming precedes these abnormalities. In adult offspring, we observe amygdalar transcriptional changes demonstrating sex-specific dysfunction in synaptic transmission and neurotransmitter systems. We find these abnormalities are primarily driven by in-utero stress exposure. Importantly, maternal care changes postnatally reverse anxiety-related behaviors and partially rescue gene alterations associated with neurotransmission. Our data demonstrate the influence maternal environment exerts in shaping offspring emotional development despite deleterious effects of intrauterine stress.
A novel pathogenic variant of the FH gene in a family with hereditary leiomyomatosis and renal cell carcinoma
Authors: Yagi Yasuto , Abeto Naoko , Shiraishi Junichi , Miyata Chieko , Inoue Satomi , Murakami Haruka , Nakashima Moeko , Sugano Kokichi , Ushiama Mineko , Yoshida Teruhiko , Yamazawa Kazuki
Published: January 2022

Hereditary leiomyomatosis and renal cell carcinoma caused by loss-of-function germline variants of the FH gene can develop into aggressive renal cell carcinoma (RCC). We report the case of a 27-year-old man who died of RCC. Genetic testing revealed a novel pathogenic variant of FH, NM_000143.3:c.1013_1014del (p.Ile338Serfs*3), that was also identified in healthy siblings. Identification of genetic causes in the proband helped us to provide relatives with precise genetic counseling and appropriate surveillance programs.
Obligate mutualistic cooperation limits evolvability
Authors: Pauli Benedikt , Oña Leonardo , Hermann Marita , Kost Christian
Published: January 2022

Cooperative mutualisms are widespread and play fundamental roles in many ecosystems. Given that these interactions are often obligate, the Darwinian fitness of the participating individuals is not only determined by the information encoded in their own genomes, but also the traits and capabilities of their corresponding interaction partners. Thus, a major outstanding question is how obligate cooperative mutualisms affect the ability of organisms to adapt evolutionarily to changing environmental conditions. Here we address this issue using a mutualistic cooperation between two auxotrophic genotypes of Escherichia coli that reciprocally exchanged costly amino acids. Amino acid-supplemented monocultures and unsupplemented cocultures were exposed to stepwise increasing concentrations of different antibiotics. This selection experiment reveals that metabolically interdependent bacteria are generally less able to adapt to environmental stress than autonomously growing strains. Moreover, obligate cooperative mutualists frequently regain metabolic autonomy, resulting in a collapse of the mutualistic interaction. Together, our results identify a limited evolvability as a significant evolutionary cost that individuals have to pay when entering into an obligate mutualistic cooperation.
Au-activated N motifs in non-coherent cupric porphyrin metal organic frameworks for promoting and stabilizing ethylene production
Authors: Xie Xulan , Zhang Xiang , Xie Miao , Xiong Likun , Sun Hao , Lu Yongtao , Mu Qiaoqiao , Rummeli Mark H. , Xu Jiabin , Li Shuo , Zhong Jun , Deng Zhao , Ma Bingyun , Cheng Tao , Goddard William A. , Peng Yang
Published: January 2022

Direct implementation of metal-organic frameworks as the catalyst for CO2 electroreduction has been challenging due to issues such as poor conductivity, stability, and limited > 2e− products. In this study, Au nanoneedles are impregnated into a cupric porphyrin-based metal-organic framework by exploiting ligand carboxylates as the Au3+ -reducing agent, simultaneously cleaving the ligand-node linkage. Surprisingly, despite the lack of a coherent structure, the Au-inserted framework affords a superb ethylene selectivity up to 52.5% in Faradaic efficiency, ranking among the best for metal-organic frameworks reported in the literature. Through operando X-ray, infrared spectroscopies and density functional theory calculations, the enhanced ethylene selectivity is attributed to Au-activated nitrogen motifs in coordination with the Cu centers for C-C coupling at the metalloporphyrin sites. Furthermore, the Au-inserted catalyst demonstrates both improved structural and catalytic stability, ascribed to the altered charge conduction path that bypasses the incoherent framework. This study underlines the modulation of reticular metalloporphyrin structure by metal impregnation for steering the CO2 reduction reaction pathway.
Abrupt conclusion of the late Miocene-early Pliocene biogenic bloom at 4.6-4.4 Ma
Authors: Karatsolis B. – Th. , Lougheed B. C. , De Vleeschouwer D. , Henderiks J.
Published: January 2022

The late Miocene-early Pliocene biogenic bloom was an extended time interval characterised by elevated ocean export productivity at numerous locations. As primary productivity is nutrient-limited at low-to-mid latitudes, this bloom has been attributed to an increase or a redistribution of available nutrients, potentially involving ocean-gateway or monsoon-related mechanisms. While the exact causal feedbacks remain debated, there is even less consensus on what caused the end of the biogenic bloom. Here, we compile Mio-Pliocene paleoproductivity proxy data from all major ocean basins to evaluate the timing and pacing of this termination. This systematic analysis reveals an abrupt and sustained reduction in low-latitude ocean productivity at 4.6–4.4 Ma. The decline in productivity coincided with a prolonged period of low orbital eccentricity and a shift towards lower-amplitude obliquity, an astronomical configuration linked to reduced East Asian Monsoon intensity and decreased riverine nutrient supply.
Distinct kinetics of antibodies to 111 Plasmodium falciparum proteins identifies markers of recent malaria exposure
Authors: Yman Victor , Tuju James , White Michael T. , Kamuyu Gathoni , Mwai Kennedy , Kibinge Nelson , Asghar Muhammad , Sundling Christopher , Sondén Klara , Murungi Linda , Kiboi Daniel , Kimathi Rinter , Chege Timothy , Chepsat Emily , Kiyuka Patience , Nyamako Lydia , Osier Faith H. A. , Färnert Anna
Published: January 2022

Strengthening malaria surveillance is a key intervention needed to reduce the global disease burden. Reliable serological markers of recent malaria exposure could improve current surveillance methods by allowing for accurate estimates of infection incidence from limited data. We studied the IgG antibody response to 111Plasmodium falciparumproteins in 65 adult travellers followed longitudinally after a natural malaria infection in complete absence of re-exposure. We identified a combination of five serological markers that detect exposure within the previous three months with >80% sensitivity and specificity. Using mathematical modelling, we examined the antibody kinetics and determined that responses informative of recent exposure display several distinct characteristics: rapid initial boosting and decay, less inter-individual variation in response kinetics, and minimal persistence over time. Such serological exposure markers could be incorporated into routine malaria surveillance to guide efforts for malaria control and elimination.
RNF43/ZNRF3 loss predisposes to hepatocellular-carcinoma by impairing liver regeneration and altering the liver lipid metabolic ground-state
Authors: Belenguer Germán , Mastrogiovanni Gianmarco , Pacini Clare , Hall Zoe , Dowbaj Anna M. , Arnes-Benito Robert , Sljukic Aleksandra , Prior Nicole , Kakava Sofia , Bradshaw Charles R. , Davies Susan , Vacca Michele , Saeb-Parsy Kourosh , Koo Bon-Kyoung , Huch Meritxell
Published: January 2022

RNF43/ZNRF3 negatively regulate WNT signalling. Both genes are mutated in several types of cancers, however, their contribution to liver disease is unknown. Here we describe that hepatocyte-specific loss of Rnf43/Znrf3 results in steatohepatitis and in increase in unsaturated lipids, in the absence of dietary fat supplementation. Upon injury, Rnf43/Znrf3 deletion results in defective hepatocyte regeneration and liver cancer, caused by an imbalance between differentiation/proliferation. Using hepatocyte-, hepatoblast- and ductal cell-derived organoids we demonstrate that the differentiation defects and lipid alterations are, in part, cell-autonomous. Interestingly, ZNRF3 mutant liver cancer patients present poorer prognosis, altered hepatic lipid metabolism and steatohepatitis/NASH signatures. Our results imply that RNF43/ZNRF3 predispose to liver cancer by controlling the proliferative/differentiation and lipid metabolic state of hepatocytes. Both mechanisms combined facilitate the progression towards malignancy. Our findings might aid on the management of those RNF43/ZNRF3 mutated individuals at risk of developing fatty liver and/or liver cancer.
Impact of bulk-edge coupling on observation of anyonic braiding statistics in quantum Hall interferometers
Authors: Nakamura J. , Liang S. , Gardner G. C. , Manfra M. J.
Published: January 2022

Quantum Hall interferometers have been used to probe fractional charge and statistics of quasiparticles. We present measurements of a small Fabry–Perot interferometer in which the electrostatic coupling constants which affect interferometer behavior can be determined experimentally. Near the center of the ν = 1/3 state this device exhibits Aharonov–Bohm interference interrupted by a few discrete phase jumps, and Φ0 oscillations at higher and lower magnetic fields, consistent with theoretical predictions for detection of anyonic statistics. We estimate the electrostatic parameters KI and KIL by two methods: using the ratio of oscillation periods in compressible versus incompressible regions, and from finite-bias conductance measurements. We find that the extracted KI and KIL can account for the deviation of the phase jumps from the theoretical anyonic phase θa = 2π/3. At integer states, we find that KI and KIL can account for the Aharonov–Bohm and Coulomb-dominated behavior of different edge states.
Identification of a diarylpentanoid-producing polyketide synthase revealing an unusual biosynthetic pathway of 2-(2-phenylethyl)chromones in agarwood
Authors: Wang Xiao-Hui , Gao Bo-Wen , Nakashima Yu , Mori Takahiro , Zhang Zhong-Xiu , Kodama Takeshi , Lee Yuan-E , Zhang Ze-Kun , Wong Chin-Piow , Liu Qian-Qian , Qi Bo-Wen , Wang Juan , Li Jun , Liu Xiao , Abe Ikuro , Morita Hiroyuki , Tu Peng-Fei , Shi She-Po
Published: January 2022

2-(2-Phenylethyl)chromones (PECs) are the principal constituents contributing to the distinctive fragrance of agarwood. How PECs are biosynthesized is currently unknown. In this work, we describe a diarylpentanoid-producing polyketide synthase (PECPS) identified fromAquilaria sinensis. Through biotransformation experiments using fluorine-labeled substrate, transient expression of PECPS inNicotiana benthamiana, and knockdown ofPECPSexpression inA. sinensiscalli, we demonstrate that the C6–C5–C6scaffold of diarylpentanoid is the common precursor of PECs, and PECPS plays a crucial role in PECs biosynthesis. Crystal structure (1.98 Å) analyses and site-directed mutagenesis reveal that, due to its small active site cavity (247 Å3), PECPS employs a one-pot formation mechanism including a “diketide-CoA intermediate-released” step for the formation of the C6–C5–C6scaffold. The identification of PECPS, the pivotal enzyme of PECs biosynthesis, provides insight into not only the feasibility of overproduction of pharmaceutically important PECs using metabolic engineering approaches, but also further exploration of how agarwood is formed.
Stratification constrains future heat and carbon uptake in the Southern Ocean between 30°S and 55°S
Authors: Bourgeois Timothée , Goris Nadine , Schwinger Jörg , Tjiputra Jerry F.
Published: January 2022

The Southern Ocean between 30°S and 55°S is a major sink of excess heat and anthropogenic carbon, but model projections of these sinks remain highly uncertain. Reducing such uncertainties is required to effectively guide the development of climate mitigation policies for meeting the ambitious climate targets of the Paris Agreement. Here, we show that the large spread in the projections of future excess heat uptake efficiency and cumulative anthropogenic carbon uptake in this region are strongly linked to the models’ contemporary stratification. This relationship is robust across two generations of Earth system models and is used to reduce the uncertainty of future estimates of the cumulative anthropogenic carbon uptake by up to 53% and the excess heat uptake efficiency by 28%. Our results highlight that, for this region, an improved representation of stratification in Earth system models is key to constrain future carbon budgets and climate change projections.
Pantothenate biosynthesis is critical for chronic infection by the neurotropic parasite Toxoplasma gondii
Authors: Lunghi Matteo , Kloehn Joachim , Krishnan Aarti , Varesio Emmanuel , Vadas Oscar , Soldati-Favre Dominique
Published: January 2022

Coenzyme A (CoA) is an essential molecule acting in metabolism, post-translational modification, and regulation of gene expression. While all organisms synthesize CoA, many, including humans, are unable to produce its precursor, pantothenate. Intriguingly, like most plants, fungi and bacteria, parasites of the coccidian subgroup of Apicomplexa, including the human pathogen Toxoplasma gondii, possess all the enzymes required for de novo synthesis of pantothenate. Here, the importance of CoA and pantothenate biosynthesis for the acute and chronic stages of T. gondii infection is dissected through genetic, biochemical and metabolomic approaches, revealing that CoA synthesis is essential for T. gondii tachyzoites, due to the parasite’s inability to salvage CoA or intermediates of the pathway. In contrast, pantothenate synthesis is only partially active in T. gondii tachyzoites, making the parasite reliant on its uptake. However, pantothenate synthesis is crucial for the establishment of chronic infection, offering a promising target for intervention against the persistent stage of T. gondii.
Nanobubbles explain the large slip observed on lubricant-infused surfaces
Authors: Vega-Sánchez Christopher , Peppou-Chapman Sam , Zhu Liwen , Neto Chiara
Published: January 2022

Lubricant-infused surfaces hold promise to reduce the huge frictional drag that slows down the flow of fluids at microscales. We show that infused Teflon wrinkled surfaces induce an effective slip length 50 times larger than expected based on the presence of the lubricant alone. This effect is particularly striking as it occurs even when the infused lubricant’s viscosity is several times higher than that of the flowing liquid. Crucially, the slip length increases with increasing air content in the water but is much higher than expected even in degassed and plain Milli-Q water. Imaging directly the immersed interface using a mapping technique based on atomic force microscopy meniscus force measurements reveals that the mechanism responsible for this huge slip is the nucleation of surface nanobubbles. Using a numerical model and the height and distribution of these surface nanobubbles, we can quantitatively explain the large fluid slip observed in these surfaces.
Pre-configuring chromatin architecture with histone modifications guides hematopoietic stem cell formation in mouse embryos
Authors: Li Chen C. , Zhang Guangyu , Du Junjie , Liu Di , Li Zongcheng , Ni Yanli , Zhou Jie , Li Yunqiao , Hou Siyuan , Zheng Xiaona , Lan Yu , Liu Bing , He Aibin
Published: January 2022

The gene activity underlying cell differentiation is regulated by a diverse set of transcription factors (TFs), histone modifications, chromatin structures and more. Although definitive hematopoietic stem cells (HSCs) are known to emerge via endothelial-to-hematopoietic transition (EHT), how the multi-layered epigenome is sequentially unfolded in a small portion of endothelial cells (ECs) transitioning into the hematopoietic fate remains elusive. With optimized low-input itChIP-seq and Hi-C assays, we performed multi-omics dissection of the HSC ontogeny trajectory across early arterial ECs (eAECs), hemogenic endothelial cells (HECs), pre-HSCs and long-term HSCs (LT-HSCs) in mouse embryos. Interestingly, HSC regulatory regions are already pre-configurated with active histone modifications as early as eAECs, preceding chromatin looping dynamics within topologically associating domains. Chromatin looping structures between enhancers and promoters only become gradually strengthened over time. Notably, RUNX1, a master TF for hematopoiesis, enriched at half of these loops is observed early from eAECs through pre-HSCs but its enrichment further increases in HSCs. RUNX1 and co-TFs together constitute a central, progressively intensified enhancer-promoter interactions. Thus, our study provides a framework to decipher how temporal epigenomic configurations fulfill cell lineage specification during development.
Contribution of the medial eye field network to the voluntary deployment of visuospatial attention
Authors: Herbet Guillaume , Duffau Hugues
Published: January 2022

Historically, the study of patients with spatial neglect has provided fundamental insights into the neural basis of spatial attention. However, lesion mapping studies have been unsuccessful in establishing the potential role of associative networks spreading on the dorsal-medial axis, mainly because they are uncommonly targeted by vascular injuries. Here we combine machine learning-based lesion-symptom mapping, disconnection analyses and the longitudinal behavioral data of 128 patients with well-delineated surgical resections. The analyses show that surgical resections in a location compatible with both the supplementary and the cingulate eye fields, and disrupting the dorsal-medial fiber network, are specifically associated with severely diminished performance on a visual search task (i.e., visuo-motor exploratory neglect) with intact performance on a task probing the perceptual component of neglect. This general finding provides causal evidence for a role of the frontal-medial network in the voluntary deployment of visuo-spatial attention.
Fibroblast-mediated uncaging of cancer cells and dynamic evolution of the physical microenvironment
Authors: Liu Chang , Mak Michael
Published: January 2022

Stromal cells are prominent in solid tumor microenvironments and contribute to tumor progression. In particular, fibroblasts are common cell types in the tumor stroma that play important roles in remodeling the extracellular matrix (ECM). Here, we perform co-culture experiments with tumor cells and fibroblasts embedded in 3D collagen I matrices. We investigate the impact of fibroblasts on the migratory behavior of neighboring tumor cells and on the evolution of the surrounding ECM. We find that fibroblasts increase tumor cell motility and facilitate the transition from confined to diffusive tumor cell motions, indicative of an uncaging effect. Furthermore, the ECM is globally and locally remodeled substantially with the presence of fibroblasts. Moreover, these fibroblast-mediated phenomena are in part dependent on matrix metalloproteinases.
Extracting phylogenetic dimensions of coevolution reveals hidden functional signals
Authors: Colavin Alexandre , Atolia Esha , Bitbol Anne-Florence , Huang Kerwyn Casey
Published: January 2022

Despite the structural and functional information contained in the statistical coupling between pairs of residues in a protein, coevolution associated with function is often obscured by artifactual signals such as genetic drift, which shapes a protein’s phylogenetic history and gives rise to concurrent variation between protein sequences that is not driven by selection for function. Here, we introduce a background model for phylogenetic contributions of statistical coupling that separates the coevolution signal due to inter-clade and intra-clade sequence comparisons and demonstrate that coevolution can be measured on multiple phylogenetic timescales within a single protein. Our method, nested coevolution (NC), can be applied as an extension to any coevolution metric. We use NC to demonstrate that poorly conserved residues can nonetheless have important roles in protein function. Moreover, NC improved the structural-contact predictions of several coevolution-based methods, particularly in subsampled alignments with fewer sequences. NC also lowered the noise in detecting functional sectors of collectively coevolving residues. Sectors of coevolving residues identified after application of NC were more spatially compact and phylogenetically distinct from the rest of the protein, and strongly enriched for mutations that disrupt protein activity. Thus, our conceptualization of the phylogenetic separation of coevolution provides the potential to further elucidate relationships among protein evolution, function, and genetic diseases.
Intestinal ion regulation exhibits a daily rhythm in Gymnocypris przewalskii exposed to high saline and alkaline water
Authors: Wang Fei , Zhu Lin , Wei Yuxing , Gao Pengcheng , Liu Yimeng , Zhou Kai , Sun Zhen , Lai Qifang , Yao Zongli
Published: January 2022

Naked carp (Gymnocypris przewalskii), endemic to the saline-alkaline Lake Qinghai, have the capacity to tolerate combinations of high salinity and alkalinity, but migrate to spawn in freshwater rivers each year. In this study, we measured the drinking rate over a 24 h period for naked carp exposed to saline-alkaline lake waters with salinities of 15 (L15) and 17 (L17). We also assessed the daily feed intakes of naked carp exposed to L15 and fresh water (FW). Additionally, we studied the daily expression of acid–base regulation and osmoregulation related genes and proteins in the intestine of naked carp exposed to saline-alkaline lake waters. Our results revealed that the drinking rate at night was significantly higher than in daytime when exposed to either L15 or L17, while feed intakes in daytime were significantly higher than at night. The relative expression of Na+/K+-ATPase α (NKA-α), solute carrier family members 26A6 (SLC26A6) and 4A4 (SLC4A4) in the intestine of naked carp exposed to L17 at night was higher than in daytime. Specifically, NKA-α mRNA expression at 4:00 was 7.22-fold and 5.63-fold higher than that at 10:00 and 16:00, respectively, and the expression at 22:00 was 11.29-fold and 8.80-fold higher than that at 10:00 and 16:00, respectively. Similarly, SLC26A6 mRNA expression was greatest at 22:00, exceeding that observed at 4:00, 10:00 and 16:00 by 3.59, 4.44 and 11.14-fold, respectively. Finally, the expression of NKA-α and SLC26A6 protein at the single cell level was also higher at night than during the day, which was 1.65-fold and 1.37-fold higher at 22:00 respectively compared to 16:00. Overall, the present findings revealed that naked carp drinks at night and feeds during the day, demonstrating that intestinal ion regulation exhibits a daily rhythm when exposed to high saline and alkaline lake water.
Multi-objective optimization of water resources allocation in Han River basin (China) integrating efficiency, equity and sustainability
Authors: Deng Lele , Guo Shenglian , Yin Jiabo , Zeng Yujie , Chen Kebing
Published: January 2022

The hydrological cycle, affected by climate change and rapid urbanization in recent decades, has been altered to some extent and further poses great challenges to three key factors of water resources allocation (i.e., efficiency, equity and sustainability). However, previous studies usually focused on one or two aspects without considering their underlying interconnections, which are insufficient for interaction cognition between hydrology and social systems. This study aims at reinforcing water management by considering all factors simultaneously. The efficiency represents the total economic interests of domesticity, industry and agriculture sectors, and the Gini coefficient is introduced to measure the allocation equity. A multi-objective water resources allocation model was developed for efficiency and equity optimization, with sustainability (the river ecological flow) as a constraint. The Non-dominated sorting genetic algorithm II (NSGA-II) was employed to derive the Pareto front of such a water resources allocation system, which enabled decision-makers to make a scientific and practical policy in water resources planning and management. The proposed model was demonstrated in the middle and lower Han River basin, China. The results indicate that the Pareto front can reflect the conflicting relationship of efficiency and equity in water resources allocation, and the best alternative chosen by cost performance method may provide rich information as references in integrated water resources planning and management.
Construction of a potential microRNA and messenger RNA regulatory network of acute lung injury in mice
Authors: Zhang Yufeng , Jiang Weilong , Xia Qingqing , Lin Jinfeng , Xu Junxian , Zhang Suyan , Tian Lijun , Han Xudong
Published: January 2022

Acute lung injury (ALI) is a life-threatening clinical condition associated with critically ill patients, and the construction of potential microRNA (miRNA) and messenger RNA (mRNA) regulatory networks will help to fully elucidate its underlying molecular mechanisms. First, we screened fifteen upregulated differentially expressed miRNAs (DE-miRNAs) and six downregulated DE-miRNAs from the Gene Expression Omnibus (GEO) database. Then, the predicted target genes of the upregulated and downregulated DE-miRNAs were identified from the miRNet database. Subsequently, differentially expressed mRNAs (DE-mRNAs) were identified from the GEO database and subjected to combined analysis with the predicted DE-miRNA target genes. Eleven target genes of the upregulated DE-miRNAs and one target gene of the downregulated DE-miRNAs were screened out. To further validate the prediction results, we randomly selected a dataset for subsequent analysis and found some accurate potential miRNA-mRNA regulatory axes, including mmu-mir-7b-5p-Gria1, mmu-mir-486a-5p-Shc4 and mmu-mir-486b-5p-Shc4 pairs. Finally, mir-7b and its target gene Gria1 and mir-486b and its target gene Shc4 were further validated in a bleomycin-induced ALI mouse model. We established a potential miRNA-mRNA regulatory network of ALI in mice, which may provide a basis for basic and clinical research on ALI and advance the available treatment options.
A role for community-level socioeconomic indicators in targeting tuberculosis screening interventions
Authors: Brooks Meredith B. , Jenkins Helen E. , Puma Daniela , Tzelios Christine , Millones Ana Karina , Jimenez Judith , Galea Jerome T. , Lecca Leonid , Becerra Mercedes C. , Keshavjee Salmaan , Yuen Courtney M.
Published: January 2022

Tuberculosis screening programs commonly target areas with high case notification rates. However, this may exacerbate disparities by excluding areas that already face barriers to accessing diagnostic services. We compared historic case notification rates, demographic, and socioeconomic indicators as predictors of neighborhood-level tuberculosis screening yield during a mobile screening program in 74 neighborhoods in Lima, Peru. We used logistic regression and Classification and Regression Tree (CART) analysis to identify predictors of screening yield. During February 7, 2019–February 6, 2020, the program screened 29,619 people and diagnosed 147 tuberculosis cases. Historic case notification rate was not associated with screening yield in any analysis. In regression analysis, screening yield decreased as the percent of vehicle ownership increased (odds ratio [OR]: 0.76 per 10% increase in vehicle ownership; 95% confidence interval [CI]: 0.58–0.99). CART analysis identified the percent of blender ownership (≤ 83.1% vs > 83.1%; OR: 1.7; 95% CI: 1.2–2.6) and the percent of TB patients with a prior tuberculosis episode (> 10.6% vs ≤ 10.6%; OR: 3.6; 95% CI: 1.0–12.7) as optimal predictors of screening yield. Overall, socioeconomic indicators were better predictors of tuberculosis screening yield than historic case notification rates. Considering community-level socioeconomic characteristics could help identify high-yield locations for screening interventions.
Biomechanical comparison of lag screw and non-spiral blade fixation of a novel femoral trochanteric nail in an osteoporotic bone model
Authors: Fuse Yoshifumi , Zenke Yukichi , Okimoto Nobukazu , Yoshioka Toru , Yamanaka Yoshiaki , Kawasaki Makoto , Terayama Hiroshi , Sakai Akinori
Published: January 2022

There is no consensus regarding the advantages of the lag screw type over the blade type for treating femoral trochanteric fractures. We aimed to investigate whether non-spiral blade (Conventional-Blade, Fid-Blade) nails provide better biomechanical fixation than lag screws in a severe osteoporotic bone model. Different severities of osteoporotic cancellous bone were modelled using polyurethane foam blocks of three densities (0.24, 0.16, and 0.08 g/cm3). Three torsional tests were performed using each component for each density of the polyurethane block, and the maximum torque was recorded; subsequently, the energy required to achieve 30° rotation was calculated. Using a push-in test, the maximum force was recorded, and the energy required to achieve 4-mm displacement was calculated. For 0.08-g/cm3 density, the peak torques to achieve 30° rotation, energy required to achieve 30° rotation, peak force to achieve 4-mm displacement, and energy required to achieve 4-mm displacement were significantly greater for Conventional-Blade and Fid-Blade than those for Lag Screw. The fixation stability of the blade-type Magnum nail component is better than that of the lag screw type under any test condition. The blade-type nail component may have better fixation stability than the lag screw type in a severe osteoporotic bone model.
Increasing the performance of cucumber (Cucumis sativus L.) seedlings by LED illumination
Authors: Hamedalla Ali Mohamed , Ali Muhammad Moaaz , Ali Waleed M. , Ahmed Mohamed A. A. , Kaseb Mohamed Omar , Kalaji Hazem M. , Gajc-Wolska Janina , Yousef Ahmed Fathy
Published: January 2022

Light is one of the most important limiting factors for photosynthesis and the production of plants, especially in the regions where natural environmental conditions do not provide sufficient sunlight, and there is a great dependence on artificial lighting to grow plants and produce food. The influence of light intensity, quality, and photoperiod on photosynthetic pigments content and some biochemical and growth traits of cucumber seedlings grown under controlled conditions was investigated. An orthogonal design based on a combination of different light irradiances, ratio of LEDs and photoperiods was used. Treaments consisted of three light irradiance regimes (80, 100, and 150 µmol m−2 s−1) provided by light-emitting diodes (LEDs) of different ratios of red and blue (R:B) (30:70, 50:50, and 70:30) and three different photoperiods (10/14, 12/12, and 14/10 h). The white light was used as a control/reference. Plant height, hypocotyl length, stem diameter, leaf area, and soluble sugar content were highest when exposed to LM9 (150 µmol m−2 s−1; R70:B30; 12/12 h) light mode, while the lowest values for the above parameters were obtained under LM1 (80 µmol m−2 s−1; R30:B70; 10/14 h). Higher pigments contents (chlorophyll a, chlorophyll b, and carotenoid) were obtained when light regime LM9 (150 µmol m−2 s−1; R70:B30; 12/12 h) was applied. In general, cucumber seedlings grown under the LM9 regime showed a significant increase in growth as well as photosynthetic capacity. It seems that the content of photosynthetic pigments is the key factor responsible for the performance of cucumber seedlings grown under different lighting modes, compared to other traits studied. We recommend monitoring the content of chlorophyll a, b, and their ratio value when studying the light requirement of cucumber plants.
A computational analysis of atrial fibrillation effects on coronary perfusion across the different myocardial layers
Authors: Saglietto Andrea , Fois Matteo , Ridolfi Luca , De Ferrari Gaetano Maria , Anselmino Matteo , Scarsoglio Stefania
Published: January 2022

Patients with atrial fibrillation (AF) may present ischemic chest pain in the absence of classical obstructive coronary disease. Among the possible causes, the direct hemodynamic effect exerted by the irregular arrhythmia has not been studied in detail. We performed a computational fluid dynamics analysis by means of a 1D-0D multiscale model of the entire human cardiovascular system, enriched by a detailed mathematical modeling of the coronary arteries and their downstream distal microcirculatory districts (subepicardial, midwall and subendocardial layers). Three mean ventricular rates were simulated (75, 100, 125 bpm) in both sinus rhythm (SR) and atrial fibrillation, and an inter-layer and inter-frequency analysis was conducted focusing on the ratio between mean beat-to-beat blood flow in AF compared to SR. Our results show that AF exerts direct hemodynamic consequences on the coronary microcirculation, causing a reduction in microvascular coronary flow particularly at higher ventricular rates; the most prominent reduction was seen in the subendocardial layers perfused by left coronary arteries (left anterior descending and left circumflex arteries).
Comparative chloroplast genome analyses of cultivated spinach and two wild progenitors shed light on the phylogenetic relationships and variation
Authors: She Hongbing , Liu Zhiyuan , Xu Zhaosheng , Zhang Helong , Cheng Feng , Wu Jian , Wang Xiaowu , Qian Wei
Published: January 2022

Spinacia is a genus of important leafy vegetable crops worldwide and includes cultivated Spinacia oleracea and two wild progenitors, Spinacia turkestanica and Spinacia tetrandra. However, the chloroplast genomes of the two wild progenitors remain unpublished, limiting our knowledge of chloroplast genome evolution among these three Spinacia species. Here, we reported the complete chloroplast genomes of S. oleracea, S. turkestanica, and S. tetrandra obtained via Illumina sequencing. The three chloroplast genomes exhibited a typical quadripartite structure and were 150,739, 150,747, and 150,680 bp in size, respectively. Only three variants were identified between S. oleracea and S. turkestanica, whereas 690 variants were obtained between S. oleracea and S. tetrandra, strongly demonstrating the close relationship between S. turkestanica and S. oleracea. This was further supported by phylogenetic analysis. We reported a comprehensive variant dataset including 503 SNPs and 83 Indels using 85 Spinacia accessions containing 61 S. oleracea, 16 S. turkestanica, and eight S. tetrandra accessions. Thirteen S. oleracea accessions were derived through introgression from S. turkestanica that acts as the maternal parent. Together, these results provide a valuable resource for spinach breeding programs and improve our understanding of the phylogenetic relationships within Amaranthaceae.