bluuebunny/crossref_metadata_2025 huggingface dataset:
Unraveling the genetic susceptibility of irritable bowel syndrome: integrative genome-wide analyses in 845 492 individuals: a diagnostic study
Authors: Huang Wentao , Zhang Lijun , Ma Yuying , Yu Shiyi , Lyu Yanlin , Tong Shuangshuang , Wang Jiaxuan , Jiang Rui , Meng Meijun , Wu Yanjun , Luo Ruibang , Qiu Xinqi , Sha Weihong , Chen Hao
Published: August 2024

Background:

Irritable bowel syndrome (IBS) significantly impacts individuals due to its prevalence and negative effect on quality of life. Current genome-wide association studies (GWAS) have only identified a small number of crucial single nucleotide polymorphisms (SNPs), not fully elucidating IBS’s pathogenesis.

Objective:

To identify genomic loci at which common genetic variation influences IBS susceptibility.

Methods:

Combining independent cohorts that in total comprise 65 840 cases of IBS and 788 652 controls, the authors performed a meta-analysis of genome-wide association studies (GWAS) of IBS. The authors also carried out gene mapping and pathway enrichment to gain insights into the underlying genes and pathways through which the associated loci contribute to disease susceptibility. Furthermore, the authors performed transcriptome analysis to deepen their understanding. IBS risk models were developed by combining clinical/lifestyle risk factors with polygenic risk scores (PRS) derived from the GWAS meta-analysis. The authors detect the phenotype association for IBS utilizing PRS-based phenome-wide association (PheWAS) analyses, linkage disequilibrium score regression, and Mendelian randomization.

Results:

The GWAS meta-analysis identified 10 IBS risk loci, seven of which were novel (rs12755507, rs34209273, rs34365748, rs67427799, rs2587363, rs13321176, rs1546559). Multiple methods identified nine promising IBS candidate gene (PRRC2A, COP1, CADM2, LRP1B, SUGT1, MED12L, P2RY14, PHF2, SHISA6) at 10 GWAS loci. Transcriptome validation also revealed differential expression of these genes. Phenome-wide associations between PRS-IBS and nine traits (neuroticism, diaphragmatic hernia, asthma, diverticulosis, cholelithiasis, depression, insomnia, COPD, and BMI) were identified. The six diseases (asthma, diaphragmatic hernia, diverticulosis, insomnia major depressive disorder and neuroticism) were found to show genetic association with IBS and only major depressive disorder and neuroticism were found to show causality with IBS.

Conclusion:

The authors identified seven novel risk loci for IBS and highlighted the substantial influence on genetic risk harbored. The authors’ findings offer novel insights into etiology and phenotypic association of IBS and lay the foundation for therapeutic targets and interventional strategies.
Exploring time-to-event analysis models: A study of accelerated failure time and weighted least square estimation
Authors: Hasim Sherhana , Nads Azman , Jal-Usman Ebni , Zhang Zhongheng
Published: August 2024

Background:

This study explores time-to-event analysis models, focusing on the comparison between accelerated failure time (AFT) and weighted least square estimation (WLSE) methods in analyzing survival data, emphasizing the challenge of heteroscedasticity in real-world datasets.

Methods:

Using the North Central Cancer Treatment Group (NCCTG) Lung Cancer dataset, five parametric AFT distributions (exponential, Weibull, log-logistic, log-normal, and generalized gamma) were evaluated. The log-likelihood method was utilized to calculate the AIC and BIC values for each distribution to determine the best fit model.

Results:

Among the different distributions tested, the Weibull distribution was identified as the best fit model based with the lowest AIC and BIC values of 2311.70 and 2318.56, respectively. This distribution played a crucial role in determining factors associated with the cancer data. Specifically, the variablecalories consumed at a meal (meal.cal) was associated with cancer patient recovery, with an estimate of 0.00004 and a standard error of 0.0002. Results indicated homoscedastic data through the Breusch-Pagan test. Moreover, the results demonstrated that when dealing with homoscedastic data, the Weibull AFT model outperformed WLSE in producing statistically significant effects and precise estimates.

Conclusion:

For data exhibiting homoscedasticity, the AFT method yielded superior results compared to WLSE in terms of statistical significance and precision. Therefore, it is advisable to employ AFT for homoscedastic data and WLSE for heteroscedastic data to enhance the accuracy of covariate effect estimates in survival analysis.
How does musical rhythm influence grammatical processing at the neurophysiological level?
Authors: Markevich Maksim , Rebreikina Anna , Logvinenko Tatiana , Grigorenko Elena L. , Sysoeva Olga
Published: August 2024

Numerous behavioral studies have demonstrated a rhythmic priming effect (RPE) on grammatical processing using grammaticality judgment tasks (GJT), where participants performed better following regular rhythmic sequences compared to baseline conditions or irregular rhythmic sequences (i.e. auditory rhythmic sequences with violated metrical structure). Only a few studies, however, have explored neurophysiological RPE in grammatical processing. Such neurophysiological investigations have been limited to GJT presented auditorily, have been primarily focused on the French- and German-speaking adult participants, and have rarely used baseline nonpriming conditions. The objective of the present study was to investigate neurophysiological correlates of the RPE in the GJT presented in visual modality. In the current study, we registered a 128-channel electroencephalogram while Russian-speaking adolescents performed a visual GJT, where each sentence was presented word by word in a self-paced manner. Before each experimental block, participants listened to regular rhythmic sequences, irregular rhythmic sequences, or silence. We observed that the late negativity in the event-related potential was larger for the ungrammatical condition compared to the grammatical condition only after the presentation of irregular rhythmic sequences. This effect, referred to as the N600 component in previous research, has been associated with increased cognitive complexity. In conclusion, results suggest that exposure to irregular rhythmic stimulation may lead to increased cognitive demand. This is attributed to the complexity associated with concurrently executing the GJT and managing rhythmic disruption, consequently increasing the strain on working memory resources.
Effect of early postmenopause and premenopause on resting-state electroencephalographic and their correlation with ovarian hormone levels
Authors: González-Pérez Erika G. , Figueroa-Vega Nicté , Solís-Ortiz Silvia
Published: August 2024

This study aimed to compare the effect of the early postmenopausal period on resting-state electroencephalographic spectral power with that of the premenopausal period and to analyze the correlation between electroencephalographic spectral power values and endogenous ovarian hormone levels. This study involved 13 early postmenopausal women and 10 premenopausal women in the early follicular, 10 in the ovulatory phase, and 10 in the early luteal phase who underwent resting-state quantitative electroencephalographic spectral power with eyes closed and endogenous ovarian hormone measurements. The delta, theta, alpha1, alpha2, beta1, and beta2 absolute power were compared between the early postmenopausal and premenopausal groups. Correlations between electroencephalographic spectral power values and 17β estradiol, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone levels were analyzed in early postmenopausal women. Compared with the premenopausal group, the early postmenopausal group showed significantly higher resting-state theta power in the frontal region, alpha1 and alpha2 power in the frontal and central regions, beta1 power in the frontal, central, parietal, and occipital regions, and beta2 power in the centroparietal region. Beta2 power values were positively correlated with FSH levels. The current findings highlight that early postmenopausal women show greater resting-state alpha and beta power, which suggests cortical excitability of fast frequency bands involved in states of alertness, focus of attention, cognition, and emotion. Additionally, we emphasized the effect of FSH levels on fast cortical activation in early postmenopausal women.
Association between driving status and visiting places among older adults in a suburban area in Japan: Findings from a cross-sectional survey
Authors: Noguchi Taiji , Komatsu Ayane , Okahashi Sayaka , Nakagawa Takeshi , Jin Xueying , Shindo Yumi , Saito Tami
Published: August 2024

Introduction

Driving is an important mobility resource of increased outings and social activities among older adults; yet, little is known about the impact of driving restrictions on visiting places. We examined the association between driving status and the number of visiting places and the moderating role of alternative transportation use.

Methods

This cross-sectional study recruited community-dwelling individuals aged 65 years and above with functional independence from a suburban area through a mailed self-administered questionnaire. Visiting places were scored by assessing a total of 34 specific places over the past year using the Participation in ACTivities and Places OUTside Home Questionnaire (ACT-OUT); four subdomains of these paces were also measured: (A) consumer, administration, and self-care places (e.g., grocery shop, hairdresser, bank, post office, and government office); (B) places for medical and health care (e.g., the dentist or doctor’s office and hospital); (C) social, cultural, and spiritual places (e.g., family, relative and friend’s home, restaurant, cafe, and entertainment and cultural places); and (D) places of recreation and physical activities (e.g., park, sports facility, and forest, mountain, and sea). Driving status (self-driving or not) and other available transportation options (public transportation and ride-sharing with family/friends) were assessed.

Results

Data from 432 individuals were analyzed (mean age 74.8 years; 52.8% women). Multivariable linear regression analysis revealed that not driving was associated with lower scores of visiting places (β=-0.40,P<0.001). For subdomains, not driving was associated with lower scores for consumer, administration, and self-care places (β=-0.32,P=0.007) and social, cultural, and spiritual places (β=-0.44,P<0.001). Sensitivity analysis with inverse probability weighting confirmed the robustness of these results. Public transportation availability (trains and buses) moderated the association between not driving and visiting places.

Conclusions

These findings suggest that driving restrictions have the potential to reduce the visiting places among older adults, particularly life-related and social and cultural places.
Transcriptional dynamics of sleep deprivation and subsequent recovery sleep in the male mouse cortex
Authors: Popescu Alexander , Ottaway Caitlin , Ford Kaitlyn , Patterson Taylor Wintler , Ingiosi Ashley , Medina Elizabeth , Hicks Stephanie C. , Singletary Kristan , Peixoto Lucia
Published: August 2024

Sleep is an essential, tightly regulated biological function. Sleep is also a homeostatic process, with the need to sleep increasing as a function of being awake. Acute sleep deprivation (SD) increases sleep need, and subsequent recovery sleep (RS) discharges it. SD is known to alter brain gene expression in rodents, but it remains unclear which changes are linked to sleep homeostasis, SD-related impairments, or non-sleep-specific effects. To investigate this question, we analyzed RNA-seq data from adult wild-type male mice subjected to 3 and 5-6 hours of SD and 2 and 6 hours of RS after SD. We hypothesized molecular changes associated with sleep homeostasis mirror sleep pressure dynamics as defined by brain electrical activity, peaking at 5-6 hours of SD, and are no longer differentially expressed after 2 hours of RS. We report 5-6 hours of SD produces the largest effect on gene expression, affecting approximately half of the cortical transcriptome, with most differentially expressed genes (DEGs) downregulated. The majority of DEGs normalize after 2 hours of RS and are involved in redox metabolism, chromatin regulation, and DNA damage/repair. Additionally, RS affects gene expression related to mitochondrial metabolism and Wnt-signaling, potentially contributing to its restorative effects. DEGs associated with cholesterol metabolism and stress response do not normalize within 6 hours and may be non-sleep-specific. Finally, DEGs involved in insulin signaling, MAPK signaling, and RNA-binding may mediate the impairing effects of SD. Overall, our results offer insight into the molecular mechanisms underlying sleep homeostasis and the broader effects of SD.

New & Noteworthy

This study investigates different time points of sleep deprivation and recovery sleep to better understand the molecular processes influenced by sleep and lack of sleep. This study highlights redox metabolism, chromatin regulation, and DNA damage/repair as molecular mechanisms linked to sleep homeostasis while showing the effects of stress are probably non-sleep-specific based on transcriptional dynamics.
Impacts of nucleosome positioning elements and pre-assembled chromatin states on expression and retention of transgenes
Authors: Kwizera Ronard , Xie Junkai , Nurse Nathan , Yuan Chongli , Kirchmaier Ann L
Published: August 2024

Transgene applications ranging from gene therapy to development of stable cell lines and organisms rely on maintaining expression of transgenes. To-date, the use of plasmid-based transgenes has been limited by loss of their expression shortly after delivery into target cells. This short-lived expression of plasmid-based transgenes has been largely attributed to host cell-mediated degradation and/or silencing of transgenes. To assess the impact of “priming” plasmid-based transgenes to adopt accessible chromatin states to promote gene expression, nucleosome positioning elements were introduced at promoters of transgenes, or vectors were pre-assembled into nucleosomes containing unmodified histones or histone mutants mimicking constitutively acetylated states at residues 9 and 14 of histone H3 or residue 16 of histone H4 prior to their introduction into cells, then transgene expression was monitored over time. DNA sequences capable of positioning nucleosomes could positively impact expression of adjacent transgenes in a distance-dependent manner in the absence of pre-assembly into chromatin. Intriguingly, pre-assembly of plasmids into chromatin facilitated prolonged expression of transgenes relative to plasmids that were not pre-packaged into chromatin. Interactions between pre-assembled chromatin states and nucleosome positioning-derived effects on expression of reporter genes were also assessed and, generally, nucleosome positioning played the predominant role in influencing gene expression relative to priming with hyperacetylated chromatin states.
Structures of Multiple Peptide Resistance Factor fromPseudomonas aeruginosa
Authors: Jha Shaileshanand , Vinothkumar Kutti R.
Published: August 2024

The aminoacylation of lipid head group in many bacteria is carried out by bi-functional enzymes called MprF, which encode for a soluble synthase domain that typically transfers lysine or alanine from a tRNA to lipid head groups, and the modified lipid is translocated across the leaflets by a transmembrane domain. This modification of the lipids probably evolved to adapt to the environment where the microbes reside. Here, we describe the cryoEM structures of MprF enzyme fromPseudomonas aeruginosarevealing a dimeric enzyme with a distinct architecture when compared with the homologous Rhizobium enzymes and validate this arrangement with biochemical analysis. The cryoEM maps and the models in detergent micelle and nanodisc reveal a conformational change of the terminal helix of the synthase domain, highlighting the dynamic elements in the enzyme that might facilitate catalysis. Several lipid-like densities are observed in the cryoEM maps, which might indicate the path taken by the lipids and the coupling function of the two functional domains. Thus, the structure of a well-characterised PaMprF lays a platform for understanding the mechanism of amino acid transfer to a lipid head group and subsequent flipping across the leaflet that changes the property of the membrane.
A fluorophore–ligand conjugate for the rapid and reversible staining of native AMPA receptors in living neurons
Authors: Soga Kyohei , Fujiwara Takaaki , Nakagawa Mayu , Shibata Akihiro , Adriel Hansel , Yatsuzuka Kenji , Kakegawa Wataru , Yuzaki Michisuke , Hamachi Itaru , Nango Eriko , Kiyonaka Shigeki
Published: August 2024

The subcellular localizations of neurotransmitter receptors are strictly regulated in neurons. Changes in the trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-type glutamate receptors (AMPARs) play an essential role in synaptic plasticity, which is the cellular basis of learning and memory. To explore receptor trafficking, genetically encoded approaches (e.g., the fusion of fluorescent proteins to receptors) are often used. However, concerns remain that genetic approaches cannot fully reproduce the receptor function that is inherent to neurons. Herein, we report a chemical probe, PFQX1(AF488), for the visualization of cell-surface AMPARs without any genetic manipulation to neurons. The rapid and reversible staining features of this probe allowed the visualization of AMPAR accumulation in dendritic spines during synaptic plasticity in living hippocampal neurons. Moreover, the mechanisms of this synaptic accumulation, for which genetically encoded approaches have given controversial results, were revealed by integrating two chemical methods: PFQX1(AF488) and covalent chemical labeling.
Anatomically resolved oscillatory bursts orchestrate visual thalamocortical activity during naturalistic stimulus viewing
Authors: Meyerolbersleben Lukas S. , Sirota Anton , Busse Laura
Published: August 2024

Natural vision involves encoding of complex visual input, which engages a plethora of interacting circuit mechanisms. In the mammalian forebrain, one signature of such interacting circuit mechanisms is fast oscillatory dynamics, which can be reflected in the local field potential (LFP). We here used data from the Allen Neuropixels Visual Coding project to show that local visual features in naturalistic stimuli induce retinotopically specific V1 oscillations in various frequency bands. These LFP oscillations occurred in bursts, were localized to specific V1 layers, and were associated with phase coupling of V1 translaminar spiking, pointing to feature-specific circuit motifs. Finally, we discovered that these visually-induced circuit motifs occurred across a range of stimuli, suggesting that they might constitute general routes for feature-specific information flow. Together, our analyses demonstrate visually-induced, fast oscillations, which likely reflect the operation of distinct mesoscale circuits for the differential and multiplexed coding of complex visual input and feature-specific thalamo-cortical information propagation.
Single-stranded DNA drives σ subunit loading onto RNA polymerase to unlock initiation-competent conformations
Authors: Vishwakarma Rishi Kishore , Marechal Nils , Morichaud Zakia , Blaise Mickaël , Margeat Emmanuel , Brodolin Konstantin
Published: August 2024

Initiation of transcription requires the formation of the “open” promoter complex (RPo). For this, the σ subunit of bacterial RNA polymerase (RNAP) binds to the non-template strand of the -10 element sequence of promoters and nucleates DNA unwinding. This is accompanied by a cascade of conformational changes on RNAP the mechanics of which remains elusive. Here, using single-molecule Förster resonance energy transfer and cryo-electron microscopy, we explored the conformational landscape of RNAP from the human pathogenMycobacterium tuberculosisupon binding to a single-stranded DNA fragment that includes the -10 element sequence (-10 ssDNA). We found that like the transcription activator RbpA, -10 ssDNA induced σ subunit loading onto the DNA/RNA channels of RNAP. This triggered RNAP clamp closure and unswiveling that are required for RPo formation and RNA synthesis initiation. Our results reveal a mechanism of ssDNA-guided RNAP maturation and identify the σ subunit as a regulator of RNAP conformational dynamics
Compartmentalized sesquiterpenoid biosynthesis and functionalization in theChlamydomonas reinhardtiiplastid
Authors: Gutiérrez Sergio , Overmans Sebastian , Wellman Gordon B. , Lauersen Kyle J.
Published: August 2024

Terpenoids play key roles in cellular metabolism, with some organisms having evolved expanded terpenoid profiles for specialized functions such as signaling and defense. Many terpenoids have applications in pharmaceuticals, fragrances, and agriculture, but their harvest from natural sources can be challenging. Heterologous production of specialty terpenoids in microbial hosts offers an alternative, using terpene synthases and further enzymatic decoration to expand chemical complexity and functionality. Here, we explored the heterologous production of 10 different sesquiterpenoids (STPs, C15) and their further biofunctionalization mediated by cytochrome P450s (CYPs) in the green algaChlamydomonas reinhardtii. STP synthases were expressed from the nuclear genome and localized to the algal plastid, coupled with co-expression of selected CYPs. STP production in the plastid was supported by farnesyl pyrophosphate synthase fusions to STP synthases, and CYPs were modified for soluble localization in the plastid stroma by removing transmembrane domains. Various target CYPs were screened for STP functionalization in the alga, and different product ratios were generated based on trophic modes. Overall STP yields ranged between 250-2500 μg/L under screening conditions, with CYP-mediated functionalization reaching up to 80% of accumulated heterologous STP products. Living two-phase terpenoid extractions with different perfluorinated solvents revealed variable performances based on sesquiterpenoid functionalization and solvent type. This work demonstrates the feasibility of generating heterologous functionalized terpenoid products in alga using soluble, plastid-localized CYPs without reductase partners. However, overall improvements in photobioreactor cultivation concepts will be required to facilitate the use of algal chassis for scaled production.
Deep inverse modeling reveals dynamic-dependent invariances in neural circuit mechanisms
Authors: Gao Richard , Deistler Michael , Schulz Auguste , Gonçalves Pedro J. , Macke Jakob H.
Published: August 2024

Neural population dynamics are shaped by many cellular, synaptic, and network properties. Not only is it important to understand how coordinated changes in circuit parameters alter neural activity, but also when dynamics are unaffected by—or invariant to—such changes. Computational modeling has revealed invariances in single neurons and small circuits that are thought to reflect their robustness against variability and perturbations. However, generalizing these insights to larger circuits in cortex and other brain areas remains challenging. A key bottleneck lies in inverse modeling of neural circuits with spiking network models, i.e., identifying parameter configurations that quantitatively match dynamics observed in neural recordings. Here, we present Automated Model Inference from Neural Dynamics (AutoMIND) for efficient discovery of invariant circuit model configurations. AutoMIND leverages a mechanistic model with adaptive spiking neurons and clustered connectivity, which displays a rich variety of spatiotemporal dynamics. Probabilistic deep generative models—trained on network simulations only—then returns many parameter configurations consistent with a given target observation of neural activity. Applied to several datasets, AutoMIND discovers circuit models of synchronous network bursting in human brain organoids across early development, as well as models capturing complex frequency profiles of Neuropixels recordings in mouse hippocampus and cortex. In each case, we obtain hundreds of configurations that compose a (nonlinear) parameter subspace in which population dynamics remain unchanged. Surprisingly, global and local geometries of the invariant subspace are not fixed, but differ for different dynamics. Together, our results shed light on dynamic-dependent invariances of circuit parameters underlying diverse population dynamics, while demonstrating the flexibility of AutoMIND for inverse modeling of neural circuits.
Enhanced Maturity and Functionality of Vascularized Human Liver Organoids through 3D Bioprinting and Pillar Plate Culture
Authors: Lekkala Vinod Kumar Reddy , Shrestha Sunil , Al Qaryoute Ayah , Dhinoja Sanchi , Acharya Prabha , Raheem Abida , Jagadeeswaran Pudur , Lee Moo-Yeal
Published: August 2024

Liver tissues, composed of hepatocytes, cholangiocytes, stellate cells, Kupffer cells, and sinusoidal endothelial cells, are differentiated from endodermal and mesodermal germ layers. By mimicking the developmental process of the liver, various differentiation protocols have been published to generate human liver organoids (HLOs)in vitrousing induced pluripotent stem cells (iPSCs). However, HLOs derived solely from the endodermal germ layer often encounter technical hurdles, such as insufficient maturity and functionality, limiting their utility for disease modeling and hepatotoxicity assays. To overcome this, we separately differentiated EpCAM+endodermal progenitor cells (EPCs) and mesoderm-derived vascular progenitor cells (VPCs) from the same human iPSC line. These cells were then mixed in BME-2 matrix and concurrently differentiated into vascular human liver organoids (vHLOs). Remarkably, vHLOs exhibited significantly higher maturity than vasculature-free HLOs, as demonstrated by increased coagulation factor secretion, albumin secretion, drug-metabolizing enzyme (DME) expression, and bile acid transportation. To enhance assay throughput and miniaturize vHLO culture, we 3D bioprinted expandable HLOs (eHLOs) in BME-2 matrix on a pillar plate platform derived from EPCs and VPCs and compared with HLOs derived from endoderm alone. Compared to HLOs cultured in a 50 μL BME-2 matrix dome in a 24-well plate, vHLOs cultured on the pillar plate exhibited superior maturity, likely due to enhanced nutrient and signaling molecule diffusion. The integration of physiologically relevant patterned liver organoids with the unique pillar plate platform enhanced the capabilities for high-throughput screening and disease modeling.
Direct detection of endogenous Gαi activity in cells with a sensitive conformational biosensor
Authors: Luebbers Alex , Janicot Remi , Zhao Jingyi , Philibert Clementine E , Garcia-Marcos Mikel
Published: August 2024

Activation of heterotrimeric G-proteins (Gαβγ) by G-protein-coupled receptors (GPCRs) is not only a mechanism broadly used by eukaryotes to transduce signals across the plasma membrane, but also the target for a large fraction of clinical drugs. However, approaches typically used to assess this signaling mechanism by directly measuring G-protein activity, like optical biosensors, suffer from limitations. On one hand, many of these biosensors require expression of exogenous GPCRs and/or G-proteins, compromising readout fidelity. On the other hand, biosensors that measure endogenous signaling may still interfere with the signaling process under investigation or suffer from having a small dynamic range of detection, hindering broad applicability. Here, we developed an optical biosensor that detects the endogenous G-protein active species Gαi-GTP upon stimulation of endogenous GPCRs more robustly than current state-of-the-art sensors for the same purpose. Its design is based on the principle of bystander Bioluminescence Resonance Energy Transfer (BRET) and leverages the Gαi-binding protein named GINIP as a high affinity and specific detector module of the GTP-bound conformation of Gαi. We optimized this design to prevent interference with Gi-dependent signaling (cAMP inhibition) and to enable implementation in different experimental systems with endogenous GPCRs, including neurotransmitter receptors in primary astroglial cells or opioid receptors in cell lines, which revealed opioid neuropeptide-mediated activation profiles different from those observed with other biosensors involving exogenous GPCRs and G-proteins. Overall, we introduce a biosensor that directly and sensitively detects endogenous activation of G-proteins by GPCRs across different experimental settings without interfering with the subsequent propagation of signaling.
A Hippocampal-parietal Network for Reference Frame Coordination
Authors: Zheng Yicheng , Zhou Xinyu , Moseley Shawn C. , Ragsdale Sydney M. , Alday Leslie J. , Wu Wei , Wilber Aaron A.
Published: August 2024

Navigating space and forming memories based on spatial experience are crucial for survival, including storing memories in an allocentric (map-like) framework and conversion into body-centered action. The hippocampus and parietal cortex (PC) comprise a network for coordinating these reference frames, though the mechanism remains unclear. We used a task requiring remembering previous spatial locations to make correct future action and observed that hippocampus can encode the allocentric place, while PC encodes upcoming actions and relays this to hippocampus. Transformation from location to action unfolds gradually, with 'Came From' signals diminishing and future action representations strengthening. PC sometimes encodes previous spatial locations in a route-based reference frame and conveys this to hippocampus. The signal for the future location appears first in PC, and then in hippocampus, in the form of an egocentric direction of future goal locations, suggesting egocentric encoding recently observed in hippocampus may originate in PC (or another "upstream" structure). Bidirectional signaling suggests a coordinated mechanism for integrating map-like, route-centered, and person-centered spatial reference frames at the network level during navigation.
Multi-scale dynamics influence the division potential of stomatal lineage ground cells inArabidopsis
Authors: Fung Hannah F. , Amador Gabriel O. , Dale Renee , Gong Yan , Vollbrecht Macy , Erberich Joel M. , Mair Andrea , Bergmann Dominique C.
Published: August 2024

During development, many precursor lineages are flexible, producing variable numbers and types of progeny cells. What factors determine whether a precursor cell differentiates or retains the capacity to divide? Here, we leverage the developmental flexibility of the stomatal lineage ground cell (SLGC) inArabidopsisleaves as a model for how flexible decisions are regulated. Using a quantitative approach that combines long-term live imaging and statistical modeling, we discover that cell size is a strong predictor of SLGC behaviour: larger SLGCs divide less often than smaller cells. We propose that cell size is linked to division behaviour at multiple spatial scales. At the neighbourhood scale, cell size correlates with the strength of cell-cell signaling, which affects the rate at which SPEECHLESS (SPCH), a division-promoting transcription factor, is degraded. At the subcellular scale, cell size correlates with nuclear size, which modulates the concentration of SPCH in the nucleus. Our work shows how initial differences in SPCH levels are canalized by nuclear size and cell-cell signaling to inform the behaviour of a flexible cell type.
Insecticide resistance and population structure of the invasive malaria vector,Anopheles stephensi, from Fiq, Ethiopia
Authors: Samake Jeanne N. , Yared Solomon , Hassen Mussie Abdosh , Zohdy Sarah , Carter Tamar E.
Published: August 2024

Anopheles stephensiinvasion in Ethiopia poses a risk of increased malaria disease burden in the region. Thus, understanding the insecticide resistance profile and population structure of the recently detectedAn. stephensi population in Fiq, Ethiopia, is critical to inform vector control to stop the spread of this invasive malaria species in the country. Following entomological surveillance forAn. stephensiin Fiq, Somali region, Ethiopia, we confirmed the presence ofAn. stephensimorphologically and molecularly in Fiq. Characterization of larval habitats and insecticide susceptibility tests revealed that FiqAn. stephensiis most often found in artificial containers and is resistant to most adult insecticides tested (organophosphates, carbamates, pyrethroids) except for pirimiphos-methyl and PBO-pyrethroids. However, the immature larval stage was susceptible to temephos. Further comparative genomic analyses with previousAn. stephensi populations from Ethiopia using 1,704 biallelic SNPs revealed genetic relatedness between FiqAn. stephensiand east-central EthiopiaAn. stephensipopulations, particularly JigjigaAn. stephensi. Our findings of the insecticide resistance profile, coupled with the likely source population of FiqAn. stephensi, can inform vector control strategies against this malaria vector in Fiq and Jigjiga to limit further spread out of these two locations to other parts of the country and continent.
Identification and Functional Characterization of Up-Regulated Hub Genes in Adenocarcinoma Across Multiple Organ Sites
Authors: Romero Ricardo , Bastida Dulce M. A.
Published: August 2024

Abstract Adenocarcinoma is a prevalent and aggressive form of cancer affecting various organ systems. To gain deeper insights into the molecular mechanisms underlying adenocarcinoma, we conducted a comprehensive bioinformatics analysis to identify consistently up-regulated hub genes and their regulatory networks across multiple adenocarcinoma types. By integrating gene expression data from GEO and GEPIA2 databases, we identified 129 commonly up-regulated genes, from which 10 key hub genes were further characterized: CHEK1, CDC20, ANLN, RRM2, CCNB1, CCNA2, KIF23, TOP2A, BUB1, and KIF11. These hub genes were found to be significantly overexpressed in several adenocarcinoma types, including colorectal, lung, pancreatic, and ovarian cancer, except for prostate adenocarcinoma. The regulatory network analysis revealed that the expression of these hub genes is controlled by transcription factors, such as YBX1, E2F1, MYC, E2F3, and TP53, as well as miRNAs, including hsa-miR-103a-3p, hsa-let-7e-5p, and hsa-miR-15b-5p, which were consistently downregulated across the adenocarcinoma types studied. Functional enrichment analysis highlighted the involvement of these hub genes in critical cellular processes, including cell cycle regulation, mitotic division, and cellular senescence. These findings provide a comprehensive understanding of the molecular landscape of adenocarcinoma and identify potential therapeutic targets and prognostic biomarkers for further investigation.
Investigating the influence of iron parameters in regulating platelet recovery in Apheresis Platelet Donors
Authors: De Ranita , Stephen Leo , Mathews Vikram , George Biju , Edison Eunice Sindhuvi
Published: August 2024

Introduction: The present study investigates changes in haematological parameters in the donor during apheresis and following donation. Effect of iron parameters in influencing platelet recovery was studied. Methods: Blood samples were collected in EDTA tubes for analyses of haematological parameters. Serum samples were isolated for estimation of iron parameters. Results: Hb, RBC count and Hct increased during apheresis, but no significant changes were observed after 48 hrs post donation. Platelet recovery rates increased from 78 % after 48 hours to > 100% on day 10 (p < 0.001). Ferritin, serum iron & Transferrin saturation initially increased and subsequently declined from day 7 post donation, which may influence platelet recovery. Recovery rates were also higher in donors with lower iron stores. Conclusions: Changes in haematological parameters during plateletpheresis are transient and optimal time required for platelet recovery is dependent on pre-donation counts. Recovery of platelet counts may be positively regulated by donor iron parameters.
Transient dynamics response analysis of the limb under impact loading
Authors: song mengjun , Wei Jinggong , Zhang Liping
Published: August 2024

The limb vibrations are initiated at paw-strike in animal’s normal movement. The short ground contact duration suggests that there exists the transient dynamic response of the impact between the leg and ground, which is a high nonlinear problem and not well understood. The purpose of this study is to investigate the transient dynamic response of the lower limb of the felid during the moving. A kinematic model of the musculoskeletal system of a small felid is constructed from the anatomical measurement data. The elastic moduli are measured and calculated for different parts of the lower limb by a Nano-indentation technique. On the basis of the measured material parameters, the substructure technique is employed to numerically solve the contact-impact behavior of the lower limb. The high speed imaging system and a designed electronic detection system are employed in the experiment to testify the numerical results, which demonstrate that the initial impact has an important influence on the performance of the lower limb during the movement especially the high speed movement, and the paw-pad has good damping effects during the impact. The multiple impacts exist between limbs and the soil, which may provide the feedback energy for the felid’s high-speed running, though it may also increase the risk of the stress fracture of the limbs.
Digital marketing ecosystems and global market expansion: current state and future research agenda
Authors: Nim Nandini , Pedada Kiran , Hewett Kelly
Published: August 2024

Purpose

This article aims to provide greater clarity regarding the conceptualization and critical role of digital marketing ecosystems for the global expansion of multinational enterprises (MNEs) and offer novel research directions to prompt future research.

Design/methodology/approach

The authors first review the marketing literature related to marketing ecosystems, highlighting the evolution of this body of work across a range of domains such as services, innovation and new product development, communications and marketing strategy more broadly. Next, two case examples of MNEs whose global expansion efforts have been supported by their marketing ecosystems are used to highlight the role of marketing ecosystems in global market expansion. Finally, novel research directions are offered to prompt future research and provide greater insight into this emerging area.

Findings

The case examples we examine yield important insights into the role of marketing ecosystems for MNEs expanding from emerging markets (EMs) to developed markets (DMs). EM-MNEs such as TEMU face more communication and payment ecosystem challenges while opening their supply chain to DMs. Contrary to EM-MNEs, DM-MNEs face institutional and sociocultural challenges that require different marketing ecosystem orchestration approaches.

Originality/value

Marketing ecosystems can provide MNEs with greater multinational flexibility, enabling them to adapt their global strategies to navigate increasing complexities in global markets, such as trends toward increased protectionism and geopolitical disruptions. However, there is surprisingly little research addressing this issue.
Potential drivers of differences in breeding phenology as a component of life history strategies among coexisting species
Authors: Martin Thomas E. , Lloyd Penn
Published: August 2024

Breeding phenology can have strong demographic consequences. Yet, the reasons why coexisting animal species differ in breeding phenology have received little attention.

We tested selection pressures that underlie life history variation, such as age‐specific mortality, diet, and body size to explain breeding phenology of 16 coexisting songbird species in arid shrubland in South Africa.

The average start and end dates for the earliest and latest species differed by 1.5 months, with a gradient among remaining species. Nest predation risk generally increased through the season, although species differed in seasonal patterns. Species with lower annual adult mortality, greater seasonal increases in nest predation, and greater nest predation rates had earlier start and stop dates, thereby reducing demographic risks. Species with higher adult mortality had larger brood sizes that require more food and they bred later when food was more abundant. Evolved timing of breeding thereby reflected risk management and food availability related to longevity and brood size.

These factors may place unrecognized constraints on within‐species responses to climate change. Given the importance of phenology for fitness, phenology should be integrated as a core life history trait in future theory, and evolutionary constraints need to be considered in responses to climate change.

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Entomopathogenic Bacillus cereus impairs the fitness of the spotted‐wing drosophila, Drosophila suzukii
Authors: He Nana , Zhou Shaojie , Zhou Chuanming , Yang Weikang , Zhang Sheng , Yan Deqiang , Ji Xiaowen , Liu Wei
Published: August 2024

Drosophila suzukii is a notorious pest which causes devastating damage to thin‐skinned fruits, and the larvae feed on the fruit, causing extensive agricultural economic loss. The current application of insecticides to manage this pest results in serious resistance and environmental hazards, so an alternative strategy for D. suzukii biocontrol is urgently needed. Here, we reported that entomopathogenic Bacillus cereus has the potential to biocontrol D. suzukii. We isolated and identified the bacterial strain, B. cereus H1, that was detrimental to the fitness of both D. suzukii progenies and parents. D. suzukii was robustly repelled to depositing eggs on the halves with metabolites of B. cereus H1. Both males and females of D. suzukii were susceptible to B. cereus H1. B. cereus H1 significantly arrested larval development with at least 40% lethal larvae. The median lethal time (LT50) of males and females of D. suzukii challenged with B. cereus H1 was 3 and 2 d, respectively. Moreover, B. cereus H1 disrupted the intestinal integrity and pH value of D. suzukii and resulted in an increase in bacterial load of guts and hemolymph. Mechanistically, infection of B. cereus H1 led to the activation of the dual oxidase (DUOX)‐ROS‐Jun N‐terminal kinase (JNK) pathway. The findings showed that the entomopathogen B. cereus H1 could potentially act as a biological control agent against D. suzukii, advancing fundamental concepts of integrated pest management programs against D. suzukii.
Modeling of moisture content during baking with different approaches for effective diffusivity and evaluation of quality variables in baked potato slices
Authors: Pacheco‐Plata Felícitas , Gutiérrez‐Dorado Roberto , Iribe‐Salazar Rosalina , Carrazco‐Escalante Marco , Caro‐Hernández Olivia , Camacho‐Hernández Leticia , Vázquez‐López Yessica , Cronin Kevin , Caro‐Corrales José
Published: August 2024

Baking is a healthier alternative to frying, since texture, color, smell, and flavor are developed, without adding oil. The objective was to estimate the moisture content in potato slices, during baking using Fick's law of diffusion to model internal moisture transport and to assess the impact on quality attributes. Moisture transport kinetics were examined at three baking temperatures of 120, 130, and 140°C. Fick's law was employed to estimate average moisture content using different methods: considering both a constant (method of slopes by subperiods, MSS; and method of successive approximations, MSA) and a variable (represented as a quadratic function of time, QFT) behavior of effective diffusivity (De). Three quality variables were analyzed: water activity (aw, dew point hygrometry), total color difference (∆E, colorimetry), and fracturability (F, universal testing machine). The diffusivity estimated with the time‐varying De method provided a more realistic description of moisture migration during baking. The aw, ∆E, and F for baked potato slices ranged from 0.234 to 0.276, 17.9 to 24.6, and 5.20 to 5.49 N, respectively. These attributes imply improved stability and extended shelf life, showing typical colors and texture changes for baked snacks. These changes are linked to variations in diffusivity, influenced by the size and quantity of micropores within the food structure. This study could allow an accurate prediction of mass transfer by considering variable De, facilitating the optimization of baking conditions.

Practical Application

The analysis of the moisture content using Fick's law, considering a time‐varying diffusivity, enables the optimization of the baking process for foods. This helps minimize the occurrence of defective products.
The rootstock modifies the arbuscular mycorrhizal community of the root system, while the influence of the scion is limited in grapevines
Authors: Lailheugue Vincent , Darriaut Romain , Tran Joseph , Morel Marine , Marguerit Elisa , Lauvergeat Virginie
Published: August 2024

Understanding the effects of grapevine rootstock and scion genotypes on arbuscular mycorrhizal fungi (AMF), as well as the roles of these fungi in plant development, could provide new avenues for adapting viticulture to climate change and reducing agrochemical inputs. The root colonization of 10 rootstock/scion combinations was studied using microscopy and metabarcoding approaches and linked to plant development phenotypes. The AMF communities were analysed using 18S rRNA gene sequencing. The 28S rRNA gene was also sequenced for some combinations to evaluate whether the method changed the results. Root colonization indexes measured by microscopy were not significantly different between genotypes. Metabarcoding analyses showed an effect of the rootstock genotype on the β‐diversity and the enrichment of several taxa with both target genes, as well as an effect on the Chao1 index with the 18S rRNA gene. We confirm that rootstocks recruit different AMF communities when subjected to the same pedoclimatic conditions, while the scion has little or no effect. Significant correlations were observed between AMF community composition and grapevine development, suggesting that AMF have a positive effect on plant growth. Given these results, it will be important to define consensus methods for studying the role of these beneficial micro‐organisms in vineyards.