bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphology of Jupiter's Polar Auroral Bright Spot Emissions via Juno‐UVS Observations
Authors: Haewsantati K. , Bonfond B. , Wannawichian S. , Gladstone G. R. , Hue V. , Versteeg M. H. , Greathouse T. K. , Grodent D. , Yao Z. , Dunn W. , Gérard J.‐C. , Giles R. , Kammer J. , Guo R. , Vogt M. F.
Published: February 2021

Since 2016, the Juno‐UVS (Ultraviolet Spectrograph) instrument has been taking spectral images of Jupiter's auroras in their full extent, including the nightside, which cannot be viewed from Earth. We present a systematic analysis of features in Jupiter's polar auroras called auroral bright spots, which were observed by Juno‐UVS during the first 25 orbits of the spacecraft. An auroral bright spot is an isolated localized and transient brightening in the polar region. Bright spots were identified in 16 perijoves (PJ) out of 24, mostly in either the northern or the southern hemisphere but rarely in both during the same PJ. The emitted power of the bright spots is time variable with peak power ranging from a few tens to a hundred of gigawatts. Moreover, we found that, for some PJs, bright spots exhibit quasiperiodic behavior. The spots, within PJ4 and PJ16, each reappeared within <2,000 km from the previous position in System III with periods of 28 and 22 min, respectively. This period is similar to periods previously identified in X‐rays and various other observations. The bright spot positions are in a specific region in the northern hemisphere in System III, but are scattered around the magnetic pole in the southern hemisphere, near the edge of the swirl region. Furthermore, the bright spots can be seen at any local time, rather than being confined to the noon sector as previously thought from Earth‐based observations. This suggests that the bright spots might not be firmly connected to the noon facing magnetospheric cusp processes.
Nighttime Magnetic Perturbation Events Observed in Arctic Canada: 3. Occurrence and Amplitude as Functions of Magnetic Latitude, Local Time, and Magnetic Disturbance Indices
Authors: Engebretson Mark J. , Pilipenko Viacheslav A. , Steinmetz Erik S. , Moldwin Mark B. , Connors Martin G. , Boteler David H. , Singer Howard J. , Opgenoorth Hermann , Schillings Audrey , Ohtani Shin , Gjerloev Jesper , Russell Christopher T.
Published: February 2021

Rapid changes of magnetic fields associated with nighttime magnetic perturbation events (MPEs) with amplitudes |ΔB| of hundreds of nT and 5–10 min duration can induce geomagnetically induced currents (GICs) that can harm technological systems. This study compares the occurrence and amplitude of nighttime MPEs with |dB/dt| ≥ 6 nT/s observed during 2015 and 2017 at five stations in Arctic Canada ranging from 64.7° to 75.2° in corrected geomagnetic latitude (MLAT) as functions of magnetic local time (MLT), the SME (SuperMAG version of AE) and SYM/H magnetic indices, and time delay after substorm onsets. Although most MPEs occurred within 30 min after a substorm onset, ∼10% of those observed at the four lower latitude stations occurred over two hours after the most recent onset. A broad distribution in local time appeared at all five stations between 1700 and 0100 MLT, and a narrower distribution appeared at the lower latitude stations between 0200 and 0700 MLT. There was little or no correlation between MPE amplitude and the SYM/H index; most MPEs at all stations occurred for SYM/H values between −40 and 0 nT. SME index values for MPEs observed >1 h after the most recent substorm onset fell in the lower half of the range of SME values for events during substorms, and dipolarizations in synchronous orbit at GOES 13 during these events were weaker or more often nonexistent. These observations suggest that substorms are neither necessary nor sufficient to cause MPEs, and hence predictions of GICs cannot focus solely on substorms.
Integrative analysis of physiological responses to high fat feeding with diffusion tensor images and neurochemical profiles of the mouse brain
Authors: Guadilla Irene , Lizarbe Blanca , Barrios Laura , Cerdán Sebastián , López-Larrubia Pilar
Published: February 2021

Background

Obesity proceeds with important physiological and microstructural alterations in the brain, but the precise relationships between the diet and feeding status, its physiological responses, and the observed neuroimaging repercussions, remain elusive. Here, we implemented a mouse model of high fat diet (HFD) feeding to explore specific associations between diet, feeding status, phenotypic and endocrine repercussions, and the resulting microstructural and metabolic alterations in the brain, as detected by diffusion tensor imaging (DTI) and neurochemical metabolic profiling.

Methods

Brain DTI images were acquired from adult male C57BL6/J mice after 6 weeks of HFD, or standard diet (SD) administrations, both under the fed, and overnight fasted conditions. Metabolomic profiles of the cortex (Ctx), hippocampus (Hipc), and hypothalamus (Hyp) were determined by 1H high-resolution magic angle spinning (HRMAS) spectroscopy, in cerebral biopsies dissected after microwave fixation. Mean diffusivity (MD), fractional anisotropy (FA) maps, and HRMAS profiles were complemented with determinations of phenotypic alterations and plasma levels of appetite-related hormones, measured by indirect calorimetry and multiplex assays, respectively. We used Z-score and alternating least squares scaling (ALSCAL) analysis to investigate specific associations between diet and feeding status, physiological, and imaging parameters.

Results

HFD induced significant increases in body weight and the plasma levels of glucose and fatty acids in the fed and fasted conditions, as well as higher cerebral MD (Ctx, Hipc, Hyp), FA (Hipc), and mobile saturated fatty acids resonances (Ctx, Hipc, Hyp). Z-score and ASLCAL analysis identified the precise associations between physiological and imaging variables.

Conclusions

The present study reveals that diet and feeding conditions elicit prominent effects on specific imaging and spectroscopic parameters of the mouse brain that can be associated to the alterations in phenotypic and endocrine variables. Together, present results disclose a neuro-inflammatory response to HFD, characterized primarily by vasogenic edema and compensatory responses in osmolyte concentrations.
A membrane-bound ankyrin repeat protein confers race-specific leaf rust disease resistance in wheat
Authors: Kolodziej Markus C. , Singla Jyoti , Sánchez-Martín Javier , Zbinden Helen , Šimková Hana , Karafiátová Miroslava , Doležel Jaroslav , Gronnier Julien , Poretti Manuel , Glauser Gaétan , Zhu Wangsheng , Köster Philipp , Zipfel Cyril , Wicker Thomas , Krattinger Simon G. , Keller Beat
Published: February 2021

Plasma membrane-associated and intracellular proteins and protein complexes play a pivotal role in pathogen recognition and disease resistance signaling in plants and animals. The two predominant protein families perceiving plant pathogens are receptor-like kinases and nucleotide binding-leucine-rich repeat receptors (NLR), which often confer race-specific resistance. Leaf rust is one of the most prevalent and most devastating wheat diseases. Here, we clone the race-specific leaf rust resistance gene Lr14a from hexaploid wheat. The cloning of Lr14a is aided by the recently published genome assembly of ArinaLrFor, an Lr14a-containing wheat line. Lr14a encodes a membrane-localized protein containing twelve ankyrin (ANK) repeats and structural similarities to Ca2+-permeable non-selective cation channels. Transcriptome analyses reveal an induction of genes associated with calcium ion binding in the presence of Lr14a. Haplotype analyses indicate that Lr14a-containing chromosome segments were introgressed multiple times into the bread wheat gene pool, but we find no variation in the Lr14a coding sequence itself. Our work demonstrates the involvement of an ANK-transmembrane (TM)-like type of gene family in race-specific disease resistance in wheat. This forms the basis to explore ANK-TM-like genes in disease resistance breeding.
High resolution ensemble description of metamorphic and intrinsically disordered proteins using an efficient hybrid parallel tempering scheme
Authors: Appadurai Rajeswari , Nagesh Jayashree , Srivastava Anand
Published: February 2021

Mapping free energy landscapes of complex multi-funneled metamorphic proteins and weakly-funneled intrinsically disordered proteins (IDPs) remains challenging. While rare-event sampling molecular dynamics simulations can be useful, they often need to either impose restraints or reweigh the generated data to match experiments. Here, we present a parallel-tempering method that takes advantage of accelerated water dynamics and allows efficient and accurate conformational sampling across a wide variety of proteins. We demonstrate the improved sampling efficiency by benchmarking against standard model systems such as alanine di-peptide, TRP-cage and β-hairpin. The method successfully scales to large metamorphic proteins such as RFA-H and to highly disordered IDPs such as Histatin-5. Across the diverse proteins, the calculated ensemble averages match well with the NMR, SAXS and other biophysical experiments without the need to reweigh. By allowing accurate sampling across different landscapes, the method opens doors for sampling free energy landscape of complex uncharted proteins.
Self-assembly and regulation of protein cages from pre-organised coiled-coil modules
Authors: Lapenta Fabio , Aupič Jana , Vezzoli Marco , Strmšek Žiga , Da Vela Stefano , Svergun Dmitri I. , Carazo José María , Melero Roberto , Jerala Roman
Published: February 2021

Coiled-coil protein origami (CCPO) is a modular strategy for the de novo design of polypeptide nanostructures. CCPO folds are defined by the sequential order of concatenated orthogonal coiled-coil (CC) dimer-forming peptides, where a single-chain protein is programmed to fold into a polyhedral cage. Self-assembly of CC-based nanostructures from several chains, similarly as in DNA nanotechnology, could facilitate the design of more complex assemblies and the introduction of functionalities. Here, we show the design of a de novo triangular bipyramid fold comprising 18 CC-forming segments and define the strategy for the two-chain self-assembly of the bipyramidal cage from asymmetric and pseudo-symmetric pre-organised structural modules. In addition, by introducing a protease cleavage site and masking the interfacial CC-forming segments in the two-chain bipyramidal cage, we devise a proteolysis-mediated conformational switch. This strategy could be extended to other modular protein folds, facilitating the construction of dynamic multi-chain CC-based complexes.
Designed folding pathway of modular coiled-coil-based proteins
Authors: Aupič Jana , Strmšek Žiga , Lapenta Fabio , Pahovnik David , Pisanski Tomaž , Drobnak Igor , Ljubetič Ajasja , Jerala Roman
Published: February 2021

Natural proteins are characterised by a complex folding pathway defined uniquely for each fold. Designed coiled-coil protein origami (CCPO) cages are distinct from natural compact proteins, since their fold is prescribed by discrete long-range interactions between orthogonal pairwise-interacting coiled-coil (CC) modules within a single polypeptide chain. Here, we demonstrate that CCPO proteins fold in a stepwise sequential pathway. Molecular dynamics simulations and stopped-flow Förster resonance energy transfer (FRET) measurements reveal that CCPO folding is dominated by the effective intra-chain distance between CC modules in the primary sequence and subsequent folding intermediates, allowing identical CC modules to be employed for multiple cage edges and thus relaxing CCPO cage design requirements. The number of orthogonal modules required for constructing a CCPO tetrahedron can be reduced from six to as little as three different CC modules. The stepwise modular nature of the folding pathway offers insights into the folding of tandem repeat proteins and can be exploited for the design of modular protein structures based on a given set of orthogonal modules.
Facilitation of molecular motion to develop turn-on photoacoustic bioprobe for detecting nitric oxide in encephalitis
Authors: Qi Ji , Feng Leyan , Zhang Xiaoyan , Zhang Haoke , Huang Liwen , Zhou Yutong , Zhao Zheng , Duan Xingchen , Xu Fei , Kwok Ryan T. K. , Lam Jacky W. Y. , Ding Dan , Xue Xue , Tang Ben Zhong
Published: February 2021

Nitric oxide (NO) is an important signaling molecule overexpressed in many diseases, thus the development of NO-activatable probes is of vital significance for monitoring related diseases. However, sensitive photoacoustic (PA) probes for detecting NO-associated complicated diseases (e.g., encephalitis), have yet to be developed. Herein, we report a NO-activated PA probe for in vivo detection of encephalitis by tuning the molecular geometry and energy transformation processes. A strong donor-acceptor structure with increased conjugation can be obtained after NO treatment, along with the active intramolecular motion, significantly boosting “turn-on” near-infrared PA property. The molecular probe exhibits high specificity and sensitivity towards NO over interfering reactive species. The probe is capable of detecting and differentiating encephalitis in different severities with high spatiotemporal resolution. This work will inspire more insights into the development of high-performing activatable PA probes for advanced diagnosis by making full use of intramolecular motion and energy transformation processes.
Mapping of susceptible variants for cold medicine-related Stevens–Johnson syndrome by whole-genome resequencing
Authors: Kawai Yosuke , Hitomi Yuki , Ueta Mayumi , Khor Seik-Soon , Nakatani Ken , Sotozono Chie , Kinoshita Shigeru , Nagasaki Masao , Tokunaga Katsushi
Published: February 2021

Stevens–Johnson syndrome (SJS) and its severe condition with extensive skin detachment and a poor prognosis, toxic epidermal necrolysis (TEN), are immunologically mediated severe cutaneous reactions of the skin and mucous membranes such as the ocular surface. Genetic variations on the HLA-A and other autosomal genes have been identified as risk factors for cold medicine-related SJS/TEN with severe ocular complications (CM-SJS/TEN with SOC). Using a whole-genome sequencing (WGS) approach, we explored other susceptible variants of CM-SJS/TEN with SOC, especially among rare variants and structural variants (SVs). WGS was performed on samples from 133 patients with CM-SJS/TEN with SOC and 418 healthy controls to obtain single nucleotide polymorphisms (SNPs) and SVs. Genome-wide association tests were performed with these variants. Our genome-wide association test reproduced the associations of the common variants of HLA-A and loci on chromosome 16q12.1. We also identified novel associations of SVs on these loci and an aggregation of rare coding variants on the TPRM8 gene. In silico gene expression analysis on the HLA-A locus revealed that the SNP (rs12202296), which was significantly associated with susceptibility to CM-SJS/TEN with SOC, was correlated to an increase in HLA-A expression levels in the whole blood (P = 2.9 × 10−17), from the GTEx database. The majority of variants that were significantly associated with CM-SJS/TEN with SOC were found in non-coding regions, indicating the regulatory role of genetic variations in the pathogenesis of CM-SJS/TEN with SOC.
Alterations of 5-hydroxymethylation in circulating cell-free DNA reflect molecular distinctions of subtypes of non-Hodgkin lymphoma
Authors: Chiu Brian C.-H. , Chen Chang , You Qiancheng , Chiu Rudyard , Venkataraman Girish , Zeng Chang , Zhang Zhou , Cui Xiaolong , Smith Sonali M. , He Chuan , Zhang Wei
Published: February 2021

The 5-methylcytosines (5mC) have been implicated in the pathogenesis of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). However, the role of 5-hydroxymethylcytosines (5hmC) that are generated from 5mC through active demethylation, in lymphomagenesis is unknown. We profiled genome-wide 5hmC in circulating cell-free DNA (cfDNA) from 73 newly diagnosed patients with DLBCL and FL. We identified 294 differentially modified genes between DLBCL and FL. The differential 5hmC in the DLBCL/FL-differentiating genes co-localized with enhancer marks H3K4me1 and H3K27ac. A four-gene panel (CNN2, HMG20B, ACRBP, IZUMO1) robustly represented the overall 5hmC modification pattern that distinguished FL from DLBCL with an area under curve of 88.5% in the testing set. The median 5hmC modification levels in signature genes showed potential for separating patients for risk of all-cause mortality. This study provides evidence that genome-wide 5hmC profiles in cfDNA differ between DLBCL and FL and could be exploited as a non-invasive approach.
Differences in MTHFR and LRRK2 variant’s association with sporadic Parkinson’s disease in Mexican Mestizos correlated to Native American ancestry
Authors: Romero-Gutiérrez Elizabeth , Vázquez-Cárdenas Paola , Moreno-Macías Hortensia , Salas-Pacheco José , Tusié-Luna Teresa , Arias-Carrión Oscar
Published: February 2021

Parkinson’s disease (PD), a common neurodegenerative disorder, has a complex etiology where environmental and genetic factors intervene. While a number of genes and variants have been identified in recent decades as causative or protective agents of this condition, a limited number of studies have been conducted in mixed populations, such as Mexican Mestizos. The historical convergence of two founding groups and three ethnicities, and the increasing north-to-south gradient of Native American ancestry in Mexico resulted in a subpopulation structure with considerable genetic diversity. In this work, we investigate the influence of 21 known susceptibility variants for PD. Our case–control study, with a cohort of 311 Mexican Mestizo subjects, found a significant risk association for the variant rs1491942 inLRRK2. However, when stratification by ancestry was performed, a risk effect forMTHFRrs1801133 was observed only in the group with the highest percentage of European ancestry, and the PD risk effect forLRRK2rs1491942 was significant in subjects with a higher ratio of Native American ancestry. Meta-analyses of these SNP revealed the effect ofLRRK2rs1491942 to be even more significant than previously described in populations of European descent. Although corroboration is necessary, our findings suggest that polymorphism rs1491942 may be useful as a risk marker of PD in Mexican Mestizos with greater Native American ancestry. The absence of associations with the remaining known risk factors is, in itself, a relevant finding and invites further research into the shared risk factors’ role in the pathophysiological mechanisms of this neurodegenerative disorder.
Specialist respiratory outreach: a case-finding initiative for identifying undiagnosed COPD in primary care
Authors: Ray Emma , Culliford David , Kruk Helen , Gillett Kate , North Mal , Astles Carla M. , Hicks Alexander , Johnson Matthew , Lin Sharon Xiaowen , Orlando Rosanna , Thomas Mike , Jordan Rachel E. , Price David , Konstantin Mita , Wilkinson Tom M. A.
Published: February 2021

COPD remains largely undiagnosed or is diagnosed late in the course of disease. We report findings of a specialist outreach programme to identify undiagnosed COPD in primary care. An electronic case-finding algorithm identified 1602 at-risk patients from 12 practices who were invited to attend the clinic. Three hundred and eighty-three (23.9%) responded and 288 were enrolled into the study. Forty-eight (16.6%) had undiagnosed mild and 28 (9.7%) had moderate airway obstruction, meeting spirometric diagnostic criteria for COPD. However, at 12 months only 8 suspected COPD patients (10.6%) had received a diagnostic label in their primary care record. This constituted 0.38% of the total patient population, as compared with 0.31% of control practices, p = 0.306. However, if all patients with airway obstruction received a coding of COPD, then the diagnosis rate in the intervention group would have risen by 0.84%. Despite the low take-up and diagnostic yield, this programme suggests that integrated case-finding strategies could improve COPD recognition.
Electrochemical metrics for corrosion resistant alloys
Authors: Nyby Clara , Guo Xiaolei , Saal James E. , Chien Szu-Chia , Gerard Angela Y. , Ke Huibin , Li Tianshu , Lu Pin , Oberdorfer Christian , Sahu Sarita , Li Sirui , Taylor Christopher D. , Windl Wolfgang , Scully John R. , Frankel Gerald S.
Published: February 2021

Corrosion is an electrochemical phenomenon. It can occur via different modes of attack, each having its own mechanisms, and therefore there are multiple metrics for evaluating corrosion resistance. In corrosion resistant alloys (CRAs), the rate of localized corrosion can exceed that of uniform corrosion by orders of magnitude. Therefore, instead of uniform corrosion rate, more complex electrochemical parameters are required to capture the salient features of corrosion phenomena. Here, we collect a database with an emphasis on metrics related to localized corrosion. The six sections of the database include data on various metal alloys with measurements of (1) pitting potential, Epit, (2) repassivation potential, Erp, (3) crevice corrosion potential, Ecrev, (4) pitting temperature, Tpit, (5) crevice corrosion temperature, Tcrev, and (6) corrosion potential, Ecorr, corrosion current density, icorr, passivation current density, ipass, and corrosion rate. The experimental data were collected from 85 publications and include Al- and Fe-based alloys, high entropy alloys (HEAs), and a Ni-Cr-Mo ternary system. This dataset could be used in the design of highly corrosion resistant alloys.
Chromosome-scale genome assembly of the sea louse Caligus rogercresseyi by SMRT sequencing and Hi-C analysis
Authors: Gallardo-Escárate Cristian , Valenzuela-Muñoz Valentina , Nuñez-Acuña Gustavo , Valenzuela-Miranda Diego , Gonçalves Ana Teresa , Escobar-Sepulveda Hugo , Liachko Ivan , Nelson Bradley , Roberts Steven , Warren Wesley
Published: February 2021

Caligus rogercresseyi, commonly known as sea louse, is an ectoparasite copepod that impacts the salmon aquaculture in Chile, causing losses of hundreds of million dollars per year. In this study, we report a chromosome-scale assembly of the sea louse (C. rogercresseyi) genome based on single-molecule real-time sequencing (SMRT) and proximity ligation (Hi-C) analysis. Coding RNAs and non-coding RNAs, and specifically long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) were identified through whole transcriptome sequencing from different life stages. A total of 23,686 protein-coding genes and 12,558 non-coding RNAs were annotated. In addition, 6,308 lncRNAs and 5,774 miRNAs were found to be transcriptionally active from larvae to adult stages. Taken together, this genomic resource for C. rogercresseyi represents a valuable tool to develop sustainable control strategies in the salmon aquaculture industry.
Gene expression and epigenetics reveal species-specific mechanisms acting upon common molecular pathways in the evolution of task division in bees
Authors: Araujo Natalia de Souza , Arias Maria Cristina
Published: February 2021

A striking feature of advanced insect societies is the existence of workers that forgo reproduction. Two broad types of workers exist in eusocial bees: nurses who care for their young siblings and the queen, and foragers who guard the nest and forage for food. Comparisons between these two worker subcastes have been performed in honeybees, but data from other bees are scarce. To understand whether similar molecular mechanisms are involved in nurse-forager differences across distinct species, we compared gene expression and DNA methylation profiles between nurses and foragers of the buff-tailed bumblebee Bombus terrestris and the stingless bee Tetragonisca angustula. These datasets were then compared to previous findings from honeybees. Our analyses revealed that although the expression pattern of genes is often species-specific, many of the biological processes and molecular pathways involved are common. Moreover, the correlation between gene expression and DNA methylation was dependent on the nucleotide context, and non-CG methylation appeared to be a relevant factor in the behavioral changes of the workers. In summary, task specialization in worker bees is characterized by a plastic and mosaic molecular pattern, with species-specific mechanisms acting upon broad common pathways across species.
Comparative study on heat transfer and friction drag in the flow of various hybrid nanofluids effected by aligned magnetic field and nonlinear radiation
Authors: Khan M. Riaz , Li Mingxia , Mao Shipeng , Ali Rashid , Khan Suliman
Published: February 2021

The key purpose of the existing article is to discuss the effects of various hybrid nanofluids and a simple nanofluid over the heat transfer and friction drags along a stretched surface. The various kinds of hybrid nanofluids and a simple nanofluid together with the effects of aligned magnetic field, nonlinear radiation and suction have been taken into consideration. These hybrid nanofluids are prepared by suspending a couple of distinct nanoparticles $$Cu$$

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. The comparison of various graphical results of skin friction coefficient, rate of heat transfer, velocity and temperature for two different hybrid nanofluids $$Cu{-}A{l}_{2}{O}_{3}$$

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is considered. Moreover, the impact of surface stretching, aligned magnetic field and thermal radiation over the velocity, temperature, skin friction coefficient and local Nusselt number are also considered. The outcomes drawn from this modern research is that the hybrid nanofluid $$Cu{-}A{l}_{2}{O}_{3}$$

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. Based on these findings we could say that the suspension of multiple particles in the composition of two or more base fluids provides a better rate of heat transfer and limits the friction drag.
Non-collinear Hox gene expression in bivalves and the evolution of morphological novelties in mollusks
Authors: Salamanca-Díaz David A. , Calcino Andrew D. , de Oliveira André L. , Wanninger Andreas
Published: February 2021

Hox genes are key developmental regulators that are involved in establishing morphological features during animal ontogeny. They are commonly expressed along the anterior–posterior axis in a staggered, or collinear, fashion. In mollusks, the repertoire of body plans is widely diverse and current data suggest their involvement during development of landmark morphological traits in Conchifera, one of the two major lineages that comprises those taxa that originated from a uni-shelled ancestor (Monoplacophora, Gastropoda, Cephalopoda, Scaphopoda, Bivalvia). For most clades, and bivalves in particular, data on Hox gene expression throughout ontogeny are scarce. We thus investigated Hox expression during development of the quagga mussel, Dreissena rostriformis, to elucidate to which degree they might contribute to specific phenotypic traits as in other conchiferans. The Hox/ParaHox complement of Mollusca typically comprises 14 genes, 13 of which are present in bivalve genomes including Dreissena. We describe here expression of 9 Hox genes and the ParaHox gene Xlox during Dreissena development. Hox expression in Dreissena is first detected in the gastrula stage with widely overlapping expression domains of most genes. In the trochophore stage, Hox gene expression shifts towards more compact, largely mesodermal domains. Only few of these domains can be assigned to specific developing morphological structures such as Hox1 in the shell field and Xlox in the hindgut. We did not find traces of spatial or temporal staggered expression of Hox genes in Dreissena. Our data support the notion that Hox gene expression has been coopted independently, and to varying degrees, into lineage-specific structures in the respective conchiferan clades. The non-collinear mode of Hox expression in Dreissena might be a result of the low degree of body plan regionalization along the bivalve anterior–posterior axis as exemplified by the lack of key morphological traits such as a distinct head, cephalic tentacles, radula apparatus, and a simplified central nervous system.
A randomized controlled trial investigating the impact of maternal dietary supplementation with pomegranate juice on brain injury in infants with IUGR
Authors: Ross Madeline M. , Cherkerzian Sara , Mikulis Nicole D. , Turner Daria , Robinson Julian , Inder Terrie E. , Matthews Lillian G.
Published: February 2021

Animal studies have demonstrated the therapeutic potential of polyphenol-rich pomegranate juice. We recently reported altered white matter microstructure and functional connectivity in the infant brain following in utero pomegranate juice exposure in pregnancies with intrauterine growth restriction (IUGR). This double-blind exploratory randomized controlled trial further investigates the impact of maternal pomegranate juice intake on brain structure and injury in a second cohort of IUGR pregnancies diagnosed at 24–34 weeks’ gestation. Ninety-nine mothers and their eligible fetuses (n = 103) were recruited from Brigham and Women’s Hospital and randomly assigned to 8 oz pomegranate (n = 56) or placebo (n = 47) juice to be consumed daily from enrollment to delivery. A subset of participants underwent fetal echocardiogram after 2 weeks on juice with no evidence of ductal constriction. 57 infants (n = 26 pomegranate,n = 31 placebo) underwent term-equivalent MRI for assessment of brain injury, volumes and white matter diffusion. No significant group differences were found in brain volumes or white matter microstructure; however, infants whose mothers consumed pomegranate juice demonstrated lower risk for brain injury, including any white or cortical grey matter injury compared to placebo. These preliminary findings suggest pomegranate juice may be a safe in utero neuroprotectant in pregnancies with known IUGR warranting continued investigation.

Clinical trial registration: NCT04394910,https://clinicaltrials.gov/ct2/show/NCT04394910, Registered May 20, 2020, initial participant enrollment January 16, 2016.
IgG acquisition against PfEMP1 PF11_0521 domain cassette DC13, DBLβ3_D4 domain, and peptides located within these constructs in children with cerebral malaria
Authors: Badaut Cyril , Visitdesotrakul Pimnitah , Chabry Aurélie , Bigey Pascal , Tornyigah Bernard , Roman Jocelyne , Maroufou Jules Alao , Amoussou Annick , Ayivi Blaise Serge , Sagbo Gratien , Ndam Nicaise Tuikue , Oleinikov Andrew V. , Tahar Rachida
Published: February 2021

The Plasmodium falciparum erythrocyte-membrane-protein-1 (PF3D7_1150400/PF11_0521) contains both domain cassette DC13 and DBLβ3 domain binding to EPCR and ICAM-1 receptors, respectively. This type of PfEMP1 proteins with dual binding specificity mediate specific interactions with brain micro-vessels endothelium leading to the development of cerebral malaria (CM). Using plasma collected from children at time of hospital admission and after 30 days, we study an acquisition of IgG response to PF3D7_1150400/PF11_0521 DC13 and DBLβ3_D4 recombinant constructs, and five peptides located within these constructs, specifically in DBLα1.7_D2 and DBLβ3_D4 domains. We found significant IgG responses against the entire DC13, PF11_0521_DBLβ3_D4 domain, and peptides. The responses varied against different peptides and depended on the clinical status of children. The response was stronger at day 30, and mostly did not differ between CM and uncomplicated malaria (UM) groups. Specifically, the DBLβ3 B3-34 peptide that contains essential residues involved in the interaction between PF11_0521 DBLβ3_D4 domain and ICAM-1 receptor demonstrated significant increase in reactivity to IgG1 and IgG3 antibodies at convalescence. Further, IgG reactivity in CM group at time of admission against functionally active (ICAM-1-binding) PF11_0521 DBLβ3_D4 domain was associated with protection against severe anemia. These results support development of vaccine based on the PF3D7_1150400/PF11_0521 structures to prevent CM.
A self-referenced in-situ arrival time monitor for X-ray free-electron lasers
Authors: Diez Michael , Galler Andreas , Schulz Sebastian , Boemer Christina , Coffee Ryan N. , Hartmann Nick , Heider Rupert , Wagner Martin S. , Helml Wolfram , Katayama Tetsuo , Sato Tokushi , Sato Takahiro , Yabashi Makina , Bressler Christian
Published: February 2021

We present a novel, highly versatile, and self-referenced arrival time monitor for measuring the femtosecond time delay between a hard X-ray pulse from a free-electron laser and an optical laser pulse, measured directly on the same sample used for pump-probe experiments. Two chirped and picosecond long optical supercontinuum pulses traverse the sample with a mutually fixed time delay of 970 fs, while a femtosecond X-ray pulse arrives at an instant in between both pulses. Behind the sample the supercontinuum pulses are temporally overlapped to yield near-perfect destructive interference in the absence of the X-ray pulse. Stimulation of the sample with an X-ray pulse delivers non-zero contributions at certain optical wavelengths, which serve as a measure of the relative arrival time of the X-ray pulse with an accuracy of better than 25 fs. We find an excellent agreement of our monitor with the existing timing diagnostics at the SACLA XFEL with a Pearson correlation value of 0.98. We demonstrate a high sensitivity to measure X-ray pulses with pulse energies as low as 30 $$\upmu $$
μ
J. Using a free-flowing liquid jet as interaction sample ensures the full replacement of the sample volume for each X-ray/optical event, thus enabling its utility even at MHz repetition rate XFEL sources.
Interevent-time distribution and aftershock frequency in non-stationary induced seismicity
Authors: Post Richard A. J. , Michels Matthias A. J. , Ampuero Jean-Paul , Candela Thibault , Fokker Peter A. , van Wees Jan-Diederik , Hofstad Remco W. van der , Heuvel Edwin R. van den
Published: February 2021

The initial footprint of an earthquake can be extended considerably by triggering of clustered aftershocks. Such earthquake–earthquake interactions have been studied extensively for data-rich, stationary natural seismicity. Induced seismicity, however, is intrinsically inhomogeneous in time and space and may have a limited catalog of events; this may hamper the distinction between human-induced background events and triggered aftershocks. Here we introduce a novel Gamma Accelerated-Failure-Time model for efficiently analyzing interevent-time distributions in such cases. It addresses the spatiotemporal variation and quantifies, per event, the probability of each event to have been triggered. Distentangling the obscuring aftershocks from the background events is a crucial step to better understand the causal relationship between operational parameters and non-stationary induced seismicity. Applied to the Groningen gas field in the North of the Netherlands, our model elucidates geological and operational drivers of seismicity and has been used to test for aftershock triggering. We find that the hazard rate in Groningen is indeed enhanced after each event and conclude that aftershock triggering cannot be ignored. In particular we find that the non-stationary interevent-time distribution is well described by our Gamma model. This model suggests that 27.0(± 8.5)% of the recorded events in the Groningen field can be attributed to triggering.
Copper-67 radioimmunotheranostics for simultaneous immunotherapy and immuno-SPECT
Authors: Hao Guiyang , Mastren Tara , Silvers William , Hassan Gedaa , Öz Orhan K. , Sun Xiankai
Published: February 2021

Copper-67 (t1/2 = 2.58 days) decays by β− ($$\text{E}_{{\upbeta^{-}\text{max}}}$$

E

β
-

max

: 562 keV) and γ-rays (93 keV and 185 keV) rendering it with potential for both radionuclide therapy and single-photon emission computed tomography (SPECT) imaging. Prompted by the recent breakthrough of 67Cu production with high specific activity, high radionuclidic purity, and sufficient quantities, the interest in the theranostic potential of 67Cu has been rekindled. This work addresses the practicability of developing 67Cu-labeled antibodies with substantially improved quality for cancer radioimmunotheranostics. Proof of concept is demonstrated with pertuzumab, a US-FDA-approved monoclonal antibody for combination therapies of HER2-positive breast cancer. With an average number of 1.9 chelators coupled to each antibody, we achieved a two-order of magnitude increase in radiolabeling efficiency compared to literature reports. In a preclinical therapeutic study, mice (n = 4–7/group) bearing HER2+ xenografts exhibited a 67Cu-dose dependent tumor-growth inhibition from 67Cu-labeled-Pertuzumab co-administered with trastuzumab. Furthermore, greater tumor size reduction was observed with 67Cu-labeled-pertuzumab formulations of higher specific activity. The potential of SPECT imaging with 67Cu radiopharmaceuticals was tested after 67Cu-labeled-Pertuzumab administration. Impressively, all tumors were clearly visualized by SPECT imaging with 67Cu-labeled-Pertuzumab even at day 5 post injection. This work demonstrates it is practical to use 67Cu radioimmunoconjugates for cancer radioimmunotheranostics.
Feasibility and safety study of a high resolution wide field-of-view scanning endoscope for circumferential intraluminal intestinal imaging
Authors: Lai Lily L. , Invernizzi Marta , White Michael , Han Chao , Jiangtao Huangfu , Lu Helen , Yang Changhuei , Lin James
Published: February 2021

Global anal cancer incidence is increasing. High resolution anoscopy (HRA) currently screens for anal cancer, although the definitive test remains unknown. To improve on intraluminal imaging of the anal canal, we conducted a first-in-human study to determine feasibility and safety of a high-resolution, wide field-of-view scanning endoscope. Fourteen patients, under an IRB-approved clinical study, underwent exam under anesthesia, HRA, and imaging with the experimental device. HRA findings were photographed using an in-line camera attached to the colposcope and compared with the scanning endoscope images. Patients were followed up within 2 weeks of the procedure. The imaging device is inserted into the anal canal and the intraluminal surface is digitally photographed in 10 s and uploaded to a computer monitor for review. Ten patients completed imaging with the device. Three patients were not imaged due to severe anal stenosis. One patient was not imaged due to technical device malfunction. The device images were compared to the HRA images. No adverse event attributable to the device was reported. The intraluminal scanning endoscope can be used for circumferential anal canal imaging and is safe for clinical use. Future clinical studies are needed to evaluate the performance of this device.
An antibacterial coated polymer prevents biofilm formation and implant-associated infection
Authors: Ishihama Hiroko , Ishii Ken , Nagai Shigenori , Kakinuma Hiroaki , Sasaki Aya , Yoshioka Kenji , Kuramoto Tetsuya , Shiono Yuta , Funao Haruki , Isogai Norihiro , Tsuji Takashi , Okada Yasunori , Koyasu Shigeo , Toyama Yoshiaki , Nakamura Masaya , Aizawa Mamoru , Matsumoto Morio
Published: February 2021

To prevent infections associated with medical implants, various antimicrobial silver-coated implant materials have been developed. However, these materials do not always provide consistent antibacterial effects in vivo despite having dramatic antibacterial effects in vitro, probably because the antibacterial effects involve silver-ion-mediated reactive oxygen species generation. Additionally, the silver application process often requires extremely high temperatures, which damage non-metal implant materials. We recently developed a bacteria-resistant coating consisting of hydroxyapatite film on which ionic silver is immobilized via inositol hexaphosphate chelation, using a series of immersion and drying steps performed at low heat. Here we applied this coating to a polymer, polyetheretherketone (PEEK), and analyzed the properties and antibacterial activity of the coated polymer in vitro and in vivo. The ionic silver coating demonstrated significant bactericidal activity and prevented bacterial biofilm formation in vitro. Bio-imaging of a soft tissue infection mouse model in which a silver-coated PEEK plate was implanted revealed a dramatic absence of bacterial signals 10 days after inoculation. These animals also showed a strong reduction in histological features of infection, compared to the control animals. This innovative coating can be applied to complex structures for clinical use, and could prevent infections associated with a variety of plastic implants.
Obstructive sleep apnoea increases lipolysis and deteriorates glucose homeostasis in patients with type 2 diabetes mellitus
Authors: Trinh Minh Duc , Plihalova Andrea , Gojda Jan , Westlake Katerina , Spicka Jan , Lattova Zuzana , Pretl Martin , Polak Jan
Published: February 2021

Obstructive sleep apnoea (OSA) is associated with type 2 diabetes mellitus (T2DM). However, mechanisms mediating association between these two conditions remain unclear. This study investigated, whether the OSA-associated changes in adipose tissue lipolysis might contribute to impaired glucose homeostasis in patient with T2DM. Thirty-five matched subjects were recruited into three groups: T2DM + severe OSA (T2DM + OSA, n = 11), T2DM with mild/no OSA (T2DM, n = 10) and healthy controls (n = 14). Subcutaneous abdominal adipose tissue microdialysis assessed spontaneous, epinephrine- and isoprenaline-stimulated lipolysis. Glucose metabolism was assessed by intravenous glucose tolerance test. Spontaneous lipolysis was higher in the T2DM + OSA compared with the T2DM (60.34 ± 23.40 vs. 42.53 ± 10.16 μmol/L, p = 0.013), as well as epinephrine-stimulated lipolysis (236.84 ± 103.90 vs. 167.39 ± 52.17 µmol/L, p < 0.001). Isoprenaline-stimulated lipolysis was unaffected by the presence of OSA (p = 0.750). The α2 anti-lipolytic effect was decreased in T2DM + OSA by 59% and 315% compared with T2DM and controls (p = 0.045 and p = 0.007, respectively). The severity of OSA (AHI) was positively associated with spontaneous (p = 0.037) and epinephrine-stimulated (p = 0.026) lipolysis. The α2-adrenergic anti-lipolytic effect (p = 0.043) decreased with increasing AHI. Spontaneous lipolysis was positively associated with Insulin resistance (r = 0.50, p = 0.002). Epinephrine-stimulated lipolysis was negatively associated with the Disposition index (r =  − 0.34, p = 0.048). AHI was positively associated with Insulin resistance (p = 0.017) and negatively with the Disposition index (p = 0.038). Severe OSA in patients with T2DM increased adipose tissue lipolysis, probably due to inhibition of the α2-adrenergic anti-lipolytic effect. We suggest that dysregulated lipolysis might contribute to OSA-associated impairments in insulin secretion and sensitivity.
Use of multiple metrics to assess antibiotic use in Italian children’s hospitals
Authors: D’Amore Carmen , Ciofi degli Atti Marta Luisa , Zotti Carla , Prato Rosa , Guareschi Giuliano , Spiazzi Raffaele , Petitti Gaetano , Moro Maria Luisa , Raponi Massimiliano
Published: February 2021

Quantification of antibiotic utilization is an essential component of antibiotic stewardship programs. In this multicentric study, we used different metrics to evaluate inpatient antibiotic use in children. The study objectives were to describe point prevalence of antibiotic use by indication and patient characteristics, to evaluate DOTs, LOTs and PDDs, and to compare PDDs to DDDs, which assume average maintenance dose per day in adults. All children hospitalized on the days of the study were included. Trained personnel collected demographic and clinical data from patients’ clinical records. We recorded information about antibiotics administered on the date of data collection, and in the previous 30 days of hospitalization. Of 810 patients, 380 (46.9%; CI 95%: 43.4–50.4) received one or more antibiotics; prevalence of use was 27.0% for prophylaxis (219/810), and 20.7% (168/810) for treatment. Overall, 587 drugs were issued to the 380 patients receiving antibiotics (1.5 antibiotic per patient). When considering treatments, DOT and LOT per 100 patient-days were 30.5 and 19.1, respectively, resulting in a DOT/LOT ratio of 1.6. PDDs increased with age and approached DDDs only in children aged ≥ 10 years; the ratio between PDDs estimated in children aged ≥ 10 years and in 0–11 month-old infants ranged from 2 for sulfamethoxazole and trimethoprim, to 25 for meropenem. Our results confirm that DOT, LOT and PDD are better alternatives to DDD in children.
Negative shocks predict change in cognitive function and preferences: assessing the negative affect and stress hypothesis
Authors: Bogliacino Francesco , Codagnone Cristiano , Montealegre Felipe , Folkvord Frans , Gómez Camilo , Charris Rafael , Liva Giovanni , Lupiáñez-Villanueva Francisco , Veltri Giuseppe A.
Published: February 2021

In the context of the current COVID-19 pandemic, households throughout the world have to cope with negative shocks. Previous research has shown that negative shocks impair cognitive function and change risk, time and social preferences. In this study, we analyze the results of a longitudinal multi-country survey conducted in Italy (N = 1652), Spain (N = 1660) and the United Kingdom (N = 1578). We measure cognitive function using the Cognitive Reflection Test and preferences traits (risk, time and social preferences) using an experimentally validated set of questions to assess the differences between people exposed to a shock compared to the rest of the sample. We measure four possible types of shocks: labor market shock, health shock, occurrence of stressful events, and mental health shock. Additionally, we randomly assign participants to groups with either a recall of negative events (more specifically, a mild reinforcement of stress or of fear/anxiety), or to a control group (to recall neutral or joyful memories), in order to assess whether or not stress and negative emotions drive a change in preferences. Results show that people affected by shocks performed worse in terms of cognitive functioning, are more risk loving, and are more prone to punish others (negative reciprocity). Data do not support the hypotheses that the result is driven by stress or by negative emotions.