bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying the linkages between California sea lion (Zalophus californianus) strandings and particulate domoic acid concentrations at piers across Southern California
Authors: Smith Jayme , Cram Jacob A. , Berndt Malena , Hoard Vanessa , Shultz Dana , Deming Alissa C.
Published: August 2023

Domoic acid producing blooms of the diatom genusPseudo-nitzschiaare pervasive in coastal environments globally. Domoic acid, a neurotoxin, accumulates via trophic transfer into marine food webs and are often associated with mass marine mammal mortality and stranding events. In Southern California, California sea lions (Zalophus californiaus) are an indicator species for food web impacts of domoic acid because they are abundant secondary consumers, sensitive to domoic acid intoxication, and are actively monitored by stranding networks. However, domoic acid exposure may occur a distance from where a sea lion ultimately strands. This spatiotemporal variation complicates coupling domoic acid observations in water to strandings. Therefore, we sought to quantify whether monitoring data from four pier sites across the region, covering nearly 700 km of coastline from 2015-2019, could be used to predict adult and subadult sea lion strandings along the 68 km Orange County coastline surveyed by the Pacific Marine Mammal Center. We found that increased sea lion strandings were often observed just prior to an increase in particulate domoic acid at the piers, confirming that clusters of subadult and adult sea lion strandings with clinical signs of domoic acid intoxication a serve as indicators of bloom events. In addition, domoic acid concentrations at Stearns Wharf, nearly 200 km from stranding locations, best predicted increased total sea lion strandings, and strandings of sea lions with domoic acid intoxication symptoms. Particulate domoic acid concentrations greater than 0.05 μg/L at Stearns Wharf led to a detectable increase in stranding probability in Orange County, and concentrations over 0.25 μg/L resulted in a nearly 1.6-fold increase in stranding probabilities for a given week.
Individual genotype but not phenotype predicts river migration success in Atlantic salmon
Authors: Moccetti Paolo , Bolland Jonathan D. , Adams Colin E. , Rodger Jessica R. , Honkanen Hannele M. , Newton Matthew , Lothian Angus J. , Nunn Andy D. , Joyce Domino A.
Published: August 2023

Migratory species typically undertake demanding long-distance journeys, across different habitat types during which they are exposed to multiple natural and anthropogenic stressors. Mortality during migration is typically high, and may be exacerbated by human-induced pressures. Understanding individual responses to these selection pressures is rarely attempted, because of the challenges of relating individual phenotypic and genetic data to migration success. Here we show distinct Single Nucleotide Polymorphism (SNP) sets significantly differentiated between Atlantic salmon smolts making successful migrations to sea and those that failed to migrate, in two different rivers. In contrast, morphological variation was not diagnostic of migration success. Populations from each river were genetically distinct, and while different genes were possibly implicated in migration success in each river, they related to common biological processes (for example osmoregulation and immune and stress response). Given that migration failure should quickly purge polymorphism at selected SNPs from a population, the question of how genetic diversity in these populations is maintained is an important one. Standing genetic variation could be maintained by different life history strategies and/or environmentally driven balancing selection. Our work highlights the importance of preserving genetic diversity to ensure evolutionary resilience at the population level, and has practical implications for management.
Accurate determination of house dust mite sensitization in asthma and allergic rhinitis through cytometric detection of Der p 1 and Der p 2 binding on Basophils (CytoBas)
Authors: Hsin Lin , Varese Nirupama , Aui Pei Mun , Wines Bruce D. , Mascarell Laurent , Hogarth Mark P. , Hew Mark , O’Hehir Robyn E. , van Zelm Menno C.
Published: August 2023

Background

House dust mite (HDM) is the commonest allergen trigger globally for allergic rhinitis and atopic asthma. To expedite accurate confirmation of allergen sensitization, we designed fluorescent allergen tetramers to directly stain specific IgE on basophils to detect allergen sensitization using the flow cytometric CytoBas assay.

Methods

Recombinant proteins of major HDM allergens (component), Der f 1, Der p 1 and Der p 2 were biotinylated and conjugated with fluorochrome streptavidins as tetramers. Blood samples from 64 HDM-allergic patients and 26 non-HDM-sensitized controls were incubated with allergen tetramers for evaluation of basophil binding (CytoBas) and activation (BAT) with flow cytometry.

Results

The tetramers effectively bound and activated basophils from allergic patients but not non-sensitized controls. CytoBas with Der p 1 as a single allergen had comparable sensitivity and specificity (92% and 100%) to BAT (91% and 100%), similarly for CytoBas with a single Der p 2 (95% and 96%) to BAT (95% and 87%) in detecting allergen sensitization. A positive staining for Der p 1 and/or Der p 2 was 100% sensitive and 96% specific for HDM allergy.

Conclusions

CytoBas has diagnostic accuracy for group 1 and group 2 HDM allergens that is comparable to a BAT assay, but with additional advantages of multiple allergen components in a single tube and no requirement forin vitrobasophil activation. These findings endorse a single, multiplex CytoBas assay for accurate and component-resolved diagnosis of aeroallergen sensitization in patients with allergic asthma and/or rhinitis.

CAPSULE SUMMARY

A single flow cytometry stain of basophils (CytoBas) with both Der p 1 and Der p 2 provides >95% specificity and sensitivity for detection of functional HDM allergen sensitization.

Highlights

Fluorescent tetramers of recombinant Der f 1, Der p 1 and Der p 2 can be used to detect functional IgE sensitization to house dust mite (HDM) by flowcytometric detection on basophils (CytoBas).

A single CytoBas assay with inclusion of both Der p 1 and Der p 2 can detect HDM sensitization with >95% sensitivity and specificity.
An in-silico approach to identify bioactive phytochemicals fromHouttuynia cordataThunb. As potential inhibitors of Human Glutathione Reductase
Authors: Sangeet Satyam , Khan Arshad
Published: August 2023

Cellular infections underpin the pathogenesis of cancer and malaria. Mitigating cellular oxidative stress via glutathione reductase (GR) inhibition emerges as a promising therapeutic avenue. Exploiting the antioxidant-richHouttuynia cordataThunb., we investigated natural GR inhibitors. Among 13 docked phytochemicals, Quercetin, Quercitrin, and Sesamin exhibited exceptional GR binding affinities. Molecular Docking analysis highlighted their propensity to precisely target the GR active site. Subsequent 150 ns molecular dynamics simulations corroborated their robust interactions, unveiling dynamic stabilizing effects on the protein structure and bolstering their antioxidant potential. Furthermore, ADME-Tox profiling affirmed their favourable drug-like attributes. These findings underscoreH. cordata’sreservoir of potent antioxidants, poised to combat various maladies, including malaria and cancer. This study distinctly accentuates the distinctive outcomes and paramount significance of harnessingH. cordataphytochemicals as efficacious antioxidants, unravelling novel therapeutic avenues.
Flexible gating between subspaces in a neural network model of internally guided task switching
Authors: Liu Yue , Wang Xiao-Jing
Published: August 2023

Behavioral flexibility relies on the brain's ability to switch rapidly between multiple tasks, even when the task rule is not explicitly cued but must be inferred through trial and error. The underlying neural circuit mechanism remains poorly understood. We investigated recurrent neural networks (RNNs) trained to perform an analog of the classic Wisconsin Card Sorting Test. The networks consist of two modules responsible for rule representation and sensorimotor mapping, respectively, where each module is comprised of a circuit with excitatory neurons and three major types of inhibitory neurons. We found that rule representation by self-sustained persistent activity across trials, error monitoring and gated sensorimotor mapping emerged from training. Systematic dissection of trained RNNs revealed a detailed circuit mechanism that is consistent across networks trained with different hyperparameters. The networks' dynamical trajectories for different rules resided in separate subspaces of population activity; the subspaces collapsed and performance was reduced to chance level when dendrite-targeting somatostatin-expressing interneurons were silenced, illustrating how a phenomenological description of representational subspaces is explained by a specific circuit mechanism.
Breakups and Hookups: a Markov model for karyotype evolution
Authors: Setter Derek
Published: August 2023

Chromosome rearrangements represent a prominent form of genetic variation that plays a key role in creating genetic isolation between emergent species. Despite their significance, the mechanisms and constraints governing chromosome evolution remain poorly understood. Relatively few species have karyotypes with very high chromosome counts, and the chromosome sizes of most species tend to be narrowly distributed around the mean length. Here, we develop and analyze a Markov model for the evolution of chromosome number and relative sizes through fission and fusion events, exploring several alternative models for the dynamics of each as well as the effect of enforcing limits on chromosome length. We compare the distribution of chromosome lengths predicted by the Markov model to karyotype data for a range of Eukaryote species to identify the best-fitting fission/fusion dynamics. We find broad support for a model which (i) favours the breaking of long chromosomes, (ii) favours the fusion of pairs of small chromosomes, and (iii) does not require size limitations to provide a good fit to the data. However, there are exceptions. On the one hand, species with micro chromosomes fit best to models with more uniform rates of fission and/or fusion. On the other hand, many species have chromosome sizes that are much more narrowly distributed than our models predict, suggesting the need to explore alternative dynamics and/or limitations to chromosome lengths.
Chemogenetic silencing of NaV1.8 positive sensory neurons reverses chronic neuropathic and bone cancer pain in FLEx PSAM4-GlyR mice
Authors: Haroun Rayan , Gossage Samuel J , Luiz Ana Paula , Arcangeletti Manuel , Sikandar Shafaq , Cox James J , Zhao Jing , Wood John N
Published: August 2023

Drive from peripheral neurons is essential in almost all pain states, but pharmacological silencing of these neurons to effect analgesia has proved problematic. Reversible gene therapy using long-lived chemogenetic approaches is an appealing option. We used the genetically-activated chloride channel PSAM4-GlyR to examine pain pathways in mice. Using recombinant AAV9-based delivery to sensory neurons, we found a reversal of acute pain behavior and diminished neuronal activity usingin vitroandin vivoGCaMP imaging upon activation of PSAM4-GlyR with varenicline. A significant reduction in inflammatory heat hyperalgesia and oxaliplatin-induced cold allodynia was also observed. Importantly, there was no impairment of motor coordination, but innocuous von Frey sensation was inhibited. We generated a transgenic mouse that expresses a CAG-driven FLExed PSAM4-GlyR downstream of theRosa26locus that requires Cre recombinase to enable the expression of PSAM4-GlyR and tdTomato. We used NaV1.8 Cre to examine the role of predominantly nociceptive NaV1.8+ neurons in cancer-induced bone pain (CIBP) and neuropathic pain caused by chronic constriction injury (CCI). Varenicline activation of PSAM4-GlyR in NaV1.8-positive neurons reversed CCI-driven mechanical, thermal, and cold sensitivity. Additionally, varenicline treatment of mice with CIBP expressing PSAM4-GlyR in NaV1.8+ sensory neurons reversed cancer pain as assessed by weight-bearing. Moreover, when these mice were subjected to acute pain assays, an elevation in withdrawal thresholds to noxious mechanical and thermal stimuli was detected, but innocuous mechanical sensations remained unaffected. These studies confirm the utility of PSAM4-GlyR chemogenetic silencing in chronic pain states for mechanistic analysis and potential future therapeutic use.

Significance statement

Chronic pain is a massive problem. Peripheral nerve block is effective in many chronic pain conditions, demonstrating the importance of peripheral drive in chronic pain. We used chemogenetic tools based on the modified ligand-gated chloride channel PSAM4-GlyR to silence dorsal root ganglion neuronsin vitroandin vivo. This approach reduces pain-like behavior in acute and chronic pain models, including resistant pain conditions like neuropathic pain or cancer-induced bone pain. We generated a mouse line that expresses PSAM4-GlyR in a Cre-dependent manner, providing a useful research tool to address not only the role of nociceptive sensory neurons in pain states but also the function of genetically defined sets of neurons throughout the nervous system in normal and pathological conditions.
Analyzing heterogeneity in Alzheimer Disease using multimodal normative modeling on imaging-based ATN biomarkers
Authors: Kumar Sayantan , Earnest Tom , Yang Braden , Kothapalli Deydeep , Aschenbrenner Andrew J. , Hassenstab Jason , Xiong Chengie , Ances Beau , Morris John , Benzinger Tammie L. S. , Gordon Brian A. , Payne Philip , Sotiras Aristeidis ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: August 2023

Structured Abstract

INTRODUCTION

Previous studies have applied normative modeling on a single neuroimaging modality to investigate Alzheimer Disease (AD) heterogeneity. We employed a deep learning-based multimodal normative framework to analyze individual-level variation across ATN (amyloid-tau-neurodegeneration) imaging biomarkers.

METHODS

We selected cross-sectional discovery (n = 665) and replication cohorts (n = 430) with available T1-weighted MRI, amyloid and tau PET. Normative modeling estimated individual-level abnormal deviations in amyloid-positive individuals compared to amyloid-negative controls. Regional abnormality patterns were mapped at different clinical group levels to assess intra-group heterogeneity. An individual-level disease severity index (DSI) was calculated using both the spatial extent and magnitude of abnormal deviations across ATN.

RESULTS

Greater intra-group heterogeneity in ATN abnormality patterns was observed in more severe clinical stages of AD. Higher DSI was associated with worse cognitive function and increased risk of disease progression.

DISCUSSION

Subject-specific abnormality maps across ATN reveal the heterogeneous impact of AD on the brain.
An eQTL-based Approach Reveals Candidate Regulators of LINE-1 RNA Levels in Lymphoblastoid Cells
Authors: Bravo Juan I. , Mizrahi Chanelle R. , Kim Seungsoo , Zhang Lucia , Suh Yousin , Benayoun Bérénice A.
Published: August 2023

Long interspersed element 1 (L1) are a family of autonomous, actively mobile transposons that occupy ∼17% of the human genome. A number of pleiotropic effects induced by L1 (promoting genome instability, inflammation, or cellular senescence) have been observed, and L1’s contributions to aging and aging diseases is an area of active research. However, because of the cell type-specific nature of transposon control, the catalogue of L1 regulators remains incomplete. Here, we employ an eQTL approach leveraging transcriptomic and genomic data from the GEUVADIS and 1000Genomes projects to computationally identify new candidate regulators of L1 RNA levels in lymphoblastoid cell lines. To cement the role of candidate genes in L1 regulation, we experimentally modulate the levels of top candidatesin vitro, includingIL16, STARD5, HSDB17B12,andRNF5, and assess changes in TE family expression by Gene Set Enrichment Analysis (GSEA). Remarkably, we observe subtle but widespread upregulation of TE family expression followingIL16andSTARD5overexpression. Moreover, a short-term 24-hour exposure to recombinant human IL16 was sufficient to transiently induce subtle, but widespread, upregulation ofL1subfamilies. Finally, we find that many L1 expression-associated genetic variants are co-associated with aging traits across genome-wide association study databases. Our results expand the catalogue of genes implicated in L1 RNA control and further suggest that L1-derived RNA contributes to aging processes. Given the ever-increasing availability of paired genomic and transcriptomic data, we anticipate this new approach to be a starting point for more comprehensive computational scans for transposon transcriptional regulators.
The 3’ exonuclease TOE1 selectively processes snRNAs through recognition of Sm complex assembly and 5’ cap trimethylation
Authors: Ma Tiantai , Xiong Erica S , Lardelli Rea M , Lykke-Andersen Jens
Published: August 2023

Competing exonucleases that promote 3’ end maturation or degradation direct quality control of small non-coding RNAs, but how these enzymes distinguish normal from aberrant RNAs is poorly understood. The Pontocerebellar Hypoplasia 7 (PCH7)-associated 3’ exonuclease TOE1 promotes maturation of canonical small nuclear RNAs (snRNAs). Here, we demonstrate that TOE1 achieves specificity towards canonical snRNAs by recognizing Sm complex assembly and cap trimethylation, two features that distinguish snRNAs undergoing correct biogenesis from other small non-coding RNAs. Indeed, disruption of Sm complex assembly via snRNA mutations or protein depletions obstructs snRNA processing by TOE1, and in vitro snRNA processing by TOE1 is stimulated by a trimethylated cap. An unstable snRNA variant that normally fails to undergo maturation becomes fully processed by TOE1 when its degenerate Sm binding motif is converted into a canonical one. Our findings uncover the molecular basis for how TOE1 distinguishes snRNAs from other small non-coding RNAs and explain how TOE1 promotes maturation specifically of canonical snRNAs undergoing proper processing.
Deciphering Salt Stress Responses inSolanum pimpinellifoliumthrough High-Throughput Phenotyping
Authors: Morton Mitchell , Fiene Gabriele , Ahmed Hanin Ibrahim , Rey Elodie , Abrouk Michael , Angel Yoseline , Johansen Kasper , Saber Noha O. , Malbeteau Yoann , Al-Mashharawi Samir , Ziliani Matteo G. , Aragon Bruno , Oakey Helena , Berger Bettina , Brien Chris , Krattinger Simon G. , Mousa Magdi A.A. , McCabe Matthew F. , Negrão Sónia , Tester Mark , Julkowska Magdalena M.
Published: August 2023

Soil salinity is a major environmental stressor affecting agricultural productivity worldwide. Understanding plant responses to salt stress is crucial for developing resilient crop varieties. Wild relatives of cultivated crops, such as wild tomato,Solanum pimpinellifolium, can serve as a useful resource to further expand the resilience potential of the cultivated germplasm,S. lycopersicum. In this study, we employed high-throughput phenotyping in the greenhouse and field conditions to explore salt stress responses of aS. pimpinellifoliumdiversity panel. Our study revealed extensive phenotypic variations in response to salt stress, with traits such as transpiration rate, shoot mass, and ion accumulation showing significant correlations with plant performance. We found that while transpiration was a key determinant of plant performance in the greenhouse, shoot mass strongly correlated with yield under field conditions. Conversely, ion accumulation was the least influential factor under greenhouse conditions. Through a Genome Wide Association Study, we identified candidate genes not previously associated with salt stress, highlighting the power of high-throughput phenotyping in uncovering novel aspects of plant stress responses. This study contributes to our understanding of salt stress tolerance inS. pimpinellifoliumand lays the groundwork for further investigations into the genetic basis of these traits, ultimately informing breeding efforts for salinity tolerance in tomato and other crops.
Omissions of Threat Trigger Subjective Relief and Prediction Error-Like Signaling in the Human Reward and Salience Systems
Authors: Willems Anne L. , Van Oudenhove Lukas , Vervliet Bram
Published: August 2023

The unexpected absence of danger constitutes a pleasurable event that is critical for the learning of safety. Accumulating evidence points to similarities between the processing of absent threat and the well-established reward prediction error (PE). However, clear-cut evidence for this analogy in humans is scarce. In line with recent animal data, we showed that the unexpected omission of (painful) electrical stimulation triggers activations within key regions of the reward and salience pathways and that these activations correlate with the pleasantness of the reported relief. Furthermore, by parametrically violating participants' probability and intensity related expectations of the upcoming stimulation, we showed for the first time in humans that omission-related activations in the VTA/SN were stronger following omissions of more probable and intense stimulations, like a positive reward PE signal. Together, our findings provide additional support for an overlap in the neural processing of absent danger and rewards in humans.
Decoding reveals the neural representation of perceived and imagined musical sounds
Authors: Quiroga Martinez David R. , Rubio Gemma Fernández , Bonetti Leonardo , Achyutuni Kriti G. , Tzovara Athina , Knight Robert T. , Vuust Peter
Published: August 2023

Vividly imagining a song or a melody is a skill that many people accomplish with relatively little effort. However, we are only beginning to understand how the brain represents, holds, and manipulates these musical “thoughts”. Here, we decoded perceived and imagined melodies from magnetoencephalography (MEG) brain data (N = 71) to characterize their neural representation. We found that, during perception, auditory regions represent the sensory properties of individual sounds. In contrast, a widespread network including fronto-parietal cortex, hippocampus, basal nuclei, and sensorimotor regions hold the melody as an abstract unit during both perception and imagination. Furthermore, the mental manipulation of a melody systematically changes its neural representation, reflecting volitional control of auditory images. Our work sheds light on the nature and dynamics of auditory representations, informing future research on neural decoding of auditory imagination.
Sulfasalazine promotes myogenic differentiation via increasing of fast myosin heavy chain isoforms
Authors: Cho Seungju , Choi Seonggyu , Chang Hyunjun , Tran Nguyen Khoi , Lee Hyunji , Ryu Sunyoung , Park Mihee , Choi Sangchul , Park Jisoo , Park Jongsun
Published: August 2023

Sarcopenia is a debilitating condition characterized by the progressive and generalized degeneration of skeletal muscle mass and function. As of now, there is no approved pharmacological treatment for sarcopenia. Previously, our research revealed that Yin Yang 1 (YY1) plays a crucial role in PHD finger protein 20 (PHF20)-mediated myogenic differentiation. A significant enhancement in YY1 transcription, mediated by PHF20, was observed in C2C12myoblasts. Within skeletal muscle, YY1 is traditionally considered to inhibit myogenesis by directly repressing the synthesis of late-stage differentiation genes, such as skeletal muscle actin, muscle creatine kinase, and myosin heavy chain IIb. Through screening of a drug library using a PHF20/YY1 promoter reporter assay, sulfasalazine emerged as a promising candidate. Sulfasalazine is known for its anti-inflammatory and immunomodulatory properties and is commonly prescribed for autoimmune diseases. In this study, the treatment of C2C12myoblasts with sulfasalazine accelerated the myogenic differentiation and bolstered the gene and protein expression of fast myosin heavy chain via a metabolic shift towards glycolysis. Additionally, oral administration of sulfasalazine demonstrated improvement in physical performance in aged mice, as well as in mice models with hindlimb disuse or damage. Moreover, sulfasalazine exhibited a remarkable ability to facilitate the recovery of muscle fibers damaged by Velcro immobilization. Collectively, our findings suggest that sulfasalazine could represent a novel therapeutic avenue for the amelioration of muscle weakness, including sarcopenia.
3D-Mol: A Novel Contrastive Learning Framework for Molecular Property Prediction with 3D Information
Authors: Kuang Taojie , Ren Yiming , Ren Zhixiang
Published: August 2023

Abstract

Molecular property prediction offers an effective and efficient approach for early screening and optimization of drug candidates. Although deep learning based methods have made notable progress, most existing works still do not fully utilize 3D spatial information. This can lead to a single molecular representation representing multiple actual molecules. To address these issues, we propose a novel 3D structure-based molecular modeling method named 3D-Mol. In order to accurately represent complete spatial structure, we design a novel encoder to extract 3D features by deconstructing the molecules into three geometric graphs. In addition, we use 20M unlabeled data to pretrain our model by contrastive learning. We consider conformations with the same topological structure as positive pairs and the opposites as negative pairs, while the weight is determined by the dissimilarity between the conformations. We compare 3D-Mol with various state-of-the-art(SOTA) baselines on 7 benchmarks and demonstrate our outstanding performance in 5 benchmarks.
How is sleep-disordered breathing linked with biomarkers of Alzheimer’s disease?
Authors: Akradi Mohammad , Farzane-Daghigh Tara , Ebneabbasi Amir , Bi Hanwen , Drzezga Alexander , Mander Bryce A. , Eickhoff Simon B. , Tahmasian Masoud ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: August 2023

Sleep-disordered breathing (SDB) is prevalent in Alzheimer’s disease (AD). We assessed whether and how SDB affects neuroimaging biomarkers of AD, including amyloid-beta plaque burden (Aβ), regional uptake of fluorodeoxyglucose using positron emission tomography (rFDG-PET), grey matter volume (GMV), as well as cognitive scores and cerebrospinal fluid (CSF) biomarkers.

Methods

We selected 757 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database based on cognitive status (AD, mild cognitive impairment (MCI), cognitively unimpaired (CU)), and SDB condition (with/without SDB). To ensure the reliability of our findings and considering imbalanced sample size across groups, we used a stratified subsampling approach generating 10,000 subsamples (n=10/group). We then selected 512 subsamples with matched covariates. The effect size of the cognitive status-SDB interaction was computed for each biomarker and cognitive score. For reference, we computed 1000 null models by shuffling group labels randomly. The average value of effect sizes for each biomarker in each region was estimated through bootstrapping with 10,000 iterations for both the main and null models and compared with the null model’s distribution. Linear regression models were next implemented to identify associations between the effect size on Aβ, rFDG, and GMV with the effect size on cognitive scores and CSF biomarkers across all subsamples.

Results

The cognitive status-SDB interaction had a medium-sized effect on Aβ, rFDG and GMV biomarkers in several brain areas. The effect sizes of the mentioned interactions on Aβ plaque burden in the right precuneus, left middle temporal gyrus, and left occipital fusiform gyrus were associated with the effect sizes of the interactions on cognitive scores. Further, the interaction effect sizes on CSF Aβ42 were related to the interaction effect sizes on Aβ in the right precuneus and posterior cingulate cortex, as well as rFDG in the left precuneus cortex and GMV in bilateral angular gyrus and right occipital fusiform gyrus. Effect sizes on CSF p-tau were also correlated with the effect sizes on Aβ in the left lateral occipital cortex and GMV in the left middle temporal gyrus.

Conclusion

We observed that SDB interacts with neuroimaging and CSF biomarkers of AD. Specifically, SDB has a robust association with markers of Aβ pathology in PET and CSF relative to rFDG and GMV in the AD group. The cognitive status-SDB interaction on Aβ is associated with cognitive decline. This study further supports the hypothesis that SDB may precipitate AD pathology.
Opsin gene duplication in Lepidoptera: retrotransposition, sex linkage, and gene expression
Authors: Mulhair Peter O. , Crowley Liam , Boyes Douglas H. , Lewis Owen T. , Holland Peter W.H.
Published: August 2023

Colour vision in insects is determined by signalling cascades, central to which are opsin proteins, resulting in sensitivity to light at different wavelengths. In certain insect groups, lineage specific evolution of opsin genes, in terms of copy number, shifts in expression patterns, and functional amino acid substitutions, has resulted in changes in colour vision with subsequent behavioural and niche adaptations. Lepidoptera are a fascinating model to address whether evolutionary change in opsin content and sequence evolution are associated with changes in vision phenotype. Until recently, the lack of high quality genome data representing broad sampling across the lepidopteran phylogeny has greatly limited our ability to accurately address this question. Here, we annotate opsin genes in 219 lepidopteran genomes representing 33 families, reconstruct their evolutionary history, and analyse shifts in selective pressures and expression between genes and species. We discover 44 duplication events in opsin genes across ∼300 million years of lepidopteran evolution. While many duplication events are species or family specific, we find retention of an ancient long-wavelength sensitive (LW) opsin duplication derived by retrotransposition within the speciose superfamily Noctuoidea (in the families Nolidae, Erebidae, and Noctuidae). This conserved LW retrogene shows life stage specific expression suggesting visual sensitivities or other sensory functions specific to the early larval stage. This study provides a comprehensive order-wide view of opsin evolution across Lepidoptera, showcasing high rates of opsin duplications and changes in expression patterns.
Whole genome sequencing provides novel insights into the evolutionary history and genetic adaptations of reindeer populations in northern Eurasia
Authors: Pokharel Kisun , Weldenegodguad Melak , Dudeck Stephan , Honkatukia Mervi , Lindeberg Heli , Mazzullo Nuccio , Paasivaara Antti , Peippo Jaana , Soppela Päivi , Stammler Florian , Kantanen Juha
Published: August 2023

Semi-domestic reindeer (Rangifer tarandus tarandus) play a vital role in the culture and livelihoods of indigenous people across the northern Eurasia. These animals are well adapted to harsh environmental conditions, such as extreme cold, limited feed availability and long migration distances. Therefore, understanding the genomics of reindeer is crucial for improving their management, conservation, and utilization. Here we have generated a new genome assembly for the Fennoscandian semi-domestic reindeer with high contiguity, making it the most complete reference genome for reindeer to date. The new genome assembly was utilized to explore genetic diversity, population structure and selective sweeps in EurasianRangifer taranduspopulations which was based on the largest population genomic dataset for reindeer, encompassing 58 individuals from diverse populations. Phylogenetic analyses revealed distinct gene clusters, with the Finnish wild forest reindeer standing out as a unique sub-species. Divergence time estimates suggested a separation of ∼52,000 years ago between Northern-EuropeanRangifer tarandus fennicusandRangifer tarandus tarandus. Our study identified three main genetic clusters: Fennoscandian, the eastern/northern Russian and Alaskan group, and the Finnish forest reindeer. Furthermore, two independent reindeer domestication events were inferred suggesting separate origins for the semi-domestic Fennoscandian and eastern/northern Russian reindeer. Notably, shared genes under selection, including retroviral genes, point towards molecular domestication processes that aided adaptation of this species to diverse environments.
Biophysical Mechanism of Allosteric Regulation of Actin Capping Protein
Authors: Mooren Olivia L. , Stuchell-Brereton Melissa D. , McConnell Patrick , Yan Chenbo , Wilkerson Emily M. , Goldfarb Dennis , Cooper John A. , Sept David , Soranno Andrea
Published: August 2023

Actin capping protein (CP) can be regulated by steric and allosteric mechanisms. The molecular mechanism of the allosteric regulation at a biophysical level includes linkage between the binding sites for three ligands: F-actin, Capping-Protein-Interacting (CPI) motifs, and V-1/myotrophin, based on biochemical functional studies and solvent accessibility experiments. Here, we investigated the mechanism of allosteric regulation at the atomic level using single-molecule Förster resonance energy transfer (FRET) and molecular dynamics (MD) to assess the conformational and structural dynamics of CP in response to linked-binding site ligands. In the absence of ligand, both single-molecule FRET and MD revealed two distinct conformations of CP in solution; previous crystallographic studies revealed only one. CPI-motif peptide association induced conformational changes within CP that propagate in one direction, while V-1 association induced conformational changes in the opposite direction. Comparing CPI-motif peptides from different proteins, we identified variations in CP conformations and dynamics that are specific to each CPI motif. MD simulations for CP alone and in complex with a CPI motif and V-1 reveal atomistic details of the conformational changes. Analysis of the interaction of CP with wildtype (wt) and chimeric CPI-motif peptides using single-molecule FRET, isothermal calorimetry (ITC) and MD simulation indicated that conformational and affinity differences are intrinsic to the C-terminal portion of the CPI-motif. We conclude that allosteric regulation of CP involves changes in conformation that disseminate across the protein to link distinct binding-site functions. Our results provide novel insights into the biophysical mechanism of the allosteric regulation of CP.
The Role of Potassium and Calcium Currents in the Bistable Firing Transition
Authors: Borges Fernando S. , Protachevicz Paulo R. , Souza Diogo L. M. , Bittencourt Conrado F. , Gabrick Enrique C. , Bentivoglio Lucas E. , Szezech José D. , Batista Antonio M. , Caldas Iberê L. , Dura-Bernal Salvador , Pena Rodrigo F. O.
Published: August 2023

Abstract

Healthy brains display a wide range of firing patterns, from synchronized oscillations during slowwave sleep to desynchronized firing during movement. These physiological activities coexist with periods of pathological hyperactivity in the epileptic brain, where neurons can fire in synchronized bursts. Most cortical neurons are pyramidal regular spiking cells (RS) with frequency adaptation and do not exhibit bursts in current-clamp experiments (in vitro). In this work, we investigate the transition mechanism of spike-to-burst patterns due to slow potassium and calcium currents, considering a conductance-based model of a cortical RS cell. The joint influence of potassium and calcium ion channels on high synchronous patterns is investigated for different synaptic couplings (gsyn) and external current inputs (I). Our results suggest that slow potassium currents play an important role in the emergence of high-synchronous activities, as well as in the spike-to-burst firing pattern transitions. This transition is related to bistable dynamics of the neuronal network, where physiological asynchronous states coexist with pathological burst synchronization. The hysteresis curve of the coefficient of variation of the inter-spike interval demonstrates that a burst can be initiated by firing states with neuronal synchronization. Furthermore, we notice that high-threshold (IL) and low-threshold (IT) ion channels play a role in increasing and decreasing the parameter conditions (gsynandI) in which bistable dynamics occur, respectively. For high values ofILconductance, a synchronous burst appears when neurons are weakly coupled and receive more external input. On the other hand, when the conductanceITincreases, higher coupling and lowerIare necessary to produce burst synchronization. In light of our results, we suggest that channel subtype-specific pharmacological interactions can be useful to induce transitions from pathological high bursting states to healthy states.
Prioritizing the survival determinants of quantity surveying firms in economic contraction
Authors: Moyanga Dorcas , Ojo Lekan Damilola , Awodele Oluseyi Alabi , Ogunsemi Deji Rufus
Published: August 2023

Purpose

Micro, small and medium-sized enterprises are the live wire of construction industry in developing countries. These classes of establishments are most affected by economic contraction and turmoil, thus affecting their performance and survivability. Hence, the purpose of this study is to investigate and prioritize the survival determinants of construction consulting organization during economic contraction in Nigeria using quantity surveying firms as a focal point.

Design/methodology/approach

The study adopted the descriptive-survey design and quantitative data were collected through questionnaire purposely administered to quantity surveying firms in the Southwestern part of Nigeria. The data obtained from 99 quantity surveying firms on survival determinants were analysed using various statistical analysis such as mean score, standard deviation, Mann–Whitney U test, Kruskal–Wallis H test, and so on. Principal component analysis was used to identify the principal components of survival determinants, while the factors were prioritized using fuzzy synthetic evaluation (FSE).

Findings

The result of the analysis reveals eight factors that significantly determines the survival of firms during the period of economic contraction. Furthermore, the eight grouped factors were prioritized accordingly namely firm's innovation and diversification, ownership structure and networking, education level and management skills, and so on.

Practical implications

This study investigated the survival determinants of quantity surveying firms and prioritized it with the opinions of principal partners in quantity surveying establishments. As against obtaining large survey responses from all quantity surveyors in the study area that may not have practical experience of managing firms, the limited responses received provide valid basis to broaden the horizon of professionals and other stakeholders on the key determinants for firms to survive economic turmoil.

Originality/value

This study contributes to the body of knowledge by providing information on prioritized factors that must be considered in an appropriate order by quantity surveying firms to survive economic contraction.
An investigation of the Iranian audit firms’ transparency: evidence from an Islamic context
Authors: Asnaashari Hamideh , Safarzadeh Mohammad Hossein , Beygpanah Behzad
Published: August 2023

Purpose

This study aims to investigate factors that drive or deter audit firms (AFs) from disclosing audit quality (AQ) information to stakeholders in Iran. Furthermore, information items that should be contained in their disclosures are examined.

Design/methodology/approach

The study followed an interpretive approach. In this regard, 21 semi-structured and face-to-face interviews were conducted to explore the viewpoints of audit partners and investment managers. Interviewees were selected by snowball sampling method. The transcripts of audio records were prepared, and a thematic perspective was applied to evaluate transcriptions.

Findings

Participants’ interpretations indicate that certain factors, such as signaling to stakeholders, active audit committees and investor demand, promote transparency among Iranian AFs. Nonetheless, this inclination is deterred by some concerns, including poor AQ, lack of financial resources, lack of legal enforcement, fear of raising stakeholders’ expectations, inactive professional associations and contextual factors which should be addressed. Interviewees believe five items should be contained in AFs’ disclosures to enhance transparency.

Practical implications

This study contributes to recognizing factors explaining AFs’ behavior in the context of an Islamic country. Furthermore, the type of disclosure that should be contained can provide good insight for standard setters or oversight bodies.

Originality/value

The semi-structured interviews shed light on the contextual factors that influence transparency within the accountancy profession, either enabling or hindering it. Additionally, it is crucial to consider each country’s unique characteristics when determining the disclosure items in transparency reports.
BACE2 beyond β‐processing of APP, its neuroprotective role in cerebrovascular endothelium
Authors: Sáez‐Valero Javier , Pérez‐González Rocío
Published: August 2023

Several proteases are involved in the proteolytic processing of the amyloid precursor protein (APP) generating the amyloidogenic Aβ peptide, which can act as the triggering pathological effector of Alzheimer's disease (AD). Among these proteases, the β‐site amyloid precursor protein cleaving enzyme 2 (BACE2) is of particular interest because it was first proposed as an alternative β‐secretase to its homolog BACE1; however, accumulating evidence suggests that BACE2 acts as a non‐amyloidogenic α‐secretase and exerts neuroprotective effects. In this issue of J Neurochem, Katusic et al. present an interesting article reporting that BACE2 plays a role in preservation of cerebral vascular endothelial nitric oxide synthase (eNOS) function, thus exerting protective functions. Their data support that the process is mediated by the large soluble non‐amyloidogenic APP fragment sAPPα through the γ‐aminobutyric acid type B receptor 1, which enhances the expression of a major transcription factor for eNOS gene expression in endothelial cells, the Krüppel‐like factor 2. These protective functions of BACE2 contrast with the pathogenic role of BACE1 as a key player in the AD amyloidogenic pathway. Indeed, many efforts have been invested in BACE1 inhibitors as potential disease modifiers for AD. Unfortunately, the results in clinical trials have been disappointing. In this scenario, a better understanding of the functions of BACE2, as well as the selectivity of BACE1 inhibitors with respect to other β‐secretases (mainly BACE2), is crucial for the development of new therapeutic agents. Furthermore, specific cellular targeting should also be considered to improve such therapies due to the diverse balance of secretases targeting APP and the complex cross‐talk between them and the generated APP fragments.

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Destrucción e invención del patrimonio cultural de El Socorro
Authors: Pérez Pinzón Luis Rubén
Published: August 2023

El Club del Socorro es una corporación distintiva de El Socorro y de su condición como ciudad declarada monumento nacional y pueblo patrimonio de Colombia, cuyas sedes han sido representativas del acervo cultural y los imaginarios históricos que fortalecen los destinos turísticos y los espacios significativos del patrimonio urbano en la provincia comunera. A partir de las consecuencias del incendio del 11 de agosto de 1973, el artículo tiene como objetivo describir la importancia que tuvo la casona histórica, que sirvió como casa de gobierno, al ser tomada como sede del club (1941-1973) y el posterior traslado de este al patrimonio creado como “Quinta Fominaya”, antes de ser adecuada como actual sede del club (1974-2021). La investigación cualitativa mediada por análisis de contenidos documentales y orales concluye que, mientras el incendio fortaleció las representaciones históricas y los imaginarios culturales mantenidos sobre la sede del club hasta 1973, paralelamente, las acciones y los discursos de historiadores locales justificaron la creación y apropiación de un sitio histórico como lugar patrimonial.
Temperature-Dependent Classification of Geopolymers Derived From Granite Designed for Well Cementing Applications
Authors: Chamssine Fawzi , Agista Madhan Nur , Khalifeh Mahmoud
Published: August 2023

Alternative materials such as geopolymers appear to have potential advantages compared to Portland cement. However, the application of geopolymers for all sections of the well is still a major challenge due to the difference in temperature ranges. To that end, the classification of the granite-based geopolymer mix designs requires a thorough investigation of various properties at a range of different operational temperatures. In this study, three mix designs are presented for different well sections at temperatures ranging from 5 °C to 60 °C. The mix designs for low temperatures (<50 °C) were tuned by adding CaO to the dry solid blend. Workability, rheology, short-term compressive strength, and X-ray diffraction (XRD) analysis were conducted to conclude the performance of the mix designs under study. Results highlight the presence of Ca content (wt%) in mix designs and its role in enhancing material performance at low operational temperatures. The study reveals a promising future application of the granite-based geopolymer for well construction and abandonment at varying depths with recommendations for further improving the performance by the addition of chemical admixtures. In addition, the relation between temperature and Ca content was highlighted, and more investigations into the kinetics governing these two parameters were recommended.
NIH project probes the human body’s multitude of genomes
Authors: Leslie Mitch
Published: August 2023

Agency launches major effort to explore importance of accumulating mutations in somatic cells