bluuebunny/crossref_metadata_2025 huggingface dataset:
Medication Abortion With Pharmacist Dispensing of Mifepristone
Authors: Grossman Daniel , Baba C. Finley , Kaller Shelly , Biggs M. Antonia , Raifman Sarah , Gurazada Tanvi , Rafie Sally , Averbach Sarah , Meckstroth Karen R. , Micks Elizabeth A. , Berry Erin , Raine-Bennett Tina R. , Creinin Mitchell D.
Published: March 2021

OBJECTIVE:

To estimate effectiveness and acceptability of medication abortion with mifepristone dispensed by pharmacists.

METHODS:

We conducted a prospective cohort study at eight clinical sites and pharmacies in California and Washington State from July 2018 to March 2020. Pharmacists at participating pharmacies underwent a 1-hour training on medication abortion. We approached patients who had already been evaluated, counseled, and consented for medication abortion per standard of care. Patients interested in study participation gave consent, and the clinician electronically sent a prescription to the pharmacy for mifepristone 200 mg orally, followed 24–48 hours later by misoprostol 800 micrograms buccally. Participants were sent web-based surveys about their experience and outcomes on days 2 and 14 after enrollment and had routine follow-up with study sites. We extracted demographic and clinical data, including abortion outcome and adverse events, from medical records. We performed multivariable logistic regression to assess the association of pharmacy experience and other covariates with satisfaction.

RESULTS:

We enrolled 266 participants and obtained clinical outcome information for 262 (98.5%), of whom two reported not taking either medication. Of the 260 participants with abortion outcome information, 252 (96.9%) and 237 (91.2%) completed day 2 and 14 surveys, respectively. Complete medication abortion (primary outcome) occurred for 243 participants (93.5%, 95% CI 89.7–96.1%). Four participants (1.5%, 95% CI 0.4–3.9%) had an adverse event, none of which was serious or related to pharmacist dispensing. In the day 2 survey, 91.3% (95% CI 87.1–94.4%) of participants reported satisfaction with the pharmacy experience. In the day 14 survey, 84.4% (95% CI 79.1–88.8%) reported satisfaction with the medication abortion experience. Those reporting being very satisfied with the pharmacy experience had higher odds of reporting overall satisfaction with medication abortion (adjusted odds ratio 2.96, 95% CI 1.38–6.32).

CONCLUSION:

Pharmacist dispensing of mifepristone for medication abortion is effective and acceptable to patients, with a low prevalence of adverse events.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT03320057.
Contraception Choice Among Those Seeking Abortion for Fetal Indication or Management of Pregnancy Loss
Authors: Meurice Marielle E. , Lovio Marissa , Chang Jenny J. , Perry Rachel
Published: March 2021

OBJECTIVE:

To compare contraception choices of those who are undergoing abortion procedures for fetal indications or surgical management of pregnancy loss with those who are having abortions for another indication.

METHODS:

We conducted a cross-sectional study at University of California, Irvine, from December 1, 2017, through December 31, 2018, and included gestational ages up to 24 0/7 weeks. We abstracted data from electronic medical records and analyzed them using descriptive statistics, χ2, Fisher exact tests, and a multivariate logistic regression model for primary outcome (whether a contraception method was chosen) and secondary outcome (whether a long-active reversible contraception was chosen).

RESULTS:

Those with fetal indication were less likely to choose contraception than those with other indication (68/134, 50.7% vs 142/158, 89.9%, P<.001), and among those choosing contraception those with fetal indication were less likely to choose long-acting reversible contraception (LARC) (19/68, 27.9% vs 94/142, 66.2%, P<.001). Differences remained significant in multivariable analysis that controlled for age, gestational age in weeks, race, parity, procedure type, and comorbidities (among those with fetal indication for choosing any contraception: adjusted odds ratio [aOR] 0.11, 95% CI 0.05–0.23; choosing LARC: aOR 0.17, 95% CI 0.07–0.39).

CONCLUSION:

Only half of those seeking abortion for a fetal indication or surgical management of pregnancy loss were interested in contraception.
Genomic investigation of clinically significant coagulase-negative staphylococci
Authors: Cole Kevin , Atkins Bridget , Llewelyn Martin , Paul John
Published: March 2021

Introduction. Coagulase-negative staphylococci have been recognized both as emerging pathogens and contaminants of clinical samples. High-resolution genomic investigation may provide insights into their clinical significance.

Aims. To review the literature regarding coagulase-negative staphylococcal infection and the utility of genomic methods to aid diagnosis and management, and to identify promising areas for future research.

Methodology. We searched Google Scholar with the terms (

Staphylococcus

) AND (sequencing OR (infection)). We prioritized papers that addressed coagulase-negative staphylococci, genomic analysis, or infection.

Results. A number of studies have investigated specimen-related, phenotypic and genetic factors associated with colonization, infection and virulence, but diagnosis remains problematic.

Conclusion. Genomic investigation provides insights into the genetic diversity and natural history of colonization and infection. Such information allows the development of new methodologies to identify and compare relatedness and predict antimicrobial resistance. Future clinical studies that employ suitable sampling frames coupled with the application of high-resolution whole-genome sequencing may aid the development of more discriminatory diagnostic approaches to coagulase-staphylococcal infection.
Sex differences in brain development in fetuses and infants who are at low or high likelihood for autism
Authors: Villa L. M. , Hampton S. , Aydin E. , Tait R. , Leming M. J. , Tsompanidis A. , Patterson I. , Allison C. , Austin T. , Suckling J. , Baron-Cohen S. , Holt R. J.
Published: March 2021

Background

It is unknown whether the neural underpinnings of autism are presentin utero. In addition, it is unclear whether typical neural sexual differentiation, which is associated with the development of autism, is evidentin utero. We longitudinally investigated fetal and infant sex differences in brain structure and function, and differences in brain development in those at low and high likelihood for autism. Here, we use the term ‘typical’ interchangeably with the term ‘low-autism likelihood’.

Methods

Participants were longitudinally studiedin uterofirst at 30-33 weeks of gestation, and then as infants 8-12 weeks after birth. We compared total brain volumes and resting-state functional connectivity between 15 female and 15 male low-autism likelihood fetuses (defined as having no first degree autistic relative). We also compared the brain structure and function of these 30 fetuses to a rare group of 11 fetuses (5 females and 6 males) who had an autistic mother or sibling, and therefore a higher likelihood of developing autism. Although a small sample, the high-autism likelihood group are reported as they are challenging to recruit. Additionally, we correlated sex differences in functional connectivity with autism likelihood group differences across the fetal and infant brains.

Results

There was a group-by-sex interaction in fetal total brain volume. Typical males, on average, showed faster total brain volume growth in the perinatal period than typical females. The high-autism likelihood group showed lower resting-state functional connectivity at both time-points compared to the typical group, and regions indicating sex differences overlapped with those associated with high-autism likelihood group differences in functional connectivity.

Conclusions

In uterosexual differentiation of brain structure was more pronounced in fetuses with a high likelihood for autism. Moreover, sexual differentiation of the fetal and infant brain may overlap with the neural development of autism.
Comparing Interventions Aimed at Improving Influenza Vaccination Coverage Among Vulnerable Populations: A Systematic Review and Meta-Analysis Protocol
Authors: Wu Pei Chen , McPherson Lyn , Lambert Stephen B , Wnukowski-Mtonga Peter , Lennox Nicholas G , Ware Robert S
Published: March 2021

Background

Influenza is a major contributor to global disease burden. Vaccination recommendations specifically target populations at increased risk of serious influenza sequelae. The aim of this study is to conduct a systematic review and meta-analysis to evaluate the effectiveness of different quality improvement interventions to increase vaccination rates in high-risk populations.

Methods

Randomized and nonrandomized studies with concurrent control groups will be identified. Interventions to increase vaccination rates will be categorized by strategy type. Overall intervention effects will be calculated using random effects models. Study quality will be assessed using a modified Cochrane Risk of Bias tool.
Development of Equine Immunoglobulin Fragment F(ab’)2with High Neutralizing Capability against SARS-CoV-2
Authors: Gupta Divya , Ahmed Farhan , Tandel Dixit , Parthasarathy Haripriya , Vedagiri Dhiviya , Sah Vishal , Krishna Mohan B , Daga Siddarth , Khan Rafiq Ahmad , Kondiparthi Chiranjeevi , Savari Prabhudas , Jain Sandesh , Daga Jaya , Reddy Shashikala , Khan Nooruddin , Harshan Krishnan Harinivas
Published: March 2021

The ongoing pandemic, COVID-19, caused by SARS-CoV-2 has taken the world, and especially the scientific community by storm. While vaccines are being introduced into the market, there is also a pressing need to find potential drugs and therapeutic modules. Remdesivir is one of the antivirals currently being used with a limited window of action. As more drugs are being vetted, passive immunotherapy in the form of neutralizing antibodies can provide immediate action to combat the increasing numbers of COVID-positive cases. Herein, we demonstrate that equines hyper-immunized with chemically inactivated SARS-CoV-2 generate high titers of antibody with a strong virus neutralizing potential. ELISA performed with pooled antisera displayed highest immunoglobulin titer on 42 days post-immunization, at 1:51,200 dilutions. F(ab’)2immunoglobulin fragments generated from the pools also showed very high, antigen-specific affinity at 1:102,400 dilutions. Finally,in vitrovirus neutralization assays confirmed that different pools of F(ab’)2fragments could successfully neutralize SARS-CoV-2 with titers well above 25,000, indicating the potential of this strategy in treating severe COVID-19 cases with high titers. The F(ab’)2was able to cross neutralize another SARS-CoV-2 strain, demonstrating its efficacy against the emerging viral variants and the importance of this approach in our efforts of eradication of COVID-19. In conclusion, this study demonstrates that virus-neutralizing antibodies raised in equines can potentially be used as a treatment regimen in the form of effective passive immunotherapy to combat COVID-19.
ChexMix: A Literature Content Extraction Tool for Bioentities
Authors: Yang Heejung , Park Beomjun , Park Jinyoung , Lee Jiho , Jang Hyeon Seok , Lee Namgil , Yoo Hojin
Published: March 2021

Biomedical databases grow by more than a thousand new publications every day. The large volume of biomedical literature that is being published at an unprecedented rate hinders the discovery of relevant knowledge from keywords of interest to gather new insights and form hypotheses. A text-mining tool, PubTator, helps to automatically annotate bioentities, such as species, chemicals, genes, and diseases, from PubMed abstracts and full-text articles. However, the manual re-organization and analysis of bioentities is a non-trivial and highly time-consuming task. ChexMix was designed to extract the unique identifiers of bioentities from query results. Herein, ChexMix was used to construct a taxonomic tree with allied species among Korean native plants and to extract the medical subject headings unique identifier of the bioentities, which co-occurred with the keywords in the same literature. ChexMix discovered the allied species related to a keyword of interest and experimentally proved its usefulness for multi-species analysis.
Chromosomal rearrangements with stable repertoires of genes and transposable elements in an invasive forest-pathogenic fungus
Authors: Demené Arthur , Laurent Benoît , Cros-Arteil Sandrine , Boury Christophe , Dutech Cyril
Published: March 2021

Abstract

Chromosomal rearrangements have been largely described among eukaryotes, and may have important consequences on evolution of species. High genome plasticity has been often reported in Fungi, which may explain their apparent ability to quickly adapt to new environments.Cryphonectria parasitica, causing the Chestnut blight disease, is an invasive fungal pathogen species associated with several recent host shifts during its successive introductions from Asia to North America and Europe. Previous cytological karyotyping and genomic studies suggested several chromosomal rearrangements which remains to be described in detail for this species. A serious limitation for valid genome comparisons is the access to robust genome assemblies that usually contain genomic regions of low complexity. We present a new de novo whole-genome assembly obtained from a new method of DNA extraction and long-reads sequencing Nanopore technology obtained from a Japanese isolate sampled in the native area of the species. The comparison with a recently published reference genome revealed stable gene and transposable elements (TEs) repertoires. We also showed that theC. parasiticagenome is lowly compartmentalized, with a poor association between TEs and genes, such as those potentially involved in host interactions (i.e., genes coding for small secreted proteins or for secondary metabolites). This genome comparison, however, detected several large chromosomal rearrangements that may have important consequences in gene regulations and sexual mating in this invasive species. This study opens the way for more comparisons of high-quality assembled genomes, and questions the role of structural variations in the invasive success of this fungal pathogen species.
DEVELOPMENT OF A SOYBEAN MATURITY PREDICTION MODEL FOR SOYBEAN GROWN IN AFRICAN ENVIRONMENTS
Authors: Marcillo Guillermo S. , Martin Nicolas F. , Diers Brian , Da Fonseca Michelle S. , Leles Erica
Published: March 2021

Abstract

Time-to-maturity (TTM) is an important trait in soybean breeding programs. However, soybean is a relatively new crop in Africa. As such, TTM information is not yet well defined as in other major producing areas. Multi Environment trials (MET) allow breeders to analyze crop performance across diverse conditions but also pose statistical challenges (e.g. unbalanced data). Modern statistical methods, e.g.. Generalized Additive Models (GAM), can flexibly smooth a range of responses while retaining observations that could be lost under other approaches. We leveraged 5 years of data from a MET breeding program in Africa to identify the best geographical and seasonal variables to explain site and genotypic differences in soybean TTM. Using soybean-cycle features (minimum temperature, daylength) along with trial geolocation (longitude, latitude), a GAM model predicted soybean TTM within ± 10 days of the average observed TTM [days post-planting]. Further, we found significant differences between cultivars (p<0.05) in TTM sensitivity to minimum temperature and daylength. Our results show promise to advance the design of maturity systems that enhance soybean planting and breeding decisions in Africa.
Systematic evaluation of transcriptomics-based deconvolution methods and references using thousands of clinical samples
Authors: Nadel Brian B. , Oliva Meritxell , Shou Benjamin L. , Mitchell Keith , Ma Feiyang , Montoya Dennis J. , Mouton Alice , Kim-Hellmuth Sarah , Stranger Barbara E. , Pellegrini Matteo , Mangul Serghei
Published: March 2021

Estimating cell type composition of blood and tissue samples is a biological challenge relevant in both laboratory studies and clinical care. In recent years, a number of computational tools have been developed to estimate cell type abundance using gene expression data. While these tools use a variety of approaches, they all leverage expression profiles from purified cell types to evaluate the cell type composition within samples. In this study, we compare ten deconvolution tools and evaluate their performance while using each of eleven separate reference profiles. Specifically, we have run deconvolution tools on over 4,000 samples with known cell type proportions, spanning both immune and stromal cell types. Twelve of these represent in vitro synthetic mixtures and 300 represent in silico synthetic mixtures prepared using single cell data. A final 3,728 clinical samples have been collected from the Framingham Cohort, for which cell populations have been quantified using electrical impedance cell counting. When tools are applied to the Framingham dataset, the tool EPIC produces the highest correlation while GEDIT produces the lowest error. The best tool for other datasets is varied, but CIBERSORT and GEDIT most consistently produce accurate results. In terms of reference choice, we find that the Human Primary Cell Atlas (HPCA) and references published by the EPIC authors produce accurate results for the largest number of tools and datasets. When applying deconvolution to blood samples, the leukocyte reference matrix LM22 is also a suitable choice, usually (but not always) outperforming HPCA and EPIC. Running time varies substantially across tools. For as many as 5052 samples, SaVanT and dtangle reliably finish in under one minute, while slower tools may require up to two hours. However, when using custom references, CIBERSORT can run very slowly, taking over 24 hours to complete for large datasets. We conclude that combining the best tools with optimal reference datasets can provide significant gains in accuracy when carrying out deconvolution tasks.
The ubiquitous terpene geosmin is a warning chemical
Authors: Zaroubi Liana , Ozugergin Imge , Mastronardi Karina , Imfeld Anic , Law Chris , Gélinas Yves , Piekny Alisa , Findlay Brandon L.
Published: March 2021

Known as the smell of earth after rain, geosmin is an odorous terpene detectable by humans at picomolar concentrations. Geosmin production is heavily conserved in actinobacteria, myxobacteria, cyanobacteria, and some fungi, but its biological activity is poorly understood. We theorized that geosmin was an aposematic signal used to indicate the unpalatability of toxin-producing microbes, discouraging predation by eukaryotes. Consistent with this hypothesis we found that geosmin and the related terpene 2-methylisoborneol reduced predation ofStreptomyces coelicolorandMyxococcus xanthusby the bacteriophagousCaenorhabditis elegans. Predation was restored by the removal of both terpene biosynthetic pathways or deletion of theC. elegansASE sensory neuron, and resulted in the death of the nematodes. Geosmin itself was non-toxic. This is the first warning chemical to be identified in bacteria or fungi, and suggests molecular signalling affects microbial predator-prey interactions in a manner similar to the well-studied visual markers of poisonous animal prey.
Cell-specific alterations inPitx1regulatory landscape activation caused by the loss of a single enhancer
Authors: Rouco Raquel , Bompadre Olimpia , Rauseo Antonella , Fazio Olivier , Thorel Fabrizio , Peraldi Rodrigue , Andrey Guillaume
Published: March 2021

Most developmental genes rely on multiple transcriptional enhancers for their accurate expression during embryogenesis. Because enhancers may have partially redundant activities, the loss of one of them often leads to a partial loss of gene expression and concurrent moderate phenotypic outcome, if any. While such a phenomenon has been observed in many instances, the nature of the underlying mechanisms remains elusive. We used thePitx1testbed locus to characterize in detail the regulatory and cellular identity alterations following the deletionin vivoof one of its enhancers (Pen), which normally accounts for 30 percent ofPitx1expression in hindlimb buds. By combining single cell transcriptomics and a novelin embryocell tracing approach, we observed that this global decrease inPitx1expression results from both an increase in the number of non- or low-expressing cells, and a decrease in the number of high-expressing cells. We found that the over-representation ofPitx1non/low-expressing cells originates from a failure of thePitx1locus to coordinate enhancer activities and 3D chromatin changes. The resulting increase inPitx1non/low-expressing cells eventually affects the proximal limb more severely than the distal limb, leading to a clubfoot phenotype likely produced through a localized heterochrony and concurrent loss of irregular connective tissue. This data suggests that, in some cases, redundant enhancers may be used to locally enforce a robust activation of their host regulatory landscapes.
CASPAM: a triple modality biosensor for multiplexed imaging of caspase network activity
Authors: Habif Martín , Corbat Agustín A. , Silberberg Mauro , Grecco Hernán E.
Published: March 2021

Understanding signal propagation across biological networks requires to simultaneously monitor the dynamics of several nodes to uncover correlations masked by inherent intercellular variability. To monitor the enzymatic activity of more than two components over short time scales has proven challenging. Exploiting the narrow spectral width of homoFRET-based biosensors, up to three activities can be imaged through fluorescence polarization anisotropy microscopy. We introduce CASPAM (Caspase Activity Sensor by Polarization Anisotropy Multiplexing) a single-plasmid triple-modality-reporter of key nodes of the apoptotic network. Apoptosis provides an ideal molecular framework to study interactions between its three composing pathways (intrinsic, extrinsic and effector). We characterized the biosensor performance and demonstrated the advantages that equimolar expression has both in simplifying experimental procedure and reducing observable variation, thus enabling robust data-driven modelling. Tools like CASPAM become essential to analyze molecular pathways where multiple nodes need to be simultaneously monitored.
Complex landscapes partially mitigate negative pesticide effects on tropical pollinator communities
Authors: Obregon Diana , Guerrero Olger R. , Stashenko Elena , Poveda Katja
Published: March 2021

Land-use change and pesticides have been identified as two of the main causes behind pollinator decline. Understanding how these factors affect crop pollinator communities is crucial to inform practices that generate optimal pollination and ensure sustainable food production. In this study, we investigated the effects of landscape composition and pesticide residues on bee communities and their pollination services inSolanum quitoense“lulo” crops in Colombia. On 10 farms, located along a gradient of landscape complexity that varied from 0.15 to 0.62 in their natural habitat proportion, we characterized the bee community visiting the crop, and carried out pollination experiments with bagged and open inflorescences to later estimate fruit set, weight, and diameter at every site. Additionally, we performed pesticide analysis on collected anthers through liquid chromatography to estimate pesticide risk coming from the crop fields using hazard quotients (HQ). Bee abundance and species richness decreased with increased HQ, but these negative pesticide effects were less detrimental in farms with higher natural habitat proportions. However, this buffer effect was lost at sites with very high HQs. Imidacloprid was frequently found in the anthers and there were extremely high concentrations in some farms (0.6 to 13063 μg/kg), representing the molecule of greater risk for bees in this context. Pollinator’s importance to crop yield was demonstrated in the exclusion experiments, where we found a reduction in fruit set (51%), weight (39%), and diameter (25%). We found a significant effect of bee richness on fruit set, while landscape composition and HQ had no significant effect on fruit set, suggesting that the last two factors do not affect yield directly, but indirectly through a decrease in pollinator diversity. Our results provide novel evidence that the natural habitat loss due to the expansion of pastures for cattle ranching and pesticide residues in anthers reduce bee diversity and abundance in this Andean cropping system, but strategies to protect and restore natural habitat can help to buffer, until certain levels, these negative effects.

Highlights

- We explored how landscape composition and pesticide residues impact bee communities and pollination services inSolanum quitoensecrops.

- As the proportion of natural habitat in the landscape increased, bee richness also increased. While as pesticide hazard quotients inS. quitoenseanthers increased, bee diversity and abundance decreased.

- The natural habitat surrounding farms mitigates the negative pesticide effects on bees when hazard quotients are low/medium, but not when they are high.

-S. quitoensecrops are highly dependent on bees for optimum yield.
Subthreshold repetitive transcranial magnetic stimulation drives structural synaptic plasticity in the young and aged motor cortex
Authors: Tang Alexander D , Bennett William , Bindoff Aidan D , Bolland Samuel , Collins Jessica , Langley Ross C , Garry Michael I , Summers Jeffery J , Hinder Mark R , Rodger Jennifer , Canty Alison J
Published: March 2021

Background

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive tool commonly used to drive neural plasticity in the young adult and aged brain. Recent data from mouse models have shown that even at subthreshold intensities (0.12 Tesla), rTMS can drive neuronal and glial plasticity in the motor cortex. However, the physiological mechanisms underlying subthreshold rTMS induced plasticity and whether these are altered with normal ageing are unclear.

Objective

To assess the effect of subthreshold rTMS, using the intermittent theta burst stimulation (iTBS) protocol on structural synaptic plasticity in the mouse motor cortex of young and aged mice.

Methods

Longitudinalin vivo2-photon microscopy was used to measure changes to the structural plasticity of pyramidal neuron dendritic spines in the motor cortex following a single train of subthreshold rTMS (in young adult and aged animals) or the same rTMS train administered on 4 consecutive days (in young adult animals only). Data were analysed with Bayesian hierarchical generalized linear regression models and interpreted with the aid of Bayes Factors (BF).

Results

We found strong evidence (BF>10) that subthreshold rTMS altered the rate of dendritic spine losses and gains, dependent on the number of stimulation sessions and that a single session of subthreshold rTMS was effective in driving structural synaptic plasticity in both young adult and aged mice.

Conclusion

These findings provide further evidence that rTMS drives synaptic plasticity in the brain and uncovers structural synaptic plasticity as a key mechanism of subthreshold rTMS induced plasticity.
Cooperative herbivory between two important pests of rice
Authors: Liu Qingsong , Hu Xiaoyun , Su Shuangli , Peng Yufa , Ye Gongyin , Lou Yonggen , Turlings Ted C. J. , Li Yunhe
Published: March 2021

Normally, when different species of herbivorous arthropods feed on the same plant this leads to fitness reducing competition. We found this to be uniquely different for two of Asia’s most destructive rice pests, the brown planthopper and the rice striped stem borer. Both insects directly and indirectly benefit from jointly attacking the same host plant. Double infestation improved plant quality, particularly for the stemborer because the planthopper fully suppresses caterpillar-induced production of proteinase inhibitors. It also drastically reduced the risk of egg parasitism, due to diminished parasitoid attraction. Females of both pests have adapted their oviposition behaviour accordingly. Their strong preference for plants infested by the other species even overrides their avoidance of plants already attacked by conspecifics. This uncovered cooperation between herbivores is telling of the exceptional adaptations resulting from the evolution of plant-insect interactions, and points out mechanistic vulnerabilities that can be targeted to control two major pests.
Factors Shaping Young and Mature Bacterial Biofilm Communities in Two Drinking Water Distribution Networks
Authors: Cheng Dan , Leifels Mats , Miccolis Carlo , Wuertz Stefan , Thompson Janelle R. , Szewzyk Ulrich , Whittle Andrew J.
Published: March 2021

The presence of biofilms in drinking water distribution systems (DWDS) can affect both water quality and system integrity; yet these systems remain poorly studied due to lack of accessibility. We established two independent full-scale DWDS Testbeds (A and B) on two different campuses situated in a tropical urban environment and equipped them with online sensors. Testbed B experienced higher levels of monochloramine and lower water age than Testbed A within the campus. Based on long amplicon-sequencing of bacterial 16S rRNA genes extracted from the mature biofilms (MPB) growing on pipes and young biofilms (YSB) growing on the sensors, a core community was identified in the two testbeds. The relative abundances of operational taxonomic units at the family level, includingMycobacteriaceae, Methylobacteriaceae, Rhodospirillaceae, Nitrosomonadaceae,andMoraxellaceae,were consistent for MPB and YSB on each campus. The MPB community was found to be influenced by conductivity, sample age, and pipe diameter as determined by both canonical correlation analysis and fuzzy set ordination. MPB displayed higher α-diversity based on Hill numbers than YSB; in general, second order Hill numbers correlated positively with conductivity and sample age, but negatively with ORP and nitrite.Pseudomonasspp. together withBacillusspp. likely initiated biofilm formation of YSB on Testbed A under conditions of reduced monochloramine and high water age. Significant levels of orthophosphate were detected in YSB samples at two stations and associated with higher levels of stagnation based on long-term differential turbidity measurement (DTM). Orthophosphate and DTM may act as indicators of the biofilm growth potential within DWDS.

Highlights

- Established two testbeds to study biofilms in full-scale distribution system

- Biofilms on pipes and sensors had core community

- Temporal effect and higher α-diversity for biofilms on pipes

- Water chemistry was related to biofilm community differences

Graphical Abstract
Diversify your workflow! - An inconvenient suggestion to analyze spike data from intracranial recordings
Authors: Okkesim Şükrü , Rastogi Shavika , Christ Olaf , Hubka Peter , Rosskothen-Kuhl Nicole , Hofmann Ulrich G.
Published: March 2021

An important challenge of neuroscience research and future brain machine interfacing is the reliable assignment of spikes to putative neurons. By means of extracellular recordings, researchers try to match different types action potentials with their putative neuronal source and timing. Unfortunately, this procedure is by far not standardized and reliable, leading to many different suggestions and as many differing results. It appears that sharing of data is thus hampered by different processing pipelines in different labs, thus playing along the reproducibility crisis in neurosciences. To systematically shed light on this issue, we present preliminary results of several easy event detection schemes on one data set, meant to illustrate the inconsistencies arising from different processing pipelines already in its initial step. The results indicate that thresholding choices alter findings due to a lack of a ground truth for spike sorting. We suggest to increase reliability in findings by only accepting and further processing events accepted by more than one processing pipeline.
Low-Cost, Modular Modification to a Desktop 3D Printer for General Purpose Gel/Paste Extrusion & Direct Ink Writing
Authors: Leech D. J. , Lightfoot S. , Huson D. , Stratakos A.
Published: March 2021

We propose a design for a simple paste extruder modification that can be used for the selective deposition and patterning of gels and pastes, using a desktop 3D printer as the primary platform. This technology has found use with a variety of materials in seemingly disparate fields, including the printing of ceramics, food and biological materials, each with a variety of material-specific solutions to enhance printability. However, we focus on a syringe-pump driven system that is simple, low-cost, modular, easily assembled and highly modifiable with a low barrier of entry in order to maximise the generalisability and range of printable materials.
Corticosterone differentially modulates time-dependent fear generalization following mild or moderate fear conditioning training in rats
Authors: dos Santos Corrêa Moisés , dos Santos Vaz Barbara , Menezes Beatriz Scazufca , Ferreira Tatiana Lima , Tiba Paula Ayako , Fornari Raquel Vecchio
Published: March 2021

Stressful and emotionally arousing experiences create strong memories that seem to lose specificity over time. It is uncertain, however, how the stress system contributes to the phenomenon of time-dependent fear generalization. Here, we investigated whether post-training corticosterone (CORT-HBC) injections, given after different training intensities, affect contextual fear memory specificity at several time points. We trained male Wistar rats on the contextual fear conditioning (CFC) task using two footshock intensities (mild CFC, 3 footshocks of 0.3 mA, or moderate CFC, 3x 0.6 mA) and immediately after the training session we administered CORT-HBC systemically. We first tested the animals in a novel context and then in the training context at different intervals following training (2, 14, 28 or 42 days). By measuring freezing in the novel context and then contrasting freezing times shown in both contexts, we inferred contextual fear generalization for each rat, classifying them into Generalizers or Discriminators. Following mild CFC training, the glucocorticoid injection promoted an accurate contextual memory at the recent time point (2 days), and increase the contextual memory accuracy 28 days after training. In contrast, after the moderate CFC training, CORT-HBC facilitated contextual generalization at 14 days, compared to the control group that maintained contextual discrimination at this timepoint. For this training intensity, however, CORT-HBC did not have any effect on recent memory specificity. These findings indicate that treatment with CORT-HBC immediately after the encoding of mild or moderately arousing experiences may differentially modulate memory consolidation and time-dependent fear generalization.

HIGHLIGHTS

- Rats were trained in a contextual fear task and tested for fear generalization.

- Corticosterone (CORT) injected after a mild training promoted accuracy up to 28 days.

- CORT injected after a moderate training facilitated time-dependent fear generalization.
Pool choice in a vertical landscape: tadpole rearing site flexibility in phytotelm-breeding frogs
Authors: Fouilloux Chloe A. , Serrano-Rojas Shirley Jennifer , Carvajal-Castro Juan David , Valkonen Janne K. , Gaucher Philippe , Fischer Marie-Therese , Pašukonis Andrius , Rojas Bibiana
Published: March 2021

Many species of Neotropical frogs have evolved to deposit their tadpoles in small water bodies inside plant structures called phytotelmata. These pools are small enough to exclude large predators but have limited nutrients and high desiccation risk. Here, we explore phytotelm use by three common Neotropical species:Osteocephalus oophagus, an arboreal frog that periodically feeds eggs to its tadpoles;Dendrobates tinctorius, a tadpole-transporting poison frog with cannibalistic tadpoles; andAllobates femoralis, a terrestrial tadpole-transporting poison frog with omnivorous tadpoles. We found thatD. tinctoriusoccupies pools across the chemical and vertical gradient, whereasA. femoralisandO. oophagusappear to have narrower niches that are restricted primarily by pool height, water capacity, alkalinity, and salinity.Dendrobates tinctoriustadpoles are particularly flexible, and can survive in a wide range of chemical, physical, and biological conditions, whereasO. oophagusseems to prefer small, clear pools andA. femoralisoccupies medium-sized pools with abundant leaf litter and low salinity. Together, these results show the possible niche partitioning of phytotelmata among frogs, and provide insight into stressors and resilience of phytotelm breeders.
The cAMP effector PKA mediates Moody GPCR signaling inDrosophilablood-brain barrier formation and maturation
Authors: Li Xiaoling , Fetter Richard , Schwabe Tina , Jung Christophe , Steller Hermann , Gaul Ulrike
Published: March 2021

The blood-brain barrier (BBB) ofDrosophilais comprised of a thin epithelial layer of subperineural glia (SPG), which ensheath the nerve cord and insulate it against the potassium-rich hemolymph by forming intercellular septate junctions (SJs). Previously, we identified a novel Gi/Go protein-coupled receptor (GPCR), Moody, as a key factor in BBB formation at the embryonic stage. However, the molecular and cellular mechanisms of Moody signaling in BBB formation and maturation remain unclear. Here, we identify cAMP-dependent protein kinase A (PKA) as a crucial antagonistic Moody effector that is required for the formation, as well as for the continued SPG growth and BBB maintenance in the larva and adult stage. We show that PKA is enriched at the basal side of the SPG cell and that this polarized Moody/PKA pathway finely tunes the enormous cell growth and BBB integrity, by precisely regulating the actomyosin contractility, vesicle trafficking, and the proper SJ organization in a highly coordinated spatiotemporal manner. These effects are mediated in part by PKA’s molecular targets MLCK and Rho1. Moreover, 3D reconstruction of SJ ultrastructure demonstrates that the continuity of individual SJ segments and not their total length is crucial for generating a proper paracellular seal. Based on these findings, we propose a model that polarized Moody/PKA signaling plays a central role in controlling the cell growth and maintaining BBB integrity during the continuous morphogenesis of the SPG secondary epithelium, which is critical for maintain tissue size and brain homeostasis during organogenesis.
Novel inhibition mechanism of SARS-CoV-2 main protease by ebselen and its derivatives
Authors: Amporndanai Kangsa , Meng Xiaoli , Shang Weijuan , Jin Zhenmig , Zhao Yao , Rao Zihe , Liu Zhi-Jie , Yang Haitao , Zhang Leike , O’Neill Paul M. , Hasnain S. Samar
Published: March 2021

The global emergence of SARS-CoV-2 has triggered numerous efforts to develop therapeutic options for COVID-19 pandemic. The main protease of SARS-CoV-2 (Mpro), which is a critical enzyme for transcription and replication of SARS-CoV-2, is a key target for therapeutic development against COVID-19. An organoselenium drug called ebselen has recently been demonstrated to have strong inhibition against Mproand antiviral activity but its molecular mode of action is unknown preventing further development. We have examined the binding modes of ebselen and its derivative in Mprovia high resolution co-crystallography and investigated their chemical reactivity via mass spectrometry. Stronger Mproinhibition than ebselen and potent ability to rescue infected cells were observed for a number of ebselen derivatives. A free selenium atom bound with cysteine 145 of Mprocatalytic dyad has been revealed by crystallographic studies of Mprowith ebselen and MR6-31-2 suggesting hydrolysis of the enzyme bound organoselenium covalent adduct, formation of a phenolic by-product is confirmed by mass spectrometry. The target engagement of these compounds with an unprecedented mechanism of SARS-CoV-2 Mproinhibition suggests wider therapeutic applications of organo-selenium compounds in SARS-CoV-2 and other zoonoticbeta-corona viruses.
The zebrafish presomitic mesoderm elongates through compression-extension
Authors: Thomson Lewis , Muresan Leila , Steventon Benjamin
Published: March 2021

In vertebrate embryos the presomitic mesoderm become progressively segmented into somites at the anterior end while extending along the anterior-posterior axis. A commonly adopted model to explain how this tissue elongates is that of posterior growth, driven in part by the addition of new cells from uncommitted progenitor populations in the tailbud. However, in zebrafish, much of somitogenesis is associated with an absence of overall volume increase and posterior progenitors do not contribute new cells until the final stages of somitogenesis. Here, we perform a comprehensive 3D morphometric analysis of the paraxial mesoderm and reveal that extension is linked to a volumetric decrease, compression in both dorsal-ventral and medio-lateral axes, and an increase in cell density. We also find that individual cells decrease in their cell volume over successive somite stages. Live cell tracking confirms that much of this tissue deformation occurs within the presomitic mesoderm progenitor zone and is associated with non-directional rearrangement. Furthermore, unlike the trunk somites that are laid down during gastrulation, tail somites develop from a tissue that can continue to elongate in the absence of functional PCP signalling. Taken together, we propose a compression-extension mechanism of tissue elongation that highlights the need to better understand the role of tissue intrinsic and extrinsic forces play in regulating morphogenesis.
Handling of intracellular K+determines voltage dependence of plasmalemmal monoamine transporter function
Authors: Bhat Shreyas , Niello Marco , Schicker Klaus , Pifl Christian , Sitte Harald H. , Freissmuth Michael , Sandtner Walter
Published: March 2021

The concentrative power of the transporters for dopamine (DAT), norepinephrine (NET) and serotonin (SERT) is thought to be fueled by the transmembrane Na+gradient, but it is conceivable that they can also tap other energy sources, e.g. membrane voltage and/or the transmembrane K+gradient. We address this by recording uptake of endogenous substrates or the fluorescent substrate APP+((4-(4-dimethylamino)phenyl-1-methylpyridinium) under voltage control in cells expressing DAT, NET or SERT. We show that DAT and NET differ from SERT in intracellular handling of K+. In DAT and NET, substrate uptake was voltage-dependent due to the transient nature of intracellular K+binding, which precluded K+antiport. SERT, however, antiports K+and achieves voltage-independent transport. Thus, there is a trade-off between maintaining constant uptake and harvesting membrane potential for concentrative power, which we conclude to occur due to subtle differences in the kinetics of co-substrate ion binding in closely related transporters.
Learning from incidents in aircraft maintenance and continuing airworthiness: regulation, practice and gaps
Authors: Clare James , Kourousis Kyriakos I.
Published: March 2021

Purpose

The ability to learn from previous events in support of preventing future similar events is a valuable attribute of aviation safety systems. A primary constituent of this mechanism is the reporting of incidents and its importance in support of developing learning material. Many regulatory requirements clearly define a structure for the use of learning material through organisational and procedural continuation training programmes. This paper aims to review aviation regulation and practice, highlighting the importance of learning as a key tenet of safety performance.

Design/methodology/approach

Applicable International Civil Aviation Organisation requirements and the European Union (EU) regulation in aircraft maintenance and continuing airworthiness management have been critically reviewed through content analysis.

Findings

This review has identified gaps in the European implementing rules that could be addressed in the future to support a more effective approach to the delivery of lessons in the aircraft maintenance and continuing airworthiness management sector. These include light-touch of learning and guidance requirements, lack of methodologies for the augmentation of safety culture assessment, absence of competence requirements for human factors trainers and lack of guidance on standardised root-cause analyses.

Practical implications

This paper offers aviation safety practitioners working within the European Aviation Safety Agency regulatory regime an insight into important matters affecting the ability to learn from incidents.

Originality/value

This paper evaluates critically and independently the regulation and practice that can affect the ability of EU regulated aircraft maintenance and continuing airworthiness management organisations to learn from incidents. The outputs from this research present a fresh and independent view of organisational practices that, if left unchecked, are capable of impeding the incident learning process.
What are the mechanisms through which inter-organizational relationships contribute to supply chain resilience?
Authors: Fayezi Sajad , Ghaderi Hadi
Published: March 2021

Purpose

Our study advances theory in supply chain resilience (SCRes) by identifying and describing the mechanisms through which interorganizational relationships (IORs) contribute to SCRes.

Design/methodology/approach

We employ a multi-method conceptual development design combining structured and narrative review of the literature, supported by illustrative case studies. A four-stage refinement process was used for data reduction, and analysis was informed by complex adaptive systems (CAS) theory.

Findings

Our findings identify connectivity, collectivity and scalability as key mechanisms through which relationships between organizations contribute to SCRes. These mechanisms draw on IOR elements of information sharing, decision synchronization and incentive alignment to augment self-organization and emergence, and adaptation and coevolution via modifying/advancing resilience strategies and practices.

Originality/value

Our study advances theory and practice of SCRes by expounding on how connectivity, collectivity and scalability act as mechanisms that drive and diffuse the contribution of resilient strategies/practices to resilience capability. This is significant for strategic alignment between IORs and SCRes.