bluuebunny/crossref_metadata_2025 huggingface dataset:
A Malaria Knowledge, Attitudes and Practice Survey in a Rural Community in Guinea
Authors: Holsted Erin , Kadiebwe Barclay , Sattar Amer , Salthouse Abigail , Ravi Nirmal
Published: June 2021

Malaria is the top public health problem in the Republic of Guinea. In 2016, we conducted a cross-sectional household survey in Timbi-Touni, Guinea using community workers. The survey included respondent demographic characteristics, child health, child health promotion related to malaria knowledge, water and sanitation, and health services access. Majority of our respondents were women (89.41%) and had never been to school (71.18%). Slightly more than half the children were reported to have ever had malaria and 45% reported to have ever had diarrhea. We did not find any statistically significant association between gender or level of education and malaria knowledge. Eighty six percent of respondents had received a free bednet during national campaigns and 61% slept under a bednet the night before the survey. We found a statistically significant association between receiving information on malaria prevention and sleeping under a bednet. There was no statistically significant association between drinking water source and malaria or diarrhea. Both malaria and diarrhea were considered to be serious illnesses for adults and children by nearly all respondents. Insights from our detailed KAP survey can guide policy makers and practitioners who design and implement malaria control and prevention measures in Guinea.
SARS-CoV-2 under an elimination strategy in Hong Kong
Authors: Gu Haogao , Xie Ruopeng , Adam Dillon C. , Tsui Joseph L.-H. , Chu Daniel K. , Chang Lydia D.J. , Cheuk Sammi S.Y. , Gurung Shreya , Krishnan Pavithra , Ng Daisy Y.M. , Liu Gigi Y.Z. , Wan Carrie K.C. , Edwards Kimberly M. , Leung Kathy S.M. , Wu Joseph T. , Tsang Dominic N.C. , Leung Gabriel M. , Cowling Benjamin J. , Peiris Malik , Lam Tommy T.Y. , Dhanasekaran Vijaykrishna , Poon Leo L.M.
Published: June 2021

Hong Kong utilized an elimination strategy with intermittent use of public health and social measures and increasingly stringent travel regulations to control SARS-CoV-2 transmission. By analyzing >1700 genome sequences representing 17% of confirmed cases from 23-January-2020 to 26-January-2021, we reveal the effects of fluctuating control measures on the evolution and epidemiology of SARS-CoV-2 lineages in Hong Kong. Despite numerous importations, only three introductions were responsible for 90% of locally-acquired cases, two of which circulated cryptically for weeks while less stringent measures were in place. We found that SARS-CoV-2 within-host diversity was most similar among transmission pairs and epidemiological clusters due to a strong transmission bottleneck through which similar genetic background generates similar within-host diversity.

One sentence summary

Out of the 170 detected introductions of SARS-CoV-2 in Hong Kong during 2020, three introductions caused 90% of community cases.
The Digital Brain Bank, an open access platform for post-mortem datasets
Authors: Tendler Benjamin C. , Hanayik Taylor , Ansorge Olaf , Bangerter-Christensen Sarah , Berns Gregory S. , Bertelsen Mads F. , Bryant Katherine L. , Foxley Sean , van den Heuvel Martijn P. , Howard Amy F.D. , Huszar Istvan N. , Khrapitchev Alexandre A. , Leonte Anna , Manger Paul R. , Menke Ricarda A.L. , Mollink Jeroen , Mortimer Duncan , Pallebage-Gamarallage Menuka , Roumazeilles Lea , Sallet Jerome , Scholtens Lianne H. , Scott Connor , Smart Adele , Turner Martin R. , Wang Chaoyue , Jbabdi Saad , Mars Rogier B. , Miller Karla L.
Published: June 2021

Post-mortem MRI provides the opportunity to acquire high-resolution datasets to investigate neuroanatomy, and validate the origins of image contrast through microscopy comparisons. We introduce the Digital Brain Bank (open.win.ox.ac.uk/DigitalBrainBank), a data release platform providing open access to curated, multimodal post-mortem neuroimaging datasets. Datasets span three themes - Digital Neuroanatomist: datasets for detailed neuroanatomical investigations; Digital Brain Zoo: datasets for comparative neuroanatomy; Digital Pathologist: datasets for neuropathology investigations. The first Digital Brain Bank release includes twenty one distinctive whole-brain diffusion MRI datasets for structural connectivity investigations, alongside microscopy and complementary MRI modalities. This includes one of the highest-resolution whole-brain human diffusion MRI datasets ever acquired, whole-brain diffusion MRI in fourteen non-human primate species, and one of the largest post-mortem whole-brain cohort imaging studies in neurodegeneration. The Digital Brain Bank is the culmination of our lab’s investment into post-mortem MRI methodology and MRI-microscopy analysis techniques. This manuscript provides a detailed overview of our work with post-mortem imaging to date, including the development of diffusion MRI methods to image large post-mortem samples, including whole, human brains. Taken together, the Digital Brain Bank provides crossscale, cross-species datasets facilitating the incorporation of post-mortem data into neuroimaging studies.
Exploring cell surface-nanopillar interactions with 3D super-resolution microscopy
Authors: Roy Anish R. , Zhang Wei , Jahed Zeinab , Tsai Ching-Ting , Cui Bianxiao , Moerner W.E.
Published: June 2021

Plasma membrane topography has been shown to strongly influence the behavior of many cellular processes such as clathrin-mediated endocytosis, actin rearrangements, and others. Recent studies have used 3D nanostructures such as nanopillars to imprint well-defined membrane curvatures (the “nano-bio interface”). In these studies, proteins and their interactions were probed by 2D fluorescence microscopy. However, the low resolution and limited axial detail of such methods are not optimal to determine the relative spatial position and distribution of proteins along a 100 nm-diameter object, which is below the optical diffraction limit. Here, we introduce a general method to explore the nanoscale distribution of proteins at the nano-bio interface with 10-20 nm precision using 3D single-molecule super-resolution (SR) localization microscopy. This is achieved by combining a silicone oil immersion objective and 3D double-helix point-spread function microscopy. We carefully optimize the objective to minimize spherical aberrations between quartz nanopillars and the cell. To validate the 3D SR method, we imaged the 3D shape of surface-labeled nanopillars and compared the results with electron microscopy measurements. Turning to transmembrane-anchored labels in cells, the high quality 3D SR reconstructions reveal the membrane tightly wrapping around the nanopillars. Interestingly, the cytoplasmic protein AP-2 involved in clathrin-mediated endocytosis accumulates along the nanopillar above a specific threshold of 1/R membrane curvature. Finally, we observe that AP-2 and actin preferentially accumulate at positive Gaussian curvature near the pillar caps. Our results establish a general method to investigate the nanoscale distribution of proteins at the nano-bio interface using 3D SR microscopy.
A novel Toxoplasma IMC sutures-associated protein regulates suture protein targeting and colocalizes with membrane trafficking machinery
Authors: Chern Jessica H. , Moon Andy S. , Chen Allan L. , Sha Jihui , Wohlschlegel James A. , Bradley Peter J.
Published: June 2021

The cytoskeleton ofToxoplasma gondiiis composed of the inner membrane complex (IMC) and an array of underlying microtubules that provide support at the periphery of the parasite. Specific subregions of the IMC carry out distinct roles in replication, motility, and host cell invasion. Building on our previousin vivobiotinylation (BioID) experiments of the IMC, we identify here a novel protein that localizes to discrete punctae that are embedded in the parasite’s cytoskeleton along the IMC sutures. Gene knockout analysis shows that loss of the protein results in defects in cytoskeletal suture protein targeting, cytoskeletal integrity, parasite morphology, and host cell invasion. We then use deletion analyses to identify a domain in the N-terminus of the protein that is critical for both localization and function. Finally, we use the protein as bait forin vivobiotinylation which identifies several other proteins that colocalize in similar spot-like patterns. These putative interactors include several proteins that are implicated in membrane trafficking and are also associated with the cytoskeleton. Together, this data reveals an unexpected link between the IMC sutures and membrane trafficking elements of the parasite and suggests that the sutures punctae are likely a portal for trafficking cargo across the IMC.
A Multiparametric Activity Profiling Platform for Neuron Disease Phenotyping and Drug Screening
Authors: Boivin Bruno , Roet Kasper C.D. , Huang Xuan , Karhohs Kyle W. , Rohban Mohammad H. , Sandoe Jack , Wiskow Ole , Maeda Rie , Grantham Alyssa , Dornon Mary K. , Shao Jenny , Frost Devlin , Baker Dylan , Eggan Kevin , Carpenter Anne E. , Woolf Clifford J.
Published: June 2021

Patient stem cell-derived models enable imaging of complex disease phenotypes and the development of scalable drug discovery platforms. Current preclinical methods for assessing cellular activity do not, however, capture the full intricacies of disease-induced disturbances, and instead typically focus on a single parameter, which impairs both the understanding of disease and the discovery of effective therapeutics. Here, we describe a cloud-based image processing and analysis platform that captures the intricate activity profile revealed by GCaMP fluorescent recordings of intracellular calcium changes and enables discovery of molecules that correct 153 parameters that define the amyotrophic lateral sclerosis motor neuron disease phenotype. In a high-throughput screen we identified compounds that revert the multiparametric disease profile to that found in healthy cells, a novel and robust measure of therapeutic potential quite distinct from unidimensional screening. This platform can guide the development of therapeutics that counteract the multifaceted pathological features of diseased cellular activity.
Multiple modes of regulation control dynamic transcription patterns during the mitosis-G1 transition
Authors: Wojenski Luke A. , Wainman Lauren M. , Villafano Geno , Kuhlberg Chris , Nanda Pariksheet , Core Leighton
Published: June 2021

Following cell division, genomes must reactivate gene expression patterns that reflect the identity of the cell. Here, we use PRO-seq to examine the mechanisms that reestablish transcription patterns after mitosis. We uncover regulation of the transcription cycle at multiple steps including initiation, promoter-proximal pause positioning and escape, poly-A site cleavage and termination during the mitotic-G1 transition. During mitosis, RNA polymerase activity is retained at initiation sites, albeit shifted in position relative to non-mitotic cells. This activity is strongly linked to maintenance of local chromatin architecture during mitosis and is more predictive of rapid gene reactivation than histone modifications previously associated with bookmarking. These molecular bookmarks, combined with sequence-specific transcription factors, direct expression of select cell growth and cell specific genes during mitosis followed by reactivation of functional gene groups with distinct kinetics after mitosis. This study details how dynamic regulation of transcription at multiple steps contributes to gene expression during the cell cycle.
The noncoding RNA PRANCR regulates splicing of Fibronectin-1 to control keratinocyte proliferation and migration
Authors: Otten Auke B.C. , Amarbayar Oyumergen , Cai Pengfei , Cheng Binbin , Qu Kun , Sun Bryan K.
Published: June 2021

Most human genes undergo alternative splicing (AS), but the regulation and functional consequences of most splicing events remain unknown. Long noncoding RNAs (lncRNAs) have recently been discovered to have novel roles in the regulation of AS. Here we investigate whether PRANCR, a lncRNA recently identified to be essential for epidermis formation, functions by controlling AS of cell fate genes. Using transcriptome-wide analysis, we identified 238 exonic splicing events regulated by PRANCR. Among these is alternative splicing of an exon containing the extra domain A (EDA) in the gene fibronectin-1 (FN1). Expression of the FN1-EDA+ isoform is enriched in proliferating keratinocytes. We find that PRANCR regulates EDA inclusion by controlling expression of the serine/arginine-rich splicing factors (SRSFs) 1 and 7. Depletion of PRANCR or FN1-EDA resulted in decreased proliferation, increased CDKN1A/p21, and inhibition of keratinocyte migration. We find that these cellular phenotypes can be explained by reduced phosphorylation of focal adhesion kinase (FAK). Collectively, these results identify a lncRNA regulating skin function through alternative splicing of a cell fate gene.
Molecular evidence for sweeping discontinuity between peracarid (Crustacea) fauna of Macaronesian islands and nearby continental coasts: over fifty candidate endemic species
Authors: Vieira Pedro E , Desiderato Andrea , Azevedo Sofia L , Esquete Patricia , Costa Filipe O , Queiroga Henrique
Published: June 2021

Oceanic islands are recognized evolutionary hotspots for terrestrial organisms, but little is known about their impact on marine organisms’ evolution and biogeography. The volcanic archipelagos of Macaronesia occupy a vast and complex region which is particularly suitable to investigate marine island biogeography.

In this study, we used mitochondrial DNA sequences to investigate the genetic diferentiation between the populations from Webbnesia (i.e. Madeira, Selvagens and Canaries) and adjacent coasts, of 23 intertidal peracarid species. All species had unexpectedly high intraspecific genetic distances, reaching more than 20% in some cases. Between 79 and 95 Molecular Operational Taxonomic Units (MOTUs) were found in these species. Webbnesia populations displayed an impressive genetic diversity and high endemicity, with 83% of the MOTUs being private to these islands, particularly La Palma and Madeira. Network analyses suggested higher similarity between Webbnesia and Azores than with adjacent continental coasts.

These results reveal an unanticipated and sweeping biogeographic discontinuity of peracaridean fauna between Webbnesia and the Iberian Peninsula, raising suspicion about the possible occurrence of identical patterns in other groups of marine invertebrates in the region. We emphasize the unique genetic heritage hosted by these islands, underlining the need to consider the fine scale endemicity in marine conservation efforts.
Structurally conserved domains between flavivirus and alphavirus fusion glycoproteins contribute to replication in mammals and infectious virion production
Authors: Rangel Margarita V. , Catanzaro Nicholas , Thannickal Sara A. , Crotty Kelly A. , Noval Maria G. , Johnson Katherine E.E. , Ghedin Elodie , Lazear Helen M. , Stapleford Kenneth A.
Published: June 2021

Alphaviruses and flaviviruses have class II fusion glycoproteins that are essential for virion assembly and infectivity. Importantly, the tip of domain II is structurally conserved between the alphavirus and flavivirus fusion proteins, yet whether these structural similarities between virus families translate to functional similarities is unclear. Using in vivo evolution of Zika virus (ZIKV), we identified several novel emerging variants including an envelope glycoprotein variant in β-strand c (V114M) of domain II. We have previously shown that the analogous β-strand c and the ij loop, located in the tip of domain II of the alphavirus E1 glycoprotein, are important for infectivity. This led us to hypothesize that flavivirus E β-strand c also contributes to flavivirus infection. We generated this ZIKV glycoprotein variant and found that while it had little impact on infection in mosquitoes, it reduced replication in human cells and mice, and increased virus sensitivity to ammonium chloride, as seen for alphaviruses. In light of these results and given our alphavirus ij loop studies, we mutated a conserved alanine at the tip of the flavivirus ij loop to valine to test its effect on ZIKV infectivity. Interestingly, this mutation inhibited infectious virion production of ZIKV and yellow fever virus, but not West Nile virus. Together, these studies show that structurally analogous residues in the alphavirus and flavivirus class II fusion proteins contribute to virus infection in vivo and highlight these shared domains as targets for broad-spectrum arbovirus therapies.

Author Summary

Arboviruses are a significant global public health threat, yet there are no antivirals targeting these viruses. This problem is in part due to our lack of knowledge on the molecular mechanisms involved in the arbovirus life cycle. In particular, virus entry and assembly are essential processes in the virus life cycle and steps that can be targeted for the development of antiviral therapies. Therefore, understanding common, fundamental mechanisms used by different arboviruses for entry and assembly is essential. In this study, we show that flavivirus and alphavirus residues located in structurally conserved and analogous regions of the class II fusion proteins contribute to common mechanisms of entry, dissemination, and infectious virion production. These studies highlight how class II fusion proteins function and provide novel targets for development of antivirals.
High CXCL6 drives matrix expression and correlate with markers of poor outcome in IPF
Authors: Bahudhanapati Harinath , Tan Jiangning , Apel Rosa Marie , Seeliger Benjamin , Li Xiaoyun , Chen Ting-Yun , Sullivan Daniel , Sembrat John , Rojas Mauricio , Tabib Tracy , Valenzi Eleanor , Lafyatis Robert , Jawale Chetan , Biswas Partha , Tedrow John , Adams Taylor , Kaminski Naftali , Wuyts Wim A , McDyer John F , Alder Jonathan K , Zhang Yingze , Nouraie Mehdi , Prasse Antje , Kass Daniel J
Published: June 2021

Signaling via G protein-coupled receptors (GPCRs) can modulate levels of cyclic adenosine monophosphate (cAMP) and shape the functions of fibroblasts in idiopathic pulmonary fibrosis (IPF). We have identified Chemokine (C-X-C) Motif Ligand 6 (CXCL6) as a potential pro-fibrotic GPCR ligand. We tested the function of CXCL6 inex vivohuman donor and fibrotic lung fibroblasts and in an animal model of pulmonary fibrosis. We also measured levels of CXCL6 in the blood and bronchoalveolar lavage (BAL) of patients with IPF. CXCL6 decreased cAMP levels in a dose-dependent manner in Donor and IPF Fibroblasts. CXCL6 mRNA and protein were localized to epithelial cells. Administration of mCXCL5 (LIX, murine CXCL6 homologue) to mice increased collagen synthesis with and without bleomycin. CXCL6 increased Collagen I and α-SMA levels in Donor and IPF Fibroblasts. Silencing of CXCR1/2 as well as Reparixin, a CXCR1/2 inhibitor, blocked effects of CXCL6. Treprostinil blocked effects of CXCL6 only on levels of α-SMA but not on Collagen I. CXCL6 levels in the BAL of two separate cohorts of patients with IPF was associated with poor survival. We conclude that high CXCL6 drives fibroblast function and correlates with poor outcomes in IPF.
Norepinephrine Potentiates and Serotonin Depresses Visual Cortical Responses by Transforming Eligibility Traces
Authors: Hong Su Z. , Mesik Lukas , Grossman Cooper D. , Cohen Jeremiah Y. , Lee Boram , Lee Hey-Kyoung , Hell Johannes W. , Kirkwood Alfredo
Published: June 2021

Reinforcement allows organisms to learn which stimuli predict subsequent biological relevance. Hebbian mechanisms of synaptic plasticity are insufficient to account for reinforced learning because neuromodulators signaling biological relevance are delayed with respect to the neural activity associated with the stimulus. A theoretical solution is the concept of eligibility traces (eTraces), silent synaptic processes elicited by activity which upon arrival of a neuromodulator are converted into a lasting change in synaptic strength. Previously we demonstrated in visual cortical slices the Hebbian induction of eTraces and their conversion into LTP and LTD by the retroactive action of norepinephrine and serotonin Here we show in vivo in V1 that the induction of eTraces and their conversion to LTP/D by norepinephrine and serotonin respectively potentiates and depresses visual responses. We also show that the integrity of this process is crucial for ocular dominance plasticity, a canonical model of experience-dependent plasticity.
Engineering 3D Vascularized Adipose Tissue Construct using a Decellularized Lung Matrix
Authors: DeBari Megan K. , Ng Wai Hoe , Griffin Mallory D. , Kokai Lauren E. , Marra Kacey G. , Rubin J. Peter , Ren Xi , Abbott Rosalyn D.
Published: June 2021

Critically sized defects in subcutaneous white adipose tissue result in extensive disfigurement and dysfunction and remain a reconstructive challenge for surgeons; as larger defect sizes are correlated with higher rates of complications and failure due to insufficient vascularization following implantation. Our study demonstrates for the first-time a method to engineer perfusable, pre-vascularized, high-density adipose grafts that combine patient-derived adipose cells with a decellularized lung matrix (DLM). The lung is one of the most vascularized organs with high flow, low resistance, and a large blood-alveolar interface separated by a thin basement membrane. For our work, the large volume capacity within the alveolar compartment was repurposed for high-density adipose cell filling, while the acellular vascular bed provided efficient graft perfusion throughout. Both adipocytes and hASCs were successfully delivered and remained in the alveolar space even after weeks of culture. While adipose derived cells maintained their morphology and functionality in both static and perfusion DLM cultures, perfusion culture offered enhanced outcomes over static culture. Furthermore, we demonstrate that endothelial cells seamlessly integrate into the acellular vascular tree of the DLM with adipocytes. These results support that the DLM is a unique platform for creating vascularized adipose tissue grafts for large defect filling.
Trash-basket epiphytes as secondary foundation species: a review of their distribution and effects on biodiversity and ecosystem functions
Authors: Ortega-Solis Gabriel , Díaz Iván A. , Mellado-Mansilla Daniela , Tejo Camila , Tello Francisco , Craven Dylan , Kreft Holger , Armesto Juan J.
Published: June 2021

Background

Secondary foundation species (FS) are organisms that inhabit ecosystems structurally defined by a primary foundation species, providing additional structure to habitats and communities. Trash-basket epiphytes (TBE) are secondary FS that enhance arboreal soil accumulation, providing shelter to animals, and rooting sites for plants. While their importance may vary across biomes, TBE have been overlooked as drivers of biodiversity and ecosystem functions. Here, we discuss the prevalence of TBE across biomes, their effects on biodiversity and ecosystem functions, and future research directions.

Methods

We performed a systematic literature review of articles, books and theses and collated and synthesised information about the taxonomic distribution of TBE, their effects on ecosystem functions, and reports of plant-animal and plant-plant interactions. Then, we analysed the global distribution of TBE using a generalized linear model and summarised two studies to assess their effects on soil invertebrates.

Results

We identified 120 publications describing 209 species of TBE. Most TBE belong to Araceae (43%), Polypodiaceae (23%), and Orchidaceae (14%) and occur in all tropical and southern temperate forests. TBE richness peaks in the South-American Pacific mangroves, Eastern Cordillera Real, and the Napo moist forests. TBE effects on ecosystem functions include arboreal soil accumulation, water retention and temperature regulation in the canopy, and nutrient leaching through stem-flow. TBE provide shelter to species in more than 97 animal families, including from invertebrates to mammals, while 72 vascular plants have been reported to root in arboreal soil of TBE.

Conclusions

TBE are a compelling group of model organisms that can be used to study ecological processes such as facilitation cascades, niche construction, extended phenotypes, or the effects of secondary FS on biodiversity and ecosystem functioning. TBE should also be included in forest management plans to enhance the availability of microhabitats in the canopy supporting its associated flora and fauna.
Dopamine release in nucleus accumbens core during social behaviors in mice
Authors: Dai Bing , Sun Fangmiao , Kuang Amy , Li Yulong , Lin Dayu
Published: June 2021

Social behaviors are among the most important and rewarding motivational behaviors. How dopamine, a “reward” signal, releases in the nucleus accumbens (NAc) during social behaviors has become a topic of interest for decades. However, limitations in early recording methods, such as microdialysis, prevented a complete understanding of moment-to-moment dopamine responses during social behaviors. Here, we employ a genetically encoded dopamine sensor, GRABDA2h, to record dopamine activity in the NAc core in mice and find acute changes in extracellular dopamine levels during all three phases of social behaviors: approach, investigation and consummation. Dopamine release during approach phase correlates with animal’s motivation towards the conspecific whereas its release during consummatory phase signals the valence of the experience. Furthermore, dopamine release during sexual and aggressive behaviors shows sex differences that correlate with the potential value of those experiences. Overall, our results reveal rich and temporally precise motivation and value information encoded by NAc dopamine during social behaviors and beyond.
Parvalbumin interneuron dendrites enhance gamma oscillations
Authors: Kriener Birgit , Hu Hua , Vervaeke Koen
Published: June 2021

Dendrites are important determinants of the input-output relationship of single neurons, but their role in network computations is not well understood. Here, we used a combination of dendritic patch-clamp recordings and in silico modeling to determine how dendrites of parvalbumin (PV)-expressing basket cells contribute to network oscillations in the gamma frequency band. Simultaneous soma-dendrite recordings from PV basket cells in the dentate gyrus revealed that the slope, or gain, of the dendritic input-output relationship is exceptionally low, thereby reducing the cell’s sensitivity to changes in its input. By simulating gamma oscillations in detailed network models, we demonstrate that the low gain is key to increase spike synchrony in PV neuron assemblies when cells are driven by spatially and temporally heterogeneous synaptic input. These results highlight the role of dendritic computations in synchronized network oscillations.
Parameter identifiability and model selection for sigmoid population growth models
Authors: Simpson Matthew J , Browning Alexander P , Warne David J , Maclaren Oliver J , Baker Ruth E
Published: June 2021

Sigmoid growth models, such as the logistic, Gompertz and Richards’ models, are widely used to study population dynamics ranging from microscopic populations of cancer cells, to continental-scale human populations. Fundamental questions about model selection and parameter estimation are critical if these models are to be used to make practical inferences. However, the question of parameter identifiability – whether a data set contains sufficient information to give unique or sufficiently precise parameter estimates – is often overlooked. We use a profile-likelihood approach to explore practical parameter identifiability using data describing the re-growth of hard coral. With this approach, we explore the relationship between parameter identifiability and model misspecification, finding that the logistic growth model does not suffer identifiability issues for the type of data we consider whereas the Gompertz and Richards’ models encounter practical non-identifiability issues. This analysis of parameter identifiability and model selection is important because different growth models are used within areas of the biological modelling literature without necessarily considering whether parameters are identifiable, or checking statistical assumptions underlying model adequacy. Standard practices that do not consider parameter identifiability can lead to unreliable or imprecise parameter estimates and potentially misleading mechanistic interpretations. While tools developed here focus on three standard sigmoid growth models only, our theoretical developments are applicable to any sigmoid growth model and any relevant data set. MATLAB implementations of all software are available onGitHub.
Why Environmental Biomarkers Work: Transcriptome-Proteome Correlations and Modeling of Multi-Stressor Experiments in the Marine BacteriumTrichodesmium
Authors: Walworth Nathan G. , Saito Mak A. , Lee Michael D. , McIlvin Matthew R. , Moran Dawn M. , Kellogg Riss M. , Fu Fei-Xue , Hutchins David A. , Webb Eric A.
Published: June 2021

Ocean microbial communities are important contributors to the global biogeochemical reactions that sustain life on Earth. The factors controlling these communities are being increasingly explored through the use of metatranscriptomic and metaproteomic environmental biomarkers, despite ongoing uncertainty about the coherence between RNA and protein signals. Using published proteomes and transcriptomes from the abundant colony-forming cyanobacteriumTrichodesmium(strainT. erythraeumIMS101) grown under varying Fe and/or P limitation and/or co-limitation in low and high CO2, we observed robust correlations of stress induced proteins and RNAs (i.e., those involved in transport and homeostasis) that can yield useful information on nutrient status under low and/or high CO2. Conversely, transcriptional and translational correlations of many other central metabolism pathways exhibit broad discordance. A cellular RNA and protein production/degradation model demonstrates how biomolecules with small initial inventories, such as environmentally responsive proteins, can achieve large increases in fold-change units, as opposed to those with higher basal expression and inventory such as metabolic systems. Microbial cells, due to their close proximity to the environment, tend to show large adaptive responses to environmental stimuli in both RNA and protein that result in transcript-protein correlations. These observations and model results demonstrate a multi-omic coherence for environmental biomarkers and provide the underlying mechanism for those observations, supporting the promise for global application in detecting responses to environmental stimuli in a changing ocean.
nzffdr: an R package to import, clean and update data from the New Zealand Freshwater Fish Database
Authors: Lee Finnbar , Young Nick
Published: June 2021

The New Zealand Freshwater Fish Database (NZFFD) is a repository of more than 155,000 records of freshwater fish observations from around New Zealand, maintained by the National Institute of Water and Atmospheric Research (NIWA). Records from the NZFFD can be downloaded using a web interface. The statistical computing language R is now widely used for data wrangling, analysis, and visualisation. Here, we present nzffdr, an open source R software package that: i) allows users to query and download data from the New Zealand Freshwater Fish Database directly in R, ii) provides functions to clean imported data, iii) facilitates the addition of information such as species names and Department of Conservation threat classification status, and iv) a workflow for visualising information from the NZFFD. The nzffdr package aims to standardise, simplify, and speed up a workflow likely already used in anad hocmanner by scientists across New Zealand and abroad.
Transfer rate of enveloped and non-enveloped viruses between fingerpads and surfaces
Authors: Anderson Claire E. , Boehm Alexandria B.
Published: June 2021

Fomites can represent a reservoir for pathogens, which may be subsequently transferred from surfaces to skin. In this study we aim to understand how different factors (including virus type, surface type, time since last handwash, and direction of transfer) affect virus transfer rates, defined as the fraction of virus transferred, between fingerpads and fomites. To determine this, 360 transfer events were performed with 20 volunteers using Phi6 (a surrogate for enveloped viruses) and MS2 (a surrogate for non-enveloped viruses), and three clean surfaces (stainless steel, painted wood, and plastic). Considering all transfer events (all surfaces and both transfer directions combined), the mean transfer rates of Phi6 and MS2 were 0.17 and 0.26, respectively. Transfer of MS2 was significantly higher than Phi6 (P<0.05). Surface type was a significant factor that affected the transfer rate of Phi6: Phi6 is more easily transferred to and from stainless steel and plastic than to and from painted wood. Direction of transfer was a significant factor affecting MS2 transfer rates: MS2 is more easily transferred from surfaces to fingerpads than from fingerpads to surfaces. Data from these virus transfer events, and subsequent transfer rate distributions, provide information which can be used to refine quantitative microbial risk assessments. This study is the first to provide a large-scale data set of transfer events with a surrogate for enveloped viruses, which extends the reach of the study to the role of fomites in the transmission of human enveloped viruses like influenza and SARS-CoV-2.

Importance

This study created the first large-scale data set for the transfer of enveloped viruses between skin and surfaces. The data set produced by this study provides information on modelling the distribution of enveloped and non-enveloped virus transfer rates, which can aid in the implementation of risk assessment models in the future. Additionally, enveloped and non enveloped viruses were applied to experimental surfaces in an equivalent matrix to avoid matrix effects, so results between different viral species can be directly compared without confounding effects of different matrices. Our results indicating how virus type, surface type, time since last handwash, and direction of transfer affect virus transfer rates can be used in decision-making processes to lower the risk of viral infection from transmission through fomites.
Regulation of GTPase function by autophosphorylation
Authors: Johnson Christian W. , Seo Hyuk-Soo , Terrell Elizabeth M. , KleinJan Fenneke , Gebregiworgis Teklab , Gasmi-Seabrook Genevieve M. C. , Geffken Ezekiel A. , Lakhani Jimit , Song Kijun , Popow Olesja , Paulo Joao A. , Liu Andrea , Mattos Carla , Marshall Christopher B. , Ikura Mitsuhiko , Morrison Deborah K. , Dhe-Paganon Sirano , Haigis Kevin M.
Published: June 2021

A unifying feature of the RAS superfamily is a functionally conserved GTPase cycle that proteins use to transition between active and inactive states. Here, we demonstrate that active site autophosphorylation of some small GTPases is an intrinsic regulatory mechanism that reduces nucleotide hydrolysis and enhances nucleotide exchange, thus altering the on/off switch that forms the basis for their signaling functions. Using x-ray crystallography, nuclear magnetic resonance spectroscopy, biolayer interferometry binding assays, and molecular dynamics on autophosphorylated mutants of H-RAS and K-RAS, we show that phosphoryl transfer from GTP requires dynamic movement of the switch II domain and that autophosphorylation promotes nucleotide exchange by opening of the active site and extraction of the stabilizing Mg. Finally, we demonstrate that autophosphorylated K-RAS exhibits altered effector interactions, including a reduced affinity for RAF proteins. Thus, autophosphorylation leads to altered active site dynamics and effector interaction properties, creating a pool of GTPases that are functionally distinct from the non-phosphorylated counterpart.
Bacterial response to spatial gradients of algal-derived nutrients in a porous microplate
Authors: Kim Hyungseok , Kimbrel Jeffrey A. , Vaiana Christopher A. , Wollard Jessica R. , Mayali Xavier , Buie Cullen R.
Published: June 2021

Abstract

Photosynthetic microalgae are responsible for 50% of the global atmospheric CO2 fixation into organic matter and hold potential as a renewable bioenergy source. Their metabolic interactions with the surrounding microbial community (the algal microbiome) play critical roles in carbon cycling, but due to methodological limitations, it has been challenging to examine how community is developed by spatial proximity to their algal host. Here we introduce a hydrogel-based porous microplate to co-culture algae and bacteria, where metabolites are constantly exchanged between the microorganisms while maintaining physical separation. In the microplate we found that the diatom Phaeodactylum tricornutum accumulated to cell abundances ~20 folds higher than under normal batch conditions due to constant replenishment of nutrients through the hydrogel. We also demonstrate that algal-associated bacteria, both single isolates and complex communities, responded to inorganic nutrients away from their host as well as organic nutrients originating from the algae in a spatially predictable manner. These experimental findings coupled with a mathematical model suggest that host proximity and algal culture growth phase impact bacterial community development in a taxon-specific manner through organic and inorganic nutrient availability. Our novel system presents a useful tool to investigate universal metabolic interactions between microbes in aquatic ecosystems.
INTRINSIC MOTOR NEURONE EXCITABILITY IS REDUCED IN SOLEUS AND TIBIALIS ANTERIOR OF OLDER ADULTS
Authors: Orssatto Lucas B. R. , Borg David N. , Blazevich Anthony J. , Sakugawa Raphael L. , Shield Anthony J. , Trajano Gabriel S.
Published: June 2021

Age-related deterioration within both motor neurones and monoaminergic systems should theoretically reduce neuromodulation by weakening motor neuronal persistent inward current (PIC) amplitude. However, this assumption remains untested. Surface electromyographic signals were collected using two 32-channel electrode matrices placed on soleus and tibialis anterior of 25 older adults (70±4years) and 17 young adults (29±5 years) to investigate motor unit discharge behaviours. Participants performed triangular-shaped plantar and dorsiflexion contractions to 20% of maximum torque at a rise-decline rate of 2%/s of each participant’s maximal torque. Pairwise and composite paired-motor unit analyses were adopted to calculate delta frequency (ΔF), which has been used to differentiate between the effects of synaptic excitation and intrinsic motor neuronal properties and is assumed to be proportional to PIC amplitude. Soleus and tibialis anterior motor units in older adults had lower ΔFs calculated with either the pairwise [−0.99 and −1.46 pps; −35.4 and − 33.5%, respectively] or composite (−1.18 and −2.28 pps; −32.1 and −45.2%, respectively) methods. Their motor units also had lower peak discharge rates (−2.14 and −2.03 pps; −19.7 and −13.9%, respectively) and recruitment thresholds (−1.50 and −2.06% of maximum, respectively) than young adults. These results demonstrate reduced intrinsic motor neurone excitability during low-force contractions in older adults, likely mediated by decreases in the amplitude of persistent inward currents. Our findings might be explained by deterioration in the motor neurones or monoaminergic systems and could contribute to the decline in motor function during ageing; these assumptions should be explicitly tested in future investigations.
Model sharing in the human medial temporal lobe
Authors: Glitz Leonie , Juechems Keno , Summerfield Christopher , Garrett Neil
Published: June 2021

Effective planning involves knowing where different actions will take us. However natural environments are rich and complex, leading to an exponential increase in memory demand as a plan grows in depth. One potential solution to this problem is to share the neural state transition functions used for planning between similar contexts. Here, we asked human participants to perform a sequential decision making task designed so that knowledge could be shared between some contexts but not others. Computational modelling showed that participants shared a model of state transitions between contexts where appropriate. fMRI data identified the medial temporal lobe as a locus for learning of state transitions, and within the same region, correlated BOLD patterns were observed in contexts where state transition information were shared. Finally, we show that the transition model is updated more strongly following the receipt of positive compared to negative outcomes, a finding that challenges conventional theories of planning which assume knowledge about our environment is updated independently of outcomes received. Together, these findings propose a computational and neural account of how information relevant for planning can be shared between contexts.
Pathogenic germline IKZF1 variant alters hematopoietic gene expression profiles
Authors: Brodie Seth A. , Khincha Payal P. , Giri Neelam , Bouk Aaron J. , Steinberg Mia , Dai Jieqiong , Jessop Lea , Donovan Frank X. , Chandrasekharappa Settara C. , de Andrade Kelvin C. , Maric Irina , Ellis Steven R. , Mirabello Lisa , Alter Blanche P. , Savage Sharon A.
Published: June 2021

IKZF1 encodes Ikaros, a zinc finger–containing transcription factor crucial to the development of the hematopoietic system. Germline pathogenic variants in IKZF1 have been reported in patients with acute lymphocytic leukemia and immunodeficiency syndromes. Diamond–Blackfan anemia (DBA) is a rare inherited bone marrow failure syndrome characterized by erythroid hypoplasia, associated with a spectrum of congenital anomalies and an elevated risk of certain cancers. DBA is usually caused by heterozygous pathogenic variants in genes that function in ribosomal biogenesis; however, in many cases the genetic etiology is unknown. We identified a germline IKZF1 variant, rs757907717 C > T, in identical twins with DBA-like features and autoimmune gastrointestinal disease. rs757907717 C > T results in a p.R381C amino acid change in the IKZF1 Ik-x isoform (p.R423C on isoform Ik-1), which we show is associated with altered global gene expression and perturbation of transcriptional networks involved in hematopoietic system development. These data suggest that this missense substitution caused a DBA-like syndrome in this family because of alterations in hematopoiesis, including dysregulation of networks essential for normal erythropoiesis and the immune system.
Sacrificing mackerel for sustainability: case study of a local cultural festival in northeastern Taiwan
Authors: Wu Ying-Ching
Published: June 2021

Purpose

The purpose of this paper is to describe how people in a coastal community act upon anxieties about overexploitation of a shared resource and their attempts to ease the moral tension caused by the rapid industrialization of their fishery. This anthropological study contributes to the cross-disciplinary discussion of community-based resource management.

Design/methodology/approach

The study is based on ethnographic fieldwork done at the Nanfang'ao port located in northeastern Taiwan. This port has several prosperous offshore fisheries including a mackerel fishery. The mackerel fishery has undergone important transformations in recent decades. The first was a total transformation of fishing methods in 2013. The second was the government's formulation of the “Regulations for Fishing Vessels Catching Mackerels and Jacks,” implemented in 2014. This research illustrates how people in a community take various approaches to pursue sustainability for the human beings and the more-than-human world.

Findings

In Nanfang'ao port, local people have developed a meaningful cultural festival through the integration of various symbols and rituals from different contexts in an effort to call attention to moral issues associated with the mackerel fishery.

Originality/value

This research contributes to the discussion on community resource management of marine fishery.
Integration of TQM and ERP to enhance organizational performance and excellence: empirical evidence from public sector using SEM
Authors: Al-Dhaafri Hassan , Alosani Mohammed
Published: June 2021

Purpose

The study aims to examine the joint effect of total quality management (TQM), enterprise resource planning (ERP) and organizational performance on organizational excellence.

Design/methodology/approach

To achieve the goal of this study through the hypothesized model, a survey questionnaire research design was employed. The data were collected from a Dubai Police organization. Out of 550 questionnaires, 320 questionnaires were returned. The structural equation modelling (SEM) partial least squares approach was used to analyze the data for measurement and structural models.

Findings

The statistical results confirmed the positive and significant effects of TQM, ERP and organizational performance on organizational excellence. The mediation role of organizational performance between TQM, ERP and organizational excellence also was confirmed.

Practical implications

Throughout this study, further details and valuable implications have been discussed. Findings provide several practical implications. Findings also help practitioners and managers make proper decisions when implementing TQM, ERP and excellence practices in their organizations. With the joint effect of TQM, ERP and organizational performance, organizations can achieve maximum strong excellence and remain in a competitive market. This current study presents potential to be used in didactical initiatives.

Originality/value

This study is a unique empirical research that examines the joint effect of TQM, ERP and performance on excellence relationships. In other words, the current study is one of the few studies that investigate the mediating role of organizational performance beside the organizational excellence as the ultimate variable in developing country, specifically in UAE.
Scale‐dependent shifts in functional and phylogenetic structure of Mediterranean island plant communities over two centuries
Authors: Zhang Chunhui , Cadotte Marc W. , Chiarucci Alessandro , Loreau Michel , Willis Charles G. , Si Xingfeng , Li Lanping , Cianciaruso Marcus V.
Published: June 2021

Since the Industrial Revolution, the rapid global population and economic expansion have had tremendous impacts on biodiversity across spatial scales, especially for islands. While changes in species richness are easily inferred, the impact of human activity on the underlying community assembly processes has been difficult to ascertain because of lack of long‐term community data.

Here, we document how the manifestations of plant community assembly have changed over time and space in a Mediterranean archipelago, using a long‐term dataset of plant species composition on 16 Tuscan islands sampled across two centuries. The community structure of Mediterranean island plant communities was assessed by integrating species' trait and evolutionary distances.

We found that, with increasing island area, the functional and phylogenetic structure of plant communities shifted from clustered early (1830–1950) to overdispersed more recently (1951–2015). On large islands, extirpated species were generally more phylogenetically or functionally similar to remaining residents than expected by chance, while colonists were generally more distantly related to residents. The extinction of similar species and the colonization of dissimilar species drove plant communities towards overdispersion.

Synthesis. We provide evidence that plant community assembly on islands has dramatically changed following increased human impacts during the last two centuries, and that this change is shaped by the scale dependency of species extinctions and colonizations. Our results reveal accelerated species replacements of closely related residents by distant colonists on large islands over time, reflecting changes in community assembly and which could alter the functioning of island ecosystems in the future.