bluuebunny/crossref_metadata_2025 huggingface dataset:
Bridging Neurons and Behavior in a Convolutional Neural Network with Emergent Human-like Covert Attention
Authors: Srivastava Sudhanshu , Wang William Yang , Eckstein Miguel P.
Published: September 2023

Covert visual attention allows the brain to select different regions of the visual world without eye movements. Cues predictive of a target location orient covert attention and improve perceptual performance. How entire neuronal populations represent and integrate target, cues, and location information to result in behavioral signatures of covert attention is not understood. We analyze 1.8M neurons of feedforward Convolutional Neural Networks (CNNs) that show human-like attentional cueing effects. Consistent with neurophysiology, we show early layers with retinotopic neurons separately tuned to target or cue, and later layers with neurons with joint tuning and increased influence of the cue on target responses. We show cue-inhibitory and location-opponent neurons that are unreported by neurophysiologists and identify the neuronal circuits that result in neuronal cueing effects. The cue influences the mean neuronal responses and changes target sensitivity through three mechanisms: cue-weighted summation and opponency across locations, and interaction with the thresholding Rectified Linear Unit (ReLU). Some CNN computational stages mirror a Bayesian ideal observer (BIO), but with more gradual transitions, while the opponency and ReLU interaction are distinct from the BIO. Together, the findings establish a likely system-wide characterization of the brain computations that mediate the behavioral signatures of covert attention.
Anterolateral temporal lobe localization of dysnomia after temporal lobe epilepsy surgery
Authors: Mhanna Asmaa , Bruss Joel , Sullivan Alyssa W. , Howard Matthew A. , Tranel Daniel , Boes Aaron D.
Published: September 2023

Objectives

To evaluate what factors influence naming ability after temporal lobectomy in patients with drug-resistant epilepsy.

Methods

85 participants with drug-resistant epilepsy who underwent temporal lobe (TL) resective surgery were retrospectively identified (49 left TL and 36 right TL). Naming ability was assessed before and >3 months post-surgery using the Boston Naming Test (BNT).

Multivariate lesion-symptom mapping was performed to evaluate whether lesion location related to naming deficits. Multiple regression analyses were conducted to examine if other patient characteristics were significantly associated with pre-to post-surgery changes in naming ability.

Results

Lesion laterality and location were important predictors of post-surgical naming performance. Naming performance significantly improved after right temporal lobectomy (p= 0.015) while a decrement in performance was observed following left temporal lobectomy (p= 0.002). Lesion-symptom mapping showed the decline in naming performance was associated with surgical resection of the anterior left middle temporal gyrus (Brodmann area 21,r=0.41,p= <.001). For left hemisphere surgery, later onset of epilepsy was associated with a greater reduction in post-surgical naming performance (p= 0.01).

Significance

There is a wide range of variability in outcomes for naming ability after temporal lobectomy, from significant improvements to decrements observed. If future studies support the association of left anterior middle temporal gyrus resection and impaired naming this may help in surgical planning and discussions of prognosis.
Deep learning-based prediction of one-year mortality in the entire Finnish population is an accurate but unfair digital marker of aging
Authors: Vabalas Andrius , Hartonen Tuomo , Vartiainen Pekka , Jukarainen Sakari , Viippola Essi , Rodosthenous Rodosthenis S. , Liu Aoxing , Hägg Sara , Perola Markus , Ganna Andrea
Published: September 2023

Background

Accurately predicting short-term mortality is important for optimizing healthcare resource allocation, developing risk-reducing interventions, and improving end-of-life care. Moreover, short-term mortality risk reflects individual frailty and can serve as digital aging marker. Previous studies have focused on specific, high-risk populations. Predicting all-cause mortality in an unselected population incorporating both health and socioeconomic factors has direct public health relevance but requires careful fairness considerations.

Methods

We developed a deep learning model to predict 1-year mortality using nationwide longitudinal data from the Finnish population (N= 5.4 million), including >8,000 features and spanning back up to 50 years. We used the area under the receiver operating characteristic curve (AUC) as a primary metric to assess model performance and fairness.

Findings

The model achieved an AUC of 0.944 with strong calibration, outperforming a baseline model that only included age and sex (AUC = 0.897). The model generalized well to different causes of death (AUC > 0.800 for 45 out of 50 causes), including COVID-19 which was not present in the training data. The model performed best among young females and worst in older males (AUC = 0.910 vs. AUC = 0.718). Extensive fairness analyses revealed that individuals belonging to multiple disadvantaged groups had the worst model performance, not explained by age and sex differences, reduced healthcare contact, or smaller training set sizes within these groups.

Conclusion

A deep learning model based on nationwide longitudinal multi-modal data accurately identified short-term mortality risk holding the potential for developing a population-wide in-silico aging marker. Unfairness in model predictions represents a major challenge to the equitable integration of these approaches in public health interventions.
Direct and indirect responses of the Arabidopsis transcriptome to an induced increase in trehalose 6-phosphate
Authors: Avidan Omri , Martins Marina C. M. , Feil Regina , Lohse Marc , Giorgi Federico M. , Schlereth Armin , Lunn John E. , Stitt Mark
Published: September 2023

Trehalose 6-phosphate (Tre6P) is an essential signal metabolite that reports and regulates the level of sucrose, linking growth and development to the metabolic status. We hypothesized that Tre6P plays a role in mediating the regulation of gene expression by sucrose. To test this, we performed transcriptomic profiling on Arabidopsis plants that expressed a bacterial trehalose-6-phosphate synthase (TPS) under the control of an ethanol-inducible promoter. Induction led to a 4-fold rise in Tre6P levels, a concomitant decrease in sucrose, and significant changes of over 13,000 transcripts and two-fold or larger changes of over 5000 transcripts. Comparison with nine published responses to sugar availability allowed some of these changes to be linked to the rise in Tre6P, while others were probably due to lower sucrose or other indirect effects. Changes linked to Tre6P included repression of photosynthesis and induction of many growth-related processes including ribosome biogenesis. About 500 starvation-related genes are known to be induced by SUCROSE-NON-FERMENTING-1-RELATED KINASE 1 (SnRK1). They were largely repressed by Tre6P in a manner consistent with Tre6P acting to inhibit SnRK1. SnRK1 also represses many genes that are involved in biosynthesis and growth. These responded to Tre6P in a more complex manner, pointing to Tre6P also interacting with further C-signaling pathways. In addition, elevated Tre6P modified expression of genes encoding regulatory subunits of the SnRK1 complex and TPS class II and FLZ proteins that are thought to modulate SnRK1 function, and genes involved in the circadian clock and in TOR, light, abscisic acid and other hormone signaling.

One sentence summary

An induced increase in trehalose 6-phosphate levels has direct effects on gene expression via inhibition of SUCROSE-NON-FERMENTING-1-RELATED KINASE 1 and interactions with light, circadian clock and phytohormone signaling, and widespread indirect effects on gene expression from reciprocal changes in sucrose levels.
KlebsiellaPneumoniae turns more virulent under flow stresses in capillary like microchannels
Authors: Jain Siddhant , Singh Anmol , Tiwari Nivedita , Naik Aparna , Chatterjee Ritika , Chakravortty Dipshikha , Basu Saptarshi
Published: September 2023

Fluidic habitats are very common to bacterial life, however, very little is known about the effect of the flow stresses on the virulence of the bacteria. In the present work, we conduct microfluidic experiments to understand the consequence of stresses generated by flowing fluid on the bacterial morphology and virulence. We considerKlebsiella pneumoniae(KP), an ESKAPE pathogen as the model bacteria that are responsible for blood stream infections like bacteremia apart from pneumonia, urinary tract infections and more. We generate four different stress conditions by changing the flow rate and channel geometry subsequently altering the shear rate and stressing time (τ). We observe significant changes in the structural aspects of the stressed bacteria. With an increase in stressing parameters, the viability of the bacterial sample deteriorated. Most importantly, these stressed samples proliferate much more than unstressed samples inside the RAW264.7 murine macrophages. The results shed light on the complex relationship between flow stresses and bacterial virulence. Furthermore, we challenge the bacterial samples with ciprofloxacin to see how they behave under different stress conditions. The present study can be extended to model deadly diseases like bacteremia using organ-on-a-chip technology and help understand bacterial pathogenicity under realistic environments.Figure:

A schematic representation of the present work. Figure created with BioRender (www.biorender.com)
Engineering the glioblastoma microenvironment using TLR7/8 agonist-complexed graphene oxide nanosheets
Authors: Stylianou Maria , Kisby Thomas , Despotopoulou Despoina , Parker Helen , Thawley Alexandra , Arashvand Kiana , Lozano Neus , MacDonald Andrew S. , Kostarelos Kostas
Published: September 2023

The glioblastoma (GBM) microenvironment is characterised as immunologically ‘cold’, with immunosuppressive components that compromise the efficacy of current immunotherapies. Tumour associated macrophages and microglia (TAMMs) that are activated towards an immunosuppressive, pro-tumoral state have been identified as major contributing factors to the ‘coldness’ of GBM, while further promoting tumour progression and resistance to therapy. Based on this understanding, strategies such as macrophage reprogramming have been explored but have so far been limited by poor delivery and retention of reprogramming agents to the target cell populations within the GBM microenvironment. Consequently, clinical efficacy of such approaches has thus far shown limited success. Two-dimensional, graphene oxide (GO) nanosheets have been demonstrated to spread readily throughout the entire tumour microenvironment following a single intratumoral injection, interacting primarily with TAMMs. The current study aimed to investigate whether the immunosuppressive character of TAMMs in GBM can be ameliorated using GO sheets as a vector system to selectively deliver a TLR7/8 agonist (Resiquimod, R848), into these populations. GO enhanced the activity of R848 and induced the expression of M1-like markers on bone marrow derived macrophagesin vitro. Using multi-parameter flow cytometry and histological analysis in a syngeneic, orthotopic mouse model of GBM, we observed that a single intratumoral injection of GO:R848 complex significantly elevated the proportion of macrophages and microglia expressing MHCII, TNFα and CD86 (associated with a pro-inflammatory, anti-tumoral state), while downregulating their expression of the M2 markers ARG1 and YM1 (associated with an anti-inflammatory, pro-tumoral state). This local complex administration inhibited tumour progression and significantly reduced tumour burden. These data illustrate that immunomodulatory GO nanosheets can effectively alter the immune landscape of GBM and modulate the wider GBM microenvironment.

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Allelic variants confer Arabidopsis adaptation to small regional environmental differences
Authors: Wijfjes Raúl Y. , Boesten René , Becker Frank F. M. , Theeuwen Tom P. J. M. , Snoek Basten L. , Mastoraki Maria , Verheijen Jelle J. , Güvencli Nuri , Denkers Lissy-Anne M. , Koornneef Maarten , van Eeuwijk Fred A. , Smit Sandra , de Ridder Dick , Aarts Mark G.M.
Published: September 2023

Natural populations ofArabidopsis thalianaprovide powerful systems to study adaptation of wild plant species. Previous research has predominantly focused on global populations or accessions collected from regions with diverse climates. However, little is known about the genetics underlying adaptation in regions with mild environmental clines. We have examined a diversity panel consisting of 192A. thalianaaccessions collected from the Netherlands, a region with limited climatic variation. Despite the relatively uniform climate, we identified compelling evidence of local adaptation within this population. Notably, semidwarf accessions, due to mutation of theGIBBERELLIC ACID REQUIRING 5(GA5) gene, occur at a relatively high frequency near the coast and these displayed enhanced tolerance to high wind velocities. Additionally, we evaluated the performance of the population under iron deficiency conditions and found that allelic variation in theFE SUPEROXIDE DISMUTASE 3(FSD3) gene affects tolerance to low iron levels. Moreover, we explored patterns of local adaptation to environmental clines in temperature and precipitation, observing that allelic variation atLA RELATED PROTEIN 1C(LARP1c) likely affects drought tolerance. Not only is the genetic variation observed in a diversity panel ofA. thalianacollected in a region with mild environmental clines comparable to that in collections sampled over larger geographic ranges, it is also sufficiently rich to elucidate the genetic and environmental factors underlying natural plant adaptation.
An Information-Theoretic Approach to Reward Rate Optimization in the Tradeoff Between Controlled and Automatic Processing in Neural Network Architectures
Authors: Petri Giovanni , Musslick Sebastian , Cohen Jonathan D.
Published: September 2023

This article introduces a quantitative approach to modeling the cost of control in a neural network architecture when it is required to execute one or more simultaneous tasks, and its relationship to automaticity. We begin by formalizing two forms of cost associated with a given level of performance: anintensity costthat quantifies how much information must be added to the input to achieve the desired response for a given task, that we treat as the contribution ofcontrol; and aninteraction costthat quantifies the degree to which performance is degraded as a result of interference between processes responsible for performing two or more tasks, that we treat as inversely related toautomaticity. We develop a formal expression of the relationship between these two costs, and use this to derive the optimal control policy for a desired level of performance. We use that, in turn, to quantify the tradeoff between control and automaticity, and suggest how this can be used as a normative framework for understanding how people adjudicate between the benefits of control and automaticity.
Phenotypic characterization ofHAM1, a novel mating regulator of the fungal pathogenCryptococcus neoformans
Authors: Yee Elizabeth Arsenault , Ross Robbi L. , Santiago-Tirado Felipe H.
Published: September 2023

Cryptococcus neoformansis a fungal pathogen responsible for >200,000 yearly cases with a mortality as high as 81%. This burden results, in part, from an incomplete understanding of its pathogenesis and ineffective antifungal treatments; hence, there is a pressing need to understand the biology and host interactions of this yeast to develop improved treatments. Protein palmitoylation is important for cryptococcal virulence, and we previously identified the substrates of its main palmitoyl transferase. One of them was encoded by the uncharacterized gene CNAG_02129. In the filamentous fungusNeurospora crassa, a homolog of this gene named HAM-13 plays a role in proper cellular communication and filament fusion. InCryptococcus, cellular communication is essential during mating, therefore we hypothesized that CNAG_02129, which we namedHAM1,may play a role in mating. We found thatham1Δ mutants produce more fusion products during mating, filament more robustly, and exhibit competitive fitness defects under mating and non-mating conditions. Additionally, we found several differences with the major virulence factor, the polysaccharide capsule, that may affect virulence, consistent with prior studies linking virulence to mating. We observed thatham1Δ mutants have decreased capsule attachment and transfer but exhibit higher amounts of exopolysaccharide shedding and biofilm production. Lastly,HAM1expression is significantly lower in mating media relative to non-mating conditions, consistent with it acting as a negative regulator of mating. Understanding the connection between mating and virulence inC. neoformansmay open new avenues of investigation into ways to improve the treatment of this disease.

Importance

Fungal mating is a vital part of the lifecycle of the pathogenic yeastCryptococcus neoformans. More than just ensuring the propagation of the species, mating allows for sexual reproduction to occur and generates genetic diversity as well as infectious propagules that can invade mammalian hosts. Despite its importance in the biology of this pathogen, we still do not know all of the major players regulating the mating process and if they are involved or impact its pathogenesis. Here we identified a novel negative regulator of mating that also affects certain cellular characteristics known to be important for virulence. This gene, which we callHAM1, is widely conserved across the cryptococcal family as well as in many pathogenic fungal species. This study will open new avenues of exploration regarding the function of uncharacterized but conserved genes in a variety of pathogenic fungal species, and specifically in serotype A ofC. neoformans.
Ventromedial Frontoinsular Connectivity is Associated with Long-term Smoking Behavior Change in Aging
Authors: Thovinakere Nagashree , Ai Meishan , Noriega de la Colina Adrián E. , Walker Caitlin , Baracchini Giulia , Tremblay-Mercier Jennifer , Villeneuve Sylvia ,   The PREVENT-AD Research Group, Nathan Spreng R. , Geddes Maiya R.
Published: September 2023

A central question in the field of cognitive aging and behavioral neuroscience is what enables some individuals to successfully change their behavior more than others? Smoking is a significant risk factor for cognitive decline, particularly in vulnerable populations, including those who are at an elevated risk for Alzheimer’s disease (AD). Developing effective smoking reduction strategies is therefore a public health priority. The goal of the current study is to better understand the brain mechanisms underlying long-term smoking behavior change in cognitively normal, but at-risk, older adults. Neuroimaging and human lesional studies have implicated the insula and its functional network in subjective interoceptive awareness of cigarette craving and smoking-cue reactivity. We sought to characterize the extent to which anterior insular resting-state functional connectivity MRI predicted long-term smoking reduction (mean: 2.7 years, range 8 months – 4 years) using a seed-to-voxel approach. Twenty-three (18 women; 26%APOE4carriers; 61.5 years, SD = 3.7) cognitively unimpaired older individuals who smoked cigarettes at their baseline visit and have a first-degree family history of AD (at least one parent or multiple siblings affected) were included from a prospective longitudinal cohort, PREVENT-AD (Pre-symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer Disease) in the current study. We found that reduced long-term smoking behavior was associated with diminished functional connectivity between bilateral anterior insula and ventromedial prefrontal cortex (vmPFC). In a second pre-registered replication study within a larger, independent sample of one hundred and eighteen cognitively normal older adults who smoked cigarettes at baseline from the UK Biobank (73 women; 27.9 %APOE4carriers; 60.3 years, SD = 2.7), we found that baseline diminished resting-state functional connectivity between anterior insula and vmPFC predicted long-term smoking reduction (mean 5.2 years; ranging from 3 years to 7 years). To our knowledge, this is the largest study to examine the neural substrates of long-term smoking cessation in human aging. Our results suggest that frontoinsular circuits may be a therapeutic target for smoking reduction and disease prevention in older adults at risk for AD.
Brain organoid-on-a-chip to create multiple domains in forebrain organoids
Authors: Tsai Yuan-Chen , Ozaki Hajime , Morikawa Ango , Shiraiwa Kaori , Pin Andy Prosvey , Salem Aya Galal , Phommahasay Kenneth Akady , Sugita Bret Kiyoshi , Vu Christine Hein , Mamoun Hammad Saba , Kamei Ken-ichiro , Watanabe Momoko
Published: September 2023

Brain organoids are three-dimensionally reconstructed brain tissue derived from pluripotent stem cells in vitro. 3D tissue cultures have opened new avenues for exploring development and disease modeling. However, some physiological conditions, including signaling gradients in 3D cultures, have not yet been easily achieved. Here, we introduce Brain Organoid-on-a-Chip platforms that generate signaling gradients that in turn enable the induction of topographic forebrain organoids. This creates a more continuous spectrum of brain regions and provides a more complete mimic of the human brain for evaluating neurodevelopment and disease in unprecedented detail.
Investigation ofTrypanosoma-induced vascular damage sheds insights intoTrypanosoma vivaxsequestration
Authors: Pereira Sara Silva , Brás Daniela , Porqueddu Teresa , Nascimento Ana M. , De Niz Mariana
Published: September 2023

Multiple blood-borne pathogens infecting mammals establish close interactions with the host vascular endothelium as part of their life cycles. In this work, we investigate differences in the interactions of threeTrypanosomaspecies:T. brucei, T. congolenseandT. vivaxwith the blood vasculature. Infection with these species results in vastly different pathologies, including different effects on vascular homeostasis, such as changes in vascular permeability and microhemorrhages. While all three species are extracellular parasites,T. congolenseis strictly intravascular, whileT. bruceiis capable of surviving both extra- and intravascularly. Our knowledge regardingT. vivaxtropism and its capacity of migration across the vascular endothelium is unknown. In this work, we show for the first time thatT. vivaxparasites sequester to the vascular endothelium of most organs, and that, likeT. congolense, T. vivaxY486 is largely incapable of extravasation. Infection with this parasite species results in a unique effect on vascular endothelium receptors including general downregulation of ICAM1 and ESAM, and upregulation of VCAM1, CD36 and E-selectin. Our findings on the differences between the two sequestering species (T. congolenseandT. vivax) and the non-sequestering, but extravasating,T. bruceiraise important questions on the relevance of sequestration to the parasite’s survival in the mammalian host, and the evolutionary relevance of both sequestration and extravasation.
Oscillatory correlates of threat imminence during virtual navigation
Authors: Karpov Galit , Lin Mei-Heng , Headley Drew B. , Baker Travis E.
Published: September 2023

The Predator Imminence Theory proposes that defensive behaviors depend on the proximity of a threat. While the neural mechanisms underlying this proposal have been well studied in animal models, it remains poorly understood in humans. To address this issue, we recorded EEG from twenty-four (15 female) young adults engaged in a first-person virtual reality Risk-Reward Interaction task. On each trial, participants were placed in a virtual room and then presented with either a threat or reward conditioned stimulus (CS) in the same room location (proximal) or different room location (distal). At a behavioral level, all participants learned to avoid the threat-CS, with most using the optimal behavior to actively avoid the proximal threat-CS (88% accuracy) and passively avoid the distal threat-CS (69% accuracy). By contrast, participants learned to actively approach the distal reward-CS (82% accuracy) and to remain still (passive) to the proximal reward-CS (72% accuracy). At an electrophysiological level, we observed a general increase in theta power (4-8 Hz) over right posterior channel P8 across all CS conditions, with the proximal threat-CS evoking the largest theta response. By contrast, distal CS cues induced two bursts of gamma (30-60 Hz) power over midline-parietal channel Pz (approx. 200 msec post-cue) and right frontal channel Fp2 (approx. 300 msec post-cue). Interestingly, while both bursts were sensitive to distal-CS cues, the first burst of gamma power was sensitive to the distal threat-CS requiring a passive response, and the second burst at channel Fp2 was sensitive to the distal reward-CS requiring an active response. Together, these findings demonstrate that oscillatory processes differentiate between the spatial proximity information during threat and reward encoding, likely optimizing the selection of the appropriate behavioral response.
Enhancement of neurophysiological signatures of working memory by combined yoga and tDCS
Authors: Sefat Omid , Salehinejad Mohammad Ali , Danilewitz Marlon , Shalbaf Reza , Vila-Rodriguez Fidel
Published: September 2023

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technology that can modulate cortical excitability. Similarly, yoga has been found to influence neuronal activity and cognition. The aim of this study was to investigate the impact of combined yoga and tDCS on event-related potential (ERP) components during an N-Back working memory task. In a randomized, double-blind, cross-over design study, 22 healthy participants underwent a yoga/active tDCS session (2mA; 20min; anode on F3, cathode on F4) or a yoga/sham tDCS session on two different days. During the N-Back task, ERP components were obtained before and after each intervention. Results show that active tDCS plus yoga was associated with significant changes in the amplitude of the P200 component for the 2-Back in Fz and F3 channels and P300 for 3-Back in F3 and Pz electrodes. These results suggest that combining behavioral and electrical neuromodulation techniques may have the potential to enhance cognition and neurophysiological effects.
A high-resolution cryo-EM structure of a bacterial M-protein reveals a compact structure that diverges from related M-proteins
Authors: Readnour Bradley M. , Tjia-Fleck Sheiny , McCann Nathan R. , Ayinuola Yetunde A. , Castellino Francis J.
Published: September 2023

The surface ofStreptococcus pyogenes(GAS) is studded with virulence determinants, with the most abundant being the characteristic M-protein used to serotype various strains of the bacterium. There are >250 strains of GAS serotypically distinguished by their M-proteins. Major pathogenic mechanisms of GAS require that this microorganism hijacks host components for survival, many of which are involved in hemostasis. One of these processes involves the binding of human host plasminogen (hPg) to an abundant GAS M-protein receptor (PAM). When bound to PAM, hPg is readily activated to the serine protease plasmin (hPm) by bacterial and host hPg activators, and cell-bound hPm is protected from inactivation by its natural inhibitors. This stabilizes a potent protease on GAS cells which aids in their survival and dissemination. Highly evolutionary domain-related M-proteins are assumed to form long alpha-helical projections, without tertiary structure, although no M-protein complete structure has been determined. Here, we employed cryogenic electron microscopy to solve such a structure anchored to a lentivirus particle membrane. Contrary to the belief in this field that M-proteins are extended long tropomyosin-like coils, we show that PAM folds through intra- and inter-domain interactions to a much more globular form on the cell surface. The nature of the folding and the many interactions involved in forming the PAM tertiary structure are summarized herein.

Significance

We provide a unique approach to solve high-resolution structures ofStreptococcus pyogenes(GAS) M-proteins, abundant virulence determinants on the GAS surface. Because of their unusual nature, no full high-resolution structure of any M-protein has been determined, especially when membrane-bound. Herein, we provide a unique general methodology for solving these structures by engineering a M-protein to be anchored to a lentivirus particle membrane for effective use in cryo-EM. Using this approach, we provide the first structure of a complete bacterial M-protein and show, that this M-protein is a monomeric globular structure on the cell surface, and not a dimeric coiled-coil, as generally believed. Thus, individual M-proteins may adopt structures that have evolved to accommodate their major host binding partner.
An Evaluation of Representational Similarity Analysis for Model Selection and Assessment in Computational Neuroscience
Authors: Chen Luke
Published: September 2023

An important goal in neuroscience is to determine what types of information are represented across brain regions. Often, a computational model is used to extract stimulus features that are hypothesized to be represented within a particular brain region. Any particular study tries to assess the relationship between the features extracted by the computational model and the measured activity from a brain region. In recent years, several approaches to studying this relationship have been developed in the field of cognitive neuroscience. A simple and widely used approach is representational similarity analysis (RSA). This approach attempts to quantify similarities between the representational space of a computational model and a set of brain responses. RSA begins with an estimate of the stimulus-by-stimulus representational similarity (or dissimilarity) matrix computed from a set of stimulus-evoked brain responses. Then, a stimulus-by-stimulus representational similarity matrix is obtained from a computational model. RSA computes the similarity of these similarity matrices. However, there exists little work assessing the validity of RSA. In this paper, we show that RSA actually makes very strong assumptions about the relationship between representational spaces and brain responses. When these assumptions are violated, RSA can fail to detect significant relationships. More worryingly, when used for model selection RSA can lead researchers to the wrong answer. In contrast, we show that standard encoding models that use regression methods perform better than RSA.
A connection between the ribosome and twoS. pombetRNA modification mutants subject to rapid tRNA decay
Authors: De Zoysa Thareendra , Hauke Alayna C. , Iyer Nivedita R. , Marcus Erin , Ostrowski Sarah M. , Fay Justin C. , Phizicky Eric M.
Published: September 2023

tRNA modifications are crucial in all organisms to ensure tRNA folding and stability, and accurate translation in the ribosome. In both the yeastSaccharomyces cerevisiaeand the evolutionarily distant yeastSchizosaccharomyces pombe, mutants lacking certain tRNA body modifications (outside the anticodon loop) are temperature sensitive due to rapid tRNA decay (RTD) of a subset of hypomodified tRNAs. Here we show that for each of twoS. pombemutants subject to RTD, mutations in ribosomal protein genes suppress the temperature sensitivity without altering tRNA levels. Prior work showed thatS.pombe trm8Δmutants, lacking 7-methylguanosine, were temperature sensitive due to RTD and that one class of suppressors had mutations in the general amino acid control (GAAC) pathway, which was activated concomitant with RTD, resulting in further tRNA loss. We now find that another class ofS. pombe trm8Δsuppressors have mutations inrplgenes, encoding 60S subunit proteins, and that suppression occurs with minimal restoration of tRNA levels and reduced GAAC activation. Furthermore,trm8Δsuppression extends to other mutations in the large or small ribosomal subunit. We also find thatS. pombe tan1Δmutants, lacking 4-acetylcytidine, are temperature sensitive due to RTD, that one class of suppressors haverplmutations, associated with minimal restoration of tRNA levels, and that suppression extends to otherrplandrpsmutations. However, althoughS. pombe tan1Δtemperature sensitivity is associated with some GAAC activation, suppression by anrplmutation does not significantly inhibit GAAC activation. These results suggest that ribosomal protein mutations suppress the temperature sensitivity ofS. pombe trm8Δ andtan1Δ mutants due to reduced ribosome concentrations, leading to both a reduced requirement for tRNA, and reduced ribosome collisions and GAAC activation. Results withS. cerevisiae trm8Δ trm4Δmutants are consistent with this model, and fuel speculation that similar results will apply across eukaryotes.
A Computational Account of Real-World Attentional Allocation Based on Visual Gain Fields
Authors: Harrison William J , Stead Imogen , Wallis Thomas SA , Bex Peter J , Mattingley Jason B
Published: September 2023

Coordination of goal-directed behaviour depends on the brain’s ability to recover the locations of relevant objects in the world. In humans, the visual system encodes the spatial organisation of sensory inputs, but neurons in early visual areas map objects according to their retinal positions, rather than where they are in the world. How the brain computes world-referenced spatial information across eye movements has been widely researched and debated. Here we tested whether shifts of covert attention are sufficiently precise in space and time to track an object’s real-world location across eye movements. We found that observers’ attentional selectivity is remarkably precise, and is barely perturbed by the execution of saccades. Inspired by recent neurophysiological discoveries, we developed an observer model that rapidly estimates the real-world locations of objects and allocates attention within this reference frame. The model recapitulates the human data and provides a parsimonious explanation for previously reported phenomena in which observers allocate attention to task-irrelevant locations across eye movements. Our findings reveal that visual attention operates in real-world coordinates, which can be computed rapidly at the earliest stages of cortical processing.
Dynamics of diversified A-to-I editing inStreptococcus pyogenesis governed by changes in mRNA stability
Authors: Wulff Thomas F. , Hahnke Karin , Lécrivain Anne-Laure , Schmidt Katja , Ahmed-Begrich Rina , Finstermeier Knut , Charpentier Emmanuelle
Published: September 2023

Adenosine-to-inosine (A-to-I) RNA editing plays an important role in the post-transcriptional regulation of eukaryotic cell physiology. However, our understanding of the occurrence, function and regulation of A-to-I editing in bacteria remains limited. Bacterial mRNA editing is catalysed by the deaminase TadA, which was originally described to modify a single tRNA inE. coli. Intriguingly, several bacterial species appear to perform A-to-I editing on more than one tRNA. Here, we provide evidence that in the human pathogenStreptococcus pyogenes, tRNA editing has expanded to an additional tRNA substrate. Using RNA sequencing, we identified more than 27 editing sites in the transcriptome ofS. pyogenesSF370 and demonstrate that the adaptation ofS. pyogenesTadA to a second tRNA substrate has also diversified the sequence context and recoding scope of mRNA editing. Based on the observation that editing is dynamically regulated in response to several infection-relevant stimuli, such as oxidative stress, we further investigated the underlying determinants of editing dynamics and identified mRNA stability as a key modulator of A-to-I editing. Overall, our findings reveal the presence and diversification of A-to-I editing inS. pyogenesand provide novel insights into the plasticity of the editome and its regulation in bacteria.

GRAPHICAL ABSTRACT
Sleep-related benefits to transitive inference are modulated by encoding strength and joint rank
Authors: Foldes Tamas , Santamaria Lorena , Lewis Penny
Published: September 2023

Transitive inference is a measure of relational learning that has been shown to improve across sleep. Here, we examine this phenomenon further by studying the impact of encoding strength and joint rank. In experiment 1, participants learned adjacent premise pairs and were then tested on inferential problems derived from those pairs. In line with prior work, we found improved transitive inference performance after retention across a night of sleep compared with wake alone. Experiment 2 extended these findings using a within-subject design and found superior transitive inference performance on a hierarchy, consolidated across 27 h including sleep compared with just 3 h of wake. In both experiments, consolidation-related improvement was enhanced when presleep learning (i.e., encoding strength) was stronger. We also explored the interaction of these effects with the joint rank effect, in which items were scored according to their rank in the hierarchy, with more dominant item pairs having the lowest scores. Interestingly, the consolidation-related benefit was greatest for more dominant inference pairs (i.e., those with low joint rank scores). Overall, our findings provide further support for the improvement of transitive inference across a consolidation period that includes sleep. We additionally show that encoding strength and joint rank strongly modulate this effect.
Bragg coherent modulation imaging for highly strained nanocrystals: a numerical study
Authors: Zhao Jiangtao , Vartanyants Ivan A. , Zhang Fucai
Published: September 2023

Bragg coherent diffraction imaging (BCDI) is a unique and powerful method for tracking 3D strain fields non-destructively. While BCDI has been successfully applied to many scientific research fields and is in high demand, the reconstructed results for highly strained crystals are still subject to substantial uncertainties. Here, progress in improving the suitability of BCDI for general samples by exploiting wavefront modulation is reported. Extensive numerical simulations demonstrate that significant improvements over the current method for reconstructing highly strained model nanocrystals can be achieved. The proposed method strongly suppresses the appearance of ambiguous solutions, and exhibits fast convergence and high robustness in phase retrieval. Possible experimental difficulties in implementing this method are discussed in detail.
At-wavelength characterization of X-ray wavefronts in Bragg diffraction from crystals
Authors: Shi Xianbo , Qiao Zhi , Pradhan Paresh , Liu Peifan , Assoufid Lahsen , Kim Kwang-Je , Shvyd'ko Yuri
Published: September 2023

The advent of next-generation synchrotron radiation sources and X-ray free-electron lasers calls for high-quality Bragg-diffraction crystal optics to preserve the X-ray beam coherence and wavefront. This requirement brings new challenges in characterizing crystals in Bragg diffraction in terms of Bragg-plane height errors and wavefront phase distortions. Here, a quantitative methodology to characterize crystal optics using a state-of-the-art at-wavelength wavefront sensing technique and statistical analysis is proposed. The method was tested at the 1-BM-B optics testing beamline at the Advanced Photon Source for measuring silicon and diamond crystals in a self-referencing single-crystal mode and an absolute double-crystal mode. The phase error sensitivity of the technique is demonstrated to be at the λ/100 level required by most applications, such as the characterization of diamond crystals for cavity-based X-ray free-electron lasers.
Passive doubly curved structures for determining clamping forces applied to X-ray optic assemblies
Authors: Bainbridge Eleanor Victoria , Griffiths Jonathan David , Patel Hiten , Clunan Jessica , Docker Peter
Published: September 2023

Clamping of indirectly cryogenically cooled X-ray optics is required to ensure effective heat transfer between the optic and heat exchanger. However, clamping forces can result in distortion of the optical surface of monochromators and mirror systems, which causes angular distortions of the subsequent beam. As such, there is a need for greater understanding of how these optics are assembled and how this affects their performance throughout their life cycle. In this paper, the potential for non-contact, in-process monitoring of the clamping force both during and after assembly using an additively manufactured passive structure based on a doubly curved hyperbolic paraboloid and designed for application to the first crystal for the I20 monochromator at Diamond Light Source is investigated numerically and experimentally. The performance of the passive structure both pre- and post-cryogenic quenching is characterized experimentally. Laser displacement measurements reveal approximately 9 µm total displacement in the passive structure per 100 N of bolt preload, corresponding to an effective magnification of the preload adjustment of approximately 2.5×.
Social media adoption by women entrepreneurial small businesses
Authors: Alhakimi Wail , Albashiri Sumaya
Published: September 2023

Purpose

The purpose of this study is to evaluate the factors related to the adoption of social media by women entrepreneurial small businesses (ESBs).

Design/methodology/approach

Using a structured survey instrument, this study gathered data from 101 women entrepreneurs in Yemen. Descriptive statistics were used to analyze the data.

Findings

The results confirm that social media has been widely applied by women ESBs in Yemen and has made a significant contribution to different business strategies and processes, mainly marketing, promotion and communication. Social media adoption is linked mainly with nontechnical obstacles and challenges, in specific, those “soft” factors such as management attitude, as well as “hard” technical obstacles and challenges involving cost and other practical aspects regarding social media nature.

Practical implications

This study contributes to the increase in awareness of the impact of social media among female ESB owners. A greater understanding of the impact of social media will eventually lead to better use of the tool to increase performance.

Originality/value

This study highlights the perceived benefits and challenges that give Yemeni female business owners strong decision-making power in their businesses. This study provides insight into the numerous drivers that affect owners/managers’ decisions to adopt and continuously use social media in the future.
Perceived job insecurity climate in uncertain times: implications for work-related health among leaders versus non-leaders
Authors: Glambek Mats , Arnestad Mads Nordmo , Matthiesen Stig Berge
Published: September 2023

Purpose

Previous studies have demonstrated that perceived job insecurity climate denotes an individual-level stressor. The present study reiterated this notion and investigated whether leadership responsibility moderated the association between perceived job insecurity climate and work-related strain about one year into the coronavirus disease (COVID-19) pandemic.

Design/methodology/approach

A sample of full-time workers (N = 1,399) in the USA was recruited, comprising 663 leaders and 763 non-leaders. Employing a cross-sectional design, the authors hypothesized that perceived job insecurity climate would be associated with work-related strain (i.e. burnout, absenteeism and presenteeism) and that these associations were stronger for employees with leadership responsibilities compared to non-leaders.

Findings

Findings revealed main effects of perceived job insecurity climate on burnout but not on absenteeism or presenteeism. Furthermore, leadership responsibility moderated the associations between perceived job insecurity climate and two out of three burnout measures in the hypothesized direction. The findings also revealed interaction effects regarding absenteeism and presenteeism, indicating that these associations are only positive and significant for employees with leadership responsibilities.

Practical implications

Perceptions of widespread job insecurity engender strain among leaders while simultaneously implying a heightened need for effective leadership. Organizations and practitioners should take the present findings into consideration when implementing preventive and restorative measures to address leaders' health and organizational competitiveness when job insecurity increases.

Originality/value

This study found that, as an individual stressor, perceived job insecurity climate is more detrimental to employees with leadership responsibility than to non-leaders.
Social media marketing for luxury brands: parasocial interactions and empowerment for enhanced loyalty and willingness to pay a premium
Authors: Zha Tao , Aw Eugene Cheng-Xi , Dastane Omkar , Fernando Angeline Gautami
Published: September 2023

Purpose

This research aims to unravel the intricate relationship between luxury brands' social media marketing strategies (i.e. communication and engagement) and their impact on consumers' willingness to pay a premium and brand loyalty.

Design/methodology/approach

A large online consumer panel was used to conduct an online survey of 381 consumers. Partial least squares structural equation modeling was adopted for hypothesis testing.

Findings

The study's outcomes indicated that (1) perceived interactivity and perceived openness positively influence social media brand communication, (2) social media brand communication and engagement are positive determinants for consumer empowerment and parasocial interactions, (3) consumer empowerment and parasocial interactions positively influence willingness to pay a premium and (4) parasocial interactions (but not consumer empowerment) positively influence brand loyalty.

Research limitations/implications

The study offers significant theoretical implications by unraveling the mechanism of social media marketing for luxury brands, which is under-researched in the current literature. More specifically, the study reveals the process of how social media brand communication and engagement reinforce luxury brand outcomes through parasocial interactions and consumer empowerment. In addition, the study provides empirical evidence to delineate the role of interactivity and openness in enhancing social media brand communication. Moreover, the study extends past research that emphasized initial adoption outcomes such as attitude and purchase intention by probing luxury brand loyalty and willingness to pay a premium.

Practical implications

By effectively strategizing social media marketing, luxury brand marketers can promote brand loyalty and willingness to pay a premium. Luxury brand marketers should concentrate on establishing parasocial interaction with consumers by designing optimal social media brand communication and engagement. To this end, luxury brand marketers should consider integrating the elements of interactivity and openness in their communication with consumers.

Originality/value

The study offers valuable insights for luxury brand marketers aiming to capitalize on the potential of social media marketing to enhance their revenue generation and customer retention. The study advances past luxury branding research by validating the role of consumer empowerment and parasocial interactions in luxury brands' social media marketing.