bluuebunny/crossref_metadata_2025 huggingface dataset:
Timing Matters: Lessons From Perinatal Neurogenesis in the Olfactory Bulb
Authors: Liberia Teresa , Han Kimberly , Meller Sarah , Martin-Lopez Eduardo , Greer Charles A.
Published: May 2024

In the olfactory bulb odorant receptor specific input converges into glomeruli. Deep to the glomeruli coding of odor information is tuned by local synaptic circuits. Deciphering the dendritic organization of granule cells relative to the secondary dendrites of projection neurons is a pivotal for understanding odor processing. We carried out a detailed interrogation of the granule cells including the timing of neurogenesis, laminar distribution and synaptogenesis between granule cells and projection neurons. In brief, the granule cells develop following a outside in maturation pattern from embryogenesis to adulthood following a developmental continuum. Granule cells born one week after birth exhibit a unique sublayer specific distribution pattern, marking a transition between embryonic or neonatal and adult stages. Integration into reciprocal synaptic circuits occurred 10 days post neurogenesis, We conclude that timing of neurogenesis dictates the anatomical configuration of granule cells within the olfactory bulb, which in turn regulates a preferential synaptic integration with either mitral cell or tufted cell secondary dendrites.

Summary Statement

The integration and distribution of granule cells into the olfactory bulb is determined by the timing of neurogenesis. Location of somata shifts from superficial to deep during development.
Disentangling cell-intrinsic and extrinsic factors underlying evolution
Authors: Starr Alexander L. , Nishimura Toshiya , Igarashi Kyomi J. , Funamoto Chihiro , Nakauchi Hiromitsu , Fraser Hunter B.
Published: May 2024

A key goal of developmental biology is to determine the extent to which cells and organs develop autonomously, as opposed to requiring interactions with other cells or environmental factors. Chimeras have played a foundational role in this by enabling qualitative classification of cell-intrinsically vs. extrinsically driven processes. Here, we extend this framework to precisely decompose evolutionary divergence in any quantitative trait into cell-intrinsic, extrinsic, and intrinsic-extrinsic interaction components. Applying this framework to thousands of gene expression levels in reciprocal rat-mouse chimeras, we found that the majority of their divergence is attributable to cell-intrinsic factors, though extrinsic factors also play an integral role. For example, a rat-like extracellular environment extrinsically up-regulates the expression of a key transcriptional regulator of the endoplasmic reticulum (ER) stress response in some but not all cell types, which in turn strongly predicts extrinsic up-regulation of its target genes and of the ER stress response pathway as a whole. This effect is also seen at the protein level, suggesting propagation through multiple regulatory levels. Applying our framework to a cellular trait, neuronal differentiation, revealed a complex interaction of intrinsic and extrinsic factors. Finally, we show that imprinted genes are dramatically mis-expressed in species-mismatched environments, suggesting that mismatch between rapidly evolving intrinsic and extrinsic mechanisms controlling gene imprinting may contribute to barriers to interspecies chimerism. Overall, our conceptual framework opens new avenues to investigate the mechanistic basis of developmental processes and evolutionary divergence across myriad quantitative traits in any multicellular organism.
Non-cell-autonomous regulation of mTORC2 by Hedgehog signaling maintains lipid homeostasis
Authors: VanDerMolen Kylie R. , Newman Martin A. , Breen Peter C. , Huff Laura A. , Dowen Robert H.
Published: May 2024

Organisms must appropriately allocate energetic resources between essential cellular processes to maintain homeostasis and in turn, maximize fitness. The nutritional and homeostatic regulators of energy homeostasis have been studied in detail; however, how developmental signals might impinge on these pathways to govern cellular metabolism is poorly understood. Here, we identify a non-canonical role for Hedgehog (Hh), a classic regulator of development, in maintaining intestinal lipid homeostasis inC. elegans. We find that expression of two Hh ligands, GRD-3 and GRD-4, is controlled by the LIN-29/EGR transcription factor in the hypodermis, where the Hh secretion factor CHE-14/Dispatched also facilitates non-cell autonomous Hh signaling. We demonstrate, usingC. elegansand mouse hepatocytes, that Hh metabolic regulation does not occur through the canonical Hh transcription factor, TRA-1/GLI, but rather through non-canonical signaling that engages mTOR Complex 2 (mTORC2) in the intestine. Hh mutants display impaired lipid homeostasis, including reduced lipoprotein synthesis and fat accumulation, decreased growth, and upregulation of autophagy factors, mimicking loss of mTORC2. Additionally, we found that Hh inhibits p38 MAPK signaling in parallel to mTORC2 activation and that both pathways act together to modulate of lipid homeostasis. Our findings show a non-canonical role for Hedgehog signaling in lipid metabolism via regulation of core homeostatic pathways and reveal a new mechanism by which developmental timing events govern metabolic decisions.
scBSP: A fast and accurate tool for identifying spatially variable genes from spatial transcriptomic data
Authors: Li Jinpu , Wang Yiqing , Raina Mauminah Azam , Xu Chunhui , Su Li , Guo Qi , Ma Qin , Wang Juexin , Xu Dong
Published: May 2024

Spatially resolved transcriptomics have enabled the inference of gene expression patterns within two and three-dimensional space, while introducing computational challenges due to growing spatial resolutions and sparse expressions. Here, we introduce scBSP, an open-source, versatile, and user-friendly package designed for identifying spatially variable genes in large-scale spatial transcriptomics. scBSP implements sparse matrix operation to significantly increase the computational efficiency in both computational time and memory usage, processing the high-definition spatial transcriptomics data for 19,950 genes on 181,367 spots within 10 seconds. Applied to diverse sequencing data and simulations, scBSP efficiently identifies spatially variable genes, demonstrating fast computational speed and consistency across various sequencing techniques and spatial resolutions for both two and three-dimensional data with up to millions of cells. On a sample with hundreds of thousands of sports, scBSP identifies SVGs accurately in seconds to on a typical desktop computer.
NEK1 modulates neurite outgrowth in motor neurons through coordinating retromer formation
Authors: Huang Xuan , Oses-Prieto Juan A. , Kawaguchi Riki , Perrault Laura , Frost Devlin , Chen Kuchuan , Guo Feng , Zhang Bingjie , Zhao Pinghan , Ho Tammy Szu-Yu , Pandey Roshan , Geschwind Daniel , Burlingame Alma L. , Woolf Clifford J.
Published: May 2024

Loss of function of a cell cycle-associated geneNEK1causes amyotrophic lateral sclerosis (ALS), but how this leads to motor neuron degeneration is unknown. We studied the function ofNEK1in human stem cell-derived motor neurons and found that loss ofNEK1causes decreased neurite length accompanied by transcriptional alterations. We also found that NEK1 interacts with and modulates the formation of the retromer, and that impaired retromer function contributes to neurite outgrowth deficits. We identified SMC3, which interacts with NEK1 during the cell cycle, as a kinase substrate of NEK1 in motor neurons. Notably, loss of SMC3 not only recapitulates the decreased neurite outgrowth, but also affects retromer formation. We suggest that NEK1 interacts with multiple proteins in postmitotic neurons to coordinate retromer formation, and that loss of this leads to impaired neurite outgrowth.
Promoting Vigorous Intermittent Lifestyle Physical Activity (VILPA) in middle-aged adults: An evaluation of the MovSnax mobile app
Authors: Thøgersen-Ntoumani Cecilie , Grunseit Anne , Holtermann Andreas , Steiner Sarah , Tudor-Locke Catrine , Koster Annemarie , Johnson Nathan , Maher Carol , Ahmadi Matthew , Chau Josephine Y. , Stamatakis Emmanuel
Published: May 2024

Background

Most adults fail to meet the moderate to vigorous physical activity-based recommendations needed to maintain or improve health. Vigorous Intermittent Lifestyle Physical Activity (VILPA) refers to short (1-2 mins) high-intensity activities that are integrated into activities of daily living. VILPA has shown strong potential to improve health and addresses commonly reported barriers to physical activity. However, it is unknown how VILPA can best be promoted among the adult population. This study aimed to evaluate the usability, user engagement, and satisfaction of a mobile application (MovSnax) designed to promote VILPA.

Methods

A concurrent mixed methods design was used. It comprised four parts. Part A was a survey withn=8 mHealth and physical activity experts who had used the app over 7-10 days. Part B was think- aloud interviews withn=5 end-users aged 40-65 years old. Part C was a survey with a new group of 40-65-year-old end-users (n=35) who had used the MovSnax app over 7-10 days. Part D was semi- structured interviews withn=18 participants who took part in Part C. Directed content analysis was used to analyze the results from Parts A, B, and D, and descriptive statistics were used to analyze findings from Part C.

Results

Participants reported positive views on the MovSnax app for promoting VILPA but also identified usability issues such as unclear purpose, difficulties in manual data entry, and limited customization options. Across the different data collections, they consistently emphasized the need for more motivational features, clearer feedback, and gamification elements to enhance engagement. Quantitative assessment showed satisfactory scores on objective measures but lower ratings on subjective aspects, possibly due to unfamiliarity with the VILPA concept and/or technical barriers.

Conclusions

The MovSnax app, tested in the present study, is the world’s first digital tool aimed specifically at increasing VILPA. The findings of the present study underscore the need for further app refinement, focusing on clarifying its purpose and instructions, boosting user engagement through personalization and added motivational elements, enhancing accuracy in detecting VILPA bouts, implementing clearer feedback mechanisms, expanding customization choices (such as font size and comparative data), and ensuring transparent and meaningful activity tracking.
Effect of a needs-based model of care on the characteristics of healthcare services in England: the i-THRIVE National Implementation Programme
Authors: Sippy Rachel , Efstathopoulou Lida , Simes Elizabeth , Davis Meghan , Howell Sophie , Morris Bethan , Owrid Oliver , Stoll Nkasi , Fonagy Peter , Moore Anna
Published: May 2024

Aims: Developing integrated mental health services that focus on the needs of children and young people is a key policy goal in England. The THRIVE Framework and its associated implementation programme, i-THRIVE, are now used in areas covering over 65% of England's children. This study explores the experiences of staff involved with the i-THRIVE programme, assesses its effectiveness, and examines how local system working relationships influence the programme's success. Methods: The i-THRIVE programme was evaluated using a quasi-experimental study among twenty participating sites (ten implementation and ten comparison sites). Measurements included surveys of staff and leaders at each site and assessment of the "THRIVE-like" features of each site. Additional site-level characteristics were collected from health system reports. The effect of i-THRIVE was evaluated using a four-group propensity-score weighted difference-in-differences model; the moderating effect of local system working relationships was evaluated with a difference-in-difference-in-differences model. Results: Staff at implementation sites were more likely to report using THRIVE in their own practice and exhibited better knowledge of THRIVE principles than comparison sites. The mean improvement among i-THRIVE sites was 16.7, and 8.8 among comparison sites. The results show that strong working relationships in the local system significantly enhances the effectiveness of the i-THRIVE programme. Sites with highly effective working relationships showed a notable improvement in "THRIVE-like" features, with an average increase of 16.41 points (95% confidence interval: 1.69—31.13, p-value: 0.031) compared to control sites. In contrast, sites with ineffective working relationships did not benefit from the i-THRIVE programme (-2.76, 95% confidence interval: -18.25—12.73, p-value: 0.708). This influence of working relationship effectiveness was consistent across various levels of THRIVE features. Conclusions: The findings underscore the importance of working relationship effectiveness in the successful adoption and implementation of health policies like i-THRIVE.
Bacterial family-specific enrichment and functions of secretion systems in the rhizosphere
Authors: Fourie A. , Lopez J.L. , Sánchez-Gil J.J. , Poppeliers S.W.M. , de Jonge R. , Dutilh B.E.
Published: May 2024

The plant rhizosphere is a highly selective environment where bacteria have developed traits to establish themselves or outcompete other microbes. These traits include bacterial secretion systems (SS’s) that range from Type I (T1SS) to Type IX (T9SS) and can play diverse roles. The best known functions are to secrete various proteins or other compounds into the extracellular space or into neighbouring cells, including toxins to attack other microbes or effectors to suppress plant host immune responses. Here, we aimed to determine which bacterial SS’s were associated with the plant rhizosphere. We utilised paired metagenomic datasets of rhizosphere and bulk soil samples from five different plant species grown in a wide variety of soil types, amounting to ten different studies. The T3SS and T6SS were generally enriched in the rhizosphere, as observed in studies of individual plant-associated genera. We also identified additional SS’s that have received less attention thus far, such as the T2SS, T5SS andBacteroidetes-specific T6SSiii and T9SS. The predicted secreted proteins of some of these systems (T3SS, T5SS and T6SS) could be linked to functions such as toxin secretion, adhesion to the host and facilitation of plant-host interactions (such as root penetration). The most prominent bacterial taxa with rhizosphere- or soil-enriched SS’s includedXanthomonadaceae,Oxalobacteraceae,Comamonadaceae,Caulobacteraceae, andChitinophagaceae,broadening the scope of known plant-associated taxa that use these systems. We anticipate that the SS’s and taxa identified in this study may be utilised for the optimisation of bioinoculants to improve plant productivity.
Novel plant-derived bioactive compounds shape the human gut microbiomein vitro
Authors: Flores Martinez Karla E , Bloszies Clay S. , Henrick Bethany M. , Frese Steven A
Published: May 2024

Mounting evidence supports the potential of dietary bioactive compounds to reduce chronic disease risk. Recently, the biological activity of N-trans-caffeoyltyramine (NCT) and N-trans-feruloyltyramine (NFT) has been hypothesized to drive regulation of gut permeability,but the impact of these components on the human gut microbiome composition has not been studied. The aim of this work is to determine whether purified NCT and NFT, or a hemp hull product containing NCT and NFT (Brightseed® Bio Gut Fiber), can impact the gut microbiome using anin vitrofermentation assay. To address this question, we treated three fecal inocula, representative of the human gut microbiome, with Bio Gut Fiber™ and NCT/NFT and evaluated their respective impact against starch and methylcellulose as controls. We found strong changes exerted by Bio Gut Fiber™ and NCT/NFT on the gut microbiome relative to starch and methylcellulose, with distinct responses across all microbial communities. Among communities treated with Bio Gut Fiber™, we saw increased community productivity and increased community diversity. Further, to determine whether changes found in gut microbiome profiles were dose-dependent, we tested different concentrations of NCT/NFT and found a dose-dependent impact on the resulting microbial compositions. Through this work, we provide novel insight into the potential of bioactive components to shape the gut microbiome, highlighting the potential for plant-derived bioactives to improve the human gut microbiome and host health.
A type II secreted subtilase from commensal rhizobacteria disarms the immune elicitor peptide flg22
Authors: Eastman Samuel , Jiang Ting , Ficco Kaeli , Liao Chao , Jones Britley , Wen Sarina , Olivas Biddle Yvette , Eyceoz Aya , Yatsishin Ilya , Naumann Todd A. , Conway Jonathan M.
Published: May 2024

Plant roots grow in association with a community of microorganisms collectively known as the rhizosphere microbiome. Immune activation in response to elicitors like the flagellin-derived epitope flg22 restricts bacteria on plant roots but also inhibits plant growth. Some commensal root-associated bacteria are capable of suppressing the plant immune response to elicitors. In this study, we investigated the ability of 165 root-associated bacteria to suppress flg22-induced immune activation and growth restriction. We demonstrate that a type II secreted subtilase, which we term Immunosuppressive Subtilase A (IssA), fromDyella japonicastrain MF79 cleaves the immune eliciting peptide flg22 and contributes to immune suppression. IssA homologs are found in other plant-associated commensals, with particularly high conservation in the order Xanthomonadales. This represents a novel mechanism by which commensal microbes modulate flg22-induced immunity in the rhizosphere microbiome.
MoLst8 regulates autophagy and lipid homeostasis inMagnaporthe oryzae
Authors: Cao Xingwei , Li Lin , Bao Jiandong , Wang Jiaoyu , Liu Xiaohong , Zhu Xueming , Lin Fucheng
Published: May 2024

TOR, a widely conserved eukaryotic protein kinase, forms TORC1 and TORC2 to regulate diverse cell signaling. TORC1 controls protein synthesis, cell cycle, and autophagy, whereas TORC2 manages cell polarity, cytoskeleton, and membrane structure. Our previous research found that MoVast2, along with MoVast1, regulates TOR in rice blast fungusMagnaporthe oryzae, maintaining lipid and autophagy balance. Lst8, a key TOR complex component in yeast and mammalian cells. However, the precise role of MoLst8 inM. oryzaeis still unclear. In this study, we obtained the ΔMolst8mutant through high-through gene knockout strategies. The results showed that loss ofMoLST8leading to a series of defects, such as growth and sporulation reduction, abnormal conidia, and loss of virulence. In addition, this mutant is highly sensitive to rapamycin, leading to growth arrest and autophagy impairment, indicated that MoLst8 positively regulates TORC1 for cellular growth, metabolism, and autophagy. Lipidomics analysis in the mutant revealed lipid metabolism dysregulation, sphingolipid reduction, disrupting membrane tension and homeostasis, suggested that TORC2 mediated lipid regulation is disordered in ΔMolst8mutant. Additionally, the study explored TOR-MAPK crosstalk, finding that the mutant shows heightened cell wall stress sensitivity but fails to restore integrity despite MAPK activation. These findings offer insights into MoLst8’s role in fungal pathogenesis, contributing to an understanding of fungal biology and disease control strategies.
Influence of environmental and biological factors on functional connectivity of the superior temporal sulcus in neonates scanned at term age
Authors: Mancuso Charlotte , Bacquet Maxime , Benjamin Lucas , Leroy François , Dehaene-Lambertz Ghislaine
Published: May 2024

The superior temporal sulcus (STS), one of the first sulci visible during brain development, is a key region for human communication, notably hosting linguistic functions in the left hemisphere. Fetuses and premature newborns already process external sound, but the auditory environment is vastly differentin-uteroandex-utero.Does this have an impact on the development of the auditory and linguistic networks? To answer this question, we studied the functional connectivity of regions bordering the STS, delimited in each individual including full-term and preterm male and female neonates born at different gestational ages but all scanned at term. We found that in addition to the expected contralateral connectivity, various STS parts were more strongly connected to specific distant regions, revealing the typical auditory/linguistic division across the two banks of the STS reported in adults. Furthermore, the right posterior STS was more connected to the contralateral hemisphere than the left. Finally, sex and premature birth had effects on both STS volume and connectivity. Female neonates displayed a lesser left-right asymmetry in STS depth, and heightened connectivity from the left posterior STS compared to males. Most importantly, despite equivalent scan age, full-term newborns had deeper sulci compared with preterms, and local connectivity in the right temporal region increased linearly with gestation length. These results emphasize the impact of both sex and early auditory environment on the setting up of the cerebral networks that might contribute to explain the milder impact of premature birth on language in females.
Viroporin activity from rotavirus nonstructural protein 4 induces intercellular calcium waves that contribute to pathogenesis
Authors: Gebert J. Thomas , Scribano Francesca J. , Engevik Kristen A. , Philip Asha A. , Kawagishi Takahiro , Greenberg Harry B. , Patton John T. , Hyser Joseph M.
Published: May 2024

Acute gastroenteritis remains the second leading cause of death among children under the age of 5 worldwide. While enteric viruses are the most common etiology, the drivers of their virulence remain incompletely understood. We recently found that cells infected with rotavirus, the most prevalent enteric virus in infants and young children, initiate hundreds of intercellular calcium waves that enhance both fluid secretion and viral spread. Understanding how rotavirus triggers intercellular calcium waves may allow us to design safer, more effective vaccines and therapeutics, but we still lack a mechanistic understanding of this process. In this study, we used existing virulent and attenuated rotavirus strains, as well as reverse engineered recombinants, to investigate the role of rotavirus nonstructural protein 4 (NSP4) in intercellular calcium wave induction usingin vitro, organoid, andin vivomodel systems. We found that the capacity to induce purinergic intercellular calcium waves (ICWs) segregated with NSP4 in both simian and murine-like rotavirus backgrounds, and NSP4 expression alone was sufficient to induce ICWs. NSP4’s ability to function as a viroporin, which conducts calcium out of the endoplasmic reticulum, was necessary for ICW induction. Furthermore, viroporin activity and the resulting ICWs drove transcriptional changes indicative of innate immune activation, which were lost upon attenuation of viroporin function. Multiple aspects of RV disease severityin vivocorrelated with the generation of ICWs, identifying a critical link between viroporin function, intercellular calcium waves, and enteric viral virulence.
Positional13C Enrichment Analysis of Aspartate by GC-MS to Determine PEPC ActivityIn Vivo
Authors: Wittemeier Luisa , Rajarathinam Yogeswari , Erban Alexander , Hagemann Martin , Kopka Joachim
Published: May 2024

Photoautotrophic organisms fix inorganic carbon (Ci) by two enzymes, ribulose-1,5-bisphosphate carboxylase/oxygenase (RUBISCO) and phosphoenolpyruvate carboxylase (PEPC). RUBISCO assimilates Ci (CO2) into the 1-C position of 3-phosphoglycerate (3PGA). The Calvin-Benson-Basham (CBB) cycle redistributes fixed carbon atoms into 2,3-C2of the same molecule. PEPC uses phosphoenolpyruvate (PEP) derived from 3PGA and assimilates Ci (HCO3-) into 4-C of oxaloacetate (OAA). 1,2,3-C3of OAA and of its transaminase product aspartate originate directly from 1,2,3-C3of 3PGA. Positional isotopologue analysis of aspartate, the main downstream metabolite of OAA in the model cyanobacteriumSynechocystissp. PCC 6803 (Synechocystis), allows differentiation between PEPC, RUBISCO, and CBB cycle activities within one molecule. We exploredin sourcefragmentation of gas chromatography-electron impact ionization-mass spectrometry (GC-EI-MS) at nominal mass resolution and GC-atmospheric pressure chemical ionization-MS (GC-APCI-MS) at high mass resolution. This enabled the determination of fractional13C enrichment (E13C) at each carbon position of aspartate. Two prevailing GC-MS derivatization methods, i.e. trimethylsilylation and tert-butyldimethylsilylation, were evaluated. The method was validated by13C-isotopomer mixtures of positional labeled aspartic acid. Combination with dynamic13CO2labeling ofSynechocystiscultures allowed direct measurements of PEPC activityin vivoalongside analyses of RUBISCO and CBB cycle activities. Accurate quantification of aspartate concentration and positional E13C provided molar Ci assimilation rates during the day and night phases of photoautotrophicSynechocystiscultures. The validated method offers several applications to characterize the photosynthetic Ci fixation in different organisms.
Persistent Decision-Making in Mice, Monkeys, and Humans
Authors: Laurie Veldon-James , Shourkeshti Akram , Chen Cathy S. , Herman Alexander B. , Grissom Nicola M. , Ebitz R. Becket
Published: May 2024

Humans have the capacity to persist in behavioural policies, even in challenging environments that lack immediate reward. Our persistence is the scaffold on which many higher executive functions are built. However, it remains unclear whether humans are uniquely persistent or, instead, if this capacity is widely conserved across species. To address this question, we compared humans with mice and monkeys in harmonised versions of an uncertain decision-making task. The task encouraged all species to strike a balance between persistently exploiting one policy and exploring alternative policies that could become better at any moment. Although all three species had similar strategies, we found that both primate species—humans and monkeys—were able to persist in exploitation for much longer than the mice. We speculate that the similarities in persistence patterns in humans and monkeys, as opposed to mice, may be linked to ecological, neurobiological, or cognitive factors that differ systematically between these species.

Teaser

Humans, monkeys and mice use similar decision-making strategies, but exploit valuable options for different lengths of time.
Concurrent maintenance of visual imagery and short-term memory provides evidence for their distinct representations
Authors: Saad Elyana , Silvanto Juha
Published: May 2024

Recent research indicates there is overlap in the neural resources used during imagery and visual short-term memory. But do visual short-term memory and visual imagery operate on similar representations during recall? Here we investigated this question by asking participants to perform a delayed match to sample task for the contrast of visual gratings as cues. In the “Imagery” condition, participants were asked to form an accurate mental image of the visual cue, and at the end of the trial, perform a matching task on the mental image contrast. In the “Memory” condition, participants were not required to perform visual imagery but merely instructed to perform the delayed contrast-matching task. In Experiment 1, participants were told at the beginning of each block whether to engage in memory or imagery. The results showed that for the relevant contrast feature, matching judgments were more accurately in the “Memory” than in the “Imagery” condition. Thus imagery did not maintain an accurate representation of the encoded image, even when the visual features could still be maintained in visual short-term memory. In Experiment 2, participants were required to engage in memory and imagery simultaneously, and were told which to base their judgment on after each trial. The key finding was that the superior accuracy for memory over imagery remained, indicating that the contents of VSTM and imagery are based on distinct representations.
Oct4 redox sensitivity potentiates reprogramming and differentiation
Authors: Shen Zuolian , Wu Yifan , Manna Asit , Yi Chongil , Cairns Bradley R. , Evason Kimberley J. , Chandrasekharan Mahesh B. , Tantin Dean
Published: May 2024

The transcription factor Oct4/Pou5f1 is a component of the regulatory circuitry governing pluripotency and is widely used to induce pluripotency from somatic cells. Here we used domain swapping and mutagenesis to study Oct4's reprogramming ability, identifying a redox-sensitive DNA binding domain, cysteine residue (Cys48), as a key determinant of reprogramming and differentiation. Oct4 Cys48 sensitizes the protein to oxidative inhibition of DNA binding activity and promotes oxidation-mediated protein ubiquitylation.Pou5f1C48Spoint mutation has little effect on undifferentiated embryonic stem cells (ESCs) but upon retinoic acid (RA) treatment causes retention of Oct4 expression, deregulated gene expression, and aberrant differentiation.Pou5f1C48SESCs also form less differentiated teratomas and contribute poorly to adult somatic tissues. Finally, we describePou5f1C48S(Janky) mice, which in the homozygous condition are severely developmentally restricted after E4.5. Rare animals bypassing this restriction appear normal at birth but are sterile. Collectively, these findings uncover a novel Oct4 redox mechanism involved in both entry into and exit from pluripotency.
Ribosome decision graphs for the representation of eukaryotic RNA translation complexity
Authors: Tierney Jack A.S. , Świrski Michał , Tjeldnes Håkon , Mudge Jonathan M. , Kufel Joanna , Whiffin Nicola , Valen Eivind , Baranov Pavel V.
Published: May 2024

The application of ribosome profiling has revealed an unexpected abundance of translation in addition to that responsible for the synthesis of previously annotated protein-coding regions. Multiple short sequences have been found to be translated within single RNA molecules, within both annotated protein-coding and noncoding regions. The biological significance of this translation is a matter of intensive investigation. However, current schematic or annotation-based representations of mRNA translation generally do not account for the apparent multitude of translated regions within the same molecules. They also do not take into account the stochasticity of the process that allows alternative translations of the same RNA molecules by different ribosomes. There is a need for formal representations of mRNA complexity that would enable the analysis of quantitative information on translation and more accurate models for predicting the phenotypic effects of genetic variants affecting translation. To address this, we developed a conceptually novel abstraction that we term ribosome decision graphs (RDGs). RDGs represent translation as multiple ribosome paths through untranslated and translated mRNA segments. We termed the latter “translons.” Nondeterministic events, such as initiation, reinitiation, selenocysteine insertion, or ribosomal frameshifting, are then represented as branching points. This representation allows for an adequate representation of eukaryotic translation complexity and focuses on locations critical for translation regulation. We show how RDGs can be used for depicting translated regions and for analyzing genetic variation and quantitative genome-wide data on translation for characterization of regulatory modulators of translation.
Prediction of the non-SUSY AdS conjecture on the lightest neutrino mass revisited
Authors: Nam Cao H.
Published: May 2024

We study the constraint of the nonsupersymmetric (non-SUSY) anti–de Sitter (AdS) conjecture on the three-dimensional vacua obtained from the compactification of the Standard Model coupled to Einstein gravity on a circle where the three-dimensional components of the four-dimensional metric are general functions of both noncompact and compact coordinates. We find from studying the wave function profile of the three-dimensional metric in the compactified dimension that the radius of the compactified dimension must be quantized. Consequently, the three-dimensional vacua are constrained by not only the non-SUSY AdS conjecture but also the quantization rule of the circle radius, leading to both upper and lower bounds for the mass of the lightest neutrino as 2≤mν/Λ4<3, where Λ4≃5.06×10−84  GeV2 is the observed cosmological constant. This means that the lightest neutrino should have a mass around 10−32  eV or it would be approximately massless. With this prediction, we reconstruct the light neutrino mass matrix that is fixed by the neutrino oscillation data and in terms of three new mixing angles and six new phases for both the normal ordering and inverted ordering. In the situation where the light neutrino mass matrix is Hermitian, we calculate its numerical value in the 3σ range.

Published by the American Physical Society
2024
Emergence of inertia in the low-Reynolds regime of self-diffusiophoretic motion
Authors: Zero Emmy N. , Crespi Vincent H.
Published: May 2024

For isotropic swimming particles driven by self-diffusiophoresis at zero Reynolds number (where particle velocity responds instantaneously to applied force), the diffusive timescale of emitted solute can produce an emergent quasi-inertial behavior. These particles can orbit in a central potential and reorient under second-order dynamics, not the first-order dynamics of classical zero-Reynolds motion. They are described by a simple effective model that embeds their history-dependent behavior as an effective inertia, this being the most primitive expression of memory. The system can be parameterized with dynamic quantities such as particle size and swimming speed, without detailed knowledge of the diffusiophoretic mechanism.

Published by the American Physical Society
2024
The impacts of the Ethiopian developmental state model on the competition, efficiency and profitability of banks
Authors: Hamza Abdulmenan
Published: May 2024

Purpose

This study examines the impacts of the Ethiopian developmental state model on the competition, efficiency and profitability of banks.

Design/methodology/approach

The competition, efficiency and profitability of the Ethiopian bank are measured using Panzar Rose, data envelopment analysis and financial ratio. Fixed-effect panel regression methods are applied to test the direction and strength of association between the Ethiopian developmental state model and the competition, efficiency and profitability of the country's banks while controlling bank-specific market structure and macroeconomic factors.

Findings

The Ethiopian developmental state model embeds the state-directed financial system, which affects the banking industry using a range of credit allocation instruments. Of which, directed credit schemes, interest rate control and the lack of financial freedom reduce the competition and efficiency of banks. The National Bank of Ethiopia (NBE) advances to the government and the sale of Treasury bills to a captive market enhances banking competition while negatively affecting banking efficiency. Interest rate control and the lack of financial freedom lower banking profitability. Unexpectedly, directed credit schemes improve banking profitability.

Research limitations/implications

As with any study, this one has limitations. The intra-period comparison of efficiency is based on balanced data. Future studies can use methods that can measure the efficiency of banks using unbalanced data. The computation of the yearly H-statistic is constrained by the small sample size. The use of high-frequency data for measuring competition can provide us with better insights into banking competition in Ethiopia. Furthermore, there are a number of methods for measuring banking competition, efficiency and profitability with different assumptions. Approaching the subject of this study by applying different methods will offer different insights.

Practical implications

The contributions of this study to practice are at two levels. First, at the policy level, it enhances our understanding of the impacts of developmental state model policies, as implemented in Ethiopia, on the banking industry and therefore provides suggestions to policymakers to reform the sector's policies. Second, it offers input to the management of banks regarding the factors that impact the industry.

Originality/value

The banking industry is often studied in the context of financial liberalisation. The originality of this study lies in investigating how the competition, efficiency and profitability of banks are affected when operating in the context of significant state interventions in the industry.
A model of barriers, drivers, government responses, recovery expectations and expected future changes in SME performance: digitalisation as a moderator
Authors: Al-Ajlouni Mohammed Iqbal , Hijazi Rawa , Nawafleh Sahem
Published: May 2024

Purpose

The aim of this paper is to examine a model that combines barriers, drivers, government responses, recovery expectations, expected future changes in performance and the extent of digitalisation as a moderator in SMEs.

Design/methodology/approach

This study uses exploratory causal methodologies. The study employs a quantitative methodology based on utilising an electronic questionnaire to gather the opinions of home workers and entrepreneurs in Jordan. The cross-sectional data collection approach was conducted in a single time frame, and a total of 1,179 valid questionnaires were analysed using Smart PLS along with SPSS.

Findings

The findings demonstrate that the barriers lower the expectations of recovering performance, whilst the drivers and government responses raise the expectations of both performance recovery and change in performance. Concerning digitalisation, this study discovered that firms going digital had a significant positive direct impact on expectations of performance change. This paper also found that expectations of performance change are significantly positively impacted by the interaction between drivers and digitalisation. However, the moderating influence of digitalisation on the positive impact of government responses on expectations of performance change was not verified.

Practical implications

The study's conclusions led to the formulation of several policy recommendations aimed at easing the burden on SMEs.

Originality/value

This study adds something new to the body of knowledge on SMEs by investigating the effects of barriers, drivers and government responses on expectations of performance recovery and the expected future change in performance moderated by digitalisation.
Improving care pathways through BPM and telemedicine: an Italian study
Authors: Rocco Claudio , Mitrano Gianvito , Corallo Angelo , Pontrandolfo Pierpaolo , Guerri Davide
Published: May 2024

Purpose

The future increase of chronic diseases in the world requires new challenges in the health domain to improve patients' care from the point of view of the organizational processes, clinical pathways and technological solutions of digital health. For this reason, the present paper aims to focus on the study and application of well-known clinical practices and efficient organizational approaches through an innovative model (TALIsMAn) to support new care process redesign and digitalization for chronic patients.

Design/methodology/approach

In addition to specific clinical models employed to manage chronic conditions such as the Population Health Management and Chronic Care Model, we introduce a Business Process Management methodology implementation supported by a set of e-health technologies, in order to manage Care Pathways (CPs) digitalization and procedures improvement.

Findings

This study shows that telemedicine services with advanced devices and technologies are not enough to provide significant changes in the healthcare sector if other key aspects such as health processes, organizational systems, interactions between actors and responsibilities are not considered and improved. Therefore, new clinical models and organizational approaches are necessary together with a deep technological change, otherwise, theoretical benefits given by telemedicine services, which often employ advanced Information and Communication Technology (ICT) systems and devices, may not be translated into effective enhancements. They are obtained not only through the implementation of single telemedicine services, but integrating them in a wider digital ecosystem, where clinicians are supported in different clinical steps they have to perform.

Originality/value

The present work defines a novel methodological framework based on organizational, clinical and technological innovation, in order to redesign the territorial care for people with chronic diseases. This innovative ecosystem applied in the Italian research project TALIsMAn is based on the concept of a continuum of care and digitalization of CPs supported by Business Process Management System and telemedicine services. The main goal is to organize the different socio-medical activities in a unique and integrated IT system that should be sustainable, scalable and replicable.
Genuine small talk in hospitality services encounter
Authors: Saragih Harriman Samuel
Published: May 2024

Purpose

This study proposes “genuine small talk” in hospitality settings, particularly in coffee shops and its impact on enhancing guest experiences. This study aims to delineate how genuine small talk, characterized by sincerity, mutual respect, truthfulness and empathy, differs from traditional conversational engagements and influences service outcomes.

Design/methodology/approach

The study adopts a case research approach, focusing on the global coffee shop industry, particularly in high-context cultural settings. Using an abductive research paradigm, it intertwines theoretical concepts with empirical data gathered from face-to-face interviews with coffee shop visitors and managers. Data analysis involved qualitative coding techniques to synthesize and interpret findings related to genuine small talk.

Findings

Genuine small talk in hospitality, marked by sincerity, mutual respect, truthfulness and empathy, significantly enhances customer experiences. It transforms service encounters, turning negative experiences into positive ones and fostering customer loyalty. The study finds that genuine small talk is a strategic tool for emotional resonance and repeat patronage, yet its effectiveness depends on the staff’s ability to discern and adapt to customer moods and preferences.

Social implications

This study highlights that genuine interpersonal interactions are key to enhancing customer experiences in hospitality. These genuine exchanges, characterized by sincerity, mutual respect, truthfulness and empathy, not only improve the immediate service encounter but also foster long-term customer loyalty. By transforming transactional interactions into meaningful connections, genuine small talk serves as a strategic tool in the hospitality industry, potentially reshaping service dynamics and elevating the perceived value of customer service. This research underscores the importance of staff training in emotional intelligence and adaptability to customer preferences, crucial for implementing genuine small talk effectively.

Originality/value

This research contributes to the hospitality literature by elucidating the nuanced role of genuine small talk in service encounters. It extends existing discourses of service interactions by highlighting the potential of genuine small talk in fostering connections and enhancing guest experiences.
Equivalence class of complete correlation determination of several gray incidence degrees
Authors: Wei Yong , Xi Shasha
Published: May 2024

Purpose

This paper sets out to solve a common and crucial fundamental theoretical problem of gray incidence cluster analysis: to [X]={X|ρ(X,Y)≥1−ε0} constitute an approximate classification, it must first be proven that [X]={X|ρ(X,Y)=1} constitutes a rigorous classification.

Design/methodology/approach

This paper does not study the concrete expressions of various incidence degrees but rather the perfect correlation essence of such incidence degrees, that is, sufficient and necessary conditions.

Findings

For any order difference incidence degree, the similarity incidence degree, the direct proportion incidence degree, the parallel incidence degree and the nearness incidence degree, it is proven that the perfect correlation relation is an equivalence relation. The set composed of all sequences Y that are equivalent to sequences X is studied, that is, the equivalence class of X. The structure and mutual relations of these equivalence classes are discussed, and the topological homeomorphism concept of incidence degree is introduced. The conclusion is obtained that the equivalence classes of the two incidence degrees must be the same when the topological homeomorphism is obtained.

Research limitations/implications

In this paper, only the perfect correlation relation of any order difference incidence degree, the similarity incidence degree, the direct proportion incidence degree, the parallel incidence degree and the nearness incidence degree are studied as equivalent relations.

Originality/value

Not only are the research results of several incidence degrees involved in this paper original but also many other effective incidence degrees have not done this basic research, so this paper opens up a research direction with theoretical significance.