bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of genomic-enabled cross selection criteria for the improvement of inbred line breeding populations
Authors: des Déserts Alice Danguy , Durand Nicolas , Servin Bertrand , Goudemand-Dugué Ellen , Alliot Jean-Marc , Ruiz Daniel , Charmet Gilles , Elsen Jean-Michel , Bouchet Sophie
Published: March 2023

A crucial step in inbred plant breeding is the choice of mating design to derive high-performing inbred varieties while also maintaining a competitive breeding population to secure sufficient genetic gain in future generations. In practice, the mating design usually relies on crosses involving the best parental inbred lines to ensure high mean progeny performance. This excludes crosses involving lower performing but more complementary parents in terms of favorable alleles. We predicted crosses with putative outstanding progenies (high mean and high variance progeny distribution) using genomic prediction models to assess the value of top progeny. This study compared the benefits and drawbacks of seven genomic cross selection criteria (CSC) in terms of genetic gain for one trait and genetic diversity in the next generation. Six CSC were already published and we have proposed an improved CSC that can estimate the proportion of progeny above a threshold defined for the whole mating plan. We simulated mating designs optimized using different CSC and 835 elite parents from a real breeding program that were evaluated between 2000 and 2016. We applied constraints on parental contributions and genetic similarities between parents according to usual breeder practices. Our results showed that CSC based on progeny variance estimation increased the genetic value of superior progenies by up to 5% in the next generation compared to CSC based on the progeny mean estimation (i.e. parental genetic values) alone. It also increased the genetic gain (up to 4%) and/or maintained more genetic diversity at QTLs (up to 4% more genic variance when the marker effects were perfectly estimated).
Efficient Hi-C inversion facilitates chromatin folding mechanism discovery and structure prediction
Authors: Schuette Greg , Ding Xinqiang , Zhang Bin
Published: March 2023

Genome-wide chromosome conformation capture (Hi-C) experiments have revealed many structural features of chromatin across multiple length scales. Further understanding genome organization requires relating these discoveries to the mechanisms that establish chromatin structures and reconstructing these structures in three dimensions, but both objectives are difficult to achieve with existing algorithms that are often computationally expensive. To alleviate this challenge, we present an algorithm that efficiently converts Hi-C data into contact energies, which measure the interaction strength between genomic loci brought into proximity. Contact energies are local quantities unaffected by the topological constraints that correlate Hi-C contact probabilities. Thus, extracting contact energies from Hi-C contact probabilities distills the biologically unique information contained in the data. We show that contact energies reveal the location of chromatin loop anchors, support a phase separation mechanism for genome compartmentalization, and parameterize polymer simulations that predict three-dimensional chromatin structures. Therefore, we anticipate that contact energy extraction will unleash the full potential of Hi-C data and that our inversion algorithm will facilitate the widespread adoption of contact energy analysis.

Significance Statement

The three-dimensional organization of the genome is essential to many DNA-templated processes, and numerous experimental techniques have been introduced to characterize its features. High-throughput chromosome conformation capture experiments, or Hi-C, have proven particularly useful, reporting the interaction frequency between pairs of DNA segmentsin vivoand genome-wide. However, the polymer topology of chromosomes complicates Hi-C data analysis, which often employs sophisticated algorithms without explicitly accounting for the disparate processes affecting each interaction frequency. In contrast, we introduce a computational framework based on polymer physics arguments that efficiently removes the correlation between Hi-C interaction frequencies and quantifies how each local interaction influences genome folding globally. This framework facilitates the identification of mechanistically important interactions and the prediction of three-dimensional genome structures.
How much data do we need? Reliability and data deficiency in global vertebrate biodiversity trends
Authors: Dove Shawn , Böhm Monika , Freeman Robin , McRae Louise , Murrell David J.
Published: March 2023

Global biodiversity is facing a crisis, which must be solved through effective policies and on-the-ground conservation. But governments, NGOs, and scientists need reliable indicators to guide research, conservation actions, and policy decisions. Developing reliable indicators is challenging because the data underlying those tools is incomplete and biased. For example, the Living Planet Index tracks the changing status of global vertebrate biodiversity, but taxonomic, geographic and temporal gaps and biases are present in the aggregated data used to calculate trends. But without a basis for real-world comparison, there is no way to directly assess an indicator’s accuracy or reliability. Instead, a modelling approach can be used.

We developed a model of trend reliability, using simulated datasets as stand-ins for the "real world", degraded samples as stand-ins for indicator datasets (e.g. the Living Planet Database), and a distance measure to quantify reliability by comparing sampled to unsampled trends. The model revealed that the proportion of species represented in the database is not always indicative of trend reliability. Important factors are the number and length of time series, as well as their mean growth rates and variance in their growth rates, both within and between time series. We found that many trends in the Living Planet Index need more data to be considered reliable, particularly trends across the global south. In general, bird trends are the most reliable, while reptile and amphibian trends are most in need of additional data. We simulated three different solutions for reducing data deficiency, and found that collating existing data (where available) is the most efficient way to improve trend reliability, and that revisiting previously-studied populations is a quick and efficient way to improve trend reliability until new long-term studies can be completed and made available.
Using DNA flow-stretching assay as a tool to validate the tagging of DNA-binding proteins for single-molecule experiments
Authors: Molina Miranda , Way Lindsey E. , Ren Zhongqing , Liao Qin , Wang Xindan , Kim HyeongJun
Published: March 2023

Due to the enhanced labeling capability of maleimide-based fluorescent probes, lysine-cysteine-lysine (KCK) tags are frequently added to proteins for visualization. In this study, we employedin vitrosingle-molecule DNA flow-stretching assay as a sensitive way to assess the impact of the KCK-tag on the property of DNA-binding proteins. UsingBacillus subtilisParB as an example, we show that, although no noticeable changes were detected byin vivofluorescence imaging and chromatin immunoprecipitation (ChIP) assays, the KCK-tag substantially altered ParB’s DNA compaction rates, its response to nucleotide binding and to the presence of the specific sequence (parS) on the DNA. While it is typically assumed that short peptide tags minimally perturb protein function, our results urge researchers to carefully validate the use of tags for protein labeling. Our comprehensive analysis can be expanded and used as a guide to assess the impacts of other tags on DNA-binding proteins in single-molecule assays.

Motivation

Single-molecule fluorescence microscopy has been extensively used in modern biology to define the molecular action of proteins. Appending short peptide tags is a common strategy to enhance fluorescence labeling. In this Resources article, we evaluate the impact of a commonly used tag, the lysine-cysteine-lysine (KCK) tag, on protein behavior in single-molecule DNA flow-stretching assay, which is a sensitive and versatile method to understand the action of DNA-binding proteins. Our motivation is to provide researchers with an experimental framework to validate the fluorescently labeled DNA-binding proteins in single-molecule methods.
Predicting the Distribution of Serotonergic Axons: A Supercomputing Simulation of Reflected Fractional Brownian Motion in a 3D-Mouse Brain Model
Authors: Janušonis Skirmantas , Haiman Justin H. , Metzler Ralf , Vojta Thomas
Published: March 2023

The self-organization of the brain matrix of serotonergic axons (fibers) remains an unsolved problem in neuroscience. The regional densities of this matrix have major implications for neuroplasticity, tissue regeneration, and the understanding of mental disorders, but the trajectories of single fibers are strongly stochastic and require novel conceptual and analytical approaches. In a major extension to our previous studies, we used a supercomputing simulation to model 1000 serotonergic fibers as paths of superdiffusive fractional Brownian motion (FBM), a continuous-time stochastic process. The fibers produced long walks in a complex, threedimensional shape based on the mouse brain and reflected at the outer (pial) and inner (ventricular) boundaries. The resultant regional densities were compared to the actual fiber densities in the corresponding neuroanatomically-defined regions. The relative densities showed strong qualitative similarities in the forebrain and midbrain, demonstrating the predictive potential of stochastic modeling in this system. The current simulation does not respect tissue heterogeneities, but can be further improved with novel models of multifractional FBM. The study demonstrates that serotonergic fiber densities can be strongly influenced by the geometry of the brain, with implications for brain development, plasticity, and evolution.
An analysis of NHS 111 demand for primary care services
Authors: Pilbery Richard , Smith Madeleine , Green Jonathan , Chalk Daniel
Published: March 2023

Background

The NHS 111 service triages over 16,650,745 calls per year and approximately 48% of callers are triaged to a primary care disposition, such as a telephone appointment with a general practitioner (GP). However, there has been little assessment of the ability of primary care services to meet this demand. If a timely service cannot be provided to patients, it could result in patients calling 999 or attending emergency departments (ED) instead.

This study aimed to explore the patient journey for callers who were triaged to a primary care disposition, and the ability of primary care services to meet this demand.

Methods

We obtained routine, retrospective data from the Connected Yorkshire research database, and identified all 111 calls between the 1st January 2021 and 31st December 2021 for callers registered with a GP in the Bradford or Airedale region of West Yorkshire, who were triaged to a primary care disposition. Subsequent healthcare system access (111, 999, primary and secondary care) in the 72 hours following the index 111 call was identified, and a descriptive analysis of the healthcare trajectory of patients was undertaken.

Results

There were 56,102 index 111 calls, and a primary care service was the first interaction in 26,690/56,102 (47.6%) of cases, with 15,470/26,690 (58%) commenced within the specified triage time frame. Calls to 999 were higher in the cohort who had no prior contact with primary care (58% vs 42%) as were ED attendances (58.2% vs 41.8), although the proportion of avoidable ED attendances was similar (10.5% vs 11.8%).

Conclusion

Less than half of 111 callers triaged to a primary care disposition make contact with a primary care service, and even when they do, call triage time frames are frequently not met, suggesting that current primary care provision cannot meet the demand from 111.
Body size as a metric for the affordable world
Authors: Feng Xinran , Xu Shan , Li Yuannan , Liu Jia
Published: March 2023

The physical body of an organism serves as a vital interface for interactions with its environment. Here we investigated the impact of human body size on the perception of action possibilities (affordances) offered by the environment. We found that the body size delineated a distinct boundary on affordances, dividing objects of continuous real-world sizes into two discrete categories with each affording distinct action sets. Additionally, the boundary shifted with imagined body sizes, suggesting a causal link between body size and affordance perception. Intriguingly, ChatGPT, a large language model lacking physical embodiment, exhibited a modest yet comparable affordance boundary at the scale of human body size, suggesting the boundary is not exclusively derived from organism-environment interactions. A subsequent fMRI experiment revealed evidence of affordance processing exclusively for objects within the body size range, but not for those beyond. This suggests that only objects capable of being manipulated are the objects capable of offering affordance in the eyes of an organism. In summary, our study suggests a novel definition of object-ness in an affordance-based context, advocating the concept of embodied cognition in understanding the emergence of intelligence constrained by an organism’s physical attributes.
A Framework for Systematically Evaluating the Representations Learned by A Deep Learning Classifier from Raw Multi-Channel Electroencephalogram Data
Authors: Ellis Charles A. , Sattiraju Abhinav , Miller Robyn L. , Calhoun Vince D.
Published: March 2023

The application of deep learning methods to raw electroencephalogram (EEG) data is growing increasingly common. While these methods offer the possibility of improved performance relative to other approaches applied to manually engineered features, they also present the problem of reduced explainability. As such, a number of studies have sought to provide explainability methods uniquely adapted to the domain of deep learning-based raw EEG classification. In this study, we present a taxonomy of those methods, identifying existing approaches that provide insight into spatial, spectral, and temporal features. We then present a novel framework consisting of a series of explainability approaches for insight into classifiers trained on raw EEG data. Our framework provides spatial, spectral, and temporal explanations similar to existing approaches. However, it also, to the best of our knowledge, proposes the first explainability approaches for insight into spatial and spatio-spectral interactions in EEG. This is particularly important given the frequent use and well-characterized importance of EEG connectivity measures for neurological and neuropsychiatric disorder analysis. We demonstrate our proposed framework within the context of automated major depressive disorder (MDD) diagnosis, training a high performing one-dimensional convolutional neural network with a robust cross-validation approach on a publicly available dataset. We identify interactions between frontal and central electrodes and other electrodes and identify differences in frontal δ, θ, β, and γlowbetween healthy controls and individuals with MDD. Our study represents a significant step forward for the field of deep learning-based raw EEG classification, providing new capabilities in interaction explainability and providing direction for future innovations through our proposed taxonomy.
Membrane potential phase shifts differ for excitation vs. inhibition in resonant pyramidal neurons: a computer modeling study
Authors: Kelley Craig , Antic Srdjan D. , Carnevale Nicholas T. , Kubie John L. , Lytton William W.
Published: March 2023

Rhythmic activity is ubiquitous in neural systems, and impedance analysis has been widely used to examine frequency-dependent responses of neuronal membranes to rhythmic inputs. Impedance analysis assumes the neuronal membrane is a linear system, requiring the use of small signals to stay in a near-linear regime. However, postsynaptic potentials are often large and trigger nonlinear mechanisms. We therefore augmented impedance analysis to evaluate membrane responses in this nonlinear domain, analyzing responses to injected current for subthreshold membrane voltage (Vmemb), suprathreshold spike-blocked Vmemb, and spiking in a validated neocortical pyramidal neuron computer model. Responses in these output regimes were asymmetrical, with different phase shifts during hyperpolarizing and depolarizing half-cycles. Suprathreshold chirp stimulation gave equivocal results due to nonstationarity of response, requiring us to use fixed-frequency sinusoids. Sinusoidal inputs producedphase retreat: action potentials occurred progressively later in cycles of the input stimulus, resulting from adaptation. Conversely, sinusoidal current with increasing amplitude over cycles produced a pattern ofphase advance: action potentials occurred progressively earlier. Phase retreat was dependent onIhandIAHPcurrents; phase advance was modulated by these currents. Our results suggest differential responses of cortical neurons depending on the frequency of oscillatory input in the delta – beta range, which will play a role in neuronal responses to shifts in network state. We hypothesize that intrinsic cellular properties complement network properties and contribute toin vivophase-shift phenomena such as phase precession, seen in place and grid cells, and phase roll, observed in hippocampal CA1 neurons.

New & Noteworthy

We augmented electrical impedance analysis to characterize phase shifts between large amplitude current stimuli and nonlinear, asymmetric membrane potential responses. We predict different frequency-dependent phase shifts in response excitation versus inhibition, as well as shifts in spike timing over multiple input cycles, in resonant pyramidal neurons. We hypothesize that these effects contribute to navigation-related phenomena like phase precession and phase roll. Our neuron-level hypothesis complements, rather than falsifies, prior network-level explanations of these phenomena.
Hemispheric decoupling of awareness-related activity in human auditory cortex under informational masking and divided attention
Authors: Dykstra Andrew R. , Gutschalk Alexander
Published: March 2023

The conditions under which sensory stimuli require selective attention to reach awareness is a fundamental question of cognitive neuroscience. We examined this question in the context of audition utilizing M/EEG and a dual-task informational-masking paradigm. Listeners performed a demanding primary task in one ear – detecting isochronous target-tone streams embedded in random multi-tone backgrounds and counting within-stream deviants – and retrospectively reported their awareness of secondary, masker-embedded target streams in the other ear. Irrespective of attention or ear, left-AC activity strongly covaried with target-stream detection starting as early as 50 ms post-stimulus. In contrast, right-AC activity was unmodulated by detection until later, and then only weakly. Thus, under certain conditions, human ACs can functionally decouple, such that one – here, right – is automatic and stimulus-driven while the other – here, left – supports perceptual and/or task demands, including basic perceptual awareness of nonverbal sound sequences.
Transgene Expression in Cultured Cells Using Unpurified Recombinant Adeno-Associated Viral Vectors
Authors: Benyamini Brian , Esbin Meagan N. , Whitney Oscar , Walther Nike , Maurer Anna C.
Published: March 2023

Recombinant adeno-associated viral vectors (rAAV) can achieve potent and durable transgene expression without integration in a broad range of tissue types, making them a popular choice for gene delivery in animal models and in clinical settings. In addition to therapeutic applications, rAAVs are a useful laboratory tool for delivering transgenes tailored to the researcher’s experimental needs and scientific goals in cultured cells. Some examples include exogenous reporter genes, overexpression cassettes, RNA interference, and CRISPR-based tools including those for genome-wide screens. rAAV transductions are less harmful to cells than electroporation or chemical transfection and moreover do not require any special equipment or expensive reagents to produce. Crude lysates or conditioned media containing rAAVs can be added directly to cultured cells without further purification to transduce many cell types – an underappreciated feature of rAAVs. Here, we provide protocols for basic transgene cassette cloning and demonstrate how to produce and apply crude rAAV preparations to cultured cells. As proof-of-principle, we demonstrate transduction of three cell types that have not yet been reported in rAAV applications. We discuss appropriate uses for crude rAAV preparations, the limitations of rAAVs for gene delivery, and considerations for capsid choice. The simplicity of production, exceedingly low cost, and often potent results make crude rAAV a primary choice for researchers to achieve effective DNA delivery.

Recombinant adeno-associated virus (rAAV) is widely used for clinical and preclinical gene delivery. An underappreciated use for rAAVs is the robust transduction of cultured cells without the need for purification. For researchers new to rAAV, we provide a protocol for transgene cassette cloning, crude vector production, and cell culture transduction.
Development and Feasibility of a Primary Care Provider Training Intervention to Improve Atrial Fibrillation Management
Authors: Daw J. Michael , Armbruster Tiffany , Deyo Zack , Walker Jennifer , Rosman Lindsey A , Sears Samuel F. , Mazzella Anthony J. , Gehi Anil K.
Published: March 2023

STRUCTURED ABSTRACT

Background

Disparities in atrial fibrillation (AF) care are partially attributed to inadequate access to providers with specialized training in AF. Primary care providers (PCPs) are often the sole providers of AF care in under-resourced regions.

Objective

To create a virtual education intervention for PCPs and evaluate its impact on use of stroke risk reduction strategies in AF patients.

Methods

A multi-disciplinary team mentored PCPs on AF management over 6 months using a virtual case-based training format. Surveys of participant knowledge and confidence in AF care were compared pre- and post-intervention. Hierarchical logistic regression modeling was used to evaluate change in stroke risk reduction therapies among patients seen by participants before or after training.

Results

Of 41 participants trained, 49% worked in family medicine, 41% internal medicine, and 10% general cardiology. Participants attended a mean of 14 one-hour sessions. Overall, appropriate use of oral anticoagulation (OAC) therapy (CHA2DS2-VASc score ≥1 men, ≥2 women) increased from 37% to 46% (p<.001) comparing patients seen pre- (n=1739) to post- (n=610) intervention. Factors independently associated with appropriate OAC use included participant training (OR 1.4, p=.002) and participant competence in AF management (by survey). Factors associated with decreased OAC use included patient age (OR 0.8 per 10 years, p=.008), nonwhite race (OR 0.7, p=.028). Provider knowledge and confidence in AF care both improved (p<.001).

Conclusions

A virtual case-based PCP training intervention improved use of stroke risk reduction therapy in outpatients with AF. This widely scalable intervention could improve AF care in under-resourced communities.

CONDENSED ABSTRACT

A virtual educational model was developed for primary care providers to improve competency in AF care in their community. Following a 6-month training intervention, the rate of appropriate oral anticoagulation (OAC) therapy among patients cared for by participating providers increased from 37% to 46% (p<.001). Among participants, knowledge and confidence in AF care improved. These findings suggest a virtual AF training intervention can improve PCP competency in AF care. This widely scalable intervention could help improve AF care in under-resourced communities.
The sliding motility of the bacilliform virions of Influenza A Viruses
Authors: Stevens Laurie , de Buyl Sophie , Mognetti Bortolo Matteo
Published: March 2023

Influenza A virus (IAV) infection relies on the action of the hemagglutinin (HA) and neuraminidase (NA) membrane proteins. The HA ligands anchor the IAV virion to the cell’s surface by binding the sialic acid (SA) present on the host’s receptors while NA is an enzyme capable of cleaving the SA from the extracellular environment. It is believed that the activity of NA ligands increases the motility of the virions favoring the propagation of the infection. In this work, we develop a numerical framework to study the dynamics of a virion moving across the cell surface for timescales much bigger than the typical ligand-receptor reaction times. We find that the rates controlling the ligand-receptor reactions and the maximal distance at which a pair of ligand-receptor molecules can interact greatly affect the motility of the virions. We also report on how different ways of organizing the two types of ligands on the virions’ surface result in different types of motion that we rationalize using general principles. In particular, we show how the emerging motility of the virion is less sensitive to the rate controlling the enzymatic activity when NA ligands are clustered. These results help to assess how variations in the biochemical properties of the ligand–receptor interactions (as observed across different IAV subtypes) affect the dynamics of the virions at the cell surface.
Guidelines for Optimizing Type S Non-Ribosomal Peptide Synthetases
Authors: Abbood Nadya , Effert Juliana , Bozhueyuek Kenan A. J. , Bode Helge B.
Published: March 2023

Bacterial biosynthetic assembly lines, such as non-ribosomal peptide synthetases (NRPS) and polyketide synthases, are often subject of synthetic biology – because they produce a variety of natural products invaluable for modern pharmacotherapy. Acquiring the ability to engineer these biosynthetic assembly lines allows the production of artificial non-ribosomal peptides (NRP), polyketides, and hybrids thereof with new or improved properties. However, traditional bioengineering approaches have suffered for decades from their very limited applicability and, unlike combinatorial chemistry, are stigmatized as inefficient because they cannot be linked to the high-throughput screening platforms of the pharmaceutical industry. Although combinatorial chemistry can generate new molecules cheaper, faster, and in greater numbers than traditional natural product discovery and bioengineering approaches, it does not meet current medical needs because it covers only a limited biologically relevant chemical space. Hence, methods for high-throughput generation of new natural product-like compound libraries could provide a new avenue towards the identification of new lead compounds. To this end, prior to this work, we introduced an artificial synthetic NRPS type, referred to as type S NRPS, to provide a first-of-its-kind bicombinatorial approach to parallelized high-throughput NRP library generation. However, a bottleneck of these first two generations of type S NRPS was a significant drop in production yields. To address this issue, we applied an iterative optimization process that enabled titer increases of up to 55-fold compared to the non-optimized equivalents, restoring them to wild-type levels and beyond.
SARS-CoV-2 infection activates endogenous retroviruses of the LTR69 subfamily
Authors: Arora Ankit , Kolberg Jan Eric , Badarinarayan Smitha Srinivasachar , Munot Daksha , Müller Martin , Sauter Daniel , Bansal Vikas
Published: March 2023

Accumulating evidence suggests that endogenous retroviruses (ERVs) play an important role in the host response to infection and the development of disease. By combining RNA- and ChIP-sequencing analyses with RT-qPCR, we show that SARS-CoV-2 infection induces the LTR69 subfamily of ERVs, bothin vitroandin vivo. Using functional assays, we identified one SARS-CoV-2-activated LTR69 locus, termed Dup69, which exhibits enhancer activity and is responsive to the transcription factors IRF3 and p65/RelA. LTR69-Dup69 is located about 500 bp upstream of a long non-coding RNA gene (ENSG00000289418) and within thePTPRN2gene encoding a diabetes-associated autoantigen. Both ENSG00000289418 andPTPRN2showed a significant increase in expression upon SARS-CoV-2 infection. Thus, our study sheds light on the interplay of exogenous with endogenous viruses and helps to understand how ERVs regulate gene expression during infection.
The smallest infectious substructure encoding the prion strain structural determinant revealed by spontaneous dissociation of misfolded prion protein assemblies
Authors: Bohl Jan , Moudjou Mohammed , Herzog Laetitia , Reine Fabienne , Sailler Fiona , Klute Hannah , Halgand Frederic , Van der Rest Guillaume , Boulard Yves , Béringue Vincent , Igel Angelique , Rezaei Human
Published: March 2023

It is commonly accepted that the prion replicative propensity and strain structural determinant (SSD) are encoded in the fold of PrPScamyloid fibril assemblies. By exploring the quaternary structure dynamicity of several prion strains, we revealed that all mammalian prion assemblies exhibit the generic property of spontaneously generating two sets of discreet infectious tetrameric and dimeric species differing significantly by their specific infectivity. By using perturbation approaches such as dilution and ionic strength variation, we demonstrated that these two oligomeric species were highly dynamic and evolved differently in the presence of chaotropic agents. In general, our observations of seven different prion strains from three distinct species highlight the high dynamicity of PrPScassemblies as a common and intrinsic property of mammalian prions. The existence of such small infectious PrPScspecies harboring the SSD indicates that the prion infectivity and the SSD are not restricted only to the amyloid fold but can also be encoded in other alternative quaternary structures. Such diversity in the quaternary structure of prion assemblies tends to indicate that the structure of PrPSccan be divided into two independent folding domains: a domain encoding the strain structural determinant and a second domain whose fold determines the type of quaternary structure that could adopt PrPScassemblies.

Highlights

Mammalian prion assemblies are highly dynamic

Prion assemblies spontaneously disassemble into two infectious oligomers

Prion infectivity is not exclusively encoded in the amyloid fibrils’ structure

Two independent folding domains could structure Prion assemblies
LactococcusG423 Ameliorates the Growth Performance of Broilers by Modulation of Gut Microbiota- Metabolites
Authors: Wang Mi , Ma Wei , Wang Chunqiang , Li Desheng , Wang Yuan
Published: March 2023

This study aimed to explore whetherLactococcusG423 could ameliorate growth performance of broilers by modulation of gut microbiota-metabolites based on the 16S ribosomal RNA (rRNA) and liquid chromatography-mass spectrometry (LC-MS). A total of 640 one-day-old AA broilers were randomly divided into 4 groups (Control (CON), Lac_L, Lac_H, and ABX). Average daily gain (ADG), average daily feed intake (ADFI), and feed conversion ratio (FCR) were calculated on the 42nd day. The ileum content was harvested and immediately frozen in liquid nitrogen for 16S rRNA and LC-MS analyses. Then, the results of 16S rRNA analysis were confirmed by quantitative polymerase chain reaction (qPCR). Compared with the CON group, ADG significantly increased in the Lac_H group (P<0.05), and survival rate significantly decreased in the Lac_H, Lac_H, and ABX groups (allP<0.05). A significant difference in microbial diversity was found among the four groups. Compared with the CON group, the abundance rates ofFirmicutes and Lactobacillusin the Lac_H group were significantly risen (P<0.05). The global and overview maps and membrane transport in the Lac_L, Lac_H, and ABX groups significantly changed versus those in the CON group (P<0.05). The results of LC-MS demonstrated thatLactococcuscould significantly improve the levels of some metabolites (6-hydroxy-5-methoxyindole glucuronide, 9,10-DiHOME, carbamazepine-O-quinone, N-Acetyl-L-phenylalanine, and kynurenine), and these metabolites were involved in 5 metabolic pathways. Among them, the pathways of linoleic acid metabolism, phenylalanine metabolism, and pentose and glucuronate interconversions significantly changed (P<0.05).Lactococcusimproved wight and survival rate of broilers through the gut microbiota, regulating the pathways of amino acid metabolism, lipid metabolism, bile acid metabolism, and carbohydrate metabolism. However, antibiotics may negatively influence the gut microbiota.

IMPORTANCE

Improvements in the growth rate of broiler chickens can be achieved through dietary manipulation of the naturally occurring bacterial populations while mitigating the withdrawal of antibiotic growth promoters.Lactococcusis industrially cruciallactic acid bacteria, can be incorporated into the diets of chickens to improve their growth performance. This study investigated the key mechanisms behind this progression and pinpointedLactococcusimproved wight and survival rate of broilers through the gut microbiota, regulating the pathways of amino acid metabolism, lipid metabolism, bile acid metabolism, and carbohydrate metabolism.
The timing of confidence computations in human prefrontal cortex
Authors: Xue Kai , Zheng Yunxuan , Rafiei Farshad , Rahnev Dobromir
Published: March 2023

Knowing when confidence computations take place is critical for building mechanistic understanding of the neural and computational bases of metacognition. Yet, even though substantial amount of research has focused on revealing the neural correlates and computations underlying human confidence judgments, very little is known about the timing of confidence computations. Subjects judged the orientation of a briefly presented visual stimulus and provided a confidence rating regarding the accuracy of their decision. We delivered single pulses of transcranial magnetic stimulation (TMS) at different times after stimulus presentation. TMS was delivered to either dorsolateral prefrontal cortex (DLPFC) in the experimental group or to vertex in the control group. We found that TMS to DLPFC, but not to vertex, led to increased confidence in the absence of changes to accuracy or metacognitive ability. Critically, equivalent levels of confidence increase occurred for TMS delivered between 200 and 500 ms after stimulus presentation. These results suggest that confidence computations occur during a broad window that begins before the perceptual decision has been fully made and thus provide important constraints for theories of confidence generation.
Inhibition of sensory neuron driven acute, inflammatory, and neuropathic pain using a humanised chemogenetic system
Authors: Perez-Sanchez Jimena , Middleton Steven J. , Pattison Luke A. , Hilton Helen , Awadelkareem Mosab Ali , Zuberi Sana R. , Renke Maria B. , Hu Huimin , Yang Xun , Clark Alex J. , St Ewan , Smith John , Bennett David L.
Published: March 2023

Hyperexcitability in sensory neurons is known to underlie many of the maladaptive changes associated with persistent pain. Chemogenetics has shown promise as a means to suppress such excitability, yet chemogenetic approaches suitable for human applications are needed. PSAM4-GlyR is a modular system based on the human α7 nicotinic acetylcholine and glycine receptors, which responds to inert chemical ligands and the clinically-approved drug, varenicline. Here, we demonstrated the efficacy of this channel in silencing both mouse and human sensory neurons by the activation of large shunting conductances after agonist administration. Virally-mediated expression of PSAM4-GlyR in mouse sensory neurons produced behavioural hyposensitivity upon agonist administration, which was recovered upon agonist washout. Importantly, stable expression of the channel led to similar reversible behavioural effects even after 10 months of viral delivery. Mechanical and spontaneous pain readouts were also ameliorated by PSAM4-GlyR activation in acute and joint pain inflammation models. Furthermore, suppression of mechanical hypersensitivity generated by a spared nerve injury model of neuropathic pain was also observed upon activation of the channel. Effective silencing of behavioural hypersensitivity was reproduced in a human model of hyperexcitability and clinical pain: PSAM4-GlyR activation decreased the excitability of human induced pluripotent stem-cell-derived sensory neurons and spontaneous activity due to a gain of function NaV1.7 mutation causing inherited erythromelalgia. Our results demonstrate the contribution of sensory neuron hyperexcitability to neuropathic pain and the translational potential of an effective, stable and reversible human-based chemogenetic system for the treatment of pain.
Spatiotemporal analysis of SARS-CoV-2 infection reveals an expansive wave of monocyte-derived macrophages associated with vascular damage and virus clearance in hamster lungs
Authors: Bagato Ola , Balkema-Buschmann Anne , Todt Daniel , Weber Saskia , Gömer André , Qu Bingqian , Miskey Csaba , Ivics Zoltan , Mettenleiter Thomas C. , Finke Stefan , Brown Richard J. P. , Breithaupt Angele , Ushakov Dmitry S.
Published: March 2023

Factors of the innate immune response to SARS-CoV-2 in the lungs are pivotal for the ability of the host to deal with the infection. In humans, excessive macrophage infiltration is associated with disease severity. Using 3D spatiotemporal analysis of optically cleared hamster lung slices in combination with virological, immunohistochemical and RNA sequence analyses, we visualized the spread of SARS-CoV-2 through the lungs and the rapid anti-viral response in infected lung epithelial cells, followed by a wave of monocyte-derived macrophage (MDM) infiltration and virus elimination from the tissue. These SARS-CoV-2 induced innate immune processes are closely related to the onset of necrotizing inflammatory and consecutive remodelling responses in the lungs, which manifests as extensive cell death, vascular damage, thrombosis, and cell proliferation. Here we show that MDM are directly linked to virus clearance, and appear in connection with tissue injury and blood vessel damage. Rapid initiation of prothrombotic factor upregulation, tissue repair and alveolar cell proliferation results in tissue remodelling, which is followed by fibrosis development despite a decrease in inflammatory and anti-viral activities. Thus, although the hamsters are able to resolve the infection following the MDM influx and repair lung tissue integrity, longer-term alterations of the lung tissues arise as a result of concurrent tissue damage and regeneration processes.
Partially coherent light propagation through a kinoform lens
Authors: Sun Weihong , Wang Yong , Meng Xiangyu , Ren Junchao , Cao Jiefeng , Li Junqin , Tai Renzhong
Published: March 2023

Combining wave optics propagation and geometric ray tracing, the mutual optical intensity (MOI) model is extended to quantitatively simulate the propagation of partially coherent light through a kinoform lens at high speed. The MOI model can provide both a high accuracy and a high efficiency simulation. The intensity and coherence degree distributions at the focal plane are calculated using the MOI model. It is beneficial to improve the focusing capability of the kinoform lens by reducing the coherence or increasing the number of lens steps. In addition, increasing the number of steps is also beneficial to increase the photon flux and reduce the depth of focus.
State of university-industry collaboration in quantity surveying profession in Nigeria
Authors: Alli Morufu Abolaji , Dada Joshua Oluwasuji
Published: March 2023

Purpose

University-industry collaboration (UIC) is a symbiosis relationship, brought about through knowledge and resource sharing, with the attendant benefits of innovation and technological advancement. The purpose of this paper is to investigate the state of UIC in quantity surveying profession in Nigeria with a view to ascertaining the situation and chatting the way forward.

Design/methodology/approach

Using quantitative survey research approach, primary data were collected through the administration of structured questionnaires on quantity surveying academia and practitioners. A total of 126 respondents were sampled: 52 university lecturers and 74 quantity surveying firms. Of these, 32 university lecturers (61.54%) and 34 quantity surveying firms (45.95%) provided valid responses. In all, this amounts to 52.38% response rate. The quantitative data obtained were analysed using mean score, frequency distribution, percentage and Mann Whitney test.

Findings

The findings show that collaboration is very strong in the areas of student industrial placement and research cooperation between students and academic researchers. However, collaboration in the areas of funding and staff exchange was found to be lagging behind.

Practical implications

The findings indicate strong collaboration areas (student industrial placement and research cooperation) to be sustained as well as weak areas (funding and staff exchange) to be critically looked into.

Originality/value

The paper represents the first research to empirically assess the state of UIC in quantity surveying profession in Nigeria. In addition, it shows the areas where efforts should be concentrated in maximizing the benefit of UIC.
Protean career orientation and job search: investigating the mediating role of career optimism in mentoring relationships
Authors: Gong Zhenxing , Gilal Faheem Gul , Gilal Rukhsana Gul , Jahanzeb Agha
Published: March 2023

Purpose

Protean career orientation is a key element that helps explain why workers plan and manage their careers. In the field of nursing, a protean career orientation assists nurses in job search, career mobility and adapting to changing demands. Few studies have explored how nurses’ protean career orientation will lead to job search and how to make better use of the protean career orientation. This study aims to explore how a protean career orientation influences job search via career optimism and the moderating role of mentoring relationships.

Design/methodology/approach

This study conducted a cross-sectional survey of 309 frontline nurses from China. The questionnaire was distributed to nurses through the snowball sampling method. Jamovi 1.2.2 was used for descriptive analysis and Pearson’s correlation analysis. The relationships between the variables and their significance were tested using Process Macro 3.3.

Findings

Results show that protean career orientation was significantly related to career optimism and positively related to job search. Career optimism was significantly related to job search. The indirect effect of protean career orientation on job search through career optimism was significant. The interaction between protean career orientation and mentoring relationships was also significantly related to career optimism.

Originality/value

To the best of the authors’ knowledge, this study is the first to demonstrate how nurses’ flexible career orientation significantly impacted job search through nurses’ career optimism. If nurses work in supportive mentoring relationships, the positive effect of the nurse’s protean career orientation on the job search is decreased.
Assessing the impact of wealth inequality on state capture in Latin America
Authors: Korman James Guy
Published: March 2023

Purpose

This study aims to analyze the effects of economic inequalities on state capture in Latin America. Economic inequalities are the defining issues of our time. While the effect of economic inequality has been explored before on its impact on state capture in Latin America, it has often been done in a qualitative manner. Moreover, most quantitative research to date uses poor proxy variables to assess the impact of inequalities on corruption and or state capture, such as the Gini coefficient, which suffers from a lot of missing data.

Design/methodology/approach

A random effects regression model is used to enable the exploitation of between level variation to greater generalize the results across the Latin American region while minimizing bias to the coefficient estimates.

Findings

The results demonstrate that the top 1% wealth inequality is highly statistically significant and positive in explaining the variation in state capture. The greater the share of wealth the 1% hold, the more state capture we should expect.

Originality/value

To the best of the authors’ knowledge, this paper presents the first empirical study using a novel variable, the top 1% share wealth inequality derived from the World Inequality Database that directly measures the top 1%’s share of wealth overall. The study examines the empirical effect of the top 1%’s share of wealth inequality in contributing to state capture. Nineteen Latin American countries are analyzed across the temporal period 1996–2021.
Innovation capabilities and export performance of SMEs: does managers' risk-taking propensity matter?
Authors: Ringo Denis Samwel , Tegambwage Amani Gration , Kazungu Isaac
Published: March 2023

Purpose

This paper aims to examine the relationship between innovation capabilities (INVC) and export performance (EXPERF) of manufacturing small and medium enterprises (SMEs). Moreover, the paper aims to investigate the moderating effect of risk-taking propensity (RSTP) in the relationship between INVC and the SMEs’ EXPERF.

Design/methodology/approach

A cross-sectional survey design was used and data were collected through structured questionnaires from 250 manufacturing exporting SMEs in Tanzania. Confirmatory factor analysis was used to test the measurement model. The hypotheses were empirically tested using PROCESS macro test.

Findings

The findings affirm that INVC is a significant predictor of EXPERF. Additionally, RSTP was found to be a significant moderator of the relationship between INVC and EXPERF.

Research limitations/implications

Although the study was able to accomplish its overall objective, it is limited in terms of the context under which the study was conducted. This study covered only manufacturing SMEs in a single country, Tanzania. Hence, the findings should be interpreted with caution since each country has specific institutional environments that support innovation.

Originality/value

The findings of this study expand the application of the resource-based view (RBV) theory in exporting context. The study revealed how INVC as an intangible resource can lead to successful performance. Hence, the findings of this study broaden the applicability of RBV theory. Also, this study contributes to the debate about the innovation-export performance relationship by revealing a moderating role of RSTP in the relationship between INVC and EXPERF.