bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-cell profiling uncovers regulatory programs of pathogenic Th2 cells in allergic asthma
Authors: Khan Matarr , Alteneder Marlis , Reiter Wolfgang , Krausgruber Thomas , Dobnikar Lina , Madern Moritz , Waldherr Monika , Bock Christoph , Hartl Markus , Ellmeier Wilfried , Henriksson Johan , Boucheron Nicole
Published: August 2023

Lung pathogenic T helper type 2 (pTh2) cells are important drivers of allergic asthma, but fundamental questions remain regarding their regulation and heterogeneity. The differentiation and effector functions of immune cells are tightly regulated by epigenetic processes. Histone deacetylase 1 (HDAC1) is an important epigenetic regulator of T cells, however, its role in pTh2 cells is yet to be determined. Here we investigate immune regulation in allergic asthma by single-cell RNA sequencing (scRNA-seq) in mice challenged with house dust mite, in the presence and absence of HDAC1 function. Our analyses reveal two distinct subsets of lung pTh2 cells: pathogenic effector Th2 (peTh2) and pathogenic Th2 tissue-resident memory (Th2 Trm) cells. Both pTh2 cell subsets are highly proinflammatory and exhibit distinct transcriptional and phenotypic signatures as compared with other lung Th subsets. Based on our scRNA-seq analysis, we identify conditions to generate pTh2 cellsin vitroand confirm that thesein vitrogenerated pTh2 cells have a similar transcriptional profile as lung peTh2 cells. Using our newin vitromodel, we demonstrate that the p38 mitogen-activated protein kinase pathway is critical for interleukin-5 (IL-5) and IL-13 expression in pTh2 cells. Our data further underline the importance of HDAC1 in limiting the pathogenicity of lung andin vitropTh2 cells and in the formation of lung Th2 Trm cells. In summary, we have generated novel insights into pTh2 cell biology and established a newin vitromodel for investigating pTh2 cells that will be useful for discovering molecular mechanisms involved in pTh2-mediated allergic asthma.
A Bayesian analysis of birth pulse effects on the probability of detecting Ebola virus in fruit bats
Authors: Pleydell David R.J. , Bass Innocent Ndong , Mba Djondzo Flaubert Auguste , Djomsi Dowbiss Meta , Kouanfack Charles , Peeters Martine , Cappelle Julien
Published: August 2023

Since 1976 various species of Ebolavirus have caused a series of zoonotic outbreaks and public health crises in Africa. Bats have long been hypothesised to function as important hosts for ebolavirus maintenance, however the transmission ecology for these viruses remains poorly understood. Several studies have demon-strated rapid seroconversion for ebolavirus antibodies in young bats, yet paradoxically few PCR studies have confirmed the identity of the circulating viral species causing these seroconversions. The current study presents an age-structured epidemiological model that characterises the effects of seasonal birth pulses on ebolavirus transmission within a colony of African straw-coloured fruit bats (Eidolon helvum). Bayesian calibration is performed using previously published serological data collected from Cameroon, and age-structure data from Ghana. The model predicts that annual birth pulses most likely give rise to annual outbreaks, although more complex dynamic patterns – including skip years, multi-annual cycles and chaos – may be possible. Weeks 30 to 31 of each year were estimated to be the most likely period for isolating the circulating virus in Cameroon. The probability that a previous PCR campaign failed to detect Ebola virus, assuming that it was circulating, was estimated to be one in two thousand. This raises questions such as (1) what can we actually learn from ebolavirus serology tests performed without positive controls? (2) are current PCR tests sufficiently sensitive? (3) are swab samples really appropriate for ebolavirus detection? The current results provide important insights for the design of future field studies aiming to detect Ebola viruses from sylvatic hosts, and can contribute to risk assessments concerning the timing of zoonotic outbreaks.
Three Accessory Gene Clusters Drive Host-Adaptation in Group BStreptococcus
Authors: Crestani Chiara , Forde Taya L. , Bell John , Lycett Samantha J. , Oliveira Laura M.A. , Pinto Tatiana C.A. , Cobo-Ángel Claudia G. , Ceballos-Márquez Alejandro , Phuoc Nguyen N. , Sirimanapong Wanna , Chen Swaine L. , Jamrozy Dorota , Bentley Stephen D. , Fontaine Michael , Zadoks Ruth N.
Published: August 2023

Streptococcus agalactiae(Group BStreptococcus, GBS) is a major pathogen of humans and animals, posing a threat to human health as well as food security. Here, we investigate the role of genomic mechanisms, including homologous recombination and horizontal gene transfer, in shaping the population structure of GBS and its adaptation to three major host groups (humans, cattle, fishes). We demonstrate that the GBS population comprises host-specialist, host-adapted lineages as well as host generalists, and that these categories differ in their level or recombination. Although the accessory genome at large varies by lineage rather than host, genome wide association studies show that host association is driven by three accessory genome clusters, regardless of lineage or breadth of the host spectrum. These genomic clusters (scpBin human GBS, lactose operon in bovine GBS, Locus 3 in fish GBS) are known (scpB, Lac.2) or shown here (Locus 3) to be functionally relevant and are shared with other streptococcal species occupying the same host niche. These findings demonstrate the importance of considering the role of non-human host species in the evolution of GBS, including high risk clones that may lead to interspecies transmission and affect efficacy of future GBS vaccines.
Residence-colonization trade-off and niche differentiation enable the coexistence ofEscherichia coliphylogroups in healthy humans
Authors: Morel-Journel Thibaut , Lehtinen Sonja , Cotto Olivier , Amia Rafika , Dion Sara , Figueroa Clarisse , Martinson Jonathan , Ralaimazava Pascal , Clermont Olivier , Duval Xavier , Nowrouzian Forough L. , Walk Seth , Denamur Erick , Blanquart François
Published: August 2023

Despite extensive literature on the pathogenicity and virulence of the opportunistic pathogenEscherichia coli, much less is known about its ecological and evolutionary dynamics as a commensal in healthy hosts. Based on two detailed longitudinal datasets on the gut microbiota of healthy adult individuals followed over months to years in France and in the USA, we identified a robust trade-off between the ability to establish in a new host (colonization) and the ability to remain in the host (residence). MajorE. colilineages (phylogroups) exhibited similar fitness but a diversity of strategies, from strong colonizers residing for a few days in the gut, to poor colonizers residing for years. Strains with the largest number of extra-intestinal virulence associated genes and highest pathogenicity resided for longest in hosts. Moreover, the residence time of a strain was reduced more strongly when it competed with other strains of the same phylogroup than of different phylogroups, suggesting niche differentiation between them. To investigate the consequences of the trade-off and niche differentiation for coexistence between strains, we developed a discrete-state Markov model describing the dynamics ofE. coliin a population of hosts. We found that the trade-off and niche differentiation acted together as equalizing and stabilizing mechanisms enabling the coexistence of phylogroups over extended periods of time. Our model predicted that a reduction in transmission (e.g. better hygiene) would not alter the balance between phylogroups, while disturbance of the microbiome (e.g. antibiotics) would hinder residents strains such as those of the extra-intestinal pathogenic phylogroup B2.3.
Rapid establishment of a tumor-retained state curtails the contribution of conventional NK cells to anti-tumor immunity in solid cancers
Authors: Dean Isaac , Lee Colin Y.C. , Tuong Zewen K. , Li Zhi , Tibbitt Christopher A. , Willis Claire , Gaspal Fabrina , Kennedy Bethany C. , Matei-Rascu Veronika , Fiancette Rémi , Nordenvall Caroline , Lindforss Ulrik , Baker Syed Murtuza , Stockmann Christian , Sexl Veronika , Carlesso Gianluca , Hammond Scott A. , Dovedi Simon J. , Mjösberg Jenny , Hepworth Matthew R. , Clatworthy Menna R. , Withers David R.
Published: August 2023

Immune cell dysfunction within the tumor microenvironment undermines the control of cancer progression. NK cells play critical roles in limiting early tumor growth and metastatic disease, however, established cancers contain a phenotypically distinct, tumor-specific NK cell compartment. The temporal dynamics, mechanistic underpinning and functional significance of this tumor NK pool remains incompletely understood. To address this, we exploited photo-labeling, combined with longitudinal transcriptomic and cellular analyses, to interrogate the fate of NK cells after tumor entry. In multiple murine cancer models we reveal that conventional NK cells are continuously recruited into tumors, but rapidly adopt a distinct phenotypic state with features associated with tissue-residency and complete loss of effector functions (including chemokine and cytokine production and cytotoxicity), within 48-72 hrs of entering the tumor. Depletion of NK cells from established tumors did not alter tumor growth, indicating that intratumoral NK cells cease to actively contribute to anti- tumor responses. Furthermore, comparable NK populations were identified in human colorectal cancers, confirming translational relevance and raising the possibility that interventions to reactivate NK cells within tissues may boost anti-tumor immunity in established cancers. Indeed, administration of IL-15:IL-15Ra complexes prevented the loss of NK cell function and improved tumor control, generating intratumoral NK cells with both enhanced tissue-residency characteristics and effector function. Collectively, our data reveals the fate of cNK cells after recruitment into tumors and provides insight into how intratumoral NK cell functions may be revived.

Conventional NK cells recruited from the circulation rapidly establish a tissue-resident phenotype defined by impaired cytotoxicity and chemokine production after tumor entry; administration of IL- 15:IL-15Rα complexes further promotes this tissue-residency programme but maintains core NK cell effector functions within the tumor.
DLTKcat: deep learning based prediction of temperature dependent enzyme turnover rates
Authors: Qiu Sizhe , Zhao Simiao , Yang Aidong
Published: August 2023

The enzyme turnover rate,kcat, quantifies enzyme kinetics by indicating the maximum efficiency of enzyme catalysis. Despite its importance,kcatvalues remain scarce in databases for most organisms, primarily due to the cost of experimental measurements. To predictkcatand account for its strong temperature dependence, DLTKcat was developed in this study and demonstrated superior performance (log10-scale RMSE = 0.88, R2 = 0.66) than previously published models. Through two case studies, DLTKcat showed its ability to predict the effect of protein sequence mutations and temperature changes onkcatvalues. Although its quantitative accuracy is not high enough yet to model the responses of cellular metabolism to temperature changes, DLTKcat has the potential to eventually become a computational tool to describe the temperature dependence of biological systems.
OneFlowTraX: A User-Friendly Software for Super-Resolution Analysis of Single-Molecule Dynamics and Nanoscale Organization
Authors: Rohr Leander , Ehinger Alexandra , Rausch Luiselotte , Burmeister Nina Glöckner , Meixner Alfred J. , Gronnier Julien , Harter Klaus , Kemmerling Birgit , zur Oven-Krockhaus Sven
Published: August 2023

Super-resolution microscopy (SRM) approaches revolutionize cell biology by providing insights into the nanoscale organization and dynamics of macromolecular assemblies and single molecules in living cells. A major hurdle limiting SRM democratization is post-acquisition data analysis which is often complex and time-consuming. Here, we present OneFlowTraX, a user-friendly and open-source software dedicated to the analysis of single-molecule localization microscopy (SMLM) approaches such as single-particle tracking photoactivated localization microscopy (sptPALM). Through an intuitive graphical user interface, OneFlowTraX provides an automated all-in-one solution for single-molecule localization, tracking, as well as mobility and clustering analyses. OneFlowTraX allows the extraction of diffusion and clustering parameters of millions of molecules in a few minutes. Finally, OneFlowTraX greatly simplifies data management following the FAIR (Findable, Accessible, Interoperable, Reusable) principles. We provide a detailed step-by-step manual and guidelines to assess the quality of single-molecule analyses. Applying different fluorophores including mEos3.2, PA-GFP, and PATagRFP, we exemplarily used OneFlowTraX to analyze the dynamics of plant plasma membrane-localized proteins including an aquaporin, the brassinosteroid receptor Brassinosteroid Insensitive 1 (BRI1) and the Receptor-Like Protein 44 (RLP44).
Translation as a Biosignature
Authors: McKaig Jordan M. , Kim MinGyu , Carr Christopher E.
Published: August 2023

Life on Earth relies on mechanisms to store heritable information and translate this information into cellular machinery required for biological activity. In all known life, storage, regulation, and translation are provided by DNA, RNA, and ribosomes. Life beyond Earth, even if ancestrally or chemically distinct from lifeas we know itmay utilize similar structures: it has been proposed that charged linear polymers analogous to nucleic acids may be responsible for storage and regulation of genetic information in non-terran biochemical systems. We further propose that a ribosome-like structure may also exist in such a system, due to the evolutionary advantages of separating heritability from cellular machinery. Here, we use a solid-state nanopore to detect DNA, RNA, and ribosomes, and demonstrate that machine learning can distinguish between biomolecule samples and accurately classify new data. This work is intended to serve as a proof of principal that such biosignatures (i.e., informational polymers or translation apparatuses) could be detected, for example, as part of future missions targeting extant life on Ocean Worlds. A negative detection does not imply the absence of life; however, detection of ribosome-like structures could provide a robust and sensitive method to seek extant life in combination with other methods.

One Sentence Summary

Life, defined as a chemical system capable of Darwinian evolution, likely requires an apparatus to translate heritable instructions into cellular machinery, and we propose to detect this as a biosignature of extant life beyond Earth.
Transmission and Detection of 0.1-2.5 THz Through Porcine Tympanic Membrane
Authors: Shams Reza , Vilagosh Zoltan , Sly David
Published: August 2023

Research has shown that exposure to high power THz radiation can cause thermal damage to the ear, leading to hearing loss and damage to the tympanic membrane. However, more research is needed to fully understand the effects of low intensity THz radiation on the ear and to determine safe exposure levels. This study investigates the transmission of 0.1 to 2.5 THz electromagnetic waves through porcine tympanic membrane samples. Similar to human tympanic membrane, porcine ear drum is a thin layer of tissue that separates the external ear from the middle ear and plays a crucial role in the process of hearing. Using THz time-domain spectroscopy, transmission of THz waves through ex vivo porcine tympanic membrane samples was measured. Results indicate that transmission of THz waves through the tympanic membrane is frequency dependent, with higher transmission observed at lower frequencies (0.1 to 0.5 THz) and lower transmission observed at higher frequencies (2 to 2.5 THz). This study provides new insights into the transmission of THz waves through the tympanic membrane and has potential to examine potential bioeffects as a result of THz interaction.
Short-term fasting of a single amino acid extends lifespan
Authors: Fulton Tahlia L. , Wansbrough Mia R. , Mirth Christen K. , Piper Matthew D. W.
Published: August 2023

Diet and health are strongly linked, though the strict changes in diet required to improve health outcomes are usually difficult to sustain. We sought to understand whether short term bouts of amino acid-specific modifications to the diet ofDrosophila melanogastercould mimic the lifespan and stress resistance benefits of dietary restriction, without the requirement for drastic reductions in food intake. We found that flies fed diets lacking the essential amino acid isoleucine, but otherwise nutritionally complete, exhibited enhanced nicotine tolerance, indicating elevated detoxification capacity. The protection from isoleucine deprivation increased with the duration of exposure, up to a maximum at 7-day isoleucine deprivation for flies 2, 3, or 4 weeks of age, and a 5-day deprivation when flies were 5 weeks of age. Because of these beneficial effects on toxin resistance, we intermittently deprived flies of isoleucine during the first 6 weeks of adulthood and monitored the effect on lifespan. Lifespan was significantly extended when flies experienced short term isoleucine deprivation at 3 and 5 weeks of age, regardless of whether they were also deprived at 1 week. These results indicate that short-term bouts of isoleucine deprivation can extend lifespan and highlight its cumulative and time-dependent benefits. Interestingly, we found that isoleucine-deprived flies lost their protection against nicotine within three days of returning to fully fed conditions. Therefore, the mechanisms underlying lifespan extension may involve transient damage clearance during the bouts of isoleucine deprivation rather than sustained enhanced detoxification capacity. These data highlight a new time-restricted, nutritionally precise method to extend life inDrosophila melanogasterand point to a more manageable dietary method to combat ageing.
Ovariectomy-Induced Arterial Stiffening Differs from Vascular Aging and is Reversed by GPER Activation
Authors: Kilanowski-Doroh Isabella M. , McNally Alexandra B. , Wong Tristen , Visniauskas Bruna , Blessinger Sophia A. , Imulinde Sugi Ariane , Richard Chase , Diaz Zaidmara , Horton Alec , Natale Christopher A. , Ogola Benard O. , Lindsey Sarah H.
Published: August 2023

Arterial stiffness is a cardiovascular risk factor and dramatically increases as women transition through menopause. The current study assessed whether a mouse model of menopause increases arterial stiffness in a similar manner to aging, and whether activation of the G protein-coupled estrogen receptor (GPER) could reverse stiffness. Female C57Bl/6J mice were ovariectomized (OVX) at 10 weeks of age or aged to 52 weeks, and some mice were treated with GPER agonists. OVX and aging increased pulse wave velocity to a similar extent independent of changes in blood pressure. Aging increased carotid wall thickness, while OVX increased material stiffness without altering vascular geometry. RNA-Seq analysis revealed that OVX downregulated smooth muscle contractile genes. The enantiomerically pure GPER agonist, LNS8801, reversed stiffness in OVX mice to a greater degree than the racemic agonist G-1. In summary, OVX and aging induced arterial stiffening via potentially different mechanisms. Aging was associated with inward remodeling while OVX induced material stiffness independent of geometry and a loss of the contractile phenotype. This study helps to further our understanding of the impact of menopause on vascular health and identifies LNS8801 as a potential therapy to counteract this detrimental process in women.
Unraveling the Dual-Mode Impact on Tension Gauge Tethers’ Mechanical Stability
Authors: Liu Jingzhun , Yan Jie
Published: August 2023

Tension Gauge Tethers (TGTs), short DNA segments serving as extracellular tension sensors, are instrumental in assessing tension dynamics in mechanotransduction. These TGTs feature an initial shear-stretch region and an unzip-stretch region. Despite their utility, no theoretical model has been available to estimate their tension-dependent lifetimes (τ(f)), restricting insights from cellular mechanotransduction experiments. We’ve now formulated a concise expression forτ(f) of TGTs, accommodating contributions from both stretch regions. Our model uncovers a tension-dependent energy barrier shift occurring when tension surpasses a switching force approximately 13 pN for the recently developed TGTs, greatly influencingτ(f) profiles. Experimental data from several TGTs validated our model. The calibrated expression can predictτ(f) of TGTs at 37 degrees Celsius based on their sequences with minor fold-changes, supporting future applications of TGTs.
ToxinPred 3.0: An improved method for predicting the toxicity of peptides
Authors: Rathore Anand Singh , Arora Akanksha , Choudhury Shubham , Tijare Purva , Raghava Gajendra P. S.
Published: August 2023

Toxicity emerges as a prominent challenge in the design of therapeutic peptides, causing the failure of numerous peptides during clinical trials. In 2013, our group developed ToxinPred, a computational method that has been extensively adopted by the scientific community for predicting peptide toxicity. In this paper, we propose a refined variant of ToxinPred that showcases improved reliability and accuracy in predicting peptide toxicity. Initially, we used BLAST for alignment-based toxicity prediction, yet coverage was limited. We adopted a motif-based approach with MERCI software to identify unique toxic patterns. Despite specificity gains, sensitivity was compromised. We developed alignment-free methods using machine/deep learning, achieving a balance sensitivity and specificity of prediction. A deep learning model (ANN – LSTM with fixed sequence length) developed using one-hot encoding attained a 0.93 AUROC and 0.71 MCC on independent data. The machine learning model (extra tree) developed using compositional features of peptides achieved 0.95 AUROC and 0.78 MCC. Lastly, we developed hybrid or ensemble methods combining two or more models to enhance performance. Hybrid approaches, including motif-based and machine learning, achieved a 0.98 AUROC and 0.81 MCC. Evaluation on independent data demonstrated our method’s superiority. To cater to the needs of the scientific community, we have developed a standalone software, pip package and web-based server ToxinPred3 (https://github.com/raghavagps/toxinpred3andhttps://webs.iiitd.edu.in/raghava/toxinpred3/).

Author’s Biography

Anand Singh Rathore is currently pursuing a Ph.D. in Computational Biology at the Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India.

Akanksha Arora is currently pursuing a Ph.D. in Computational Biology at the Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India.

Shubham Choudhury is currently pursuing a Ph.D. in Computational Biology at the Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India.

Purava Tijare is a Project Fellow in Computational Biology at the Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India.

Gajendra P. S. Raghava is currently working as a Professor and Head of the Department of Computational Biology, Indraprastha Institute of Information Technology, New Delhi, India.

Highlights

Implementation of alignment or similarly based techniques for predicting toxic peptides.

Discovery of toxicity-associated patterns and identification of toxic regions in peptides.

Development of machine and deep learning-based models for toxicity prediction.

Ensemble methods that combine alignment-based and alignment-free methods.

Web server and standalone software package for screening toxicity in peptides/proteins.
PRIEST - Predicting viral mutations with immune escape capability of SARS-CoV-2 using temporal evolutionary information
Authors: Saha Gourab , Sawmya Shashata , Akil Md. Ajwad , Saha Arpita , Tasnim Sadia , Rahman Md. Saifur , Rahman M. Sohel
Published: August 2023

The dynamic evolution of the SARS-CoV-2 virus is largely driven by mutations in its genetic sequence, culminating in the emergence of variants with increased capability to evade host immune responses. Accurate prediction of such mutations is fundamental in mitigating pandemic spread and developing effective control measures. In this study, we introduce a robust and interpretable deep-learning approach called PRIEST. This innovative model leverages time-series viral sequences to foresee potential viral mutations. Our comprehensive experimental evaluations underscore PRIEST’s proficiency in accurately predicting immune-evading mutations. Our work represents a substantial step forward in the utilization of deep-learning methodologies for anticipatory viral mutation analysis and pandemic response.
Large-scale analysis of the integration of enhancer-enhancer signals by promoters
Authors: Martinez-Ara Miguel , Comoglio Federico , Steensel Bas van
Published: August 2023

Genes are often regulated by multiple enhancers. It is poorly understood how the individual enhancer activities are combined to control promoter activity. Anecdotal evidence has shown that enhancers can combine sub-additively, additively, synergistically, or redundantly. However, it is not clear which of these modes are more frequent in mammalian genomes. Here, we systematically tested how pairs of enhancers activate promoters using a three-way combinatorial reporter assay in mouse cells. By assaying about 69,000 enhancer-enhancer-promoter combinations we found that enhancer pairs generally combine near-additively. This behaviour was conserved across seven developmental promoters tested. Surprisingly, these promoters scale the enhancer signals in a non-linear manner that depends on promoter strength. A housekeeping promoter showed an overall different response to enhancer pairs, and a smaller dynamic range. Thus, our data indicate that enhancers mostly act additively, but promoters transform their collective effect non-linearly.
Alternative mutational architectures producing identical M-matrices can lead to different patterns of evolutionary divergence
Authors: Jiang Daohan , Pennell Matt
Published: August 2023

Explaining macroevolutionary divergence in light of population genetics requires understanding the extent to which the patterns of mutational input contribute to long-term trends. In the context of quantitative traits, mutational input is typically described by the mutational variance-covariance matrix, or theM-matrix, which summarizes phenotypic variances and covariances introduced by new mutations per generation. However, as a summary statistic, theM-matrix does not fully capture all the relevant information from the underlying mutational architecture, and there exist infinitely many possible underlying mutational architectures that give rise to the sameM-matrix. Using individual-based simulations, we demonstrate mutational architectures that produce the sameM-matrix can lead to different levels of constraint on evolution and result in difference in within-population genetic variance, between-population divergence, and rate of adaptation. In particular, the rate of adaptation and that of neutral evolution are both reduced when a greater proportion of loci are pleiotropic. Our results reveal that aspects of mutational input not reflected by theM-matrix can have a profound impact on long-term evolution, and suggest it is important to take them into account in order to connect patterns of long-term phenotypic evolution to underlying microevolutionary mechanisms.
BBSome-deficient cells activate intraciliary CDC42 to trigger actin-dependent ciliary ectocytosis
Authors: Prasai Avishek , Ivashchenko Olha , Maskova Kristyna , Cernohorska Marketa Schmidt , Stepanek Ondrej , Huranova Martina
Published: August 2023

Bardet-Biedl syndrome (BBS) is a pleiotropic ciliopathy caused by dysfunction of the BBSome, a cargo adaptor essential for export of transmembrane receptors from cilia. Although actin-dependent ectocytosis has been proposed as compensatory cellular process for defective cargo retrieval, the underlying molecular mechanism is poorly understood, particularly in the context of BBS pathology. In this study, we investigated how actin polymerization and ectocytosis are regulated within the cilium. Our findings reveal that ciliary CDC42, a RHO-family GTPase triggersin situactin polymerization, ciliary ectocytosis, and cilia shortening in BBSome-deficient cells. Furthermore, activation of the Sonic Hedgehog pathway further enhances CDC42 activity in BBSome-deficient cilia, but not in healthy cells. Inhibition of CDC42 decreased the frequency and duration of ciliary actin polymerization events and lead to the accumulation of the GPR161 receptor in bulges along the axoneme in BBSome-deficient cells during Sonic Hedgehog signaling. Overall, our study identifies CDC42 as a key trigger of ciliary ectocytosis. Moreover, the hyperactivated ciliary CDC42-actin-ectocytosis axis in BBSome-deficient cells results in cilia shortening and loss of ciliary material, potentially impacting disease severity.
Characterization of enhancer activity in early human neurodevelopment using Massively parallel reporter assay (MPRA) and forebrain organoids
Authors: Capauto Davide , Wang Yifan , Wu Feinan , Norton Scott , Mariani Jessica , Inoue Fumitaka , Crawford Gregory E. ,   The PsychENCODE Consortium, Ahituv Nadav , Abyzov Alexej , Vaccarino Flora M.
Published: August 2023

Abstract

Regulation of gene expression through enhancers is one of the major processes shaping the structure and function of the human brain during development. High-throughput assays have predicted thousands of enhancers involved in neurodevelopment, and confirming their activity through orthogonal functional assays is crucial. Here, we utilized Massively Parallel Reporter Assays (MPRAs) in stem cells and forebrain organoids to evaluate the activity of ∼7,000 gene-linked enhancers previously identified in human fetal tissues and brain organoids. We used a Gaussian mixture model to evaluate the contribution of background noise in the measured activity signal to confirm the activity of ∼35% of the tested enhancers, with most showing temporal-specific activity, suggesting their evolving role in neurodevelopment. The temporal specificity was further supported by the correlation of activity with gene expression. Our findings provide a valuable gene regulatory resource to the scientific community.

Author summary

Enhancers are non-coding elements that play a crucial role in the regulation of gene expression during brain development. Despite the availability of various techniques available to identify enhancers, their functional activity is relatively less understood, leaving a gap in our understanding of how enhancer behavior might regulate complex transitions of neurodevelopment. To address this, we utilized forebrain organoids, a 3D model system which closely mimics the complex cellular environment of the developing human brain, and employed Massively Parallel Reporter Assay (MPRA) to validate enhancer activity at various stages of forebrain differentiation, from induced pluripotent stem cells (iPSCs) to neuronal progenitors and cortical neurons. Our study provides a comprehensive catalog of over 2,300 enhancers, showcasing their temporal activity profiles during early neuronal development and offering valuable insights into their likely biological functions. This research advances our understanding of enhancer dynamics in brain development and offers new avenues for further investigations in this field.
Examining the causal relationships among factors influencing SMEs' competitive advantage: a TISM-neutrosophic MICMAC approach
Authors: John William A. , Suresh M. , Subramanian Nagamani
Published: August 2023

Purpose

Small and medium-sized enterprises (SMEs) are a major source of employment and revenue growth in developing nations like India, but they also face challenges from resource shortages, shifting consumer demand and heightened competition. This research aims to discover the aspects that enhance SMEs' competitiveness and performance.

Design/methodology/approach

By analyzing literature and consulting experts, 10 factors that boost a firm's competitiveness were identified. The total interpretive structural modeling (TISM) method was then used to determine their interaction and structural hierarchy. Neutrosophic-MICMAC analysis was employed to assess the driving-dependence power of each factor.

Findings

The study discovered that the factor, namely “entrepreneurial orientation,” was found to be a significant one. “Manufacturing strategy” was found to be extremely dependent on the remaining competitive advantage factors.

Research limitations/implications

This SME-focused framework can be adopted by large businesses to enhance organizational performance by focusing on critical factors. The study depends on experts' judgment, which might be biased. Findings will assist SMEs in identifying significant factors influencing competitive advantage and relationships, increasing awareness of factors contributing to competitive edge.

Practical implications

The results of the research may encourage SME sector managers and practitioners to prioritize the factors that contribute to a firm's competitive advantage.

Originality/value

The majority of research on SME competitive advantage focuses on individual aspects. To add to the body of knowledge on the subject, this study applies the TISM technique to Indian SMEs to identify the contextual interactions among factors that increase long-term competitiveness.
Customized shading solutions for complex building façades: the potential of an innovative cement-textile composite material through a performance-based generative design
Authors: Zani Andrea , Speroni Alberto , Mainini Andrea Giovanni , Zinzi Michele , Caldas Luisa , Poli Tiziana
Published: August 2023

Purpose

The paper aims to investigate the comfort-related performances of an innovative solar shading solution based on a new composite patented material that consists of a cement-based matrix coupled with a stretchable three-dimensional textile. The paper’s aim is, through a performance-based generative design approach, to develop a high-performance static shading system able to guarantee adequate daylit spaces, a connection with the outdoors and a glare-free environment in the view of a holistic and occupant-centric daylight assessment.

Design/methodology/approach

The paper describes the design and simulation process of a complex static shading system for digital manufacturing purposes. Initially, the optical material properties were characterized to calibrate radiance-based simulations. The developed models were then implemented in a multi-objective genetic optimization algorithm to improve the shading geometries, and their performance was assessed and compared with traditional external louvres and overhangs.

Findings

The system developed demonstrates, for a reference office space located in Milan (Italy), the potential of increasing useful daylight illuminance by 35% with a reduced glare of up to 70%–80% while providing better uniformity and connection with the outdoors as a result of a topological optimization of the shape and position of the openings.

Originality/value

The paper presents the innovative nature of a new composite material that, coupled with the proposed performance-based optimization process, enables the fabrication of optimized shading/cladding surfaces with complex geometries whose formability does not require ad hoc formworks, making the process fast and economic.
Cyber-physical systems for facilities management: a Delphi study on the propelling measures
Authors: Ikuabe Matthew , Aigbavboa Clinton , Anumba Chimay , Oke Ayodeji Emmanuel
Published: August 2023

Purpose

Through its advanced computational capabilities, cyber–physical systems (CPS) proffer solutions to some of the cultural challenges plaguing the effective delivery of facilities management (FM) mandates. This study aims to explore the drivers for the uptake of CPS for FM functions using a qualitative approach – the Delphi technique.

Design/methodology/approach

Using the Delphi technique, the study selected experts through a well-defined process entailing a pre-determined set of criteria. The experts gave their opinions in two iterations which were subjected to statistical analyses such as the measure of central tendency and interquartile deviation in ascertaining consensus among the experts and the Mann–Whitney U test in establishing if there is a difference in the opinions given by the experts.

Findings

The study’s findings show that six of the identified drivers of the uptake of CPS for FM were attributed to be of very high significance, while 12 were of high significance. Furthermore, it was revealed that there is no significant statistical difference in the opinions given by experts in professional practice and academia.

Practical implications

The study’s outcome provides the requisite insight into the propelling measures for the uptake of CPS for FM by organisations and, by extension, aiding digital transformation for effective FM delivery.

Originality/value

To the best of the authors’ knowledge, evidence from the literature suggests that no study has showcased the drivers of the incorporation of CPS for FM. Hence, this study fills this gap in knowledge by unravelling the significant propelling measures of the integration of CPS for FM functions.
Site effect influence on the seismic vulnerability of unreinforced masonry buildings in low to moderate seismic urban areas in Algeria
Authors: Athmani Allaeddine , Ademovic Naida
Published: August 2023

Purpose

This paper aims to develop preliminary damage scenarios for unreinforced masonry buildings located in low to moderate seismic hazard areas in Algeria, taking into account the specific site effects.

Design/methodology/approach

Three soil types were considered in this analysis according to the definition of the Algerian seismic code (RPA99/2003). Peak ground acceleration values were assigned to each soil type issued from a probabilistic seismic hazard analysis (PSHA). To highlight the effect of soil conditions on the seismic vulnerability analysis of masonry buildings, a site vulnerability increment is carried out, and the macroseismic Risk-UE method has been adopted and applied by developing two main seismic scenarios according to both return periods of the PSHA, 100 and 475 years, respectively.

Findings

Based on the preliminary results of rock site condition, it can be outlined that the significant damage obtained for different earthquake scenarios discovered a substantial worldwide seismic risk to the building stock of the study area. Once the site effect is integrated into the analysis, more high values of vulnerability indexes and expected damages are obtained. Moreover, it can be concluded that soft soil (S3) is a little bit more influential than stiff soil (S2) on the final vulnerability index compared to (S1). However, the difference between the soil effect S2 and S3 on the vulnerability index can be neglected.

Research limitations/implications

Researchers are encouraged to test the mechanical approaches for more detailed outcomes of a specific building analysis.

Practical implications

This research proves to the Algerian decision-makers that due to the site effects and the vulnerability of the masonry buildings, an urgent intervention program is required even for existing buildings located in low to moderate seismic hazard areas.

Originality/value

Several seismic vulnerability types of research have been conducted in Algeria for the unreinforced masonry buildings in moderate to high seismic areas in which generally the soil effect is neglected. In this context, this research paper proves that due to the site effects and the vulnerability of the masonry buildings, special attention is required even for existing buildings located in low to moderate seismic hazard areas. With this conclusion, the requirement of taking into account the soli effect in the high seismic areas is even more pronounced and should be conducted.
New nutrients evaluation in Spirulina maxima growth for phycocyanin, carbohydrate, and biochar production
Authors: Marciano Lucas Ioran , Pedro Guilherme Arantes , dos Santos Wallyson Ribeiro , Tagliaferro Geronimo Virginio , Batista Fabio Rodolfo Miguel , Guimarães Daniela Helena Pelegrine
Published: August 2023

Purpose

The purpose of this study is to investigate the influence of light intensity and sources of carbon and nitrogen on the cultivation of Spirulina maxima.

Design/methodology/approach

Cultures were carried out in a modified Zarrouk medium using urea, sodium acetate and glycerol. A Taguchi experimental design was used to evaluate the effect on the production of biocompounds: productivities in biomass, carbohydrates, phycocyanin and biochar were analyzed.

Findings

Statistical data analysis revealed that light intensity and sodium acetate concentration were the most important factors, being significant in three of the four response variables studied. The highest productivities in biomass (46.94 mg.L−1.d−1), carbohydrates (6.11 mg.L−1.d−1), phycocyanin (3.62 mg.L−1.d−1) and biochar (22, 48 mg.L−1.d−1) were achieved in experiment 4 of the Taguchi matrix, highlighting as the ideal condition for the production of biomass, carbohydrates and phycocyanin.

Practical implications

Sodium acetate and urea can be considered, respectively, as potential sources of carbon and nitrogen to increase Spirulina maxima productivity. From the results, an optimized cultivation condition for the sustainable production of bioproducts was obtained.

Originality/value

This work focuses on the study of the influence of light intensity and the use of alternative sources of nitrogen and carbon on the growth of Spirulina maxima, as well as on the influence on the productivity of biomass and biocompounds. There are few studies in the literature focused on the phycocyanin production from microalgae, justifying the need to deepen the subject.
Mayo Clinic’s journey in transforming employee tuition assistance in response to labor challenges
Authors: Bormann Misun L. , Hahn Huh-Jung , Anderson Ashley R. , Fraser Cathy H.
Published: August 2023

Research methodology

The information used in the case study was obtained from secondary sources, such as internal documents, reports, news, and organization websites. Three of the four authors played a hands-on role in the case.

Case overview/synopsis

The COVID-19 pandemic exacerbated the global challenge of hiring and retaining health-care workers. To address its own challenges, Mayo Clinic decided to fundamentally transform its 30-year-old tuition assistance program: from a model centered on the premise that tuition assistance was an employee benefit for professional development purposes, to one that was more driven to meet the business needs of the employer by preparing internal talent for important roles throughout the institution. Herein, this case study first describes how the COVID-19 pandemic impacted health-care organizations like Mayo Clinic. Next, this study provides details on the original employee tuition assistance program, and then, focuses on the reasons for its need to be changed. Afterward, this study introduces the new tuition assistance programs. Finally, this study follows with examples of how both Mayo Clinic and its employees navigated through initial challenges, such as resistance to change and lack of engagement. In sum, this case study provides critical insight into designing workforce education programs that provide professional development for meeting the workforce needs of the organization.

Complexity academic level

This case can be used as teaching material in relevant undergraduate- and MBA-level courses, such as human resource management, human resource development and compensation and benefits. This case allows students to critically analyze workforce education programs (e.g. tuition assistance programs) and to plan how to strategically align those with the workforce needs of the organization.
Urbanisation impacts plumage colouration in a songbird across Europe: Evidence from a correlational, experimental and meta‐analytical approach
Authors: Salmón Pablo , López‐Idiáquez David , Capilla‐Lasheras Pablo , Pérez‐Tris Javier , Isaksson Caroline , Watson Hannah
Published: August 2023

Urbanisation is accelerating across the globe, transforming landscapes, presenting organisms with novel challenges, shaping phenotypes and impacting fitness. Urban individuals are claimed to have duller carotenoid‐based colouration, compared to their non‐urban counterparts, the so‐called ‘urban dullness’ phenomenon. However, at the intraspecific level, this generalisation is surprisingly inconsistent and often based on comparisons of single urban/non‐urban populations or studies from a limited geographical area.

Here, we combine correlational, experimental and meta‐analytical data on a common songbird, the great tit Parus major, to investigate carotenoid‐based plumage colouration in urban and forest populations across Europe.

We find that, as predicted, urban individuals are paler than forest individuals, although there are large population‐specific differences in the magnitude of the urban‐forest contrast in colouration. Using one focal region (Malmö, Sweden), we reveal population‐specific processes behind plumage colouration differences, which are unlikely to be the result of genetic or early‐life conditions, but instead a consequence of environmental factors acting after fledging.

Finally, our meta‐analysis indicates that the urban dullness phenomenon is well established in the literature, for great tits, with consistent changes in carotenoid‐based plumage traits, particularly carotenoid chroma, in response to anthropogenic disturbances.

Overall, our results provide evidence for uniformity in the ‘urban dullness’ phenomenon but also highlight that the magnitude of the effect on colouration depends on local urban characteristics. Future long‐term replicated studies, covering a wider range of species and feeding guilds, will be essential to further our understanding of the eco‐evolutionary implications of this phenomenon.