bluuebunny/crossref_metadata_2025 huggingface dataset:
Portable real-time colorimetric LAMP-device for rapid quantitative detection of nucleic acids in crude samples
Authors: Papadakis G. , Pantazis A. K. , Fikas N. , Chatziioannidou S. , Tsiakalou V. , Michaelidou K. , Pogka V. , Megariti M. , Vardaki M. , Giarentis K. , Heaney J. , Nastouli E. , Karamitros T. , Mentis A. , Zafiropoulos A. , Sourvinos G. , Agelaki S. , Gizeli E.
Published: July 2020

Loop-mediated isothermal amplification is known for its high sensitivity, specificity and tolerance to inhibiting-substances. We developed a device for performing real-time colorimetric LAMP combining the accuracy of lab-based quantitative molecular diagnosis with the simplicity of point-of-care testing. This handheld device employs a single reaction-pot for amplification and a mini-camera for detection. Competitive features are the rapid analysis (<30min), quantification over 9 log-units, crude sample-compatibility (saliva, tissue, swabs), low detection limit (<5copies/reaction), smartphone-operation and fast prototyping (3D-printing). The device’s clinical utility is demonstrated in cancer-mutations and COVID-19 testing. Excellent performance includes: detection of 0.01% ofBRAF-V600E-to-wild-type molecules; 97% sensitivity to SARS-CoV-2 RNA detection (89 samples); 83% (Ct<34), 98% (Ct<30) and 100% (Ct<25) to 163 nasopharyngeal-swabs; 100% specificity in all cases. The device high technology-readiness-level makes it a suitable platform for performing any colorimetric LAMP assay; moreover, its simple and inexpensive fabrication holds promise for fast deployment and application in global diagnostics.
Repeated horizontal gene transfer ofGALactose metabolism genes violates Dollo’s law of irreversible loss
Authors: Haase Max A. B. , Kominek Jacek , Opulente Dana A. , Shen Xing-Xing , LaBella Abigail L. , Zhou Xiaofan , DeVirgilio Jeremy , Hulfachor Amanda Beth , Kurtzman Cletus P. , Rokas Antonis , Hittinger Chris Todd
Published: July 2020

Dollo’s law posits that evolutionary losses are irreversible, thereby narrowing the potential paths of evolutionary change. While phenotypic reversals to ancestral states have been observed, little is known about their underlying genetic causes. The genomes of budding yeasts have been shaped by extensive reductive evolution, such as reduced genome sizes and the losses of metabolic capabilities. However, the extent and mechanisms of trait reacquisition after gene loss in yeasts have not been thoroughly studied. Here, through phylogenomic analyses, we reconstructed the evolutionary history of the yeast galactose utilization pathway and observed widespread and repeated losses of the ability to utilize galactose, which occurred concurrently with the losses ofGALactose (GAL) utilization genes. Unexpectedly, we detected three galactose-utilizing lineages that were deeply embedded within clades that underwent ancient losses of galactose utilization. We show that at least two, and possibly three, lineages reacquired theGALpathway via yeast-to-yeast horizontal gene transfer. Our results show how trait reacquisition can occur tens of millions of years after an initial loss via horizontal gene transfer from distant relatives. These findings demonstrate that the losses of complex traits and even whole pathways are not always evolutionary dead-ends, highlighting how reversals to ancestral states can occur.
Spatiotemporal dynamics between interictal epileptiform discharges and ripples during associative memory processing
Authors: Henin Simon , Shankar Anita , Borges Helen , Flinker Adeen , Doyle Werner , Friedman Daniel , Devinsky Orrin , Buzsáki György , Liu Anli
Published: July 2020

We describe the spatiotemporal course of cortical high-gamma activity (HGA), hippocampal ripple activity and interictal epileptiform discharges (IEDs) during an associative memory task in 15 epilepsy patients undergoing invasive electroencephalography. Successful encoding trials manifested significantly greater HGA in hippocampus and frontal regions. Successful cued recall trials manifested sustained HGA in hippocampus compared to failed responses. Hippocampal ripple rates were greater during successful encoding and retrieval trials. IEDs during encoding were associated with 15% decreased odds of remembering in hippocampus (95% CI 6-23%). Hippocampal IEDs during retrieval predicted 25% decreased odds of remembering (15-33%). Odds of remembering were reduced by 25-52% if IEDs occurred during the 500-2000 ms window of encoding or by 41% during retrieval. During encoding and retrieval, hippocampal IEDs were followed by a transient decrease in ripple rate. We hypothesize that IEDs impair associative memory in a regionally and temporally specific manner by decreasing physiologic hippocampal ripples necessary for effective encoding and recall. Because dynamic memory impairment arises from pathological IED events competing with physiological ripples, IEDs represent a promising therapeutic target for memory remediation in patients with epilepsy.

Hippocampal interictal epileptiform discharges in hippocampus acutely impair declarative memory, potentially by hijacking physiological processes essential for encoding and recall.
Machine intelligence identifies soluble TNFa as a therapeutic target for spinal cord injury
Authors: Huie JR , Ferguson AR , Kyritsis N , Pan J Z , Irvine K-A , Nielson JL , Schupp PG , Oldham MC , Gensel JC , Lin A , Segal MR , Ratan RR , Bresnahan JC , Beattie MS
Published: July 2020

Traumatic spinal cord injury (SCI) produces a complex syndrome that is expressed across multiple endpoints ranging from molecular and cellular changes to functional behavioral deficits. Effective therapeutic strategies for CNS injury are therefore likely to manifest multi-factorial effects across a broad range of biological and functional outcome measures. Thus, multivariate analytic approaches are needed to capture the linkage between biological and neurobehavioral outcomes. Injury-induced neuroinflammation (NI) presents a particularly challenging therapeutic target, since NI is involved in both degeneration and repair1,2. Here, we used big-data integration and large-scale analytics to examine a large dataset of preclinical efficacy tests combining 5 different blinded, fully counter-balanced treatment trials for different acute anti-inflammatory treatments for cervical spinal cord injury in rats. Multi-dimensional discovery, using topological data analysis3(TDA) and principal components analysis (PCA) revealed that only one showed consistent multidimensional syndromic benefit: intrathecal application of recombinant soluble TNFα receptor 1 (sTNFR1), which showed an inverse-U dose response efficacy. Using the optimal acute dose, we showed that clinically-relevant 90 min delayed treatment profoundly affected multiple biological indices of NI in the first 48 hrs after injury, including reduction in pro-inflammatory cytokines and gene expression of a coherent complex of acute inflammatory mediators and receptors. Further, a 90 min delayed bolus dose of sTNFR1 reduced the expression of NI markers in the chronic perilesional spinal cord, and consistently improved neurological function over 6 weeks post SCI. These results provide validation of a novel strategy for precision preclinical drug discovery that is likely to improve translation in the difficult landscape of CNS trauma, and confirm the importance of TNFα signaling as a therapeutic target.
Beneficial contribution of iPSC-progeny to connexin 47 dynamics during demyelination-remyelination
Authors: Mozafari Sabah , Deboux Cyrille , Laterza Cecilia , Ehrlich Marc , Kuhlmann Tanja , Martino Gianvito , Baron-Van Evercooren Anne
Published: July 2020

Oligodendrocytes are extensively coupled to astrocytes, a phenomenon ensuring glial homeostasis and maintenance of CNS myelin. Molecular disruption of this communication occurs in demyelinating diseases such as multiple sclerosis. Less is known about the vulnerability and reconstruction of the panglial network during adult demyelination-remyelination. Here, we took advantage of LPC-induced demyelination to investigate the expression dynamics of the oligodendrocyte specific connexin 47 (Cx47) and whether this dynamic could be modulated by grafted iPSC-neural progeny. Our data show that deconstruction of the panglial network following demyelination is larger in size than demyelination. Loss of Cx47 expression is timely rescued during remyelination and accelerated by the grafted neural precursors. Moreover, mouse and human iPS-derived oligodendrocytes express Cx47, which co-labels with astrocyte Cx43, indicating their integration into the panglial network. These data suggest that full lesion repair following transplantation occurs by panglial reconstruction in addition to remyelination. Targeting panglial elements by cell therapy or pharmacological compounds may help accelerating or stabilizing re/myelination in myelin disorders.
Meiotic sister chromatid exchanges are rare inC. elegans
Authors: Almanzar David E. , Gordon Spencer G. , Rog Ofer
Published: July 2020

Sexual reproduction shuffles the parental genomes to generate new genetic combinations. To achieve that, the genome is subjected to numerous double-strand breaks, the repair of which involves two crucial decisions: repair pathway and repair template. Use of crossover pathways with the homologous chromosome as template exchanges genetic information and directs chromosome segregation. Crossover repair, however, can compromise the integrity of the repair template and is therefore tightly regulated. The extent to which crossover pathways are used during sister-directed repair is unclear, because the identical sister chromatids are difficult to distinguish. Nonetheless, indirect assays have led to the suggestion that inter-sister crossovers, or sister chromatid exchanges (SCEs), are quite common. Here we devised a technique to directly score physiological SCEs in theC. elegansgermline using selective sister chromatid labeling with the thymidine analog 5-ethynyl-2’-deoxyuridine (EdU). Surprisingly, we find SCEs to be rare in meiosis, accounting for <2% of repair events. SCEs remain rare even when the homologous chromosome is unavailable, indicating that almost all sister-directed repair is channeled into noncrossover pathways. We identify two mechanisms that limit SCEs. First, sister-directed repair intermediates are efficiently inhibited by the RecQ helicase BLMHIM-6. Second, the Synaptonemal Complex–a conserved interface that promotes crossover repair– localizes between the homologous chromosomes and not the sister chromatids. Our data suggest that inC. eleganscrossover pathways are only used to generate the single necessary link between the homologous chromosomes. Almost all other breaks, regardless of which repair template they use, are repaired by noncrossover pathways.
Predicting cognitive abilities across individuals using sparse EEG connectivity
Authors: Hakim Nicole , Awh Edward , Vogel Edward K , Rosenberg Monica D
Published: July 2020

Human brains share a broadly similar functional organization with consequential individual variation. This duality in brain function has primarily been observed when using techniques that consider the spatial organization of the brain, such as MRI. Here, we ask whether these common and unique signals of cognition are also present in temporally sensitive, but spatially insensitive, neural signals. To address this question, we compiled EEG data from individuals performing multiple working memory tasks at two different data-collection sites (ns= 171 and 165). Results revealed that EEG connectivity patterns were stable within individuals and unique across individuals. Furthermore, models based on these connectivity patterns generalized across datasets to predict participants’ working memory capacity and general fluid intelligence. Thus, EEG connectivity provides a signature of working memory and fluid intelligence in humans and a new framework for characterizing individual differences in cognitive abilities.
What are we missing by using hydrophilic enrichment? Improving bacterial glycoproteome coverage using total proteome and FAIMS analysis
Authors: Izaham Ameera Raudah Ahmad , Ang Ching-Seng , Nie Shuai , Bird Lauren E. , Williamson Nicholas A. , Scott Nichollas E.
Published: July 2020

Hydrophilic Interaction Liquid Chromatography (HILIC) glycopeptide enrichment is an indispensable tool for the high-throughput characterisation of glycoproteomes. Despite its utility, HILIC enrichment is associated with a number of short comings including requiring large amounts of starting material, potentially introducing chemical artefacts such as formylation, and biasing/under-sampling specific classes of glycopeptides. Here we investigate HILIC enrichment independent approaches for the study of bacterial glycoproteomes. Using three Burkholderia species (B. cenocepacia, B. dolosaandB. ubonensis) we demonstrate that short aliphaticO-linked glycopeptides are typically absent from HILIC enrichments yet are readily identified in whole proteome samples. Using Field Asymmetric Waveform IMS (FAIMS) fractionation we show that at low compensation voltages (CVs) short aliphatic glycopeptides can be enriched from complex samples providing an alternative means to identify glycopeptides recalcitrant to hydrophilic based enrichment. Combining whole proteome and FAIMS analysis we show that the observable glycoproteome of these Burkholderia species is at least 30% larger than initially thought. Excitingly, the ability to enrich glycopeptides using FAIMS appears generally applicable, with theN-linked glycopeptides ofCampylobacter fetus subsp. fetusalso enrichable at low FAIMS CVs. Taken together, these results demonstrate that FAIMS provides an alternative means to access glycopeptides and is a valuable tool for glycoproteomic analysis.
A toxin-antitoxin system associated transcription factor ofCaulobacter crescentuscan influence cell cycle-regulated gene expression during the SOS response
Authors: Ghosh Koyel , Ankær Brejndal Kamilla , Kirkpatrick Clare L.
Published: July 2020

Toxin-antitoxin (TA) systems are widespread in bacterial chromosomes but their functions remain enigmatic. Although many are transcriptionally upregulated by stress conditions, it is unclear what role they play in cellular responses to stress and to what extent the role of a given TA system homologue varies between different bacterial species. In this work we investigate the role of the DNA damage-inducible TA system HigBA ofCaulobacter crescentusin the SOS response and discover that in addition to the toxin HigB affecting cell cycle gene expression through inhibition of the master regulator CtrA, HigBA possesses a transcription factor third component, HigC, which both auto-regulates the TA system and acts independently of it. Through HigC, the system exerts downstream effects on antibiotic (ciprofloxacin) resistance and cell cycle gene expression. HigB and HigC had inverse effects on cell cycle gene regulation, with HigB reducing and HigC increasing the expression of CtrA-dependent promoters. Neither HigBA nor HigC had any effect on formation of persister cells in response to ciprofloxacin. Rather, their role in the SOS response appears to be as transcriptional and post-transcriptional regulators of cell cycle-dependent gene expression, transmitting the status of the SOS response as a regulatory input into the cell cycle control network via CtrA.

Importance

Almost all bacteria respond to DNA damage by upregulating a set of genes that helps them to repair and recover from the damage, known as the SOS response. The set of genes induced during the SOS response varies between species, but frequently includes toxin-antitoxin systems. However, it is unknown what the consequence of inducing these systems is, and whether they provide any benefit to the cells. We show here that the DNA damage-induced TA system HigBA of the asymmetrically dividing bacteriumCaulobacter crescentusaffects the cell cycle regulation of this bacterium. HigBA also has a transcription factor encoded immediately downstream of it, named here HigC, which controls expression of the TA system and potentially other genes as well. Therefore, this work identifies a new role for TA systems in the DNA damage response, distinct from non-specific stress tolerance mechanisms which had been proposed previously.
Direct morpho-chemical characterization of elusive plant residues from Aurignacian Pontic Steppe ground stones
Authors: Birarda G. , Cagnato C. , Pantyukhina I. , Stani C. , Cefarin N. , Sorrentino G. , Badetti E. , Marcomini A. , Lubritto C. , Khlopachev G. , Covalenco S. , Obada T. , Skakun N. , Vaccari L. , Longo L.
Published: July 2020

Direct evidence for the intentional processing of starch-rich plants during the Paleolithic is scant, and that evidence is often compromised by concerns over preservation and contamination. Our integrated, multimodal approach couples wear-trace analysis with chemical imaging methods to identify the presence of genuine ancient starch candidates (ASC) on ground stones used in the Pontic Steppe starting around 40,000 years ago. Optical and electron microscopy coupled with infrared spectromicroscopy and imaging provide morphological and chemical profiles for ASCs, that partially match the vibrational polysaccharide features of modern reference starches, highlighting diagenetic differences ranging from partial oxidation to mineralization. The results suggest the intentional processing of roots and tubers by means of mechanical tenderization and shed light on the role of dietary carbohydrates during Homo sapiens’ (HS) colonization of Eurasia, demonstrating a long acquaintance with predictable calorific foods, crucial to maintain homeostasis during the harsh conditions of the Late MIS 3 (40-25 ky).
The tree that hides the forest: identification of common predisposing loci in several hematopoietic cancers and several dog breeds
Authors: Hédan Benoit , Cadieu Edouard , Rimbault Maud , Vaysse Amaury , Devauchelle Patrick , Botherel Nadine , Abadie Jérôme , Quignon Pascale , Derrien Thomas , André Catherine
Published: July 2020

Histiocytic sarcoma (HS) is a rare but aggressive cancer in humans and dogs. The spontaneous canine model, with the clinical, epidemiological and histological similarities with human HS and specific breed predispositions, is a unique model/opportunity to unravel the genetic bases of this cancer. In this study, we aimed to identify germline risk factors associated with the development of HS in canine predisposed breeds. We used a methodology that combined several genome-wide association studies in a multi-breed and multi-cancer approach, as well as targeted next generation sequencing, and imputation combining several breeds (Bernese mountain dog, Rottweiler, flat coated retriever and golden retriever) and three haematopoietic cancers (HS, lymphoma and mast cell tumor). Results showed that we not only refined the previously identified HS riskCDKN2Alocus but we identified new loci on canine chromosomes 2, 5, 12, 14, 20, 26 and X. Capture and targeted sequencing of specific loci pointed towards the existence of regulatory variants in non coding regions and/or methylation mechanisms linked to risk haplotypes, leading to strong cancer predispositions in specific dog breeds. Our results showed that these canine cancer predisposing loci appear to be due to the additive effect of several risk haplotype involved also in other haematopoietic cancers such lymphoma or mast cell tumor, illustrating the pleiotropic nature of these canine cancer loci as observed in human oncology, thus reinforcing the interest of predisposed dog breeds to study cancer initiation and progression.
Antimicrobial prodrug activation by the staphylococcal glyoxalase GloB
Authors: Mikati Marwa O. , Miller Justin J. , Osbourn Damon M. , Ghebremichael Naomi , Shah Ishaan T. , Burnham Carey-Ann D. , Heidel Kenneth M. , Yan Victoria C. , Muller Florian L. , Dowd Cynthia S. , Edwards Rachel L. , Odom John Audrey R.
Published: July 2020

With the rising prevalence of multidrug-resistance, there is an urgent need to develop novel antibiotics. Many putative antibiotics demonstrate promising in vitro potency but fail in vivo due to poor drug-like qualities (e.g. serum half-life, oral absorption, solubility, toxicity). These drug-like properties can be modified through the addition of chemical protecting groups, creating “prodrugs” that are activated prior to target inhibition. Lipophilic prodrugging techniques, including the attachment of a pivaloyloxymethyl group, have garnered attention for their ability to increase cellular permeability by masking charged residues and the relative ease of the chemical prodrugging process. Unfortunately, pivaloyloxymethyl prodrugs are rapidly activated by human sera, rendering any membrane permeability qualities absent during clinical treatment. Identification of the bacterial prodrug activation pathway(s) will allow for the development of host-stable and microbe-targeted prodrug therapies. Here, we use two zoonotic staphylococcal species, S. schleiferi and S. pseudintermedius, to establish the mechanism of carboxy ester prodrug activation. Using a forward genetic screen, we identify a conserved locus in both species encoding the enzyme hydroxyacylglutathione hydrolase (GloB), whose loss-of-function confers resistance to carboxy ester prodrugs. We enzymatically characterize GloB and demonstrate that it is a functional glyoxalase II enzyme, which has the capacity to activate carboxy ester prodrugs. As GloB homologs are both widespread and diverse in sequence, our findings suggest that GloB may be a useful mechanism for developing species-or genus-level prodrug targeting strategies.
HTSQualC is a Flexible and One-Step Quality Control Software for High-throughput Sequencing Data Analysis
Authors: Bedre Renesh , Avila Carlos , Mandadi Kranthi
Published: July 2020

Use of high-throughput sequencing (HTS) has become indispensable in life science research. Raw HTS data contains several sequencing artifacts, and as a first step it is imperative to remove the artifacts for reliable downstream bioinformatics analysis. Although there are multiple stand-alone tools available that can perform the various quality control steps separately, availability of an integrated tool that can allow one-step, automated quality control analysis of HTS datasets will significantly enhance handling large number of samples parallelly. Here, we developed HTSQualC, a stand-alone, flexible, and easy-to-use software for one-step quality control analysis of raw HTS data. HTSQualC can evaluate HTS data quality and perform filtering and trimming analysis in a single run. We evaluated the performance of HTSQualC for conducting batch analysis of HTS datasets with 322 samples with an average ∼1M (paired end) sequence reads per sample. HTSQualC accomplished the QC analysis in ∼3 hours in distributed mode and ∼31 hours in shared mode, thus underscoring its utility and robust performance. In addition to command-line execution, we integrated HTSQualC into the free, open-source, CyVerse cyberinfrastructure resource as a GUI interface, for wider access to experimental biologists who have limited computational resources and/or programming abilities.
Optimization of a bacterial three-hybrid assay throughin vivotitration of an RNA-DNA adapter-protein
Authors: Wang Clara D. , Mansky Rachel , LeBlanc Hannah , Gravel Chandra M. , Berry Katherine E.
Published: July 2020

Non-coding RNAs regulate gene expression in every domain of life. In bacteria, small RNAs (sRNAs) regulate gene expression in response to stress and are often assisted by RNA-chaperone proteins, such as Hfq. We have recently developed a bacterial three-hybrid (B3H) assay that detects the strong binding interactions of certainE. colisRNAs with proteins Hfq and ProQ. Despite the promise of this system, the signal-to-noise has made it challenging to detect weaker interactions. In this work, we use Hfq-sRNA interactions as a model system to optimize the B3H assay, so that weaker RNA-protein interactions can be more reliably detected. We find that the concentration of the RNA-DNA adapter is an important parameter in determining the signal in the system, and have modified the plasmid expressing this component to tune its concentration to optimal levels. In addition, we have systematically perturbed the binding affinity of Hfq-RNA interactions to define, for the first time, the relationship between B3H signal andin vitrobinding energetics. The new pAdapter construct presented here substantially expands the range of detectable interactions in the B3H assay, broadening its utility. This improved assay will increase the likelihood of identifying novel protein-RNA interactions with the B3H system, and will facilitate exploration of the binding mechanisms of these interactions.
The supramolecular landscape of growing human axons
Authors: Hoffmann Patrick C. , Giandomenico Stefano L. , Ganeva Iva , Wozny Michael R. , Sutcliffe Magdalena , Kukulski Wanda , Lancaster Madeline A.
Published: July 2020

During brain development, human axons must extend over great distances in a relatively short amount of time. How the subcellular architecture of the growing axon sustains the requirements for such rapid build-up of cellular constituents has remained elusive. Human axons have been particularly inaccessible to imaging at molecular resolution in a near-native context. Here we apply cryo-correlative light microscopy and electron tomography to growing axonal tracts from human cerebral organoids. Our data reveal a wealth of structural details on the arrangement of macromolecules, cytoskeletal components, and organelles in elongating axon shafts. In particular, the intricate shape of the endoplasmic reticulum is consistent with its role in fulfilling the high demand for lipid biosynthesis to support growth. Furthermore, the scarcity of ribosomes within the growing shaft suggests limited translational competence during expansion of this compartment. These data provide an unprecedented resource and reveal a molecular architecture that helps explain the unique biology of growing human axons.
Soluble corn fiber reduces ovalbumin-induced sinonasal inflammation via the gut microbiota-airway axis
Authors: Jaramillo Sierra A. , Borsom Emily M. , Orsini Gabrielle M. , Kask Oliver , Lee Keehoon , Hirsch Allyson H. , Settles Erik , Shi Xiaojian , Gu Haiwei , Koppisch Andrew T. , Bokulich Nicholas A. , Caporaso J. Gregory , Cope Emily K.
Published: July 2020

Asthma is a chronic airway inflammatory disease that affects approximately 300 million people worldwide, causing a substantial healthcare burden. Although there is a large degree of heterogeneity in the inflammatory response of asthmatics, a subset of patients are characterized by type-2 inflammation, which is in part mediated by TH2 cells in both the upper and lower airways. Asthma prevalence is increased in low-socioeconomic-status populations, where disparities in health behavior exist, including a shift toward a western diet characterized by low dietary fiber. Gut microbes metabolize fiber into short chain fatty acids that can reduce type-2 inflammation in peripheral organs, such as the airways. We hypothesized that soluble fiber can reduce ovalbumin (OVA)-induced upper airway inflammation in the context of the unified airway hypothesis, in mice maintained on ingredient-matched western (WD) and control diets (CD) through production of short chain fatty acids. Our results show that soluble fiber reducesIL-4andIL-13gene expression (p<0.05, Mann Whitney) in the sinonasal cavity of CD-fed mice, but this effect was lost in WD-fed mice. This loss of protection in WD-fed mice parallels compositional changes of the cecal and fecal microbiota. Mice fed a soluble fiber supplement while being maintained on a WD had altered microbial communities characterized by lower abundance of fiber fermentering bacteria. This work can be used to develop effective microbiome-based therapeutics as a low-cost method to reduce asthma morbidity.

IMPORTANCE

Previous research has supported that western-style diets, typically high-fat and low-fiber, are associated with changes in the gut microbiome and increased inflammation. Western diets are accessible and prominent in low-socioeconomic-status populations, where asthma rates are highest; however, there has yet to be a low-cost asthma therapeutic. For the first time, we investigated whether supplementation with a physiologically relevant quantity of soluble corn fiber can reduce allergic airway inflammation. Our study supports that soluble corn fiber supplementation is associated with compositional shifts of the gut microbiota and reduced airway inflammation, promoting the use of fiber as a low-cost microbiome modifying therapy to reduce asthma-associated inflammation. However, soluble corn fiber in conjunction with a western diet resulted in an alternate gut microbiome composition and loss of protection against allergic airway inflammation. These findings further support the importance of the gut microbiota in host health.
Standardizing carabid pitfall catches for trapping effort; a meta-analysis
Authors: Saska Pavel , Makowski David , Bohan David , van der Werf Wopke
Published: July 2020

Carabid beetles (Coleoptera: Carabidae) provide important ecological services and are frequently used as a bio-indicator in monitoring environmental quality. The abundance and diversity of carabids is usually determined using pitfall trapping, but trap catches are difficult to compare between studies due to variation in trapping effort. The standardization of the catch for trapping effort has not been previously addressed in a global analysis of studies in the literature.

The aims of this study are (i) to define a method for estimating the effect of trapping effort on the size of the pitfall catch, and (ii) to explore factors related to study designs, sampling method, study origin, and level of data aggregation to determine how these factors affect the catch per unit effort in pitfall trapping.

We conducted a meta-analysis on the activity-density and diversity of carabids across studies, based on published data from Europe and North-America to analyse whether standardization of catch measurements might be possible. Data were extracted from 104 publications, spanning a period of 42 years.

The total catch was proportional to the number of trap days, and ranged from 0.19-9.53 beetles/(trap day) across studies (95% range), with a mean of 1.33 beetles/(trap day). The number of species was allometrically related to the trapping effort defined as the product of the number of traps, their perimeter and the time of exposure in the field, and characterized by a power exponent of 0.25. Species richness ranged across studies from 2.30-13.18 species/(m day)0.25(95% range) with a mean of 7.15 species/(m day)0.25. The size of the catch and the number of species were higher in crops with narrow as compared to wide rows. There was no significant change in abundance or diversity of carabids in arable land over the 42 years covered. We also found that increasing trapping effort may not yield more accurate results.

The results show that it is possible to standardize activity-density-based catches and species diversity for trapping effort across studies using a power transformation, allowing meta-analysis of such data, e.g. to elucidate factors affecting abundance and diversity of the focal taxa.
Non-synaptic interactions between olfactory receptor neurons, a possible key feature of odor processing in flies
Authors: Pannunzi Mario , Nowotny Thomas
Published: July 2020

When flies explore their environment, they encounter odors in complex, highly intermittent plumes. To navigate a plume and, for example, find food, they must solve several challenges, including reliably identifying mixtures of odorants and their intensities, and discriminating odorant mixtures emanating from a single source from odorants emitted from separate sources and just mixing in the air. Lateral inhibition in the antennal lobe is commonly understood to help solving these challenges. With a computational model of theDrosophilaolfactory system, we analyze the utility of an alternative mechanism for solving them: Non-synaptic (“ephaptic”) interactions (NSIs) between olfactory receptor neurons that are stereotypically co-housed in the same sensilla.

We found that NSIs improve mixture ratio detection and plume structure sensing and they do so more efficiently than the traditionally considered mechanism of lateral inhibition in the antennal lobe. However, we also found that NSIsdecreasethe dynamic range of co-housed ORNs, especially when they have similar sensitivity to an odorant. These results shed light, from a functional perspective, on the role of NSIs, which are normally avoided between neurons, for instance by myelination.

Author summary

Myelin is important to isolate neurons and avoid disruptive electrical interference between them; it can be found in almost any neural assembly. However, there are a few exceptions to this rule and it remains unclear why. One particularly interesting case is the electrical interaction between olfactory sensory neurons co-housed in the sensilla of insects. Here, we created a computational model of the early stages of theDrosophilaolfactory system and observed that the electrical interference between olfactory receptor neurons can be a useful trait that can help flies, and other insects, to navigate the complex plumes of odorants in their natural environment.

With the model we were able to shed new light on the trade-off of adopting this mechanism: We found that the non-synaptic interactions (NSIs) improve both the identification of the concentration ratio in mixtures of odorants and the discrimination of odorant mixtures emanating from a single source from odorants emitted from separate sources – both highly advantageous. However, they also decrease the dynamic range of the olfactory sensory neurons – a clear disadvantage.
A dual prokaryotic (E. coli) expression system (pdMAX)
Authors: Murakami Manabu , Murakami Agnieszka M. , Hirota Kazuyoshi , Itagaki Shirou
Published: July 2020

In this study, we introduced an efficient subcloning and expression system with two inducible prokaryotic expression promoters, arabinose and lac, in a single plasmid inEscherichia coli. This pdMAX system is a manageable size at 5811 bp. The arabinose promoter unit allows for the expression of a FLAG-tagged protein, while the isopropyl-β-D-thiogalactoside (IPTG)-inducible unit allows for the expression of a Myc-tagged protein. An efficient subcloning (DNA insertion) system (iUnit) follows each promoter. The iUnit, based on a toxin that targets DNA topoisomerase ofE. coli, allows for effective selection with arabinose or IPTG induction.

Interestingly, the dual induction plasmid system shows limited protein expression. To analyze the expression of inserted genes, we performed anα-complementation assay, in which theα-peptide of the lacZ (β-galactosidase) gene is inserted in XL-10E. colicells.E. coliexpressing the recombinant plasmid form blue colonies when plated on ampicillin/IPTG- or arabinose/X-gal-containing plates if theα-peptide was correctly inserted in-frame to produce the tagged protein. This assay system assesses whether theα-peptide was inserted at the restriction sites (EcoRV or SmaI), whether the inserted peptide was expressed, and whether the insertedα-peptide sequence was ligated in-frame to produce a tagged protein. Frameshifts result in noα-complementation and white colonies.

With the dual promoter plasmid (pdMAX) system, expressedlacZactivity was significantly decreased comparing with the solo expression (pgMAX) system. Despite this disadvantage, we believe the pdMAX system is still useful for the analysis of distinct genes inE. coli, which will enable different types of expression analysis. Overall, the novel pdMAX system allows for efficient subcloning of two different genes. Furthermore, the pdMAX system could be used to induce and analyze the expression of two distinct genes and adopted to various types of prokaryotic gene expression analyses.
Development and validation of a clinical risk score to predict the risk of SARS-CoV-2 infection from administrative data: a population-based cohort study from Italy
Authors: Orlando Valentina , Rea Federico , Savaré Laura , Guarino Ilaria , Mucherino Sara , Perrella Alessandro , Trama Ugo , Coscioni Enrico , Menditto Enrica , Corrao Giovanni
Published: July 2020

Background

The novel coronavirus (SARS-CoV-2) pandemic spread rapidly worldwide increasing exponentially in Italy. To date, there is lack of studies describing clinical characteristics of the population most at risk of infection. Hence, we aimed to identify clinical predictors of SARS-CoV-2 infection risk and to develop and validate a score predicting SARS-CoV-2 infection risk comparing it with unspecific surrogates.

Methods

Retrospective case/control study using administrative health-related database was carried out in Southern Italy (Campania region) among beneficiaries of Regional Health Service aged over than 30 years. For each subject with Covid-19 confirmed diagnosis (case), up to five controls were randomly matched for gender, age and municipality of residence. Odds ratios and 90% confidence intervals for associations between candidate predictors and risk of infection were estimated by means of conditional logistic regression. SARS-CoV-2 Infection Score (SIS), was developed by generating a total aggregate score obtained from assignment of a weight at each selected covariate using coefficients estimated from the model. Finally, the score was categorized by assigning increasing values from 1 to 4. SIS was validated by comparison with specific and unspecific predictors of SARS-CoV-2 infection.

Results

Subjects suffering from diabetes, anaemias, Parkinson’s disease, mental disorders, cardiovascular and inflammatory bowel and kidney diseases showed increased risk of SARS-CoV-2 infection. Similar estimates were recorded for men and women and younger and older than 65 years. Fifteen conditions significantly contributed to the SIS. As SIS value increases, risk progressively increases, being odds of SARS-CoV-2 infection among people with the highest SIS value (SIS=4), 1.74 times higher than those unaffected by any SIS contributing conditions (SIS=1).

Conclusion

This study identified conditions and diseases making individuals more vulnerable to SARS-CoV-2 infection. Our results are a decision-maker support tool for identifying population most at risk allowing adoption of preventive measures to minimize a potential new relapse damage.
Ecological memory mitigates negative impacts of disturbance on biomass production in benthic diatom metacommunities
Authors: Engel Friederike G. , Matthiessen Birte , Andriana Rosyta , Eriksson Britas Klemens
Published: July 2020

Disturbance events to coastal habitats such as extreme heat events, storms, or floods have increased in magnitude and frequency in recent years due to anthropogenic climate change and the destruction of habitats. These events constitute a major threat to many ecological communities and global biodiversity. Disturbance history influences ecosystem response to novel disturbances such that communities that have previously been exposed to disturbances should be more resilient to new disturbances compared to previously sheltered communities. This principle is defined as ecological memory. Resilience should also increase with access to a larger species pool, because a larger species pool increases species and response diversity of a community. One possibility of increasing the local species pool is connectivity via adequate dispersal between habitat patches with different species compositions in metacommunities. In a laboratory experiment, we exposed benthic diatom communities of different origin to a mechanical disturbance, simulated dispersal in half of the communities, and measured their chlorophyllaconcentration over time. The local diatom communities originated from different locations on an intertidal flat that varied in hydrodynamic exposure history. Hydrodynamic exposure disturbs the sediment, and thereby determines sediment properties and the composition of intertidal diatom communities. In the experiment, disturbance negatively affected chlorophyllaconcentration across all treatments. However, the response to disturbance depended on the ecological memory of the communities; the more exposed areas the communities originated from, the less negative was the effect of the mechanical disturbance. Interestingly, dispersal did not mitigate the negative impacts of disturbance in any of the communities. Our results highlight the importance of ecological memory for ecosystem functioning and demonstrate the limitations of patch connectivity to alleviate the impacts of disturbance events in metacommunities.
Vacuolar transporter Mnr2 safeguards mitochondrial integrity in aged cells
Authors: Reza Md. Hashim , Patkar Rajesh , Sanyal Kaustuv
Published: July 2020

Aging is associated with altered mitochondrial function. Mitochondrial function is dependent on the magnesium (Mg+2) ion flux. The molecular mechanism underlying Mg+2homeostasis, especially during aging has not been well understood. We previously demonstrated that the absence of a vacuolar ion transporter Mnr2 accelerates cell death in the older part of the colony inMagnaporthe oryzaepresumably due to an altered Mg+2homeostasis. Localization of Mnr2 as dynamic puncta at the vacuolar membrane especially in the olderMagnaporthecells further suggests its association with aged cells. Interestingly, such vacuolar Mnr2 puncta colocalized with the filamentous mitochondria in the aged cells. Further, we show that agedmnr2Δ null cells displayed loss of integrity of mitochondria and vacuoles. Remarkably, exogenously added Mg+2restored the mitochondrial structure as well as improved the lifespan ofmnr2Δ null cells. Thus, we uncover a mechanism of maintenance of mitochondrial integrity and function by the ion transporter Mnr2-based Mg+2homeostasis during aging.
The Latency of Spontaneous Eye Blinks Marks Relevant Visual and Auditory Information Processing
Authors: Murali Supriya , Händel Barbara
Published: July 2020

Eye blinks are influenced by several external sensory and internal cognitive factors. However, neither the precise temporal effects of these factors on blinking nor how their timing compares between modalities is known. Our aim was to understand the influence of sensory input vs task-relevant information on blinks in the visual and auditory domain.

Using a visual and an auditory temporal judgement task, we found that blinks were suppressed during stimulus presentation in both domains and the overall input length had a significant positive relationship with blink latency i.e. the end of blink suppression. Indeed, the effect of sensory input duration on blink latency was not significantly different between visual and auditory stimuli. The precise timing of blink latency was further modulated by the duration of the task relevant input, which was independent of the overall length of sensory input. The influence of task related changes embedded in the overall stimulation suggests an additional influence of top-down processes on blink timing. Intriguingly, embedded changes as short as 40 ms in the auditory domain and 100 ms in the visual domain are reflected in blink latency differences. Importantly, we could show that task accuracy and motor response was not the driving factor of blink modulation.

Our results show a sensory domain independent modulation of blink latencies introduced by changes in the length of task-relevant information. Therefore, blinks not only mark the time of sensory input but also can act as precise indicator for periods of cognitive processing and attention.
Integration of sleep homeostasis and navigation inDrosophila
Authors: Valle Andres Flores , Gonçalves Pedro J. , Seelig Johannes D.
Published: July 2020

During sleep, the brain undergoes dynamic and structural changes. InDrosophila, such changes have been observed in the central complex, a brain area important for sleep control and navigation. The connectivity of the central complex raises the question about how navigation, and specifically the head direction system, can operate in the face of sleep related plasticity.

To address this question, we develop a model that integrates sleep homeostasis and head direction. We show that by introducing plasticity, the head direction system can function in a stable way by balancing plasticity in connected circuits that encode sleep pressure. With increasing sleep pressure, the head direction system nevertheless becomes unstable and a sleep phase with a different plasticity mechanism is introduced to reset network connectivity.

The proposed integration of sleep homeostasis and head direction circuits captures features of their neural dynamics observed in flies and mice.
Epidermal PAR-6 and PKC-3 are essential for postembryonic development ofCaenorhabditis elegansand control non-centrosomal microtubule organization
Authors: Castiglioni Victoria G. , Pires Helena R. , Bertolini Rodrigo Rosas , Riga Amalia , Kerver Jana , Boxem Mike
Published: July 2020

The cortical polarity regulators PAR-6, PKC-3 and PAR-3 are essential for the polarization of a broad variety of cell types in multicellular animals, from the first asymmetric division of theC. eleganszygote to apical–basal polarization of epithelial cells. InC. elegans, the roles of the PAR proteins in embryonic development have been extensively studied, yet little is known about their functions during larval development. Using auxin-inducible protein depletion, we here show that PAR-6 and PKC-3, but not PAR-3, are essential for postembryonic development. We also demonstrate that PAR-6 and PKC-3 are required in the epidermal epithelium to support animal growth and molting, and the proper timing and pattern of seam cell divisions. Finally, we uncovered a novel role for PAR-6 in controlling the organization of non-centrosomal microtubule arrays in the epidermis. PAR-6 was required for the localization of the microtubule organizer NOCA-1/Ninein, and microtubule defects in anoca-1mutant are highly similar to those caused by epidermal PAR-6 depletion. As NOCA-1 physically interacts with PAR-6, we propose that PAR-6 promotes non-centrosomal microtubule organization through localization of NOCA-1/Ninein.

Using inducible protein degradation, we show that PAR-6 and PKC-3/aPKC are essential for postembryonic development ofC. elegansand control the organization of non-centrosomal microtubule bundles in the epidermis, likely through recruitment of NOCA-1/Ninein.