bluuebunny/crossref_metadata_2025 huggingface dataset:
Single trial neuronal activity dynamics of attentional intensity in monkey visual area V4
Authors: Ghosh Supriya , Maunsell John H. R.
Published: March 2021

Understanding how activity of visual neurons represents distinct components of attention and their dynamics that account for improved visual performance remains elusive because single-unit experiments have not isolated the intensive aspect of attention from attentional selectivity. We isolated attentional intensity and its single trial dynamics as determined by spatially non-selective attentional performance in an orientation discrimination task while recording from neurons in monkey visual area V4. We found that attentional intensity is a distinct cognitive signal that can be distinguished from spatial selectivity, reward expectations and motor actions. V4 spiking on single trials encodes a combination of sensory and cognitive signals on different time scales. Attentional intensity and the detection of behaviorally relevant sensory signals are well represented, but immediate reward expectation and behavioral choices are poorly represented in V4 spiking. These results provide a detailed representation of perceptual and cognitive signals in V4 that are crucial for attentional performance.
In vivo activation of pH-responsive oxidase-like graphitic nanozymes for selective killing of Helicobacter pylori
Authors: Zhang Lufeng , Zhang Liang , Deng Hui , Li Huan , Tang Wentao , Guan Luyao , Qiu Ye , Donovan Michael J. , Chen Zhuo , Tan Weihong
Published: March 2021

Helicobacter pylori infection is a major etiological factor in gastric diseases. However, clinical antibiotic therapy for H. pylori is limited by continuously decreased therapeutic efficacy and side effects to symbiotic bacteria. Herein, we develop an in vivo activatable pH-responsive graphitic nanozyme, PtCo@Graphene (PtCo@G), for selective treatment of H. pylori. Such nanozymes can resist gastric acid corrosion, exhibit oxidase-like activity to stably generate reactive oxygen species only in acidic gastric milieu and demonstrate superior selective bactericidal property. C18-PEGn-Benzeneboronic acid molecules are modified on PtCo@G, improving its targeting capability. Under acidic gastric pH, graphitic nanozymes show notable bactericidal activity toward H. pylori, while no bacterial killing is observed under intestinal conditions. In mouse model, high antibacterial capability toward H. pylori and negligible side effects toward normal tissues and symbiotic bacteria are achieved. Graphitic nanozyme displays the desired enzyme-like activities at corresponding physiological sites and may address critical issues in clinical treatment of H. pylori infections.
Type I interferons affect the metabolic fitness of CD8+ T cells from patients with systemic lupus erythematosus
Authors: Buang Norzawani , Tapeng Lunnathaya , Gray Victor , Sardini Alessandro , Whilding Chad , Lightstone Liz , Cairns Thomas D. , Pickering Matthew C. , Behmoaras Jacques , Ling Guang Sheng , Botto Marina
Published: March 2021

The majority of patients with systemic lupus erythematosus (SLE) have high expression of type I IFN-stimulated genes. Mitochondrial abnormalities have also been reported, but the contribution of type I IFN exposure to these changes is unknown. Here, we show downregulation of mitochondria-derived genes and mitochondria-associated metabolic pathways in IFN-High patients from transcriptomic analysis of CD4+ and CD8+ T cells. CD8+ T cells from these patients have enlarged mitochondria and lower spare respiratory capacity associated with increased cell death upon rechallenge with TCR stimulation. These mitochondrial abnormalities can be phenocopied by exposing CD8+ T cells from healthy volunteers to type I IFN and TCR stimulation. Mechanistically these ‘SLE-like’ conditions increase CD8+ T cell NAD+ consumption resulting in impaired mitochondrial respiration and reduced cell viability, both of which can be rectified by NAD+ supplementation. Our data suggest that type I IFN exposure contributes to SLE pathogenesis by promoting CD8+ T cell death via metabolic rewiring.
Soil moisture–atmosphere feedback dominates land carbon uptake variability
Authors: Humphrey Vincent , Berg Alexis , Ciais Philippe , Gentine Pierre , Jung Martin , Reichstein Markus , Seneviratne Sonia I. , Frankenberg Christian
Published: March 2021

Year-to-year changes in carbon uptake by terrestrial ecosystems have an essential role in determining atmospheric carbon dioxide concentrations1. It remains uncertain to what extent temperature and water availability can explain these variations at the global scale2–5. Here we use factorial climate model simulations6 and show that variability in soil moisture drives 90 per cent of the inter-annual variability in global land carbon uptake, mainly through its impact on photosynthesis. We find that most of this ecosystem response occurs indirectly as soil moisture–atmosphere feedback amplifies temperature and humidity anomalies and enhances the direct effects of soil water stress. The strength of this feedback mechanism explains why coupled climate models indicate that soil moisture has a dominant role4, which is not readily apparent from land surface model simulations and observational analyses2,5. These findings highlight the need to account for feedback between soil and atmospheric dryness when estimating the response of the carbon cycle to climatic change globally5,7, as well as when conducting field-scale investigations of the response of the ecosystem to droughts8,9. Our results show that most of the global variability in modelled land carbon uptake is driven by temperature and vapour pressure deficit effects that are controlled by soil moisture.
Dietary glutamic acid and aspartic acid as biomarkers for predicting diabetic retinopathy
Authors: Park So Young , Kim Jieun , Son Jung Il , Rhee Sang Youl , Kim Do-Yeon , Chon Suk , Lim Hyunjung , Woo Jeong-Taek
Published: March 2021

The screening rate of diabetic retinopathy (DR) is low despite the importance of early diagnosis. We investigated the predictive value of dietary glutamic acid and aspartic acid for diagnosis of DR using the Korea National Diabetes Program cohort study. The 2067 patients with type 2 diabetes without DR were included. The baseline intakes of energy, glutamic acid and aspartic acid were assessed using a 3-day food records. The risk of DR incidence based on intake of glutamic acid and aspartic acid was analyzed. The DR group was older, and had higher HbA1c, longer DM duration, lower education level and income than non-DR group (all p < 0.05). The intake of total energy, glutamic acid and aspartic acid were lower in DR group than non-DR group (p = 0.010, p = 0.025 and p = 0.042, respectively). There was no difference in the risk of developing DR according to the intake of glutamic acid and ascorbic acid. But, aspartic acid intake had a negative correlation with PDR. Hence, the intake of glutamic acid and aspartic acid did not affect in DR incidence. However, lower aspartic acid intake affected the PDR incidence.
Third generation cephalosporins and piperacillin/tazobactam have distinct impacts on the microbiota of critically ill patients
Authors: Gamage Hasinika K. A. H. , Venturini Carola , Tetu Sasha G. , Kabir Masrura , Nayyar Vineet , Ginn Andrew N. , Roychoudhry Belinda , Thomas Lee , Brown Mitchell , Holmes Andrew , Partridge Sally R. , Seppelt Ian , Paulsen Ian T. , Iredell Jonathan R.
Published: March 2021

Effective implementation of antibiotic stewardship, especially in critical care, is limited by a lack of direct comparative investigations on how different antibiotics impact the microbiota and antibiotic resistance rates. We investigated the impact of two commonly used antibiotics, third-generation cephalosporins (3GC) and piperacillin/tazobactam (TZP) on the endotracheal, perineal and faecal microbiota of intensive care patients in Australia. Patients exposed to either 3GC, TZP, or no β-lactams (control group) were sampled over time and 16S rRNA amplicon sequencing was performed to examine microbiota diversity and composition. While neither treatment significantly affected diversity, numerous changes to microbiota composition were associated with each treatment. The shifts in microbiota composition associated with 3GC exposure differed from those observed with TZP, consistent with previous reports in animal models. This included a significant increase in Enterobacteriaceae and Enterococcaceae abundance in endotracheal and perineal microbiota for those administered 3GC compared to the control group. Culture-based analyses did not identify any significant changes in the prevalence of specific pathogenic or antibiotic-resistant bacteria. Exposure to clinical antibiotics has previously been linked to reduced microbiota diversity and increased antimicrobial resistance, but our results indicate that these effects may not be immediately apparent after short-term real-world exposures.
A Strepsipteran parasite extends the lifespan of workers in a social wasp
Authors: Beani Laura , Dallai Romano , Cappa Federico , Manfredini Fabio , Zaccaroni Marco , Lorenzi Maria Cristina , Mercati David
Published: March 2021

In social wasps, female lifespan depends on caste and colony tasks: workers usually live a few weeks while queens as long as 1 year.Polistes dominulapaper wasps infected by the strepsipteran parasiteXenos vesparumavoid all colony tasks, cluster on vegetation where parasite dispersal and mating occur, hibernate and infect the next generation of wasp larvae. Here, we compared the survival rate of infected and uninfected wasp workers. Workers’ survival was significantly affected by parasite sex: two-third of workers parasitized by aX. vesparumfemale survived and overwintered like future queens did, while all workers infected by aX. vesparummale died during the summer, like uninfected workers that we used as controls. We measured a set of host and parasite traits possibly associated with the observed lifespan extension. Infected overwintering workers had larger fat bodies than infected workers that died in the summer, but they had similar body size and ovary development. Furthermore, we recorded a positive correlation between parasite and host body sizes. We hypothesize that the manipulation of worker’s longevity operated byX. vesparumenhances parasite’s fitness: if workers infected by a female overwinter, they can spread infective parasite larvae in the spring like parasitized gynes do, thus contributing to parasite transmission.
Hypoxia and oxidative stress induce sterile placental inflammation in vitro
Authors: Baker Bernadette C. , Heazell Alexander E. P. , Sibley Colin , Wright Rachael , Bischof Helen , Beards Frances , Guevara Tatiana , Girard Sylvie , Jones Rebecca L.
Published: March 2021

Fetal growth restriction (FGR) and stillbirth are associated with placental dysfunction and inflammation and hypoxia, oxidative and nitrative stress are implicated in placental damage. Damage-associated molecular patterns (DAMPs) are elevated in pregnancies at increased risk of FGR and stillbirth and are associated with increase in pro-inflammatory placental cytokines. We hypothesised that placental insults lead to release of DAMPs, promoting placental inflammation. Placental tissue from uncomplicated pregnancies was exposed in vitro to hypoxia, oxidative or nitrative stress. Tissue production and release of DAMPs and cytokines was determined. Oxidative stress and hypoxia caused differential release of DAMPs including uric acid, HMGB1, S100A8, cell-free fetal DNA, S100A12 and HSP70. After oxidative stress pro-inflammatory cytokines (IL-1α, IL-1β, IL-6, IL-8, TNFα, CCL2) were increased both within explants and in conditioned culture medium. Hypoxia increased tissue IL-1α/β, IL-6, IL-8 and TNFα levels, and release of IL-1α, IL-6 and IL-8, whereas CCL2 and IL-10 were reduced. IL1 receptor antagonist (IL1Ra) treatment prevented hypoxia- and oxidative stress-induced IL-6 and IL-8 release. These findings provide evidence that relevant stressors induce a sterile inflammatory profile in placental tissue which can be partially blocked by IL1Ra suggesting this agent has translational potential to prevent placental inflammation evident in FGR and stillbirth.
Age-dependent ataxia and neurodegeneration caused by an αII spectrin mutation with impaired regulation of its calpain sensitivity
Authors: Miazek Arkadiusz , Zalas Michał , Skrzymowska Joanna , Bogin Bryan A. , Grzymajło Krzysztof , Goszczynski Tomasz M. , Levine Zachary A. , Morrow Jon S. , Stankewich Michael C.
Published: March 2021

The neuronal membrane-associated periodic spectrin skeleton (MPS) contributes to neuronal development, remodeling, and organization. Post-translational modifications impinge on spectrin, the major component of the MPS, but their role remains poorly understood. One modification targeting spectrin is cleavage by calpains, a family of calcium-activated proteases. Spectrin cleavage is regulated by activated calpain, but also by the calcium-dependent binding of calmodulin (CaM) to spectrin. The physiologic significance of this balance between calpain activation and substrate-level regulation of spectrin cleavage is unknown. We report a strain of C57BL/6J mice harboring a single αII spectrin point mutation (Sptan1 c.3293G > A:p.R1098Q) with reduced CaM affinity and intrinsically enhanced sensitivity to calpain proteolysis. Homozygotes are embryonic lethal. Newborn heterozygotes of either gender appear normal, but soon develop a progressive ataxia characterized biochemically by accelerated calpain-mediated spectrin cleavage and morphologically by disruption of axonal and dendritic integrity and global neurodegeneration. Molecular modeling predicts unconstrained exposure of the mutant spectrin’s calpain-cleavage site. These results reveal the critical importance of substrate-level regulation of spectrin cleavage for the maintenance of neuronal integrity. Given that excessive activation of calpain proteases is a common feature of neurodegenerative disease and traumatic encephalopathy, we propose that damage to the spectrin MPS may contribute to the neuropathology of many disorders.
Unveiling the unknown phylogenetic position of the scallop Austrochlamys natans and its implications for marine stewardship in the Magallanes Province
Authors: Rosenfeld Sebastián , Aldea Cristian , López Zambra , Maturana Claudia S. , Ojeda Jaime , Bahamonde Francisco , Detrée Camille , Mansilla Andrés , Poulin Elie , Gérard Karin
Published: March 2021

Two species of scallop, Austrochlamys natans (“Ostión del Sur”) and Zygochlamys patagonica (“Ostión patagonico”) are presently exploited in the southern part of the Magallanes Province (MP). The lack of clarity in taxonomic identification and ecological aspects is generating both erroneous extraction statistics and an unperceived harvesting pressure on A. natans and Z. patagonica. We aim to discriminate these Magallanes scallops accurately, improve our understanding of their complex natural history and discuss possible implications for their management and conservation status, given the current fisheries statistics. To achieve these goals, we present a complete review of the historical identification of the Magallanes scallop and a multi-locus molecular phylogeny which allowed us to recover the phylogenetic position of A. natans. We sampled 54 individuals from five localities across the southern Pacific coast of the MP. We calculated the depth of the byssal notch (BND) and shell height (VH) ratio from morphological characters and conducted phylogenetic reconstructions with mitochondrial (12S and 16S) and nuclear markers (28S) using Bayesian and maximum likelihood analyses. Both morphology and molecular phylogeny identified two distinct entities, Z. patagonica and a distinct, highly divergent lineage that corresponds to A. natans. Our study provides integrative evidence to alert the current fishery management and the need for further conservation studies.
An R package for generic modular response analysis and its application to estrogen and retinoic acid receptor crosstalk
Authors: Jimenez-Dominguez Gabriel , Ravel Patrice , Jalaguier Stéphan , Cavaillès Vincent , Colinge Jacques
Published: March 2021

Modular response analysis (MRA) is a widely used inference technique developed to uncover directions and strengths of connections in molecular networks under a steady-state condition by means of perturbation experiments. We devised several extensions of this methodology to search genomic data for new associations with a biological network inferred by MRA, to improve the predictive accuracy of MRA-inferred networks, and to estimate confidence intervals of MRA parameters from datasets with low numbers of replicates. The classical MRA computations and their extensions were implemented in a freely available R package called aiMeRA (https://github.com/bioinfo-ircm/aiMeRA/). We illustrated the application of our package by assessing the crosstalk between estrogen and retinoic acid receptors, two nuclear receptors implicated in several hormone-driven cancers, such as breast cancer. Based on new data generated for this study, our analysis revealed potential cross-inhibition mediated by the shared corepressors NRIP1 and LCoR. We designed aiMeRA for non-specialists and to allow biologists to perform their own analyses.
Effect of autogenous crack self-healing on mechanical strength recovery of cement mortar under various environmental exposure
Authors: Suleiman A. R. , Nehdi M. L.
Published: March 2021

While research on self-healing of cement-based materials has recently gained considerable attention and made sizable progress, there is still ongoing debate and controversy regarding the effect of crack closing induced by autogenous self-healing on mechanical strength recovery. Despite that several techniques have been used to capture and quantify the self-healing of surface cracks, the resulting effect on mechanical strength has not, to date, been explored and quantified in a rigorous and systematic manner. Therefore, in this study, a broad array of multi-scale techniques including non-destructive shear wave velocity, high-resolution X-ray computed tomography (µCT), and 3D image analysis was deployed to examine the effects of autogenous crack self-healing on the mechanical strength recovery in various mortar specimens. The influence of microstructural changes induced by additives such as swelling compounds, silica-based additions, and carbonating minerals on strength recovery under diverse environmental exposures was further explored. The results capture the relationship between the crack closing mechanism imparted by self-healing and mechanical strength recovery, therefore elucidating the discrepancies in mechanical strength recovery results reported in the open literature.
Individual differences in dominance-related traits drive dispersal and settlement in hatchery-reared juvenile brown trout
Authors: Sánchez-González Jorge R. , Nicieza Alfredo G.
Published: March 2021

Effective management of exploited populations is based on an understanding of population dynamics and evolutionary processes. In spatially structured populations, dispersal is a central process that ultimately can affect population growth and viability. It can be influenced by environmental conditions, individual phenotypes, and stochastic factors. However, we have a limited knowledge of the relative contribution of these components and its interactions, and which traits can be used as reliable predictors of the dispersal ability. Here, we conducted a longitudinal field experiment aimed to identify traits which can be used as proxy for dispersal in juvenile brown trout (Salmo truttaL.). We measured body size and standard metabolic rates, and estimated body shapes for 212 hatchery-reared juvenile fish that were marked with individual codes and released in a small coastal stream in northwest Spain. We registered fish positions and distances to the releasing point after 19, 41, 60 and 158 days in the stream. We detected a high autocorrelation of dispersal distances, demonstrating that most individuals settle down relatively soon and then hold stable positions over the study period. Body size and fish shape were reliable predictors of dispersal, with bigger and more robust-set individuals being more likely to settle closer to the release site than smaller and more elongated fish. In addition, the analysis of spacing and spatial patterns indicated that the dispersal of introduced fish could affect the distribution of resident conspecifics. All together, these results suggest that stocking programs aimed to the enhancement of overexploited populations at fine spatial scales can be optimized by adjusting the size and shape of the introduced fish to specific management targets and environmental conditions.
Hand rehabilitation with sonification techniques in the subacute stage of stroke
Authors: Raglio Alfredo , Panigazzi Monica , Colombo Roberto , Tramontano Marco , Iosa Marco , Mastrogiacomo Sara , Baiardi Paola , Molteni Daniele , Baldissarro Eleonora , Imbriani Chiara , Imarisio Chiara , Eretti Laura , Hamedani Mehrnaz , Pistarini Caterina , Imbriani Marcello , Mancardi Gian Luigi , Caltagirone Carlo
Published: March 2021

After a stroke event, most survivors suffer from arm paresis, poor motor control and other disabilities that make activities of daily living difficult, severely affecting quality of life and personal independence. This randomized controlled trial aimed at evaluating the efficacy of a music-based sonification approach on upper limbs motor functions, quality of life and pain perceived during rehabilitation. The study involved 65 subacute stroke individuals during inpatient rehabilitation allocated into 2 groups which underwent usual care dayweek) respectively of standard upper extremity motor rehabilitation or upper extremity treatment with sonification techniques. The Fugl-Meyer Upper Extremity Scale, Box and Block Test and the Modified Ashworth Scale were used to perform motor assessment and the McGill Quality of Life-it and the Numerical Pain Rating Scale to assess quality of life and pain. The assessment was performed at baseline, after 2 weeks, at the end of treatment and at follow-up (1 month after the end of treatment). Total scores of the Fugl-Meyer Upper Extremity Scale (primary outcome measure) and hand and wrist sub scores, manual dexterity scores of the affected and unaffected limb in the Box and Block Test, pain scores of the Numerical Pain Rating Scale (secondary outcomes measures) significantly improved in the sonification group compared to the standard of care group (time*group interaction < 0.05). Our findings suggest that music-based sonification sessions can be considered an effective standardized intervention for the upper limb in subacute stroke rehabilitation.
A primitive type of renin-expressing lymphocyte protects the organism against infections
Authors: Belyea Brian C. , Santiago Araceli E. , Vasconez Wilson A. , Nagalakshmi Vidya K. , Xu Fang , Mehalic Theodore C. , Sequeira-Lopez Maria Luisa S. , Gomez R. Ariel
Published: March 2021

The hormone renin plays a crucial role in the regulation of blood pressure and fluid-electrolyte homeostasis. Normally, renin is synthesized by juxtaglomerular (JG) cells, a specialized group of myoepithelial cells located near the entrance to the kidney glomeruli. In response to low blood pressure and/or a decrease in extracellular fluid volume (as it occurs during dehydration, hypotension, or septic shock) JG cells respond by releasing renin to the circulation to reestablish homeostasis. Interestingly, renin-expressing cells also exist outside of the kidney, where their function has remained a mystery. We discovered a unique type of renin-expressing B-1 lymphocyte that may have unrecognized roles in defending the organism against infections. These cells synthesize renin, entrap and phagocyte bacteria and control bacterial growth. The ability of renin-bearing lymphocytes to control infections—which is enhanced by the presence of renin—adds a novel, previously unsuspected dimension to the defense role of renin-expressing cells, linking the endocrine control of circulatory homeostasis with the immune control of infections to ensure survival.
Characterization of new cristamonad species from kalotermitid termites including a novel genus, Runanympha
Authors: Singh Racquel A. , Boscaro Vittorio , James Erick R. , Karnkowska Anna , Kolisko Martin , Gavelis Gregory S. , Okamoto Noriko , del Campo Javier , Fiorito Rebecca , Hehenberger Elisabeth , Irwin Nicholas A. T. , Mathur Varsha , Scheffrahn Rudolf H. , Keeling Patrick J.
Published: March 2021

Cristamonadea is a large class of parabasalian protists that reside in the hindguts of wood-feeding insects, where they play an essential role in the digestion of lignocellulose. This group of symbionts boasts an impressive array of complex morphological characteristics, many of which have evolved multiple times independently. However, their diversity is understudied and molecular data remain scarce. Here we describe seven new species of cristamonad symbionts from Comatermes, Calcaritermes, and Rugitermes termites from Peru and Ecuador. To classify these new species, we examined cells by light and scanning electron microscopy, sequenced the symbiont small subunit ribosomal RNA (rRNA) genes, and carried out barcoding of the mitochondrial large subunit rRNA gene of the hosts to confirm host identification. Based on these data, five of the symbionts characterized here represent new species within described genera: Devescovina sapara n. sp., Devescovina aymara n. sp., Macrotrichomonas ashaninka n. sp., Macrotrichomonas secoya n. sp., and Macrotrichomonas yanesha n. sp. Additionally, two symbionts with overall morphological characteristics similar to the poorly-studied and probably polyphyletic ‘joeniid’ Parabasalia are classified in a new genus Runanympha n. gen.: Runanympha illapa n. sp., and Runanympha pacha n. sp.
DOT1L inhibitors block abnormal self-renewal induced by cohesin loss
Authors: Heimbruch Katelyn E. , Fisher Joseph B. , Stelloh Cary T. , Phillips Emily , Reimer Michael H. , Wargolet Adam J. , Meyer Alison E. , Pulakanti Kirthi , Viny Aaron D. , Loppnow Jessica J. , Levine Ross L. , Pulikkan John Anto , Zhu Nan , Rao Sridhar
Published: March 2021

Acute myeloid leukemia (AML) is a high-risk malignancy characterized by a diverse spectrum of somatic genetic alterations. The mechanisms by which these mutations contribute to leukemia development and how this informs the use of targeted therapies is critical to improving outcomes for patients. Importantly, how to target loss-of-function mutations has been a critical challenge in precision medicine. Heterozygous inactivating mutations in cohesin complex genes contribute to AML in adults by increasing the self-renewal capacity of hematopoietic stem and progenitor cells (HSPCs) by altering PRC2 targeting to induce HOXA9 expression, a key self-renewal transcription factor. Here we sought to delineate the epigenetic mechanism underpinning the enhanced self-renewal conferred by cohesin-haploinsufficiency. First, given the substantial difference in the mutational spectrum between pediatric and adult AML patients, we first sought to identify if HOXA9 was also elevated in children. Next, using primary HSPCs as a model we demonstrate that abnormal self-renewal due to cohesin loss is blocked by DOT1L inhibition. In cohesin-depleted cells, DOT1L inhibition is associated with H3K79me2 depletion and a concomitant increase in H3K27me3. Importantly, we find that there are cohesin-dependent gene expression changes that promote a leukemic profile, including HoxA overexpression, that are preferentially reversed by DOT1L inhibition. Our data further characterize how cohesin mutations contribute to AML development, identifying DOT1L as a potential therapeutic target for adult and pediatric AML patients harboring cohesin mutations.
Towards global flood mapping onboard low cost satellites with machine learning
Authors: Mateo-Garcia Gonzalo , Veitch-Michaelis Joshua , Smith Lewis , Oprea Silviu Vlad , Schumann Guy , Gal Yarin , Baydin Atılım Güneş , Backes Dietmar
Published: March 2021

Spaceborne Earth observation is a key technology for flood response, offering valuable information to decision makers on the ground. Very large constellations of small, nano satellites— ’CubeSats’ are a promising solution to reduce revisit time in disaster areas from days to hours. However, data transmission to ground receivers is limited by constraints on power and bandwidth of CubeSats. Onboard processing offers a solution to decrease the amount of data to transmit by reducing large sensor images to smaller data products. The ESA’s recent PhiSat-1 mission aims to facilitate the demonstration of this concept, providing the hardware capability to perform onboard processing by including a power-constrained machine learning accelerator and the software to run custom applications. This work demonstrates a flood segmentation algorithm that produces flood masks to be transmitted instead of the raw images, while running efficiently on the accelerator aboard the PhiSat-1. Our models are trained on WorldFloods: a newly compiled dataset of 119 globally verified flooding events from disaster response organizations, which we make available in a common format. We test the system on independent locations, demonstrating that it produces fast and accurate segmentation masks on the hardware accelerator, acting as a proof of concept for this approach.
3D-printed micro bubble column reactor with integrated microsensors for biotechnological applications: From design to evaluation
Authors: Frey Lasse Jannis , Vorländer David , Ostsieker Hendrik , Rasch Detlev , Lohse Jan-Luca , Breitfeld Maximilian , Grosch Jan-Hendrik , Wehinger Gregor D. , Bahnemann Janina , Krull Rainer
Published: March 2021

With the technological advances in 3D printing technology, which are associated with ever-increasing printing resolution, additive manufacturing is now increasingly being used for rapid manufacturing of complex devices including microsystems development for laboratory applications. Personalized experimental devices or entire bioreactors of high complexity can be manufactured within few hours from start to finish. This study presents a customized 3D-printed micro bubble column reactor (3D-µBCR), which can be used for the cultivation of microorganisms (e.g., Saccharomyces cerevisiae) and allows online-monitoring of process parameters through integrated microsensor technology. The modular 3D-µBCR achieves rapid homogenization in less than 1 s and high oxygen transfer with kLa values up to 788 h−1 and is able to monitor biomass, pH, and DOT in the fluid phase, as well as CO2 and O2 in the gas phase. By extensive comparison of different reactor designs, the influence of the geometry on the resulting hydrodynamics was investigated. In order to quantify local flow patterns in the fluid, a three-dimensional and transient multiphase Computational Fluid Dynamics model was successfully developed and applied. The presented 3D-µBCR shows enormous potential for experimental parallelization and enables a high level of flexibility in reactor design, which can support versatile process development.
Differential reprogramming of breast cancer subtypes in 3D cultures and implications for sensitivity to targeted therapy
Authors: Koedoot Esmee , Wolters Liesanne , Smid Marcel , Stoilov Peter , Burger Gerhard A. , Herpers Bram , Yan Kuan , Price Leo S. , Martens John W. M. , Le Dévédec Sylvia E. , van de Water Bob
Published: March 2021

Screening for effective candidate drugs for breast cancer has shifted from two-dimensional (2D) to three-dimensional (3D) cultures. Here we systematically compared the transcriptomes of these different culture conditions by RNAseq of 14 BC cell lines cultured in both 2D and 3D conditions. All 3D BC cell cultures demonstrated increased mitochondrial metabolism and downregulated cell cycle programs. Luminal BC cells in 3D demonstrated overall limited reprogramming. 3D basal B BC cells showed increased expression of extracellular matrix (ECM) interaction genes, which coincides with an invasive phenotype not observed in other BC cells. Genes downregulated in 3D were associated with metastatic disease progression in BC patients, including cyclin dependent kinases and aurora kinases. Furthermore, the overall correlation of the cell line transcriptome to the BC patient transcriptome was increased in 3D cultures for all TNBC cell lines. To define the most optimal culture conditions to study the oncogenic pathway of interest, an open source bioinformatics strategy was established.
Identifying unknown Indian wolves by their distinctive howls: its potential as a non-invasive survey method
Authors: Sadhukhan Sougata , Root-Gutteridge Holly , Habib Bilal
Published: March 2021

Previous studies have posited the use of acoustics-based surveys to monitor population size and estimate their density. However, decreasing the bias in population estimations, such as by using Capture–Mark–Recapture, requires the identification of individuals using supervised classification methods, especially for sparsely populated species like the wolf which may otherwise be counted repeatedly. The cryptic behaviour of Indian wolf (Canis lupus pallipes) poses serious challenges to survey efforts, and thus, there is no reliable estimate of their population despite a prominent role in the ecosystem. Like other wolves, Indian wolves produce howls that can be detected over distances of more than 6 km, making them ideal candidates for acoustic surveys. Here, we explore the use of a supervised classifier to identify unknown individuals. We trained a supervised Agglomerative Nesting hierarchical clustering (AGNES) model using 49 howls from five Indian wolves and achieved 98% individual identification accuracy. We tested our model’s predictive power using 20 novel howls from a further four individuals (test dataset) and resulted in 75% accuracy in classifying howls to individuals. The model can reduce bias in population estimations using Capture-Mark-Recapture and track individual wolves non-invasively by their howls. This has potential for studies of wolves’ territory use, pack composition, and reproductive behaviour. Our method can potentially be adapted for other species with individually distinctive vocalisations, representing an advanced tool for individual-level monitoring.
Prediction of response of methotrexate in patients with rheumatoid arthritis using serum lipidomics
Authors: Maciejewski Mateusz , Sands Caroline , Nair Nisha , Ling Stephanie , Verstappen Suzanne , Hyrich Kimme , Barton Anne , Ziemek Daniel , Lewis Matthew R. , Plant Darren
Published: March 2021

Methotrexate (MTX) is a common first-line treatment for new-onset rheumatoid arthritis (RA). However, MTX is ineffective for 30–40% of patients and there is no way to know which patients might benefit. Here, we built statistical models based on serum lipid levels measured at two time-points (pre-treatment and following 4 weeks on-drug) to investigate if MTX response (by 6 months) could be predicted. Patients about to commence MTX treatment for the first time were selected from the Rheumatoid Arthritis Medication Study (RAMS). Patients were categorised as good or non-responders following 6 months on-drug using EULAR response criteria. Serum lipids were measured using ultra‐performance liquid chromatography–mass spectrometry and supervised machine learning methods (including regularized regression, support vector machine and random forest) were used to predict EULAR response. Models including lipid levels were compared to models including clinical covariates alone. The best performing classifier including lipid levels (assessed at 4 weeks) was constructed using regularized regression (ROC AUC 0.61 ± 0.02). However, the clinical covariate based model outperformed the classifier including lipid levels when either pre- or on-treatment time-points were investigated (ROC AUC 0.68 ± 0.02). Pre- or early-treatment serum lipid profiles are unlikely to inform classification of MTX response by 6 months with performance adequate for use in RA clinical management.
Predicting mortality risk for preterm infants using random forest
Authors: Lee Jennifer , Cai Jinjin , Li Fuhai , Vesoulis Zachary A.
Published: March 2021

Mortality is an unfortunately common outcome of extremely and very preterm birth. Existing clinical prediction models capture mortality risk at birth but fail to account for the remainder of the hospital course. Infants born < 32 weeks gestation with complete physiologic and clinical data were included in this retrospective study. Mortality risk was quantified by conventional means (clinical factors) using the CRIB-II score and the optimal logistic regression model. A random forest (RF) model was trained using a subset of the cohort, labeling data within 6 h of death as “worry.” The model was then tested using the remaining infants. A total of 275 infants were included in the study with a mean gestational age of 27 weeks, mean birth weight of 929 g, 49% female, and a mortality rate of 21%. The CRIB-II and logistic regression models had acceptable performance with sensitivities of 71% and 80% AUC scores of 0.78 and 0.84, respectively. The RF model had superior performance with a sensitivity of 88% and an AUC of 0.93. A random forest model which incorporates fixed clinical factors with the influence of aberrancies in subsequent physiology has superior performance for mortality prediction compared to conventional models.
Enhancing calmodulin binding to ryanodine receptor is crucial to limit neuronal cell loss in Alzheimer disease
Authors: Nakamura Yoshihide , Yamamoto Takeshi , Xu Xiaojuan , Kobayashi Shigeki , Tanaka Shinji , Tamitani Masaki , Saito Takashi , Saido Takaomi C. , Yano Masafumi
Published: March 2021

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive neuronal cell loss. Recently, dysregulation of intracellular Ca2+homeostasis has been suggested as a common proximal cause of neural dysfunction in AD. Here, we investigated (1) the pathogenic role of destabilization of ryanodine receptor (RyR2) in endoplasmic reticulum (ER) upon development of AD phenotypes inAppNL-G-Fmice, which harbor three familial AD mutations (Swedish, Beyreuther/Iberian, and Arctic), and (2) the therapeutic effect of enhanced calmodulin (CaM) binding to RyR2. In the neuronal cells fromAppNL-G-Fmice, CaM dissociation from RyR2 was associated with AD-related phenotypes, i.e. Aβ accumulation, TAU phosphorylation, ER stress, neuronal cell loss, and cognitive dysfunction. Surprisingly, either genetic (by V3599K substitution in RyR2) or pharmacological (by dantrolene) enhancement of CaM binding to RyR2 reversed almost completely the aforementioned AD-related phenotypes, except for Aβ accumulation. Thus, destabilization of RyR2 due to CaM dissociation is most likely an early and fundamental pathogenic mechanism involved in the development of AD. The discovery that neuronal cell loss can be fully prevented simply by stabilizing RyR2 sheds new light on the treatment of AD.
An integrated multimodal model of alcohol use disorder generated by data-driven causal discovery analysis
Authors: Rawls Eric , Kummerfeld Erich , Zilverstand Anna
Published: March 2021

Alcohol use disorder (AUD) has high prevalence and adverse societal impacts, but our understanding of the factors driving AUD is hampered by a lack of studies that describe the complex neurobehavioral mechanisms driving AUD. We analyzed causal pathways to AUD severity using Causal Discovery Analysis (CDA) with data from the Human Connectome Project (HCP; n = 926 [54% female], 22% AUD [37% female]). We applied exploratory factor analysis to parse the wide HCP phenotypic space (100 measures) into 18 underlying domains, and we assessed functional connectivity within 12 resting-state brain networks. We then employed data-driven CDA to generate a causal model relating phenotypic factors, fMRI network connectivity, and AUD symptom severity, which highlighted a limited set of causes of AUD. The model proposed a hierarchy with causal influence propagating from brain connectivity to cognition (fluid/crystalized cognition, language/math ability, & working memory) to social (agreeableness/social support) to affective/psychiatric function (negative affect, low conscientiousness/attention, externalizing symptoms) and ultimately AUD severity. Our data-driven model confirmed hypothesized influences of cognitive and affective factors on AUD, while underscoring that addiction models need to be expanded to highlight the importance of social factors, amongst others.
Evidence for continuity of interstitial spaces across tissue and organ boundaries in humans
Authors: Cenaj Odise , Allison Douglas H. R. , Imam Rami , Zeck Briana , Drohan Lilly M. , Chiriboga Luis , Llewellyn Jessica , Liu Cheng Z. , Park Young Nyun , Wells Rebecca G. , Theise Neil D.
Published: March 2021

Bodies have continuous reticular networks, comprising collagens, elastin, glycosaminoglycans, and other extracellular matrix components, through all tissues and organs. Fibrous coverings of nerves and blood vessels create structural continuity beyond organ boundaries. We recently validated fluid flow through human fibrous tissues, though whether these interstitial spaces are continuous through the body or discontinuous, confined within individual organs, remains unclear. Here we show evidence for continuity of interstitial spaces using two approaches. Non-biological particles (tattoo pigment, colloidal silver) were tracked within colon and skin interstitial spaces and into adjacent fascia. Hyaluronic acid, a macromolecular component of interstitial spaces, was also visualized. Both techniques demonstrate interstitial continuity within and between organs including within perineurium and vascular adventitia traversing organs and the spaces between them. We suggest that there is a body-wide network of fluid-filled interstitial spaces that has significant implications for molecular signaling, cell trafficking, and the spread of malignant and infectious disease.
Iodine(III) promotes cross-dehydrogenative coupling of N-hydroxyphthalimide and unactivated C(sp3)–H bonds
Authors: Wu Fufang , Han Xuanzhen , Li Xuejian , Shen Xiaobao , Wang Chang , Tian Zhimei , Cheng Bin , Zhang Jingbin , Sheng Liangquan , Zhai Hongbin
Published: March 2021

Cross-dehydrogenative coupling reactions provide a method to construct new chemical bonds by direct C–H activation without any pre-functionalization. Compared to functionalization of a C–H bond α- to ether oxygen, α- to carbonyl, or at a benzylic position, functionalization of unactivated hydrocarbons is difficult and often requires high temperatures, a transition-metal catalyst, or a superstoichiometric quantity of volatile, toxic, and explosive tert-butylhydroperoxide. Here, a cross-dehydrogenative C–O coupling reaction of N-hydroxyphthalimide with unactivated alkanes, nitriles, ethers, and thioethers has been realized by using iodobenzene diacetate as the radical initiator. The current protocol enables efficient functionalization of unactivated hydrocarbons and nitriles through inert C(sp3)–H bond activation under mild reaction conditions. O-substituted NHPI derivatives are generated in good yields under metal-free conditions.
Inverse design and flexible parameterization of meta-optics using algorithmic differentiation
Authors: Colburn Shane , Majumdar Arka
Published: March 2021

Ultrathin meta-optics offer unmatched, multifunctional control of light. Next-generation optical technologies, however, demand unprecedented performance. This will likely require design algorithms surpassing the capability of human intuition. For the adjoint method, this requires explicitly deriving gradients, which is sometimes challenging for certain photonics problems. Existing techniques also comprise a patchwork of application-specific algorithms, each focused in scope and scatterer type. Here, we leverage algorithmic differentiation as used in artificial neural networks, treating photonic design parameters as trainable weights, optical sources as inputs, and encapsulating device performance in the loss function. By solving a complex, degenerate eigenproblem and formulating rigorous coupled-wave analysis as a computational graph, we support both arbitrary, parameterized scatterers and topology optimization. With iteration times below the cost of two forward simulations typical of adjoint methods, we generate multilayer, multifunctional, and aperiodic meta-optics. As an open-source platform adaptable to other algorithms and problems, we enable fast and flexible meta-optical design.
Directed self-assembly of soft 3D photonic crystals for holograms with omnidirectional circular-polarization selectivity
Authors: Cho SeongYong , Takahashi Misaki , Fukuda Jun-ichi , Yoshida Hiroyuki , Ozaki Masanori
Published: March 2021

Controlling the crystallographic orientation of 3D photonic crystals is important as it determines the behavior of light propagating through the device. Blue phases self-assemble into unique soft 3D photonic crystals with chiral structures for circular-polarization selectivity, but it has remained a challenge to control its 3D orientation. Here, we show that the orientation of blue phases can be precisely controlled to follow a predefined pattern imprinted on a substrate by exploiting field-induced phase transitions. Obtaining the blue phase through the field-induced chiral nematic phase and tetragonal blue phase X results in a highly oriented blue phase I with the crystallographic [001] direction aligned along the surface anchoring. Our approach is applied to fabricating a Bragg-Berry hologram with omnidirectional circular-polarization selectivity, where the hologram is visible only for one circular-polarization under all incident angles. Such devices are difficult to fabricate using conventional optical materials, thereby demonstrating the potential of self-organizing soft matter for photonics.
Ionic-strength and pH dependent reactivities of ascorbic acid toward ozone in aqueous micro-droplets studied using aerosol optical tweezers
Authors: Chang Yuan-Pin , Wu Shan-Jung , Lin Min-Sian , Chiang Che-Yu , Huang Genin Gary
Published: March 2021

In situ measurements of pH and pH-dependent kinetics of the reaction of ascorbic acid and ozone in single aqueous droplets via aerosol optical tweezers.
From the Birkeland–Eyde process towards energy-efficient plasma-based NOX synthesis: a techno-economic analysis
Authors: Rouwenhorst Kevin H. R. , Jardali Fatme , Bogaerts Annemie , Lefferts Leon
Published: March 2021

Plasma-based NOX synthesis can be combined with renewable electricity for decarbonized fertilizer production. Renewed research interest makes it increasingly competitive with the conventional process.
1T-CrO2monolayer: a high-temperature Dirac half-metal for high-speed spintronics
Authors: He Shenda , Zhou Pan , Yang Yi , Wang Wei , Sun L. Z.
Published: March 2021

We propose the intrinsic ferromagnetic Dirac half-metallic 1T-CrO2monolayer as a promising platform for future high efficiency spintronic applications.
Interfacial interactions between protective, surface-engineered shells and encapsulated bacteria with different cell surface composition
Authors: Wei Hao , Yang Xiao-Yu , Geng Wei , van der Mei Henny C. , Busscher Henk J.
Published: March 2021

The impact of strong, intermediate and weak interfacial interactions on encapsulated probiotics are compared and finds that weakly interacting shells are preferred for better protection against antibiotics and maintenance of probiotic activities.
Characterising soft matter using machine learning
Authors: Clegg Paul S.
Published: March 2021

Machine learning is having a major impact on soft matter research.
Protein–nanoparticle interactions and a new insight
Authors: Ghosh Goutam , Panicker Lata
Published: March 2021

The RCPC interaction causes protein unfolding and cancer cell membrane lysis. Antibody-functionalized nanoparticles can be targeted to cancer cell membrane causing increase of the membrane entropy to disintegrate it and cell-death.