bluuebunny/crossref_metadata_2025 huggingface dataset:
Insights fromMelipona bicolorhybrid genome assembly: A stingless bee genome with chromosome-level scaffold
Authors: de Souza Araujo Natalia , Ogihara Fernando , Martins Pedro Mariano , Arias Maria Cristina
Published: October 2023

Background

The highly eusocial stingless bees are crucial pollinators of native and agricultural ecosystems. Nevertheless, genomic studies within this bee tribe remain scarce. We present the genome assembly of the stingless beeMelipona bicolor. This bee is a remarkable exception to the typical single-queen colony structure, since in this species, multiple queens may coexist and share reproductive duties, resulting in genetically diverse colonies with weak kinship connections. As the only known genuinely polygynous bee,M. bicolor’s genome provides a valuable resource for investigating sociality beyond kin selection.

Results

The genome was assembled employing a hybrid approach combining short and long reads, resulting in 241 contigs spanning 259 Mb (N50 of 6.2 Mb and 97.5% complete BUSCOs). Comparative analyses shed light on some evolutionary aspects of stingless bee genomics, including multiple chromosomal rearrangements inMelipona. Additionally, we explored the evolution of venom genes inM. bicolorand other stingless bees, revealing that, apart from two genes, the conserved repertoire of venom components remains under purifying selection in this clade.

Conclusion

This study advances our understanding of stingless bee genomics, contributing to the conservation efforts of these vital pollinators and offering insights into the evolutionary mechanisms driving their unique adaptations.
Remotely controlled drug release in deep brain regions of non-human primates
Authors: Wilson Matthew G. , Webb Taylor D. , Odéen Henrik , Kubanek Jan
Published: October 2023

Many areas of science and medicine would benefit from selective release of drugs in specific regions of interest. Nanoparticle drug carriers activated by focused ultrasound—remotely applied, depth-penetrating energy—may provide such selective interventions. Here, we developed stable, ultrasound-responsive nanoparticles that can be used to release drugs effectively and safely in non-human primates. The nanoparticles were used to release propofol in deep brain visual regions. The release reversibly modulated the subjects’ visual choice behavior and was specific to the targeted region and to the released drug. Gadolinium-enhanced MRI imaging suggested an intact blood-brain barrier. Blood draws showed normal clinical chemistry and hematology. In summary, this study provides a safe and effective approach to release drugs on demand in selected deep brain regions at levels sufficient to modulate behavior.
The nonlinear meccano of hyperactivity in Alzheimer
Authors: Bonifazi Giulio , Luchena Celia , Gaminde-Blasco Adhara , Ortiz-Sanz Carolina , Capetillo-Zarate Estibaliz , Matute Carlos , Alberdi Elena , De Pittà Maurizio
Published: October 2023

The pathophysiological process of Alzheimer’s disease (AD) is believed to begin many years before the formal diagnosis of AD dementia. This protracted preclinical phase offers a crucial window for potential therapeutic interventions, yet its comprehensive characterization remains elusive. Accumulating evidence suggests that amyloid-β (Aβ) may mediate neuronal hyperactivity in circuit dysfunction in the early stages of AD. At the same time, neural activity can also facilitate Aβ accumulation through intricate feed-forward interactions, complicating elucidating the conditions governing Aβ-dependent hyperactivity and its diagnostic utility. In this study, we use biophysical modeling to shed light on such conditions. Our analysis reveals that the inherently nonlinear nature of the underlying molecular interactions can give rise to various modes of hyperactivity emergence. This diversity in the mechanisms of hyperactivity may ultimately account for a spectrum of AD manifestations.
Pial collaterals develop through mosaic colonization of capillaries by arterial and microvascular endothelial cells
Authors: Perovic Tijana , Hollfinger Irene , Mayer Stefanie , Lips Janet , Dopatka Monika , Harms Christoph , Gerhardt Holger
Published: October 2023

Collaterals are unique blood vessels present in many healthy tissues that cross-connect distal-end arterioles of adjacent arterial trees, thus providing alternate routes of perfusion. Stroke patients with superior pial collateral flow respond better to treatments and present with an overall improved prognostic outcome. However, how pial collaterals develop in the embryo and how they reactivate upon stroke remains unclear. Here, using lineage tracing in combination with three-dimensional imaging, we demonstrate that mouse embryos employ a novel mechanism to build pial collaterals, distinct from their outward remodeling following stroke. Endothelial cells (ECs) of arterial and microvascular origin invade already existing pre-collateral vascular structures in a process which we termed mosaic colonization. Arterialization of these pre-collateral vascular segments happens concurrently with mosaic colonization. Despite having a smaller proliferative capacity, embryonic arterial cells represent the majority of cells that migrate to form nascent collaterals; embryonic microvascular cells, despite their higher proliferative potential, form only about a quarter of collateral endothelial cells. Moreover, postnatal collateral growth relies much more on self-replenishment of arterial cells than on microvascular contribution. Following ischemic injury, pial collateral outward remodeling relies on local cell proliferation rather than recruitment of non-arterial cells. Together, these findings establish distinct cellular mechanisms underlying pial collateral development and ischemic remodeling, raising the prospect for future research to identify novel, collateral-specific therapeutic strategies for ischemic stroke.
A feasibility study of smartphone sensors to assess the effect of acute high altitude (3,800 m) exposure on cognition and motor function in healthy participants
Authors: Goldman Oliver G. , Dubowitz Gerald , Anderson David
Published: October 2023

Acute exposure to hypoxia at attitude has neurologic effects. Some subjects develop severe neurologic symptoms, including Parkinsonism, when hypoxic at high altitude as part of an Acute Mountain Sickness syndrome. Digital health technologies can provide continuous monitoring and objective, real-world measures of movement disorders, but only limited validation data of wearable sensors is available in the high-altitude setting. This equipment validation and feasibility study assessed smartphone microphone and accelerometer function at sea level and 12470 feet (3,800 m) to assess their potential value to predict and prevent neurologic features of acute mountain sickness. A feasibility study of standardized assessments of motor, speech and cognitive tasks was performed in 3 normal subjects at sea level and at altitude. All subjects were hypoxic at altitude with O2saturations ranging from 77-81%. Shaker table (range of frequencies) and high-fidelity speaker (range of frequencies) controls confirmed high correlation of observed and expected measurements for microphone and accelerometer under all conditions. The feasibility study demonstrated that under conditions of hypoxia at attitude, fine motor skills are impaired; visual short-term memory is not impaired but has longer response time; gait and balance is impaired, and a postural tremor develops with frequencies below 10 Hz. Future studies could use these wearable sensors to further assess effects at altitude of more severe hypoxia with applications in the high-altitude environment for Parkinson’s Disease patients, with further opportunity for aviation and military use.
The single-molecule accessibility landscape of newly replicated mammalian chromatin
Authors: Ostrowski Megan S , Yang Marty G , McNally Colin P , Abdulhay Nour J , Wang Simai , Nora Elphège P , Goodarzi Hani , Ramani Vijay
Published: October 2023

The higher-order structure of newly replicated (i.e.‘nascent’) chromatin fibers remains poorly-resolved, limiting our understanding of how epigenomes are maintained across cell divisions. To address this, we presentReplication-AwareSingle-moleculeAccessibilityMapping (RASAM), a long-read sequencing method that nondestructively measures genome-wide replication-status and protein-DNA interactions simultaneously on intact chromatin templates. We report that individual human and mouse nascent chromatin fibers are ‘hyperaccessible’ compared to steady-state chromatin. This hyperaccessibility occurs at two, coupled length-scales: first, individual nucleosome core particles on nascent DNA exist as a mixture of partially-unwrapped nucleosomes and other subnucleosomal species; second, newly-replicated chromatin fibers are significantly enriched for irregularly-spaced nucleosomes on individual DNA molecules. Focusing on specificcis-regulatory elements (e.g.transcription factor binding sites; active transcription start sites [TSSs]), we discover unique modes by which nascent chromatin hyperaccessibility is resolved at the single-molecule level: at CCCTC-binding factor (CTCF) binding sites, CTCF and nascent nucleosomes compete for motifs on nascent chromatin fibers, resulting in quantitatively-reduced CTCF occupancy and motif accessibility post-replication; at active TSSs, high levels of steady-state chromatin accessibility are preserved, implying that nucleosome free regions (NFRs) are rapidly re-established behind the fork. Our study introduces a new paradigm for studying higher-order chromatin fiber organization behind the replication fork. More broadly, we uncover a unique organization of newly replicated chromatin that must be reset by active processes, providing a substrate for epigenetic reprogramming.
Identification of a binding site for bupropion inGloeobacter violaceusligand-gated ion channel
Authors: Pirayesh Elham , Do Hoa Quynh , Ferreira Garren , Pandhare Akash , Gallardo Zackary Ryan , Jansen Michaela
Published: October 2023

Bupropion is an atypical antidepressant and smoking cessation drug which causes adverse effects such as insomnia, irritability, and anxiety. Bupropion inhibits dopamine and norepinephrine reuptake transporters and eukaryotic cation-conducting pentameric ligand-gated ion channels (pLGICs), such as nicotinic acetylcholine (nACh) and serotonin type 3A (5-HT3A) receptors, at clinically relevant concentrations. However, the binding sites and binding mechanisms of bupropion are still elusive. To further understand the inhibition of pLGICs by bupropion, in this work, using a prokaryotic homologue of pLGICs as a model, we examined the inhibitory potency of bupropion inGloeobacter violaceusligand-gated ion channel (GLIC), a proton-gated ion channel. Bupropion inhibited proton-induced currents in GLIC with an inhibitory potency of 14.9 ± 2.0 μM, comparable to clinically attainable concentrations previously shown to also modulate eukaryotic pLGICs. Using single amino acid substitutions in GLIC and two-electrode voltage-clamp recordings, we further determined a binding site for bupropion in the lower third of the first transmembrane segment M1 at residue T214. The sidechain of M1 T214 together with additional residues of M1 and also of M3 of the adjacent subunit have previously been shown to contribute to binding of other lipophilic molecules like allopregnanolone and pregnanolone.

SIGNIFICANCE

GLIC,Gloeobacterligand-gated ion channel, has been extensively used as a model to identify and understand binding sites and mechanisms for cholesterol, neurosteroids, and anesthetics interacting with neurotransmitter-gated ion channels, such as, GABAAreceptors and nicotinic acetylcholine receptors. Recently, increasing evidence has revealed that another neurotransmitter-gated ion channel, the serotonin type 3A receptor, binds to an atypical antidepressant, bupropion, at clinically relevant concentrations. Our work here proposes a binding site for bupropion in GLIC and suggests a new approach to characterize binding mechanisms of bupropion in other neurotransmitter-gated ion channels.
β-catenin-mediated activation of Wnt target genes utilizes a biomolecular condensate-dependent mechanism
Authors: Stewart Richard A. , Goodman Lauren B. , Tran Jeannine J. , Zientko John P. , Sabu Malavika , Jeon Ung Seop , Cadigan Kenneth M.
Published: October 2023

The Wnt/β-catenin signaling pathway plays numerous, essential roles in animal development and tissue/stem cell maintenance. The activation of genes regulated by Wnt/β-catenin signaling requires the nuclear accumulation of β-catenin, a transcriptional co-activator. β-catenin is recruited to many Wnt-regulated enhancers through direct binding to T-cell factor/Lymphoid enhancer factor (TCF/LEF) family transcription factors. β-catenin has previously been reported to form phase-separated biomolecular condensates (BMCs), which was implicated as a component of β-catenin’s mechanism of action. This function required aromatic amino acid residues in the intrinsically disordered regions (IDRs) at the N- and C-termini of the protein. In this report, we further explore a role for β-catenin BMCs in Wnt target gene regulation. We find that β-catenin BMCs are miscible with LEF1 BMCsin vitro. We characterized a panel of β-catenin mutants with different combinations of aromatic residue mutations in human cell culture andDrosophila melanogaster. Our data support a model in which aromatic residues across both IDRs contribute to BMC formationin vitroand signaling activityin vivo. Although different Wnt targets have different sensitivities to loss of β-catenin’s aromatic residues, the activation of every target examined was compromised by aromatic substitution. These mutants are not defective in nuclear import, and residues in the N-terminal IDR with no previously known role in signaling are clearly required for the activation of various Wnt readouts. Consistent with this, deletion of the N-terminal IDR results in a loss of signaling activity, which can be rescued by the addition of heterologous IDRs enriched in aromatic residues. Overall, our work supports a model in which the ability of β-catenin to form biomolecular condensates in the nucleus is tightly linked to its function as a transcriptional co-regulator.
How to measure the controllability of an infectious disease?
Authors: Parag Kris V
Published: October 2023

Quantifying how difficult it is to control an emerging infectious disease is crucial to public health decision-making, providing valuable evidence on if targeted interventions e.g., quarantine and isolation, can contain spread or when population-wide controls e.g., lockdowns, are warranted. The disease reproduction number,R, or growth rate,r, are universally assumed to measure controllability becauseR=1 andr=0 define when infections stop growing and hence the state of critical stability. Outbreaks with largerRorrare therefore interpreted as less controllable and requiring more stringent interventions. We prove this common interpretation is impractical and incomplete. We identify a positive feedback loop among infections intrinsically underlying disease transmission and evaluate controllability from how interventions disrupt this loop. The epidemic gain and delay margins, which respectively define how much we can scale infections (this scaling is known as gain) or delay interventions on this loop before stability is lost, provide rigorous measures of controllability. Outbreaks with smaller margins necessitate more control effort. Using these margins, we quantify how presymptomatic spread, surveillance limitations, variant dynamics and superspreading shape controllability and demonstrate thatRandronly measure controllability when interventions do not alter timings between the infections and are implemented without delay. Our margins are easily computed, interpreted and reflect complex relationships among interventions, their implementation and epidemiological dynamics.
Vibration of effects resulting from network geometry in mixed-treatment comparisons: a case study on network meta-analyses of antidepressants in major depressive disorder
Authors: Vinatier Constant , Palpacuer Clement , Scanff Alexandre , Naudet Florian
Published: October 2023

Objective

It is frequent to find overlapping network meta-analyses (NMAs) on the same topic with differences in terms of both treatments included and effect estimates. We aimed to evaluate the impact on effect estimates of selecting different treatment combinations (i.e. network geometries) for inclusion in NMAs.

Design

Multiverse analysis, covering all possible NMAs on different combinations of treatments.

Setting

Data from a previously published NMA exploring the comparative effectiveness of 22 treatments (21 antidepressants and a placebo) for the treatment of acute major depressive disorder.

Participants

Cipriani et al (2018) explored a dataset of 116 477 patients included in 522 randomized controlled trials.

Main outcome measures

For each possible network geometry, we performed a NMA to estimate comparative effectiveness on treatment response and treatment discontinuation for the treatments included (231 between-treatment comparisons). The distribution of effect estimates of between-treatment comparisons across NMAs was computed, and the direction, magnitude, and statistical significance of the 1stand 99thpercentiles were compared.

Results

4 116 254 different NMAs concerned treatment response. Among possible network geometries, 172/ 231 (74%) pairwise comparisons exhibited opposite effects between the 1stand 99thpercentiles, 57/231 (25%) comparisons exhibited statistically significant results in opposite directions, 118 of 231 (51%) comparisons derived non-robust results in terms of statistical significance at 5% risk and 56/231 (24%) treatment pairs obtained robust results across meta-analyses. Comparisons based on indirect evidence only were associated with greater variability in effect estimates. Comparisons with small absolute values observed in the complete NMA more frequently obtained statistically significant results in opposite directions. Similar results were observed for treatment discontinuation.

Conclusion

In this case study we observed that the selection of treatments to be included in a NMA could have considerable consequences on treatment effect estimations.

Registration

https://osf.io/mb5dy
Surrogate virus neutralisation test based on nanoluciferase-tagged antigens to quantify inhibitory antibodies against SARS-CoV-2 and characterise Omicron-specific reactivity
Authors: Schoefbaenker M , Neddermeyer R , Guenther T , Mueller MM , Romberg ML , Classen N , Hennies MT , Hrincius ER , Ludwig S , Kuehn JE , Lorentzen EU
Published: October 2023

Virus-specific antibodies are important determinants of protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While regarded as the gold standard for detecting functional antibodies, conventional virus neutralisation tests (VNT) or pseudotyped virus neutralisation tests (pVNT) require biosafety level 2 or 3 facilities. Alternatively, the virus-free surrogate virus neutralisation test (sVNT) quantifies inhibitory antibodies that prevent the spike protein from binding to its receptor, human angiotensin-converting enzyme 2 (hACE2).

We evaluated secreted nanoluciferase (NLuc)-tagged spike (S) protein fragments as diagnostic antigens in the sVNT in the framework of a vaccination study. First, spike fragments of different lengths were tested for their suitability as diagnostic antigens in a capture enzyme immunoassay (EIA) using unprocessed culture supernatants of transfected cells, identifying the receptor binding domain (RBD) of S as the optimal construct. The sensitivity of the in-house sVNT relying on the NLuc-labelled RBD equalled or surpassed a commercial sVNT (cPass, GenScript Diagnostics) and an in-house pVNT four weeks after the first vaccination (98% vs. 94% and 72%, respectively), reaching 100% in all assays four weeks after the second and third vaccinations. Additionally, serum reactivity with spike constructs of Omicron BA.1 was tested. Compared with a capture EIA, the in-house sVNT and pVNT displayed superior discrimination between wild-type- and variant-specific reactivity of sera. Differences in reactivity were most pronounced after the first and second vaccinations, whereas the third vaccination resulted in robust, cross-reactive detection of Omicron constructs.

In conclusion, assays utilising NLuc-labelled protein fragments permit the quantification and functional assessment of SARS-CoV-2-specific antibodies and the detection of variant-specific differences in reactivity. Potential applications include monitoring therapy and vaccine efficacy and follow-up of prolonged disease courses in high-risk groups. Designed as straightforward, highly flexible modular systems, these tests can be readily adapted to further emerging viral variants.
Widespread drastic reduction of brain myelin content upon prolonged endurance exercise
Authors: Ramos-Cabrer Pedro , Cabrera-Zubizarreta Alberto , Padró Daniel , Matute-González Mario , Rodríguez-Antigüedad Alfredo , Matute Carlos
Published: October 2023

Recent evidence suggests that myelin lipids may act as glial energy reserves when glucose is lacking, a hypothesis yet to be solidly proven. Hereby, we examined the effects of running a marathon on the myelin content by MRI. Our findings show that marathon runners undergo widespread robust myelin decrease at completion of the effort. This reduction involves white and gray matter, and includes primary motor and sensory cortical areas and pathways, as well as the entire corpus callosum and internal capsule. Notably, myelin levels partially recover within two weeks after the marathon. These results reveal that myelin use and replenishment is an unprecedented form of metabolic plasticity aimed to maintain brain function during extreme conditions.

One-Sentence Summary

Brain myelin usage during strenuous exercise and recovery thereafter
Chromosome-scale Genome Assembly of Lewis Flax (Linum lewisiiPursh.)
Authors: Innes Peter A. , Smart Brian C. , Barham Joseph A.M. , Hulke Brent S. , Kane Nolan C.
Published: October 2023

Linum lewisii, a perennial blue flax native to North America, holds potential as a sustainable perennial crop for oilseed production due to its ecological adaptability, upright harvestable structure, nutritious seeds, and low insect and disease issues. Its native distribution spans a large geographic range, from the Pacific Coast to the Mississippi River, and from Alaska to Baja California. Tolerant to cold and drought conditions, this species is also important for native ecosystem rehabilitation. Its enhancement of soil health, support for pollinators, and carbon sequestration underscore its agricultural relevance.

This study presents a high-quality, chromosome-scale assembly of theL. lewisii(2n = 2x = 18) genome, derived from PacBio HiFi and Dovetail Omni-C sequencing of the “Maple Grove” variety. The initial assembly contained 642,903,787 base pairs across 2,924 scaffolds. Following HiRise scaffolding, the final assembly contained 643,041,835 base pairs, across 1,713 scaffolds, yielding an N50 contig length of 66,209,717 base pairs. Annotation of the assembly revealed 38,808 genes, including 37,599 protein-coding genes and 7,108 putative transposable elements. Analysis of synteny with other flax species revealed a striking number of chromosomal rearrangements. We also found an intriguing absence of the single-copyTSS1gene in theL. lewisiigenome, potentially linked to its transition from heterostyly to homostyly.

Taken together, these findings represent a significant advancement in our understanding of theLinumgenus and provide a resource for future domestication efforts and basic research on Lewis flax.
Regulatory Role of PKR in Systemic Inflammation-Triggered Neuroinflammation and its Modulation of Glucose Metabolism and Cognitive Functions in Cholinergic Neurons
Authors: Cheng Wai-Yin , Lee Xin-Zin , Lai Michael Siu-Lun , Ho Yuen-Shan , Chang Raymond Chuen-Chung
Published: October 2023

Systemic inflammation may promote neuroinflammation and neurodegeneration. The double-stranded RNA-dependent protein kinase (PKR) is a key signaling molecule that regulates immune responses. This study aims to examine the role of PKR in regulating systemic inflammation-induced neuroinflammation and cognitive dysfunctions using a laparotomy mouse model. In the first part, wild-type C57BL/6J and C57BL/6-Tg(CD68-EGFP)1Drg/J mice were assigned to undergo either laparotomy with sevoflurane anesthesia or sevoflurane alone to examine effects of systemic inflammation on neuroinflammation and cognition. In the second part, PKR-/-mice were used to study the role of PKR in modulating laparotomy-induced systemic inflammation, neuroinflammation, and cognition. For the third part, PKR was inhibited selectively in cholinergic neurons of ChAT-IRES-Cre-eGFP mice via intracerebroventricular injection of rAAV-DIO-PKR-K296R. This examined the effects of inhibiting PKR in cholinergic neurons on glucose metabolism and cognition in the laparotomy model. Our study revealed that genetic deletion of PKR in mice potently attenuated the laparotomy-induced peripheral and neural inflammation and cognitive deficits. Furthermore, inhibiting PKR in the cholinergic neurons rescued the laparotomy-induced brain glucose hypometabolism and cognitive impairment. Our results demonstrated the critical role of PKR in regulating neuroinflammation and cognitive dysfunctions in a peripheral inflammation model. PKR could be a pharmacological target for treating systemic inflammation-induced neuroinflammation and cognitive dysfunctions.
PopGenAdapt: Semi-Supervised Domain Adaptation for Genotype-to-Phenotype Prediction in Underrepresented Populations
Authors: Comajoan Cara Marçal , Mas Montserrat Daniel , Ioannidis Alexander G.
Published: October 2023

The lack of diversity in genomic datasets, currently skewed towards individuals of European ancestry, presents a challenge in developing inclusive biomedical models. The scarcity of such data is particularly evident in labeled datasets that include genomic data linked to electronic health records. To address this gap, this paper presents PopGenAdapt, a genotype-to-phenotype prediction model which adopts semi-supervised domain adaptation (SSDA) techniques originally proposed for computer vision. PopGenAdapt is designed to leverage the substantial labeled data available from individuals of European ancestry, as well as the limited labeled and the larger amount of unlabeled data from currently underrepresented populations. The method is evaluated in underrepresented populations from Nigeria, Sri Lanka, and Hawaii for the prediction of several disease outcomes. The results suggest a significant improvement in the performance of genotype-to-phenotype models for these populations over state-of-the-art supervised learning methods, setting SSDA as a promising strategy for creating more inclusive machine learning models in biomedical research.

Our code is available athttps://github.com/AI-sandbox/PopGenAdapt.
Neurogenesis-mediated circuit remodeling reduces engram reinstatement and promotes forgetting
Authors: Guskjolen Axel , Dhaliwal Jagroop , de la Parra Juan , Epp Jonathan R. , Ko Sangyoon , Chahley Erin , de Snoo Mitch , Solari Michela , Panesar Prabdeep , Snyder Jason , Duan Xin , Sanes Joshua R. , Josselyn Sheena A. , Frankland Paul W.
Published: October 2023

Post-training increases in hippocampal neurogenesis are associated with forgetting of hippocampus-dependent memories in adult mice. This form of forgetting might be due to increased numbers of new neurons, remodeling of hippocampal circuitry or some combination of both. Here we tested the hypothesis that neurogenesis-mediated forgetting is caused by remodeling of hippocampal circuits by engineering mice in which adult-generated granule cells hypo- or hyper-integrate into hippocampal circuits. Using gene deletion, opto- and chemogenetic strategies, we find that hypo-integration of newborn neurons prevents post- training exercise-induced forgetting of contextual fear memories. Conversely, inducing hyper- integration of newborn neurons following contextual fear conditioning is sufficient to produce forgetting. Because these interventions did not affect survival of newborn neurons, these findings suggest that neurogenesis-mediated remodeling of hippocampal circuits represents a continuous and active form of interference that alters accessibility of engrams underlying hippocampal memories. Consistent with this, using engram-labeling approaches, we found that exercise-induced forgetting was associated with reduced engram reactivation.
Decoding Internal Decision Making During Reverse Engineering Tasks
Authors: Marsh Brianna , Rego Jocelyn , Levy Mia Matsuhisa , Sayer Mitchell Peter , Waagen Alexander , Barbieux Aidan , Cranford Edward A , Morrison Donald F , Maldonado Froylan , Johnson Jeremy Phillip , DiVita Joseph , Buch Jonathan Michael , Kim Tiffany Hyun-Jin , Lebiere Christian , Fugate Sunny , Bhattacharyya Rajan
Published: October 2023

Neural decoding is often limited to tasks with known stimuli and limited response options . Real world tasks, however, are often completely stimulus free with unconstrained user response possibilities. Real time decoding of internal decision making would allow for more complex and interactive Huma Machine Teaming in a way that is not currently possible. To address this problem, we present here a novel method of decoding moments of recognition and their associated internal value judgments in the context of highly complex software reverse engineering tasks. This is done through a combination of P300 detection (a neural marker of recognition) and the Engagement Index (a ratio of neural band powers) to determine whether an item has been identified as relevant to the task (to be further explored) or irrelevant to the task (to be quickly ignored). Artificial neural networks were trained to identify P300s in each subject during the reverse engineering tasks. Dimensionality reduction of neural data during the tasks showed the existence of separately clustering subgroups of P300s with differences in Engagement Index. Subgroups of P300s differentiated by Engagement were further verified as distinct groupings with pupil dilation and user behavior metrics. This decoded information could be used to aid in the reverse engineering process via cognitive offloading of the user’s own decision making on to the visual interface in a completely automated and personalized fashion. This represents a significant advance in domain of real-time neural decoding, and opens up many further possibilities for usage in a broad range of intelligent human systems integration applications.
A label-free approach for relative spatial quantitation of c-di-GMP in microbial biofilms
Authors: McCaughey Catherine S. , Trebino Michael A. , McAtamney Allyson , Isenberg Ruth , Mandel Mark J. , Yildiz Fitnat H. , Sanchez Laura M.
Published: October 2023

Microbial biofilms represent an important lifestyle for bacteria and are dynamic three dimensional structures. Cyclic dimeric guanosine monophosphate (c-di-GMP) is a ubiquitous signaling molecule that is known to be tightly regulated with biofilm processes. While measurements of global levels of c-di-GMP have proven valuable towards understanding the genetic control of c-di-GMP production, there is a need for tools to observe the local changes of c-di-GMP production in biofilm processes. We have developed a label-free method for the direct detection of c-di-GMP in microbial colony biofilms using matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). We applied this method to the enteric pathogenVibrio cholerae, the marine symbiontV. fischeri, and the opportunistic pathogenPseudomonas aeruginosaPA14 and detected spatial and temporal changes in c-di-GMP signal that accompanied genetic alterations in factors that synthesize and degrade the compound. We further demonstrated how this method can be simultaneously applied to detect additional metabolites of interest in a single experiment.
Folding makes an imprint
Authors: Stricker Stefan H.
Published: October 2023

Imprinted gene clusters are confined genomic regions containing genes with parent-of-origin-dependent transcriptional activity. In this issue ofGenes & Development, Loftus and colleagues (pp. 829–843) made use of an insightful combination of descriptive approaches, genetic manipulations, and epigenome-editing approaches to show that differences in nuclear topology precede the onset of imprinted expression at thePeg13-Kcnk9locus. Furthermore, the investigators provide data in line with a model suggesting that parent-of-origin-specific topological differences could be responsible for parent-of-origin-specific enhancer activity and thus imprinted expression.
Determinants of the willingness to pay and willingness to accept in the valuation of informal care. The CUIDARSE study
Authors: Oliva Juan , Peña Longobardo Luz María , García-Mochón Leticia , Abellán-Perpìñan José María , García-Calvente María del Mar
Published: October 2023

Purpose

This paper aims to study the value of informal care (IC) time from the perspective of caregivers using two alternative contingent valuation tools – willingness to pay (WTP) and willingness to accept (WTA) – and to identify the variables that affect the stated values.

Design/methodology/approach

The authors used data from a multi-centre study of 610 adult caregivers conducted in two Spanish regions in 2013. The existence of “protest zeros” and “economic zeros” because of the severe budgetary constraints of the households was also considered. Two-part multivariate models were used to analyse the main factors that explained the declared values of WTA and WTP.

Findings

The average WTP and WTA were €3.12 and €5.98 per hour of care, respectively (€3.2 and €6.3 when estimated values for “protest zeros” and “economic zeros” were considered). Some explanatory variables of WTA and WTP are coincident (place of residence and intensity of care time), whereas other variables only help to explain WTP values (household and negative coping with caregiving) or WTA values (age and burden of care). Some nuances are also identified when comparing the results obtained without protest and economic zeros with the estimated values of these special zeros.

Originality/value

Studies analysing the determinants of WTP and WTA in IC settings are very scarce. This paper seeks to provide information to fill this gap. The results indicate that the variables that explain the value of IC from one perspective may differ from the variables that explain it from an alternative perspective. Given the relevance of contextual factors, studies on the topic should be expanded, and care should be taken with the extrapolation of results across countries and settings.
Ecology with artificial intelligence and machine learning in Asia: A historical perspective and emerging trends
Authors: Ryo Masahiro
Published: October 2023

The use of artificial intelligence (AI) and machine learning (ML) has significantly enhanced ecological research in Asia by improving data processing, analysis, and pattern extraction. Analyzing 1550 articles, I show an overview of the use of AI and ML for Asian ecological research. Following the last 20 year trend, I found that the topics in Asian ecological research have transitioned from technical perspectives to more applied issues, focusing on biodiversity conservation, climate change, land use change, and societal impacts. Non‐Asian countries, on the other hand, have focused more on theoretical understanding and ecological processes. The difference between Asian and non‐Asian regions may have emerged due to the ecological challenges faced by Asian countries, such as rapid economic growth, land development, and climate change impacts. In both regions, deep learning related technology has been emerging (e.g., big data collection including image and movement). Within Asia, China has been the Asia‐leading country for AI/ML applications followed by Korea, Japan, India, and Iran. The number of computer science education programs in China has been increasing 3.5× times faster than that in the United States, indicating that a nationwide strategy for computer science development is key for ecological science with AI. Overall, the adoption of AI and ML technologies in ecological studies in Asia has propelled the field forward and opened new avenues for innovative research and conservation practices.
Structure–activity relationships of bensulfuron methyl and its derivatives as novel agents against drug‐resistant Candida auris
Authors: Sun Xue‐Wen , Liu Yixuan , Wang Xiaofang , Li Hao‐Ran , Lin Xin , Tang Jin‐Yin , Xu Qing , Agnew‐Francis Kylie A. , Fraser James A. , Sun Zhi‐Juan , Guddat Luke W. , Wang Jian‐Guo
Published: October 2023

With the emergence of the human pathogen Candida auris as a threat to human health, there is a strong demand to identify effective medicines to prevent the harm caused by such drug‐tolerant human fungi. Herein, a series of 33 new derivatives of bensulfuron methyl (BSM) were synthesized and characterized by 1H NMR, 13C NMR, and HRMS. Among the target compounds, 8a possessed the best Ki value of 1.015 μM against C. auris acetohydroxyacid synthase (CauAHAS) and an MIC value of 6.25 μM against CBS10913, a clinically isolated strain of C. auris. Taken together the structures of BSM and the synthesized compounds, it was found that methoxy groups at both meta‐position of pyrimidine ring are likely to provide desirable antifungal activities. Quantum calculations and molecular dockings were performed to understand the structure–activity relationships. The present study has hence provided some interesting clues for the discovery of novel antibiotics with this distinct mode of action.
Sales manipulation strategies of competitive firms on an e‐commerce platform: Beneficial or harmful?
Authors: Zhang Qing , Li Juan , Xiao Tiaojun
Published: October 2023

Consumers are affected by the relative sizes of products’ sales volumes, which is regarded as consumers’ sales comparison behavior when purchasing online. Therefore, some firms manipulate their sales volumes to attract consumers. To shed light on firms’ sales manipulation, we develop game theoretical models to investigate sales manipulation strategies for a high‐quality firm and a low‐quality firm on a platform. We identify conditions for firms’ sales manipulation and investigate its impact on the platform. We find the following: (1) A small amount of sales manipulation volumes may harm each firm. (2) When only the high‐quality (low‐quality) firm manipulates its sales volume, the total market share shrinks (expands), and the profit of the low‐quality (high‐quality) firm is damaged. In this case, the platform can only benefit from the high‐quality firm's sales manipulation. When both firms manipulate sales volumes, each firm aims to claim a higher sales volume than its competitor. (3) At equilibrium, when the unit sales manipulation cost is intermediate, only the high‐quality firm manipulates its sales volume. When the unit sales manipulation cost is low, both firms manipulate sales volumes and consequently get trapped in a Prisoner's Dilemma. In this case, the platform's profit cannot be improved. This study then incorporates considerations of consumers’ sales comparison behavior, nonlinear cost structures for sales manipulation, firms’ long‐term vision, and sales manipulation strategy in competitive supply chains to reveal that most aforementioned results are qualitatively robust.
Considerations in geriatric dermatopathology
Authors: Brent Ashley A. , Mancuso Elizabeth , Smith Emily
Published: October 2023

This review provides an overview of considerations in geriatric dermatopathology. The nuances of specimen collection and reporting in this population, including the importance of obtaining adequate tissue, providing detailed clinical information and ethical considerations surrounding specimen collection will be discussed. The histopathologic changes associated with aging and the morphologic features of common lesions related to photoaging are outlined followed by a discussion of common interpretation pitfalls, specifically entities at risk of overinterpretation and those related to hyper‐ and hypopigmentation. Finally, the recent literature is reviewed regarding special cases and what this implies for future research both in dermatology and dermatopathology.
The intra‐matrix and gastrointestinal parameters affecting the bioaccessibility of food biopeptides
Authors: Le Thanh‐Do , Suttikhana Itthanan , Ashaolu Tolulope Joshua
Published: October 2023

The discussions around biopeptides generated from foods are associated with the numerous physiologic functions and therapeutic interventions that they potentiate, especially toward cardiovascular and degenerative diseases. The recurring issue about these biopeptides, however, is the wide gap left between laboratory experimentations and human intervention studies, apart from the fact that the conditions of testing or validation are not the same in both instances. Therefore, the gastrointestinal processing of biopeptides must be on par with their bioaccessibility, which is a critical step toward their bioavailability. The checks and balances of bioaccessibility are associated with the effects of the gastrointestinal enzymes, the interplay of other micro‐ and macro‐nutrients in whole or part, as well as the disruption of the integrity of the intestinal mucosal cells. We herein discussed the interplay of biopeptides with food matrices with regard to metal‐, phenol‐, lipid‐, and sugar‐peptide complexes, including mucins and other gastrointestinal enzyme secretion. These most common parameters and mechanistic activities led to the proposition of novel techniques for ensuring peptides' bioaccessibility and physiologic functions, a backdrop for futuristic studies that would contribute to our understanding and actualisation of bioaccessible peptides well incorporated and maintained in desirable functional food products.
Dietary fibre concentrates from avocado and mango by‐products; antioxidant capacity and polyphenols evaluation by HPLC‐IDA‐EPI‐MS
Authors: Angulo‐López Jorge E. , Losoya‐Sifuentes Carolina , Palmieri Sara , Torres‐León Cristián , Flores‐Gallegos Adriana C. , Fanti Federico , Sergi Manuel , Ascacio‐Valdes Juan A. , Contreras Esquivel Juan C. , Rúelas‐Chácon Xochil , Aguilar Cristóbal N. , Compagnone Dario
Published: October 2023

Phenolics bound to dietary fibres (DF‐PCs) represent a valuable source of antioxidants that are often wasted. DF‐PCs can be obtained as residues from conventional extraction processes of PCs derived from agro‐industrial by‐products. This study aimed to characterise DF‐PCs generated after the PC extraction process from the avocado peel (AP), mango peel (MP) and husk mango seed (testa) (MT), with a focus on solid residue or concentrated fibre (APFT: avocado peel fibre; MPFT: mango peel fibre; MTFT: mango testa fibre). The by‐products were evaluated under both non‐defatted and defatted conditions before simulating the PC extraction process. PCs were quantified (TPC) and identified (HPLC‐IDA‐EPI‐MS). Their antioxidant activity (AA) was determined (ABTS+, DPPH* and FRAP). Among the evaluated fibres, non‐defatted AP and defatted MP and MT exhibited the highest TPC content (22.64 ± 0.3, 37.31 ± 1.78 and 6.07 ± 0.08 mg GAE/g), respectively. Using the DPPH* assay, all fibre concentrates showed lower AA compared to the by‐products. Using FRAP assay, defatting gave the largest activity for mango samples. HPLC‐IDA‐EPI‐MS analysis of PC profiles resulted in the presence of 62 PC compounds in the fibre concentrates. These DF‐PCs, with a significant content of PCs, may be relevant as functional ingredients for food production.
Comparative molecular conformation, interaction, and network characteristics of wheat gluten modulated by sodium chloride and sodium carbonate
Authors: Kuang Jiwei , Xu Ke
Published: October 2023

The objective of the study was to investigate the configurational changes and aggregation mechanism of wheat gluten induced by sodium chloride (NaCl) and sodium carbonate (Na2CO3). The results showed that NaCl shielded surface charges of gluten, developed more hydrogen bonds with tyrosine, and stabilised the secondary structure, while Na2CO3 promoted significant transition of the secondary structure from random coils and β‐turn to β‐sheet. Both NaCl and Na2CO3 quenched tryptophan fluorescence and promoted the aggregation of gluten subunits, where Na2CO3 induced covalent bond formation other than disulphides and facilitated gluten network development. Atomic force microscopy images confirmed different molecular surface features in gluten network. In conclusion, both NaCl and Na2CO3 demonstrated the ability to promote rheology, aggregation, and network formation of gluten but different molecular mechanisms were involved. This work provides valuable insights for the processing of salted and alkaline noodles.
Noninvasive prenatal screening with conventional sequencing depth to screen fetal copy number variants: A retrospective study of 19 144 pregnant women
Authors: Wang Zhiwei , Tang Xinxin , Yang Shuting , Zhao Yali , Yin Ting , Chen Min , Zhang Yue , Wang Yongan , Zhang Fang , Wang Leilei
Published: October 2023

Aim

To investigate the detectability of noninvasive prenatal screening (NIPS) with conventional sequencing depth to detect fetal copy number variants.

Methods

We performed a retrospective study in a total of 19 144 pregnant women. Their cell‐free plasma DNA were assessed for trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidies, and genome‐wide copy number variants by NIPS at conventional sequencing depth.

Results

Three hundred seventy‐four cases (2.0%, 374/19 144) with abnormal results were detected, which including 84 cases (0.4%, 84/19 144) with high risk of trisomy 21, 18, and 13, 90 cases (0.5%, 90/19 144) with high risk of sex chromosome abnormalities (SCA), and 44 cases (0.2%, 44/19 144) with high risk of other chromosome aneuploidies. One hundred fifty‐six cases (0.8%, 156/19 144) with high risk of copy number variations (CNVs) were also detected. In following prenatal diagnosis, composite positive predictive value (PPV) of trisomy 21, 18, and 13 was 69.6% (48/69). The PPV of SCAs was 37.3% (19/51). And the PPVs for CNVs was detected as 51.0% (<5 Mb), 71.4% (5 Mb ≤ CNV ≤10 Mb), 56.5% (>10 Mb). Finally, a follow‐up about the pregnancy outcomes were conducted for all available cases.

Conclusions

NIPS yielded high PPVs for trisomy 21, 18, and 13 aneuploidies and moderate PPVs for SCAs and CNVs. The screening effectiveness was closely related to the size of CNV fragments. Larger CNVs, especially larger than 5 Mb, could be detected more accurately by NIPS in our analytic technique. Meanwhile, diagnostic confirmation by microarray analysis was highly recommended.
Non‐crossing quantile double‐autoregression for the analysis of streaming time series data
Authors: Jiang Rong , Kai Choy Siu , Yu Keming
Published: October 2023

Many financial time series not only have varying structures at different quantile levels and exhibit the phenomenon of conditional heteroscedasticity at the same time but also arrive in the stream. Quantile double‐autoregression is very useful for time series analysis but faces challenges with model fitting of streaming data sets when estimating other quantiles in subsequent batches. This article proposes a renewable estimation method for quantile double‐autoregression analysis of streaming time series data due to its ability to break with storage barrier and computational barrier. Moreover, the proposed flexible parametric structure of the quantile function enables us to predict any interested quantile value without quantile curve crossing problem or keeping the desirable monotone property of the conditional quantile function. The proposed methods are illustrated using current data and the summary statistics of historical data. Theoretically, the proposed statistic is shown to have the same asymptotic distribution as the standard version computed on an entire data stream with the data batches pooled into one data set, without additional condition. Simulation studies and an empirical example are presented to illustrate the finite sample performance of the proposed methods.