bluuebunny/crossref_metadata_2025 huggingface dataset:
Interpreting Null Models of Resting-State Functional MRI
Authors: Liégeois Raphaël , Yeo B. T. Thomas , Van De Ville Dimitri
Published: March 2021

Null models are necessary for assessing whether a dataset exhibits non-trivial statistical properties. These models have recently gained interest in the neuroimaging community as means to explore dynamic properties of functional Magnetic Resonance Imaging (fMRI) time series. Interpretation of null-model testing in this context may not be straightforward because (i) null hypotheses associated to different null models are sometimes unclear and (ii) fMRI metrics might be ‘trivial’, i.e. preserved under the null hypothesis, and still be useful in neuroimaging applications. In this commentary, we review several commonly used null models of fMRI time series and discuss the interpretation of the corresponding tests. We argue that, while null-model testing allows for a better characterization of the statistical properties of fMRI time series and associated metrics, it should not be considered as a mandatory validation step to assess their relevance in neuroimaging applications.
A novel theoretical framework for simultaneous measurement of excitatory and inhibitory conductances
Authors: Müller-Komorowska Daniel , Parabucki Ana , Elyasaf Gal , Katz Yonatan , Beck Heinz , Lampl Ilan
Published: March 2021

Firing of neurons throughout the brain is determined by the precise relations between excitatory and inhibitory inputs and disruption of their balance underlies many psychiatric diseases. Whether or not these inputs covary over time or between repeated stimuli remains unclear due to the lack of experimental methods for measuring both inputs simultaneously. We developed a new analytical framework for instantaneous and simultaneous measurements of both the excitatory and inhibitory neuronal inputs during a single trial under current clamp recording. This can be achieved by injecting a current composed of two high frequency sinusoidal components followed by analytical extraction of the conductances. We demonstrate the ability of this method to measure both inputs in a single trial under realistic recording constraints and from morphologically realistic CA1 pyramidal model cells. Experimental implementation of our new method will facilitate the understanding of fundamental questions about the health and disease of the nervous system.

Classification

System Neuroscience, Cellular and Molecular Neuroscience
Impact of blood storage conditions on the transcript profile of plasma cell-free RNA
Authors: Sun Jinghua , Yang Xi , Wang Taifu , Xing Yanru , Chen Haixiao , Zhu Sujun , Zeng Juan , Zhou Qing , Chen Fang , Zhang Xiuqing , Wang Wen-Jing
Published: March 2021

BACKGROUND

Plasma cell-free RNA (cfRNA) are potential biomarkers for disease prediction and diagnosis. However, pre-analysis factors, such as the delay in blood processing and storage may lead to unreliable results, though no study has systematically evaluated the effect of blood storage conditions on the whole transcriptome of plasma cfRNA yet.

METHODS

We collected peripheral blood samples from four healthy subjects and allowed them to stand at room temperature or 4◻ for different time periods (0h, 2h, 6h and 24h) prior to plasma separation. Then, plasma cfRNA stability was evaluated by measuring expression changes of cell-free mRNA, lncRNA and miRNA using high throughput sequencing-based profiling. Finally, their paired leukocyte RNA data were integrated to depict the effect of leukocytes on plasma cfRNA during storage.

RESULTS

Plasma mRNA and lncRNA presented high correlations (Pearson R2≥ 0.8) and fewer variations when blood was stored at 4◻ for 6 hours or stored at RT for 2 hours. miRNA was more stable, with minimal R2of 0.86 at 4◻ for at least 24 hours or at RT for 6 hours. Correlations of plasma RNA and leukocyte RNA increased with the incubation time, and the relative proportion of neutrophils in plasma grown from 14.3% to 61.2% at RT (P= 0.004), indicating leukocyte RNA contamination. Besides, the tissue enriched genes in plasma were down-regulated with the extension of storage time.

CONCLUSIONS

Our results characterized the effects of short-term storage of blood samples on plasma cfRNA, which will facilitate further researches or clinical applications to avoid bias resulting from sample processing.
Facilitating population genomics of non-model organisms through optimized experimental design for reduced representation sequencing
Authors: Christiansen Henrik , Heindler Franz M. , Hellemans Bart , Jossart Quentin , Pasotti Francesca , Robert Henri , Verheye Marie , Danis Bruno , Kochzius Marc , Leliaert Frederik , Moreau Camille , Patel Tasnim , Van de Putte Anton P. , Vanreusel Ann , Volckaert Filip A. M. , Schön Isa
Published: March 2021

Genome-wide data are invaluable to characterize differentiation and adaptation of natural populations. Reduced representation sequencing (RRS) subsamples a genome repeatedly across many individuals. However, RRS requires careful optimization and fine-tuning to deliver high marker density while being cost-efficient. The number of genomic fragments created through restriction enzyme digestion and the sequencing library setup must match to achieve sufficient sequencing coverage per locus. Here, we present a workflow based on published information and computational and experimental procedures to investigate and streamline the applicability of RRS. In an iterative process genome size estimates, restriction enzymes and size selection windows were tested and scaled in six classes of Antarctic animals (Ostracoda, Malacostraca, Bivalvia, Asteroidea, Actinopterygii, Aves). Achieving high marker density would be expensive in amphipods, the malacostracan target taxon, due to the large genome size. We propose alternative approaches such as mitogenome or target capture sequencing for this group. Pilot libraries were sequenced for all other target taxa. Ostracods, bivalves, sea stars, and fish showed overall good coverage and marker numbers for downstream population genomic analyses. In contrast, the bird test library produced low coverage and few polymorphic loci, likely due to degraded DNA. Prior testing and optimization are important to identify which groups are amenable for RRS and where alternative methods may currently offer better cost-benefit ratios. The steps outlined here are easy to follow for other non-model taxa with little genomic resources, thus stimulating efficient resource use for the many pressing research questions in molecular ecology.
A recombinant receptor-binding domain in trimeric form generates completely protective immunity against SARS-CoV-2 infection in nonhuman primates
Authors: Yang Limin , Tian Deyu , Han Jian-bao , Fan Wenhui , Zhang Yuan , Li Yunlong , Sun Wenqiang , Wei Yanqiu , Tian Xiaodong , Yu Dan-dan , Feng Xiao-li , Cheng Gong , Zheng Yong-tang , Bi Yuhai , Liu Wenjun
Published: March 2021

Safe and effective vaccination is critical to combatting the COVID-19 pandemic. Here, we developed a trimeric SARS-CoV-2 receptor-binding domain (RBD) subunit vaccine candidate that simulates the natural structure of the spike (S) trimer glycoprotein. Immunization with RBD-trimer induced robust humoral and cellular immune responses and a high level of neutralizing antibodies that were maintained for at least 4 months. Moreover, the antibodies that were produced in response to the vaccine effectively neutralized the SARS-CoV-2 501Y.V2 variant. Of note, when the titers of the antibodies dropped to a sufficiently low level, only one boost quickly activated the anamnestic immune response, resulting in complete protection against the SARS-CoV-2 challenge inrhesus macaqueswithout typical histopathological changes or viral replication in the lungs and other respiratory tissues. Our results indicated that immunization with SARS-CoV-2 RBD-trimer could raise long-term and broad immunity protection in nonhuman primates, thereby offering an optimal vaccination strategy against COVID-19.
High-resolution 3D reconstruction of human oocytes using FIB-SEM
Authors: Trebichalská Zuzana , Javůrek Jakub , Tatíčková Martina , Kyjovská Drahomíra , Kloudová Soňa , Otevřel Pavel , Hampl Aleš , Holubcová Zuzana
Published: March 2021

The oocyte plays a pivotal role in the reproduction of our species. Nevertheless, its biology remains poorly understood. Electron microscopy is traditionally used to inspect the ultrastructure of female gametes. However, two-dimensional micrographs contain only fragmentary information about the spatial organization of the complex oocyte cytoplasm. Here, we employed the Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) to explore human oocyte intracellular morphology in three dimensions (3D). Volume reconstruction from high-resolution image stacks provided an unprecedented view of ooplasmic architecture. Organelle distribution patterns observed in 9 donor oocytes, representing 3 maturational stages, documented structural changes underlying the process by which the egg acquires developmental competence. 3D image segmentation was performed to extract information about distinct organelle populations. The quantitative analysis of the organelle abundance revealed that mitochondrion occupies ~ 4.26 % of the maturing oocyte cytoplasm. This proof-of-concept study demonstrates the potential of FIB-SEM imaging to study human oocyte morphology.
Dissolved organic matter from tropical peatlands impacts shelf sea light availability on coral reefs in the Singapore Strait, Southeast Asia
Authors: Martin Patrick , Sanwlani Nivedita , Lee Tiffany Wan Qi , Wong Joel Meng Cheng , Chang Kristy , Wong Elizabeth Wing-See , Liew Soo Chin
Published: March 2021

Shelf seas provide valuable ecosystem services, but their productivity and ecological functioning depend critically on sunlight transmitted through the water column. Anthropogenic reductions in underwater light availability are thus recognized as a serious threat to coastal habitats. The flux of strongly light-absorbing coloured dissolved organic matter (CDOM) from land to sea may have increased world-wide, but how this has altered the availability and spectral quality of light in shelf seas remains poorly known. Here, we present time-series data from the Sunda Shelf in Southeast Asia, where the monsoon-driven reversal in ocean currents supplies water enriched in CDOM from tropical peatlands for part of the year, resulting in 5–10-fold seasonal variation in light absorption by CDOM. We show that this terrigenous CDOM can dominate underwater light absorption at wavelengths up to 500 nm, and shift in the underwater irradiance spectrum towards longer wavelengths. The seasonal presence of terrigenous CDOM also causes the depth of 10% light penetration to shoal by 1–5 m, or 10–45%. We further estimate that on average 0.6 m, or 25%, of this terrigenous CDOM-mediated shoaling might be attributable to the enhanced loss of dissolved organic matter caused by peatland disturbance. We show that the seasonal change in the light environment is correlated with photo-acclimation by phytoplankton, and infer that terrigenous CDOM likely contributes to limiting the depth distribution of photosynthetic corals. Our results thus reveal an ecologically important but largely overlooked impact of human modifications to carbon fluxes that is likely becoming increasingly important in coastal seas.
Nuclear export of the pre-60S ribosomal subunit through single nuclear pores observed in real time
Authors: Ruland Jan Andreas , Krüger Annika Marie , Dörner Kerstin , Bhatia Rohan , Wirths Sabine , Pòetes Daniel , Kutay Ulrike , Siebrasse Jan Peter , Kubitscheck Ulrich
Published: March 2021

Ribosomal subunit biogenesis within mammalian cells initiates in the nucleolus with the assembly of a 90S precursor particle, which is subsequently split into the pre-40S and pre-60S subunits. During further processing steps, pre-ribosomal subunits are loaded with export receptors, which enables their passage through the pore complexes (NPCs) into the cytoplasm. Here export factors are released and both subunits can form a mature ribosome. Ribosomal biogenesis has been studied in great detail by biochemical, genetic and electron microscopic approaches, however, until now live cell data on the in vivo kinetics are still missing.

We analysed export kinetics of the large ribosomal subunit (“pre-60S particle”) through single NPCs in living human cells. To assess the in vivo dynamics of this process, we established a stable cell line co-expressing Halo-tagged eIF6 and GFP-fused NTF2 to simultaneously label ribosomal 60S subunits (eIF6) and NPCs (NTF2). By combining single molecule tracking and super resolution confocal microscopy in a highly customized microscopic setup, we visualized the dynamics of single pre-60S particles during the interaction with and export through single NPCs. In this way we obtained unprecedented insights into this key cellular process.

Our results revealed that for export events, maximum particle accumulation is found in the centre of the pore, while unsuccessful export terminates within the nuclear basket. The export process takes place with a single rate limiting step and an export dwell time of~24 milliseconds. Only about 1/3 of attempted export events were successful. Given the molecular mass of the pre-60S particles our results show that the mass flux through a single NPC can reach up to ~125 MDa·s−1in vivo.
Conserved organ-specific microbial assemblages in different populations of a terrestrial crab
Authors: Bacci Giovanni , Fratini Sara , Meriggi Niccolò , Cheng Christine L. Y. , Ng Ka Hei , Pindo Massimo , Iannucci Alessio , Mengoni Alessio , Cavalieri Duccio , Cannicci Stefano
Published: March 2021

Brachyuran crabs originated in the oceans and evolved specific morphological and physiological adaptations to live in freshwater, intertidal and even terrestrial habitats but the role of a selection mechanism involving symbiotic microorganisms long these colonization processes are not known. In this work we investigated the associated microbiota of three populations of a terrestrial brachyuran crab,Chiromantes haematocheir, to find evidence of a conserved crab-specific microbiome unrelated to the population of origin and dissimilar from environmental microbial assemblages. Bacterial 16S rRNA gene and fungal ITS sequences were obtained from selected crab organs and environmental matrices to profile microbial communities. In spite of the presence of truly marine larval stages and no gregarious behaviour, favouring microbiota exchanges, we found common, organ-specific microbiota, associated to the gut and the gills of the crabs (with more than 15% of the genera detected specifically enriched only in one organ). Our results suggest an early establishment of a new common, stable microbiota in the transition from water to land.
Members of a highly widespread bacteriophage family are hallmarks of metabolic syndrome gut microbiomes
Authors: de Jonge Patrick A. , Wortelboer Koen , Scheithauer Torsten P.M. , van den Born Bert-Jan H. , Zwinderman Aeilko H. , Nobrega Franklin L. , Dutilh Bas E. , Nieuwdorp Max , Herrema Hilde
Published: March 2021

There is significant interest in altering the course of cardiometabolic disease development via the gut microbiome. Nevertheless, the highly abundant phage members -which impact gut bacteria- of the complex gut ecosystem remain understudied. Here, we characterized gut phageome changes associated with metabolic syndrome (MetS), a highly prevalent clinical condition preceding cardiometabolic disease. MetS gut phageome populations exhibited decreased richness and diversity, but larger inter-individual variation. These populations were enriched in phages infectingBacteroidaceaeand depleted in those infectingRuminococcaeae. Differential abundance analysis identified eighteen viral clusters (VCs) as significantly associated with either MetS or healthy phageomes. Among these are a MetS-associatedRoseburiaVC that is related to healthy control-associatedFaecalibacteriumandOscillibacterVCs. Further analysis of these VCs revealed theCandidatus Heliusviridae, a highly widespread gut phage lineage found in 90+% of the participants. The identification of the temperateCa. Heliusviridaeprovides a novel starting point to a better understanding of the effect that phages have on their bacterial hosts and the role that this plays in MetS.
Taming strong selection with large sample sizes
Authors: Krukov Ivan , Gravel Simon
Published: March 2021

1

The fate of mutations and the genetic load of populations depend on the relative importance of genetic drift and natural selection. In addition, the accuracy of numerical models of evolution depends on the strength of both selection and drift: strong selection breaks the assumptions of the nearly neutral model, and drift coupled with large sample sizes breaks Kingman’s coalescent model.

Thus, the regime with strong selection and large sample sizes, relevant to the study of pathogenic variation, appears particularly daunting. Surprisingly, we find that the interplay of drift and selection in that regime can be used to define asymptotically closed recursions for the distribution of allele frequencies that are accurate well beyond the strong selection limit.

Selection becomes more analytically tractable when the sample sizenis larger than twice the population-scaled selection coefficient:n≥ 2Ns(4Nsin diploids). That is, when the expected number of coalescent events in the sample is larger than the number of selective events. We construct the relevant transition matrices, show how they can be used to accurately compute distributions of allele frequencies, and show that the distribution of deleterious allele frequencies is sensitive to details of the evolutionary model.
Activity ofPlasmodium vivaxpromoter elements inPlasmodium knowlesi, and a centromere-containing plasmid that expresses NanoLuc throughout the parasite life cycle
Authors: Moraes Barros Roberto R. , Thawnashom Kittisak , Gibson Tyler J. , Armistead Jennifer S. , Caleon Ramoncito L. , Kaneko Miho , Kite Whitney A. , Mershon J. Patrick , Brockhurst Jacqueline K. , Engels Theresa , Lambert Lynn , Orr-Gonzalez Sachy , Adams John H. , Sá Juliana M. , Kaneko Osamu , Wellems Thomas E.
Published: March 2021

Background

Plasmodium knowlesiis now the major cause of human malaria in Malaysia, complicating malaria control efforts that must attend to the elimination of multiplePlasmodiumspecies. Recent advances in the cultivation ofP. knowlesierythrocytic-stage parasitesin vitro, transformation with exogenous DNA, and infection of mosquitoes with gametocytes from culture have opened up studies of this pathogen without the need for resource-intensive and costly non-human primate (NHP) models. For further understanding and development of methods for parasite transformation in malaria research, this study examined the activity of various trans-species transcriptional control sequences and the influence ofPlasmodium vivaxcentromeric (pvcen) repeats in plasmid-transfectedP. knowlesiparasites.

Methods

In vitrocultivatedP. knowlesiparasites were transfected with plasmid constructs that incorporatedP. vivaxorPlasmodium falciparum5’ UTRs driving the expression of bioluminescence markers (firefly luciferase or Nanoluc). Promoter activities were assessed by bioluminescence, and parasites transformed with human resistant allele dihydrofolate reductase-expressing plasmids were selected using antifolates. The stability of transformants carryingpvcen-stabilized episomes was assessed by bioluminescence over a complete parasite life cycle through a rhesus macaque monkey, mosquitoes, and a second rhesus monkey.

Results

Luciferase expression assessments show that certainP. vivaxpromoter regions, not functional in the more evolutionarily-distantP. falciparum, can drive transgene expression inP. knowlesi. Further,pvcenrepeats may improve the stability of episomal plasmids inP. knowlesiand support detection of NanoLuc-expressing elements over the full parasite life cycle from rhesus macaque monkeys toAnopheles dirusmosquitoes and back again to monkeys. In assays of drug responses to chloroquine, G418 and WR9910, antimalarial half-inhibitory concentration (IC50) values of blood stages measured by NanoLuc activity proved comparable to IC50values measured by the standard SYBR Green method.

Conclusion

All threeP. vivaxpromoters tested in this study functioned inP. knowlesiwhereas two of the three were inactive inP. falciparum. NanoLuc-expressing, centromere-stabilized plasmids may support high-throughput screenings ofP. knowlesifor new antimalarial agents, including compounds that can block the development of mosquito- and/or liver-stage parasites.
Comparative analysis of public RNA-sequencing data from human intestinal enteroid (HIEs) infected with enteric RNA viruses identifies universal and virus-specific epithelial responses
Authors: Cieza RJ , Golob JL , Colacino JA , Wobus CE
Published: March 2021

Acute gastroenteritis (AGE) has a significant disease burden on society. Noroviruses, rotaviruses and astroviruses are important viral causes of AGE but are relatively understudied enteric pathogens. Recent developments in novel biomimetic human models of enteric disease are opening new possibilities for studying human-specific hostmicrobe interactions. Human intestinal enteroids (HIE), which are epithelium-only intestinal organoids derived from stem cells isolated from human intestinal biopsy tissues, have been successfully used to culture representative norovirus, rotavirus and astrovirus strains. Previous studies investigated host-virus interactions at the intestinal epithelial interface by individually profiling the epithelial transcriptional response to a member of each virus family by RNA sequencing (RNA-seq). We used these publicly available datasets to uniformly analyze these data and identify shared and unique transcriptional changes in the human intestinal epithelium upon human enteric virus infections.
Osteoblast-Specific Wnt Secretion is Required for Skeletal Homeostasis and Loading-Induced Bone Formation in Adult Mice
Authors: Lawson Lisa Y. , Brodt Michael D. , Migotsky Nicole , Chermside-Scabbo Christopher , Palaniappan Ramya , Silva Matthew J.
Published: March 2021

Wnt signaling is critical to many aspects of skeletal regulation, but the importance of Wnt ligands in adult bone homeostasis and the anabolic response to mechanical loading is not well documented. We inhibited Wnt ligand secretion in adult (5-mo) mice using a systemic (drug) and a bone-targeted (genetic) approach, and subjected them to axial tibial loading to induce lamellar bone formation. Mice treated with the porcupine inhibitor WNT974 exhibited a decrease in bone formation in non-loaded limbs as well as a 54% decline in the periosteal bone formation response to tibial loading. Similarly, within 1-2 weeks of Wls deletion in osteoblasts (Osx-CreERT2;WlsF/Fmice), skeletal homeostasis was altered with decreased bone formation and increased resorption, and the anabolic response to loading was reduced 65% compared to control (WlsF/F). These findings establish a requirement for Wnt ligand secretion by osteoblasts for adult bone homeostasis and the anabolic response to mechanical loading.
Modulation of taste sensitivity by the olfactory system inDrosophila
Authors: Junca Pierre , Stanley Molly , Musso Pierre-Yves , Gordon Michael D
Published: March 2021

An animal’s sensory percepts are not raw representations of the outside world. Rather, they are constructs influenced by many factors including the species, past experiences, and internal states. One source of perceptual variability that has fascinated researchers for decades is the effect of losing one sensory modality on the performance of another1. Typically, dysfunction of one sense has been associated with elevated function of others, creating a type of sensory homeostasis2. For example, people with vision loss have been reported to demonstrate enhanced tactile and auditory functions, and deafness has been associated with heightened attention to visual inputs for communication3,4. By contrast, smell and taste—the two chemosensory modalities—are so intrinsically linked in their contributions to flavor that loss of smell is often anecdotally reported as leading to deficiencies in taste5–8. However, human studies specifically examining taste are mixed and generally do not support this widely-held belief, and data from animal models is largely lacking9. Here, we examine the impact of olfactory dysfunction on taste sensitivity inDrosophila melanogaster. We find that partial loss of olfactory input (hyposmia) dramatically enhances flies’ sensitivity to both appetitive (sugar, low salt) and aversive (bitter, high salt) tastes. This taste enhancement is starvation-independent and occurs following suppression of either first- or second-order olfactory neurons. Moreover, optogenetically increasing olfactory inputs reduces taste sensitivity. Finally, we observed that taste enhancement is not encoded in the activity of peripheral gustatory sensory neurons, but is associated with elevated sugar responses in protocerebrum anterior medial (PAM) dopaminergic neurons of the mushroom bodies. These results suggest a level of homeostatic control over chemosensation, where flies compensate for lack of olfactory input by increasing the salience of taste information.
Population codes enable learning from few examples by shaping inductive bias
Authors: Bordelon Blake , Pehlevan Cengiz
Published: March 2021

Learning from a limited number of experiences requires suitable inductive biases. To identify how inductive biases are implemented in and shaped by neural codes, we analyze sample-efficient learning of arbitrary stimulus-response maps from arbitrary neural codes with biologically-plausible readouts. We develop an analytical theory that predicts the generalization error of the readout as a function of the number of observed examples. Our theory illustrates in a mathematically precise way how the structure of population codes shapes inductive bias, and how a match between the code and the task is crucial for sample-efficient learning. We observe that many different codes can support the same inductive bias. By analyzing recordings from the mouse primary visual cortex, we demonstrate that biological codes have lower total activity than other codes with identical bias. Using these mouse primary visual cortex responses, we demonstrate the existence of an efficiency bias towards low frequency orientation discrimination tasks for grating stimuli and low spatial frequency reconstruction tasks for natural images. We reproduce the discrimination bias in a simple model of primary visual cortex, and further show how invariances in the code to certain stimulus variations alter learning performance. We extend our methods to time-dependent neural codes and predict the sample efficiency of readouts from recurrent networks. Finally, we discuss implications of our theory in the context of recent developments in neuroscience and artificial intelligence. Overall, our study provides a concrete method for elucidating inductive biases of the brain and promotes sample-efficient learning as a general normative coding principle.
A systematic structural comparison of all solved small proteins (4-6 kDa) reveals the weight of disulfide bonds in proteins’ foldability
Authors: Moreira Mariana H. , Almeida Fabio C. L. , Domitrovic Tatiana , Palhano Fernando L.
Published: March 2021

Defensins are small proteins, usually ranging from 4 to 6 kDa, amphipathic, disulfide-rich, and with a small or even absent hydrophobic core. Since a hydrophobic core is generally found in globular proteins that fold in an aqueous solvent, the peculiar fold of defensins can challenge tertiary protein structure predictors. We performed a PDB-wide survey of small proteins (4-6 kDa) to understand the similarities of defensins with other small disulfide-rich proteins. We found no differences when we compared defensins with non-defensins regarding the proportion and exposition to the solvent of apolar, polar, and charged residues. Then we divided all small proteins (4-6 kDa) deposited in PDB into two groups, one group with at least one disulfide bond (bonded, defensins included) and another group without any disulfide bond (unbonded). The group of bonded proteins presented apolar residues more exposed to the solvent than the unbonded group. Theab initioalgorithm for tertiary protein structure prediction Robetta was more accurate to predict unbonded than bonded proteins. Our work highlights one more layer of complexity for the tertiary protein prediction structure: small disulfide-rich proteins’ ability to fold even with a poor hydrophobic core.
Coughs, Colds and “Freshers’ Flu” Survey in the University of Cambridge, 2007-2008
Authors: Eames Ken TD , Tang Maria L , Hill Edward M , Tildesley Michael J , Read Jonathan M , Keeling Matt J , Gog Julia R
Published: March 2021

Universities provide many opportunities for the spread of infectious respiratory illnesses. Students are brought together into close proximity from all across the world and interact with one another in their accommodation, through lectures and small group teaching and in social settings. The COVID-19 global pandemic has highlighted the need for sufficient data to help determine which of these factors are important for infectious disease transmission in universities and hence control university morbidity as well as community spillover. We describe the data from a previously unpublished self-reported university survey of coughs, colds and flu-like symptoms collected in Cambridge, UK, during winter 2007-2008. The online survey collected information on symptoms and socio-demographic, academic and lifestyle factors. There were 1076 responses, 97% from University of Cambridge students (5.7% of the total university student population), 3% from staff and <1% from other participants, reporting onset of symptoms between September 2007 and March 2008. Undergraduates are seen to report symptoms earlier in the term than postgraduates; differences in reported date of symptoms are also seen between subjects and accommodation types, although these descriptive results could be confounded by survey biases. Despite the historic and exploratory nature of the study, this is one of few recent detailed datasets of flu-like infection in a university context and is especially valuable to share now to improve understanding of potential transmission dynamics in universities during the current COVID-19 pandemic.
Mutual interaction between Visual Homeostatic Plasticity and Sleep in Adult Humans
Authors: Menicucci Danilo , Lunghi Claudia , Zaccaro Andrea , Morrone Maria Concetta , Gemignani Angelo
Published: March 2021

Sleep and plasticity are highly interrelated, as sleep slow oscillations and sleep spindles are associated with consolidation of Hebbian-based processes. However, in adult humans, visual cortical plasticity is mainly sustained by homeostatic mechanisms, for which the role of sleep is still largely unknown. Here we demonstrate that non-REM sleep stabilizes homeostatic plasticity of ocular dominance induced in adult humans by short-term monocular deprivation: the counter intuitive and otherwise transient boost of the deprived eye was preserved at the morning awakening (>6 hours after deprivation). Subjects exhibiting a stronger boost of the deprived eye after sleep had increased sleep spindle density in frontopolar electrodes, suggesting the involvement of distributed processes. Crucially, the individual susceptibility to visual homeostatic plasticity soon after deprivation correlated with the changes in sleep slow oscillations and spindle power in occipital sites, consistent with a modulation in early occipital visual cortex.
Contact-tracing in cultural evolution: a Bayesian mixture model to detect geographic areas of language contact
Authors: Ranacher Peter , Neureiter Nico , van Gijn Rik , Sonnenhauser Barbara , Escher Anastasia , Weibel Robert , Muysken Pieter , Bickel Balthasar
Published: March 2021

When speakers of two or more languages interact, they are likely to influence each other: contact leaves traces in the linguistic record, which in turn can reveal geographic areas of past human interaction and migration. However the complex, multi-dimensional nature of contact has hindered the development of a rigorous methodology for detecting its traces. Specifically, other factors may contribute to similarities between languages. Inheritance (a property is passed from an ancestor to several descendant languages), and universal preference (a property is universally preferred), may both overshadow contact signals. How can we find geographic contact areas in language data, while accounting for the confounding effects of inheritance and universal preference? We presentsBayes, an algorithm for Bayesian clustering in the presence of confounding effects. The algorithm learns which similarities in a set of features are better accounted for by confounders, and which are due to contact effects. Contact areas are free to take any shape or size, but an explicit geographic prior ensures their spatial coherence. We test the clustering method on simulated data and apply it in two case studies to reveal language contact in South America and the Balkans. Our results are supported by —mostly qualitative— findings from previous studies. While we focus on the specific problem of language contact, the method can also be used to uncover other traces of shared history in cultural evolution, and more generally, to reveal latent spatial clusters in the presence of confounders.
Schizophrenia Risk Proteins ZNF804A and NT5C2 Interact at Synapses
Authors: Aabdien Afra , Sichlinger Laura , Gatford Nicholas J.F. , Raval Pooja , Jones Madeleine R. , Tanangonan Lloyd , Powell Timothy R. , Duarte Rodrigo R.R. , Srivastava Deepak P.
Published: March 2021

The zinc finger protein 804A (ZNF804A) and the 5′-nucleotidase cytosolic II (NT5C2) genes have been identified as robust susceptibility genes in large-scale genome-wide association studies of schizophrenia. The ZNF804A and NT5C2 proteins are highly expressed in developing and mature cortical neurons. ZNF804A has been implicated in regulating the development of neuronal morphology; it localises to synapses and is required for activity-dependent modifications of dendritic spines. NT5C2 has been shown to regulate 5′ adenosine monophosphate-activated protein kinase activity and implicated in influencing protein synthesis in neural progenitor cells. But despite these findings, a better understanding of the role these proteins play in regulating neuronal function is needed. A recent yeast two-hybrid screen has identified ZNF804A and NT5C2 as potential interacting proteins, but whether this occursin situ; and moreover, in cortical neurons, is unknown. Here we show that ZNF804A and Nt5C2 colocalise and interact in hEK293T cells. Furthermore, their rodent homolouges, ZFP804A and NT5C2, specifically colocalise at synapses and form a protein complex in cortical neurons. Knockdown ofZfp804AorNt5c2resulted in a significant decrease in synaptic expression of both proteins, suggesting that both proteins are required for the synaptic targeting of each other. Taken together, these data indicate that ZNF804A/ZFP804A and NT5C2 interact together in cortical neurons and indicate that these GWAS risk factors may function as a complex to regulate neuronal function.
Building reusable phage and antibiotic treatments via exploitation of bacteria-phage coevolutionary dynamics
Authors: Gurney James , Brown Sam P.
Published: March 2021

People with chronic (long-lasting) infections face the problem that treatment options diminish in time as the pathogen evolves increasing resistance. To address this challenge, we exploit phage and bacterial co-evolution, producing dynamic selection pressures that can return the pathogen to a state of susceptibility to the initial (regulator-approved) therapy. We show that phage OMKO1 alone triggers Arms Race Dynamic (ARD) co-evolution with the pathogenPseudomonas aeruginosa, leading to generalized phage resistance and crucially – failure at reuse. In contrast, co-administration of the phage with antibiotics triggers Fluctuating Selection Dynamics (FSD) co-evolution, allowing for effective reuse after 20 days of treatment. We pursue medical relevance in our experiments with the use of clinically important pathogens, antibiotics, phage, and a benchmarked synthetic sputum medium. Phenotypic and genomic characterization of evolved isolates demonstrates that efflux-targeting phage OMKO1 exerts continued selection for antibiotic susceptibility regardless of co-evolutionary dynamic or antibiotic co-treatment, opening the door for evolutionary robust phage therapy.
Production of Volatile Moth Sex Pheromones in TransgenicNicotiana benthamianaPlants
Authors: Mateos-Fernández Rubén , Moreno-Giménez Elena , Gianoglio Silvia , Quijano-Rubio Alfredo , Gavaldá-García Jose , Estellés Lucía , Rubert Alba , Rambla José Luis , Vazquez-Vilar Marta , Huet Estefanía , Fernández-del-Carmen Asunción , Espinosa-Ruiz Ana , Juteršek Mojca , Vacas Sandra , Navarro Ismael , Navarro-Llopis Vicente , Primo-Millo Jaime , Orzáez Diego
Published: March 2021

Plant-based bio-production of insect sex pheromones has been proposed as an innovative strategy to increase the sustainability of pest control in agriculture. Here we describe the engineering of transgenic plants producing(Z)-11-hexadecen-1-ol (Z11-16OH) and(Z)-11-hexadecenyl acetate (Z11-16OAc), two main volatile components in many Lepidoptera sex pheromone blends. We assembled multigene DNA constructs encoding the pheromone biosynthetic pathway and stably transformed them inNicotiana benthamianaplants. The constructs comprised theAmyelois transitella AtrΔ11desaturase gene, theHelicoverpa armigerafarnesyl reductaseHarFARgene, and theEuonymus alatusdiacylglycerol acetyltransferaseEaDActgene in different configurations. All the pheromone-producing plants showed dwarf phenotypes, whose severity correlated with pheromone levels. All but one of the recovered lines produced high levels of Z11-16OH but very low levels of Z11-16OAc, probably as a result of recurrent truncations at the level of theEaDActgene. Only one plant line (SxPv1.2) was recovered harbouring an intact pheromone pathway and producing moderate levels of Z11-16OAc (11.8 µg g-1FW), next to high levels of Z11-16OH (111.4 µg g-1). Z11-16OAc production was accompanied in SxPv1.2 by a partial recovery of the dwarf phenotype. SxPv1.2 was used to estimate the rates of volatile pheromone release, which resulted in 8.48 ng g-1FW per day for Z11-16OH and 9.44 ng g-1FW per day for Z11-16OAc. Our results suggest that pheromone release acts as a limiting factor in pheromone bio-dispenser strategies and establish a roadmap for biotechnological improvements.
Comparison and evaluation of pair distribution functions, using a similarity measure based on cross-correlation functions
Authors: Habermehl Stefan , Schlesinger Carina , Prill Dragica
Published: March 2021

An approach for the comparison of pair distribution functions (PDFs) has been developed using a similarity measure based on cross-correlation functions. The PDF is very sensitive to changes in the local structure,i.e.small deviations in the structure can cause large signal shifts and significant discrepancies between the PDFs. Therefore, a comparison based on pointwise differences (e.g. Rvalues and difference curves) may lead to the assumption that the investigated PDFs as well as the corresponding structural models are not in agreement at all, whereas a careful visual inspection of the investigated structural models and corresponding PDFs may reveal a relatively good match. To quantify the agreement of different PDFs for those cases an alternative approach is introduced: the similarity measure based on cross-correlation functions. In this paper, the power of this application of the similarity measure to the analysis of PDFs is highlighted. The similarity measure is compared with the classicalRwpvalues as representative of the comparison based on pointwise differences as well as with the Pearson product-moment correlation coefficient, using polymorph IV of barbituric acid as an example.
Unifying the concepts of scattering and structure factor in ordered and disordered samples
Authors: Li Dingning , Zhang Kai
Published: March 2021

Scattering methods are widely used in many research areas to analyze and resolve material structures. Given its importance, a large number of textbooks are devoted to this topic. However, technical details in experiments and disconnection between explanations from different perspectives often confuse and frustrate beginner students and researchers. To create an effective learning path, the core concepts of scattering and structure factor are reviewed in this article in a self-contained way. Classical examples of scattering photography and intensity scanning are calculated. Sample CPU and GPU codes are provided to facilitate the understanding and application of these methods.
2-(Naphthalen-2-yloxy)-N′-[2-(naphthalen-2-yloxy)acetyl]acetohydrazide monohydrate
Authors: El-Hiti Gamal A , Abdel-Wahab Bakr F. , Baashen Mohammed A. , Yousif Emad , Hegazy Amany S. , Kariuki Benson M.
Published: March 2021

The title compound, C24H20N2O4·H2O, crystallizes with half a molecule of 2-(naphthalen-2-yloxy)-N′-[2-(naphthalen-2-yloxy)acetyl]acetohydrazide and half a water molecule in the asymmetric unit. In the crystal, molecules form planes parallel to (011). Two molecules are connected by water molecules via O—H...O and N—H...O hydrogen bonds.
Consumers' preferences for intrinsic and extrinsic product attributes of plant-based eggs: an exploratory study in the United Kingdom and Italy
Authors: Rondoni Agnese , Millan Elena , Asioli Daniele
Published: March 2021

Purpose

Plant-based eggs have recently been developed to provide consumers with a healthier, animal-friendlier and more sustainable alternative to conventional eggs. The purpose of this paper is to investigate intrinsic and extrinsic attribute preferences for three prototypes of plant-based egg, namely the liquid, powder and egg-shaped.

Design/methodology/approach

Nine focus groups in the United Kingdom and nine in Italy were conducted, with a total of 180 participants. A thematic analysis of results was conducted.

Findings

In terms of intrinsic product attributes, consumers' preferences for colour, shape, taste, ingredients, nutrients, method of production and shelf-life for plant-based eggs were revealed. Regarding the extrinsic attributes, preferences for price, packaging, country of origin and product naming emerged. Similarities and differences between consumers from the two countries are also discussed. Differences in preferences also emerged between vegan and non-vegan consumers.

Research limitations/implications

This study adds to the existing knowledge on consumers' preferences for new plant-based food alternatives and identifies future quantitative approaches based on qualitative findings.

Practical implications

Results from this study can assist plant-based egg manufacturers in improving their products in line with consumers' expectations, which may help reducing risk of product failure.

Originality/value

This study is the first to investigate consumers' preferences, expectations and needs for new food products like plant-based eggs and provides information that can be practically applied by manufacturers, as well as suggestions for future research.
Practices and mechanisms for increasing supply chain ​​resilience: the supply chain resilience sheaf
Authors: Nascimento Adelson Pereira do , Oliveira Marcos Paulo , Pettit Timothy J. , Bronzo Marcelo
Published: March 2021

Purpose

This paper approaches the dynamics of supply chain resilience from the company from customer's point of view, seeking to illuminate which mechanisms and practices are used (intentionally or unintentionally) to increase the resilience of their critical suppliers, and thus to evaluate the impact of these mechanisms and practices on its entire supply chain (SC).

Design/methodology/approach

The authors explore some emerging developments in organizational resilience with an embedded case study of a group of focal companies operating in the automotive SC. Therefore, semi-structured interviews have been conducted with buyers and sellers using content analysis, in the light of the prospect theory and the resource dependency theory.

Findings

The results indicate the existence of a resilience sheaf that runs through the entire supply chain, formed by a set of 11 formal mechanisms and informal practices.

Practical implications

This resilience sheaf can guide managers thorough SC resilience development by taking its components as a reference and optimizing the use of resources both effectively and efficiently.

Originality/value

SC resilience has been conceptualized as a function of an organization's situational awareness, the identification and management of key vulnerabilities and the ability to successfully react in a complex, dynamic and interconnected environment. These propositions highlight the features of both internal and external mechanisms to enhance organizational resilience.
Leading entrepreneurial sustainability initiatives in emerging economies
Authors: Arya Bindu , Horak Sven , Bacouel-Jentjens Sabine , Ismail Kiran
Published: March 2021

Purpose

This conceptual paper develops a theoretical framework to provide insights with respect to enhancing focus on entrepreneurial sustainability initiatives in the context of emerging economies. The unique idiosyncrasies of the institutional environment of emerging economies are identified along the concept of scripts.

Design/methodology/approach

Sense-making and social identity theory are utilized to draw propositions along with the dimensions of the three stages of the sense-making process: enactment, selection and retention, in order to identify factors that are likely to motivate the next generation of business leaders in emerging economies to undertake greater levels of sustainability initiatives.

Findings

When organizations face competing demands of meeting both social and financial goals, sense-making by next-generation leaders becomes relevant. Leaders with greater entrepreneurial orientation (EO) are more likely to take actions decoupled from local isomorphic pressures, such that they turn opportunities for sustainability into novel sustainable initiatives.

Originality/value

This paper proposes a framework to provide insights and directions for future research with respect to enhancing an organizational focus on sustainability initiatives in the context of emerging economies.
International entrepreneurship from emerging to developed markets: an institutional perspective
Authors: Nuhu Nuraddeen Sani , Owens Martin , McQuillan Deirdre
Published: March 2021

Purpose

The authors explore how home and host market institutions impact emerging market (EM) international entrepreneurship (IE) into developed markets.

Design/methodology/approach

Based on four case studies of Nigerian entrepreneurs expanding into the USA, this qualitative research adopts an institutional perspective to the study of EM IE.

Findings

The findings show home and host formal and informal institutions simultaneously enable and constrain the IE process. Weak home institutions shape the international opportunity recognition decision but seriously impede international opportunity development and exploitation activities in the developed market. EM entrepreneurs benefit from highly functioning regulation in the developed market whilst also experiencing discriminatory treatment from institutions. The findings of the study further show the positive and constraining effects of host institutions throughout the process.

Originality/value

Based on the findings, the paper details future research ideas, managerial implications and recommendation for policymakers.