bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing oscillations in intracranial electrophysiological recordings with data-driven spatial filters
Authors: Schaworonkow Natalie , Voytek Bradley
Published: March 2021

In invasive electrophysiological recordings, a variety of neuronal oscillations can be detected across the cortex, with overlap in space and time. This overlap complicates measurement of neuronal oscillations using standard referencing schemes, like common average or bipolar referencing. Here, we illustrate the effects of spatial mixing on measuring neuronal oscillations in invasive electrophysiological recordings and demonstrate the benefits of using data-driven referencing schemes in order to improve measurement of neuronal oscillations. We discuss referencing as the application of a spatial filter. Spatio-spectral decomposition is used to estimate data-driven spatial filters, a computationally fast method which specifically enhances signal-to-noise ratio for oscillations in a frequency band of interest. We show that application of these data-driven spatial filters has benefits for data exploration, investigation of temporal dynamics and assessment of peak frequencies of neuronal oscillations. We demonstrate multiple use cases, exploring between-participant variability in presence of oscillations, spatial spread and waveform shape of different rhythms as well as narrowband noise removal with the aid of spatial filters. We find high between-participant variability in the presence of neural oscillations, a large variation in spatial spread of individual rhythms and many non-sinusoidal rhythms across the cortex. Improved measurement of cortical rhythms will yield better conditions for establishing links between cortical activity and behavior, as well as bridging scales between the invasive intracranial measurements and noninvasive macroscale scalp measurements.
Photochromic fluorophores enable imaging of lowly-expressed proteins in the autofluorescent fungusCandida albicans
Authors: Van Genechten Wouter , Demuyser Liesbeth , Duwé Sam , Vandenberg Wim , Van Dijck Patrick , Dedecker Peter
Published: March 2021

Fluorescence microscopy is a standard research tool in many fields, though collecting reliable images can be difficult in systems characterized by low expressions levels and/or high background fluorescence. We present the combination of a photochromic fluorescent protein and stochastic optical fluctuation imaging (SOFI) to deliver suppression of the background fluorescence. This strategy makes it possible to resolve lowly- or endogenously-expressed proteins, as we demonstrate for Gcn5, a histone acetyltransferase required for complete virulence, and Erg11, the target of the azole antifungals agents in the fungal pathogenC. albicans. We expect that our method can be readily used for sensitive fluorescence measurements in systems characterized by a high background fluorescence.

Importance

Understanding the spatial and temporal organization of proteins-of-interest is key to unravel cellular processes and identify novel possible antifungal targets. Only a few therapeutic targets have been discovered inCandida albicansand resistance mechanisms against these therapeutic agents is rapidly acquired. Fluorescence microscopy is a valuable tool to investigate molecular processes and assess the localization of possible antifungal targets. Unfortunately, fluorescence microscopy ofC. albicanssuffers from extensive autofluorescence. In this work we present the use of a photochromic fluorescent protein and stochastic optical fluctuation imaging to enable imaging of lowly-expressed proteins inC. albicansthrough the suppression of autofluorescence. This method can be applied inC. albicansresearch or adapted for other fungal systems allowing the visualization of intricate processes.
The CREBRF diabetes-protective rs373863828-A allele is associated with enhanced early insulin release in men of Māori and Pacific ancestry
Authors: Burden Hannah J. , Adams Shannon , Kulatea Braydon , Wright-McNaughton Morag , Sword Danielle , Ormsbee Jennifer J. , Watene-O’Sullivan Conor , Merriman Tony R. , Knopp Jennifer L. , Chase J. Geoffrey , Krebs Jeremy D. , Hall Rosemary M. , Plank Lindsay D. , Murphy Rinki , Shepherd Peter R. , Merry Troy L.
Published: March 2021

Aim

The minor A allele of rs373863828 (CREBRF p.Arg457Gln) is associated with increased body mass index (BMI), but reduced risk of type 2 and gestational diabetes in Polynesian (Pacific peoples and Aotearoa New Zealand Māori) populations. This study investigates the effect of the A allele on insulin release and sensitivity in overweight/obese men without diabetes.

Methods

A mixed meal tolerance test was completed by 172 men (56 with the A allele) of Māori or Pacific ancestry, and 44 (24 with the A allele) had a frequently sampled intravenous glucose tolerance test and hyperinsulinemic-euglycemic clamp. Mixed linear models with covariates age, ancestry and BMI were used to analyse the association between the A allele of rs373863828 and markers of insulin release and blood glucose regulation.

Results

The A allele of rs373863828 is associated with a greater increase in plasma insulin 30 min following a meal challenge without affecting the elevation in plasma glucose or incretins GLP-1 or GIP. Consistent with this point, following an intravenous infusion of a glucose bolus, participants with an A allele had higher early (p<0.05 at 2 and 4 min) plasma insulin and C-peptide concentrations for a similar elevation in blood glucose as those homozygous for the major (G) allele. Despite increased plasma insulin, rs373863828 genotype was not associated with a significant difference (p>0.05) in insulin sensitivity index or glucose disposal during hyperinsulinemic-euglycemic clamp.

Conclusion/interpretation

rs373863828-A allele associates with increased glucose-stimulated insulin release without affecting insulin sensitivity, suggesting that CREBRF p.Arg457Gln may increase maximal ability for β-cells to release insulin to reduce the risk of type 2 diabetes.
Evaluating the trade-off between transmissibility and virulence of SARS-CoV-2 by mathematical modeling
Authors: Yang Hyun Mo , Lombardi Junior Luis Pedro , Yang Ariana Campos
Published: March 2021

Background

At the beginning of 2020, SARS-CoV-2 spread to all continents, and since then, mutations have appeared in different regions of the world. The appearance of more virulent mutations leads to asseverate that they are also more transmissible. We analyzed the lower and higher virulent SARS-CoV-2 epidemics to establish a relationship between transmissibility and virulence based on a mathematical model.

Methods

A compartmental mathematical model based on the CoViD-19 natural history encompassing the age-dependent fatality was applied to evaluate the SARS-CoV-2 transmissibility and virulence. The transmissibility was measured by the basic reproduction numberR0and the virulence by the proportion of asymptomatic individuals. The model parameters were fitted considering the observed data from São Paulo State.

Results

The numbers of severe CoViD-19 and deaths are three times higher, butR0is 25% lower in more virulent SARS-CoV-2 transmission than in a less virulent one. However, the number of more virulent SARS-CoV-2 transmitting individuals is 25% lower, mainly due to symptomatic individuals’ isolation, explaining the increased transmission in lower virulence.

Conclusions

The quarantine study in São Paulo State showed that the more virulent SARS-CoV-2 resulted in a higher number of fatalities but less transmissible than the less virulent one. One possible explanation for the number of deaths surpassing that predicted by the low virulent SARS-CoV-2 infection could be the transmission of more virulent variant(s).
Brain simulation augments machine-learning-based classification of dementia
Authors: Triebkorn Paul , Stefanovski Leon , Dhindsa Kiret , Diaz-Cortes Margarita-Arimatea , Bey Patrik , Bülau Konstantin , Pai Roopa , Spiegler Andreas , Solodkin Ana , Jirsa Viktor , McIntosh Anthony Randal ,   for the Alzheimer’s Disease Neuroimaging Initiative, Ritter Petra
Published: March 2021

INTRODUCTION

Computational brain network modeling using The Virtual Brain (TVB) simulation platform acts synergistically with machine learning and multi-modal neuroimaging to reveal mechanisms and improve diagnostics in Alzheimer’s disease.

METHODS

We enhance large-scale whole-brain simulation in TVB with a cause-and-effect model linking local Amyloid β PET with altered excitability. We use PET and MRI data from 33 participants of Alzheimer’s Disease Neuroimaging Initiative (ADNI3) combined with frequency compositions of TVB-simulated local field potentials (LFP) for machine-learning classification.

RESULTS

The combination of empirical neuroimaging features and simulated LFPs significantly outperformed the classification accuracy of empirical data alone by about 10% (weighted F1-score empirical 64.34% vs. combined 74.28%). Informative features showed high biological plausibility regarding the Alzheimer’s-typical spatial distribution.

DISCUSSION

The cause-and-effect implementation of local hyperexcitation caused by Amyloid β can improve the machine-learning-driven classification of Alzheimer’s and demonstrates TVB’s ability to decode information in empirical data employing connectivity-based brain simulation.

RESEARCH IN CONTEXT

SYSTEMATIC REVIEW. Machine-learning has been proven to augment diagnostics of dementia in several ways. Imaging-based approaches enable early diagnostic predictions. However, individual projections of long-term outcome as well as differential diagnosis remain difficult, as the mechanisms behind the used classifying features often remain unclear. Mechanistic whole-brain models in synergy with powerful machine learning aim to close this gap.

INTERPRETATION. Our work demonstrates that multi-scale brain simulations considering Amyloid β distributions and cause-and-effect regulatory cascades reveal hidden electrophysiological processes that are not readily accessible through measurements in humans. We demonstrate that these simulation-inferred features hold the potential to improve diagnostic classification of Alzheimer’s disease.

FUTURE DIRECTIONS. The simulation-based classification model needs to be tested for clinical usability in a larger cohort with an independent test set, either with another imaging database or a prospective study to assess its capability for long-term disease trajectories.
Donor-derived vasculature is required to support neocortical cell grafts after stroke
Authors: Krzyspiak Joanna , Yan Jingqi , Ghosh Hiyaa , Galinski Basia , Lituma Pablo J. , Alvina Karina , Kee Samantha , Grońska-Pęski Marta , De Tai Yi , McDermott Kelsey , Zukin R. Suzanne , Weiser Daniel A. , Castillo Pablo E. , Khodakhah Kamran , Hébert Jean M.
Published: March 2021

Neural precursor cells (NPCs) transplanted into the adult neocortex generate neurons that synaptically integrate with host neurons, supporting the possibility of achieving functional tissue repair. However, poor survival of transplanted NPCs greatly limits efficient engraftment. Here, we test the hypothesis that combining blood vessel-forming vascular cells with neuronal precursors improves engraftment. By transplanting mixed embryonic neocortical cells into adult mice with neocortical strokes, we show that transplant-derived neurons synapse with appropriate targets while donor vascular cells form vessels that fuse with the host vasculature to perfuse blood within the graft. Although all grafts became vascularized, larger grafts had greater contributions of donor-derived vessels that increased as a function of their distance from the host-graft border. Moreover, excluding vascular cells from the donor cell population strictly limited graft size. Thus, inclusion of vessel-forming vascular cells with NPCs is required for more efficient engraftment and ultimately for tissue repair.
Pathology dynamics in healthy-toxic protein interaction and the multiscale analysis of neurodegenerative diseases
Authors: Pal Swadesh , Melnik Roderick
Published: March 2021

Neurodegenerative diseases are frequently associated with aggregation and propagation of toxic proteins. In particular, it is well known that along with amyloid-beta, the tau protein is also driving Alzheimer’s disease. Multiscale reaction-diffusion models can assist in our better understanding of the evolution of the disease. We have modified the heterodimer model in such a way that it can now capture some of critical characteristics of this evolution such as the conversion time from healthy to toxic proteins. We have analyzed the modified model theoretically and validated the theoretical findings with numerical simulations.
Drug repurposing: Hydroxyurea therapy improves the transfusion-free interval in HbE/beta-thalassemia–major patients with Xmn1 polymorphism
Authors: Ghosh Debojoyti , Panja Amrita , Saha Dipankar , Banerjee Uma , Dutta Asok Kumar , Basu Anupam
Published: March 2021

Aims

HbE/β-thalassemia is the prevalent form of severe β-thalassemia in Asian countries. Hydroxyurea (HU) is the most common drug used for the management of sickle-cell anemia but not thalassemia. Here, we aimed to assess clinical HU response among patients with HbE/β-thalassemia with respect to Xmn1 γGglobin polymorphism and elucidate the association between this polymorphism and HU response efficacy.

Methods

We enrolled 49 transfusion-dependent patients with HbE/β-thalassemia. Fetal hemoglobin level was measured using High-performance liquid chromatography (HPLC) and complete blood count was determined pre- and post-HU therapy. Polymerase chain reaction–Restriction fragment length polymorphism (PCR-RFLP) was performed for genotyping Xmn1 γGglobin polymorphism.

Results

A total of 30 (61.22%) patients were found to be responders, whereas the remaining 19 (38.78%) were non-responders. We found 33 patients with heterozygous (C/T) and three with homozygous mutant (T/T) genotype status. We obtained a statistically significant correlation (p < 0.001) between Xmn1 polymorphism and transfusion-free interval. Patients with Xmn1 polymorphism were found to be good responders for HU therapy and showed increased hemoglobin levels.

Conclusions

Our findings indicate that HU is a potential drug candidate for thalassemia management, particularly HbE/β-thalassemia. The results hold implications in repurposing HU as an effective and efficient therapy for HbE/β-thalassemia.
The negative consequences of failing to communicate uncertainties during a pandemic: The case of COVID-19 vaccines
Authors: Batteux Eleonore , Bilovich Avri , Johnson Samuel G. B. , Tuckett David
Published: March 2021

Uncertainties pervade our health choices, particularly in the context of a novel pandemic. Despite this, rather little is known about when and how to effectively communicate these uncertainties. The focus in the medical literature so far has been on how patients respond to mentions of uncertainty relating to diagnosis or treatment, showing that these can have detrimental effects on trust and satisfaction. On the other hand, how patients are affected by these communications over time, particularly in the face of conflicting information, has received little attention. This is particularly important in the context a novel pandemic where uncertainty is rife and information changes over time. To fill this gap, we conducted an online study with UK participants on hypothetical communications relating to COVID-19 vaccines. Participants first read a vaccine announcement, which either communicated with certainty or uncertainty, and then received information which conflicted with the announcement. Those who were exposed to the certain announcement reported a greater loss of trust and vaccination intention than those who were exposed to the uncertain announcement. This shows that communicating with unwarranted certainty can backfire in the long-term, whereas communicating uncertainties can protect people from the negative impact of exposure to conflicting information.
DLL4 and PDGF-BB regulate migration of human iPSC-derived skeletal myogenic progenitors
Authors: Ferrari Giulia , Choi SungWoo , Moyle Louise A. , Mackinlay Kirsty , Naouar Naira , Wells Christine , Muntoni Francesco , Tedesco Francesco Saverio
Published: March 2021

Muscle satellite stem cells (MuSCs) are responsible for skeletal muscle growth and regeneration. Despite their differentiation potential, human MuSCs have limitedin vitroexpansion andin vivomigration capacity, limiting their use in cell therapies for diseases affecting multiple skeletal muscle groups such as muscular dystrophies. Several protocols have been developed to derive progenitor cells similar to MuSCs from human induced pluripotent stem cells (hiPSCs), in order to establish a source of myogenic cells with controllable proliferation and differentiation capacity. However, currently available hiPSC myogenic derivatives also suffer from limitations of cell migration, ultimately delaying their clinical translation. Here we provide evidence that activation of NOTCH and PDGF pathways with DLL4 and PDGF-BB improves migration of hiPSC-derived myogenic progenitorsin vitro. Transcriptomic and functional analyses demonstrate that this property is conserved across species and multiple hiPSC lines, including genetically-corrected hiPSC derivatives from a patient with Duchenne muscular dystrophy. DLL4 and PDGF-BB treatment had no negative impact on cell proliferation; cells maintained their myogenic memory, with differentiation fully rescued by NOTCH inhibition. RNAseq analysis indicate that pathways involved in cell migration are modulated in treated myogenic progenitors, consistent with results from functional profiling of cell motility at single cell resolution. Notably, treated cells also showed enhanced trans-endothelial migration in transwell assays. Enhancing extravasation is a key translational milestone for intravascular delivery of hiPSC myogenic derivatives: our study establishes the foundations of a transgene-free, developmentally inspired strategy to achieve this goal, moving hiPSCs one step closer to future muscle gene and cell therapies.
ProxLogs: Miniaturised proximity loggers for monitoring association behaviour in small mammals
Authors: Kirkpatrick Lucinda , Hererra Olivares Ivan , Massawe Apia , Sabuni Christopher , Leirs Herwig , Berkvens Rafael , Weyn Maarten
Published: March 2021

The ability to monitor associations between wild animals is essential for understanding the processes governing gene transfer, information transfer, competition, predation and disease transmission.

Until recently, such insights have been confined to large, visible or captive animals. However, the rapid development of miniature sensors for consumer electronics is allowing ecologists to monitor the natural world in ways previously considered impossible.

Here we describe miniature (<1g) proximity loggers we have developed that use Bluetooth Low Energy transmission to register contacts between individuals. Our loggers are open source, low cost, rechargeable, able to store up to 2000 contacts, can be programmed insituand can download data remotely or through a mobile phone application, increasing their utility in remote areas or with species which are challenging to recapture.

We successfully trialled our loggers in a range of field realistic conditions, demonstrating that Bluetooth Low Energy is capable of logging associations in structurally complex habitats, and that changes in received signal strength can be equated to short range changes in distance between loggers. Furthermore, we tested the system on starlings (Sturnidae vulgaris).

The ability to include other sensors is retained in our prototypes, allowing for the potential integration of physiological and behavioural inference into social networks derived from our approach. Due to its open source nature, small size, flexibility of use and the active research currently being undertaken with Bluetooth Low Energy, we believe that our approach is a valuable addition to the biologging toolkit.
Gut microbial structural variations as determinants of human bile acid metabolism
Authors: Wang Daoming , Doestzada Marwah , Chen Lianmin , Andreu-Sánchez Sergio , van den Munckhof Inge C.L. , Augustijn Hannah , Koehorst Martijn , Bloks Vincent W. , Riksen Niels P. , Rutten Joost H.W. , Netea Mihai G. , Zhernakova Alexandra , Kuipers Folkert , Fu Jingyuan
Published: March 2021

Bile acids (BAs) facilitate intestinal fat absorption and act as important signaling molecules in host□gut microbiota crosstalk. BA-metabolizing pathways in the microbial community have been identified, but how the highly variable genomes of gut bacteria interact with host BA metabolism remains largely unknown. We characterized 8,282 structural variants (SVs) of 55 bacterial species in the gut microbiomes of 1,437 individuals from two Dutch cohorts and performed a systematic association study with 39 plasma BA parameters. Both variations in SV-based continuous genetic makeup and discrete subspecies showed correlations with BA metabolism. Metagenome-wide association analysis identified 797 replicable associations between bacterial SVs and BAs and SV regulators that mediate the effects of lifestyle factors on BA metabolism. This is the first large-scale microbial genetic association analysis to demonstrate the impact of bacterial SVs on human BA composition, and highlights the potential of targeting gut microbiota to regulate BA metabolism through lifestyle intervention.
Kinesin-4 Motor Teams Effectively Navigate Dendritic Microtubule Arrays Through Track Switching and Regulation of Microtubule Dynamics
Authors: Masucci Erin M. , Relich Peter K. , Lakadamyali Melike , Ostap E. Michael , Holzbaur Erika L. F.
Published: March 2021

Microtubules establish the directionality of intracellular transport by kinesins and dynein through their polarized assembly, but it remains unclear how directed transport occurs along microtubules organized with mixed polarity. We investigated the ability of the plus-end directed kinesin-4 motor KIF21B to navigate mixed polarity microtubules in mammalian dendrites. Reconstitution assays with recombinant KIF21B and engineered microtubule bundles or extracted neuronal cytoskeletons indicate that nucleotide- independent microtubule binding regions of KIF21B modulate microtubule dynamics and promote directional switching on antiparallel microtubules. Optogenetic recruitment of KIF21B to organelles in live neurons resulted in unidirectional transport in axons but bi-directional transport with a net retrograde bias in dendrites; microtubule dynamics and the secondary microtubule binding regions are required for this net directional bias. We propose a model in which cargo-bound KIF21B motors coordinate nucleotide- sensitive and insensitive microtubule binding sites to achieve net retrograde movement along the dynamic mixed polarity microtubule arrays of dendrites.
PDX1 directs a core developmentally and evolutionarily conserved gene program in the pancreatic islet
Authors: Yang Xiaodun , Raum Jeffrey C. , Kim Junil , Yu Reynold , Yang Juxiang , Rice Gabriella , Li Changhong , Won Kyoung-Jae , Stoffers Doris A. , Stanescu Diana E.
Published: March 2021

Pancreatic and duodenal homeobox 1 (PDX1)is crucial for pancreas organogenesis, yet the dynamic changes in PDX1 targets in mouse or human pancreas development have not been examined. We integrated the PDX1 cistrome with cell lineage-specific gene expression in both mouse and human developing pancreas. We identified a core set of developmentally and evolutionarily conserved PDX1 bound genes that reveal the broad multifaceted role of PDX1 in pancreas development. Despite the well-known, dramatic changes in PDX1 function and expression, we showed that PDX1 binding is largely stable from embryonic pancreas to adult islet. This may point towards a dual role of PDX1, activating or repressing the expression of its targets at different ages, dependent on other functionally-congruent or directly-interacting partners. Our work also suggests that PDX1 functions not only in initiating pancreas differentiation, but also as a potential keepsake of the progenitor program in the adult beta cells.
MetaFetcheR: An R package for complete mapping of small compound data
Authors: Yones Sara A. , Csombordi Rajmund , Komorowski Jan , Diamanti Klev
Published: March 2021

Motivation

Small-compound databases contain large amount of information for metabolites and metabolic pathways. However, the plethora of such databases and the redundancy of their information lead to major issues with analysis and standardization. Lack of preventive establishment of means of data access at the infant stages of a project might lead to mislabelled compounds, reduced statistical power and large delays in delivery of results.

Results

We developed MetaFetcheR, an open-source R package that links metabolite data from several small-compound databases, resolves inconsistencies and covers a variety of use-cases of data fetching. We showed that the performance of MetaFetcheR was superior to existing approaches and databases by benchmarking the performance of the algorithm in two independent case studies based on two published datasets.

Availability

MetaFetcheR is available athttps://github.com/komorowskilab/MetaFetcheR/.
Collagen polarization promotes epithelial elongation by stimulating locoregional cell proliferation
Authors: Katsuno-Kambe Hiroko , Teo Jessica L. , Ju Robert J. , Hudson James E. , Stehbens Samantha J. , Yap Alpha S.
Published: March 2021

Epithelial networks are commonly generated by processes where multicellular aggregates elongate and branch. Here we focus on understanding cellular mechanisms for elongation, using an organotypic culture system as a model of mammary epithelial anlage. Isotropic cell aggregates broke symmetry and slowly elongated when transplanted into collagen 1 gels. The elongating regions of aggregates displayed enhanced cell proliferation that was necessary for elongation to occur. Strikingly, this loco-regional increase in cell proliferation occurred where collagen 1 fibrils reorganized into bundles which were polarized with the elongating aggregates. Applying external stretch as a cell-independent way to reorganize the ECM, we found that collagen polarization stimulated regional cell proliferation to precipitate symmetry-breaking and elongation. This required β1-integrin and ERK signaling. We propose that collagen polarization supports epithelial anlagen elongation by stimulating loco-regional cell proliferation. This could provide a long-lasting structural memory of the initial axis that is generated when anlage break symmetry.
Reverse complementary matches simultaneously promote both back-splicing and exon-skipping
Authors: Cao Dong
Published: March 2021

Circular RNAs (circRNAs) play diverse roles in different biological and physiological environments and are always expressed in a tissue-specific manner. Tissue-specific circRNA expression profile can help understand how circRNAs are regulated. Here, using large-scale neuron isolation from the first larval stage ofCaenorhabditis elegans(C. elegans) followed by whole-transcriptome RNA sequencing, I provide the first neuronal circRNA data inC. elegans. I show that circRNAs are highly expressed in the neurons ofC. elegansand are preferably derived from neuronal genes. More importantly, reverse complementary matches in circRNA-flanking introns are not only required for back-splicing but also promote the skipping of exon(s) to be circularized. Interestingly, one pair of RCM inzip-2is highly conserved across five nematode ortholog genes, which show conserved exon-skipping patterns. Finally, through one-by-one mutagenesis of all the splicing sites and branch points required for exon-skipping and back-splicing in thezip-2gene, I show that exon-skipping is not absolutely required for back-splicing, neither the other way. Instead, the coupled exon-skipping and back-splicing are happening at the same time.
Molecular diet analysis in zebra and quagga mussels (Dreissenaspp.) and an assessment of the utility of aquatic filter feeders as biological eDNA filters
Authors: Weber Sven , Brink Lukas , Wörner Manuel , Künzel Sven , Veith Michael , Teubner Diana , Klein Roland , Paulus Martin , Krehenwinkel Henrik
Published: March 2021

Molecular gut content analysis is a popular tool to study food web interactions and was recently also suggested as an alternative source for DNA based biomonitoring. However, the overabundant consumer’s DNA often outcompetes that of its diet during PCR. Blocking approaches are an efficient means to reduce consumer amplification while retaining broad specificity for dietary taxa. We here designed an assay to monitor the eukaryotic diet of mussels and test their utility as biological eDNA filters to monitor planktonic communities. We designed several rDNA primer sets with a broad taxonomic suitability for eukaryotes, which suppress the amplification of mussels. The primers were tested using mussel DNA extracts and the results were compared to eDNA water samples collected next to the mussel colonies. Taxonomic recovery, as well as patterns of alpha and beta diversity, were compared between mussels and water samples. In addition, we analyzed time series samples of mussel samples from different German rivers. Our primer sets efficiently block the amplification of various mussel genera. The recovered DNA reflects a broad dietary preference across the eukaryotic tree of life and considerable taxonomic overlap with filtered water samples. We also recover various taxa of possible commensals and parasites, associated with the mussels. Our protocol will enable large scale dietary analysis in mussels, facilitate aquatic food web analysis, elucidate the ecological impact of invasive bivalves and the rapid survey of mussel aquacultures for pathogens. Moreover, we show that mussels could serve as an interesting complementary DNA source for biomonitoring.
TheopenCARPSimulation Environment for Cardiac Electrophysiology
Authors: Plank Gernot , Loewe Axel , Neic Aurel , Augustin Christoph , Huang Yung-Lin , Gsell Matthias A. F. , Karabelas Elias , Nothstein Mark , Prassl Anton J. , Sánchez Jorge , Seemann Gunnar , Vigmond Edward J.
Published: March 2021

Background and Objective

Cardiac electrophysiology is a medical specialty with a long and rich tradition of computational modeling. Nevertheless, no community standard for cardiac electrophysiology simulation software has evolved yet. Here, we present theopenCARPsimulation environment as one solution that could foster the needs of large parts of this community.

Methods and Results

openCARPand the Python-basedcarputilsframework allow developing and sharing simulation pipelines which automatein silicoexperiments including all modeling and simulation steps to increase reproducibility and productivity. The continuously expandingopenCARPuser community is supported by tailored infrastructure. Documentation and training material facilitate access to this complementary research tool for new users. After a brief historic review, this paper summarizes requirements for a high-usability electrophysiology simulator and describes howopenCARPfulfills them. We introduce theopenCARPmodeling workflow in a multi-scale example of atrial fibrillation simulations on single cell, tissue, organ and body level and finally outline future development potential.

Conclusion

As an open simulator,openCARPcan advance the computational cardiac electrophysiology field by making state-of-the-art simulations accessible. In combination with thecarputilsframework, it offers a tailored software solution for the scientific community and contributes towards increasing use, transparency, standardization and reproducibility ofin silicoexperiments.
Desalination and temperature increase will shift seasonal grazing patterns of invasiveGammarus tigrinuson charophytes
Authors: Berthold M. , Porsche C. , Hofmann A. , Nowak P.
Published: March 2021

Charophytes are a refuge for zooplankton and stabilize sediments, but they are also a food source for various animal species (water birds, fishes, invertebrates). Especially the introduction of new species, likeGammarus tigrinus, into the Baltic Sea led to yet not understood changes in the food web. Furthermore, future projections point to increased water temperatures at lowered salinity levels affecting species capacity to acclimatize to changing abiotic factors. In this study we investigated the influence of temperature and salinity on the grazing pressure ofGammarus tigrinuson two charophyte species:Chara asperaandChara tomentosa. The grazing experiments were conducted in a full factorial design with the factors salinity (3 – 13 g kg-1), temperature (5 – 30 °C), and charophyte species. Grazing rates were determined as mass deviation within 48 hours considering biomass changes in the presence and absence of gammarids. Grazing rate were further used to calculate charophyte losses in two coastal lagoons with different salinity concentrations for recent and future time periods. The potential grazing peak of about 24 °C is not yet reached in these coastal waters but may be reached in the near future as shown by our future projection results. However, the temperature increase, and desalination will cause a shift in seasonal individual grazing patterns from summer to spring and autumn. Desalination and temperature increase can lead to a shift in optimal habitats forG. tigrinusin the future.
A structural analysis of amyloid polymorphism in disease: clues for selective vulnerability?
Authors: van der Kant Rob , Louros Nikolaos , Schymkowitz Joost , Rousseau Frederic
Published: March 2021

The increasing amount of amyloid structures offers an opportunity to investigate the general principles determining amyloid stability and polymorphism in disease. We find that amyloid stability is dominated by about 30% of residues localized in few segments interspersed with regions that are often structurally frustrated in the cross-β conformation. These stable segments correspond to known aggregation-nucleating regions and constitute a cross-β structural framework that is shared among polymorphs. Alternative tertiary packing of these segments within the protofibril results in conformationally different but energetically similar polymorphs. This combination of a conserved structural framework along the axis and energetic ambiguity across the axis results in polymorphic plasticity that explains a number of fundamental amyloid properties, including fibril defects and brittleness but also the polymorphic instability of amyloids in simple aqueous buffers. Together these findings suggest a structural model for in vivo polymorphic bias and selective cellular vulnerability whereby (1) polymorphic bias is induced by particular templating interactions in susceptible cells, (2) once formed specific polymorphs are entropically primed to selectively bind similar targets in neighbouring cells, (3) conservation of polymorphic bias during pathological spreading implies the continued presence of similar templating interactions in successive susceptible cells and (4) absence of templating interactions relaxes polymorphic bias possibly allowing for the modification of cellular susceptibilities during disease progression by novel templating interactions.
Getting under the skin of Polycomb-dependent gene regulation
Authors: Blackledge Neil P. , Klose Robert J.
Published: March 2021

The Polycomb repressive system functions through chromatin to regulate gene expression and development. In this issue of Genes & Development, Cohen and colleagues (pp. 354–366) use the developing mouse epidermis as a model system to show that the two central Polycomb repressive complexes, PRC1 and PRC2, have autonomous yet overlapping functions in repressing Polycomb target genes. They show that this cooperation enables the stable repression of nonepidermal transcription factors that would otherwise compromise epidermal cell identity and disrupt normal skin development.
Cellular plasticity balances the metabolic and proliferation dynamics of a regenerating liver
Authors: Chembazhi Ullas V. , Bangru Sushant , Hernaez Mikel , Kalsotra Auinash
Published: March 2021

The adult liver has an exceptional ability to regenerate, but how it maintains its specialized functions during regeneration is unclear. Here, we used partial hepatectomy (PHx) in tandem with single-cell transcriptomics to track cellular transitions and heterogeneities of ∼22,000 liver cells through the initiation, progression, and termination phases of mouse liver regeneration. Our results uncovered that, following PHx, a subset of hepatocytes transiently reactivates an early-postnatal-like gene expression program to proliferate, while a distinct population of metabolically hyperactive cells appears to compensate for any temporary deficits in liver function. Cumulative EdU labeling and immunostaining of metabolic, portal, and central vein–specific markers revealed that hepatocyte proliferation after PHx initiates in the midlobular region before proceeding toward the periportal and pericentral areas. We further demonstrate that portal and central vein proximal hepatocytes retain their metabolically active state to preserve essential liver functions while midlobular cells proliferate nearby. Through combined analysis of gene regulatory networks and cell–cell interaction maps, we found that regenerating hepatocytes redeploy key developmental regulons, which are guided by extensive ligand-receptor-mediated signaling events between hepatocytes and nonparenchymal cells. Altogether, our study offers a detailed blueprint of the intercellular crosstalk and cellular reprogramming that balances the metabolic and proliferative requirements of a regenerating liver.
Preparing Paraffin Tissue Sections for Staining
Authors: Rodig Scott J.
Published: March 2021

Most histological studies are performed on formalin-fixed, paraffin-embedded (FFPE) tissue samples. Therefore, there is an extensive atlas of most tissues and organs prepared from these sources, and comparing the location of antigens to these data is immediately informative. Fixation and embedding procedures for preparation of paraffin tissue sections are described here. Because of the harsh fixation, embedding, and preparation conditions used in this procedure, many antigens are not well preserved. Thus, cell staining of paraffin-embedded tissue sections usually requires sensitive detection methods and may require amplification using multiple-layer techniques. The protein cross-linking associated with these fixation conditions can mask epitopes. To uncover them and thus improve antibody–antigen binding, the epitopes can be unmasked by reversing the protein cross-linking. One thermal method, heat-induced epitope retrieval, is presented here.
Obtaining Xenopus laevis Embryos
Authors: Shaidani Nikko-Ideen , McNamara Sean , Wlizla Marcin , Horb Marko E.
Published: March 2021

The embryos of the African clawed frog, Xenopus laevis, are a powerful substrate for the study of complex fundamental biological and disease mechanisms in neurobiology, physiology, molecular biology, cell biology, and developmental biology. A simple and straightforward technique for generating a large number of developmentally synchronized embryos is in vitro fertilization (IVF). IVF permits simultaneous fertilization of thousands of eggs but requires the death of the parental male, which may not be feasible if the male comes from a stock of precious animals. An alternative to euthanizing a precious male is to use a natural mating, which allows for the collection of many embryos with minimal preparation but with the potential loss of the experimental advantage of developmental synchronization. Here we present both strategies for obtaining X. laevis embryos.
Institutional work and the interplay of stability and change in public budgeting reform: the case of public universities in Iran
Authors: Jalali Aliabadi Farzaneh , Farooq Muhammad Bilal , Sharma Umesh , Mihret Dessalegn Getie
Published: March 2021

Purpose

The purpose of this study is to understand the efforts of key social actors in influencing the reform of Iranian public universities budgeting system, from incremental to performance-based budgeting (PBB), the tensions that arose as competing efforts of institutional change were undertaken, and ultimately the impact of these efforts on the extent to which the Iranian government transitioned to a system of PBB in public universities.

Design/methodology/approach

Data comprises of semi-structured interviews with managers and experts involved in the budget setting process and an analysis of budgetary policy documents, reports and archival material such as legislation. An institutional work lens is employed to interpret the findings.

Findings

While actors advocating the change were engaged in institutional work directed at disrupting the old budgetary rules by disassociating the rules moral foundations and creating new budgetary rules (through new legislation), universities undertook subtle resistance by engaging in extended evaluation of the new proposed PBB rules thereby maintaining the old budgetary rules. The reforms undertaken to introduce PBB in Iranian universities achieved minimal success whereby incremental budgeting continued to constitute by far a larger percentage of the budget allocation formula for university budgets. This finding illustrates change and continuity in university budgetary systems resulting from institutional work of actors competing to control the basis of resource allocation under the proposed PBB system by proposing contradicting models.

Practical implications

The findings highlight the importance of understanding the interplay of institutional work undertaken by competing social actors as they seek to advance their goals in shaping budgetary reforms in the public-sector. Such an understanding may inform policy makers who intend to introduce major reforms in public-sector budgeting approaches.

Originality/value

Unlike prior studies that largely focused on how organization-level budgeting practices responded to changes in public budgeting rules (i.e. at the site of implementation of the rules), this paper highlights how strategies of change and resistance are played out at the site of setting budgetary norms.
Food security and trade policies: evidence from the milk sector case study
Authors: Zolin Maria Bruna , Cavapozzi Danilo , Mazzarolo Martina
Published: March 2021

Purpose

Milk is one of the most produced, consumed and protected agricultural commodities worldwide. The purpose of this paper is to assess how trade-opening policies can foster food security in the Chinese milk sector.

Design/methodology/approach

The empirical evidence proposed in our paper is based on time series data from the National Bureau of Statistics of China (2019) and FAOSTAT (2020). Differences in income elasticity between urban and rural areas are estimated by OLS regressions. The data also provide empirical evidence to assess to what extent and to which countries China is resorting to meet its growing demand.

Findings

Per-capita milk consumption of Chinese is rising. The authors’ estimates show that milk income elasticity is higher in rural areas. China is also progressively increasing its dependence on imports. Producers who benefit the most are those from countries implementing trade-opening policies.

Research limitations/implications

Other methods could be applied, by way of example, the gravitational model.

Practical implications

Trade agreements and the removal of barriers could be effective responses to protectionist pressures and to food security concerns.

Social implications

The case examined is of particular interest as it intervenes on food security and safety.

Originality/value

The paper adds value and evidence to the effects of trade on food security in a country with limited and exploited natural resources addressing a health emergency and environmental concerns.
Exchange of knowledge in protected environments. The case of university business incubators
Authors: Redondo María , Camarero Carmen , van der Sijde Peter
Published: March 2021

Purpose

University business incubators (UBIs) are born as tools of the academic world to market research results, for the transfer of technology and to promote entrepreneurial spirit. In these contexts, the exchange of knowledge among entrepreneurs can be a key variable for the development and success of their businesses. This paper aims to analyse the characteristics of entrepreneurs' resources and the institutional logic that prevails in the incubator as determinants of the exchange of knowledge, and the authors examine the results in terms of entrepreneurial commitment and the generation of innovations.

Design/methodology/approach

The empirical study carried out on a sample of 101 entrepreneurs in UBIs in Spain and The Netherlands.

Findings

The results reveals how complementarity, supplementarity and transferability of resources, as well as incubator predisposition towards business are fundamental for the exchange of knowledge, the development of entrepreneurial spirit and the generation of innovation.

Originality/value

This study makes a contribution towards an understanding of how relationships between university entrepreneurs provide access to and help create useful knowledge for the parties, with this resource constituting one possible source of sustainable competitive advantage.
MIMO antenna miniaturization standards for future 5G
Authors: Katragadda Swetha , Jayasree PVY
Published: March 2021

Purpose

The fifth-generation technology 5G, the planned successor to 4G, is a new global standard for mobile networks that brings virtual to reality. 5G wireless technology enables the delivery of high speed, low latency, reliability, 100% coverage and availability to connect number of users as in massive IoT applications.

Design/methodology/approach

With expeditious development in wireless communication, the need for enhanced characteristic antenna design such as the size of the antenna, high data rate, demand in traffic, bandwidth, gain and efficiency increases. Various antenna designs are to be explored to meet the needs and achieve trade-offs between antenna size vs cost, high gain and efficiency vs less loss, high B.W and data rate with the selection of appropriate substrate materials and various gain & isolation enhancement techniques.

Findings

This paper thus gives scope for miniaturized MIMO antenna design for mobile applications at mm-wave frequency range.

Originality/value

This paper thus gives scope for miniaturized MIMO antenna design for mobile applications at mm-wave frequency range.