bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD4 T cell contact drives macrophage cell cycle progression and susceptibility to lentiviral transduction
Authors: Mlcochova Petra , Heilig Raphael , Fischer Roman , Gupta Ravindra K. 
Published: January 2024

AbstractMacrophages are typically quiescent cells residing in G0, though tissue macrophages have been shown to proliferate locally in tissues; we previously demonstrated that differentiated monocyte derived macrophages (MDM) can be stimulated to re-enter G1 phase of the cell cycle from G0, without cell division. Entry into G1 correlates with an increase in CDK1 expression which phosphorylates the deoxynucleotide-triphosphate hydrolase SAMHD1 at position 592. SAMHD1 not only regulates cellular dNTP levels, but is also a restriction factor for virus replication of HIV-1 and DNA viruses. Here we show that contact with autologous CD4 T cells leads to antigen-independent macrophage cell cycle progression from G0-G1, accompanied by expression of cell cycle associated proteins, including CDK1, and the activation of the canonical MEK-ERK pathway. Further, macrophage cell cycle progression can be blocked not only by anti-cancer drugs targeting the MEK-ERK axis such as Palcociclib, but also by pre-treatment with EGFR antibody, providing additional evidence for cell surface interactions driving proliferative responses. Cell contact with uninfected CD4 T cells renders macrophages ten-fold more susceptible to transduction with VSV-G pseudotyped HIV-1 particles.
Bidirectional fear modulation by discrete anterior insular circuits in male mice
Authors: Park Sanggeon , Huh Yeowool , Kim Jeansok J. , Cho Jeiwon 
Published: January 2024

ABSTRACTThe brain’s ability to appraise threats and execute appropriate defensive responses is essential for survival in a dynamic environment. Humans studies have implicated the anterior insular cortex (aIC) in subjective fear regulation and its abnormal activity in fear/anxiety disorders. However, the complex aIC connectivity patterns involved in regulating fear remain under investigated. To address this, we recorded single units in the aIC of freely moving male mice that had previously undergone auditory fear conditioning, assessed the effect of optogenetically activating specific aIC output structures in fear, and examined the organization of aIC neurons projecting to the specific structures with retrograde tracing. Single-unit recordings revealed that a balanced number of aIC pyramidal neurons’ activity either positively or negatively correlated with a conditioned tone-induced freezing (fear) response. Optogenetic manipulations of aIC pyramidal neuronal activity during conditioned tone presentation altered the expression of conditioned freezing. Neural tracing showed that non-overlapping populations of aIC neurons project to the amygdala or the medial thalamus, and the pathway bidirectionally modulated conditioned fear. Specifically, optogenetic stimulation of the aIC-amygdala pathway increased conditioned freezing, while optogenetic stimulation of the aIC-medial thalamus pathway decreased it. Our findings suggest that the balance of freezing-excited and freezing-inhibited neuronal activity in the aIC and the distinct efferent circuits interact collectively to modulate fear behavior.
A genetic and physiological model of renal dysfunction in Lowe syndrome
Authors: Ramesh Navyashree A , Kataria Vaishali , Lama Indra Sara , Thakur Rajan , Ghosh Avishek , Sharma Sanjeev , Venugopal Aishwarya , Vasudevan Anil , Padinjat Raghu 
Published: January 2024

AbstractLowe syndrome (LS) is an X-linked recessive genetic disorder characterized by renal dysfunction, neurodevelopmental defects, and cataract. The affected gene,OCRLencodes for a polyphosphoinositide 5-phosphatase. OCRL is localized to multiple sub-cellular locations in the endolysosomal system and defects in these organelles have been described in human cells depleted of OCRL. However, the relationship of the endolysosomal defects in OCRL depleted cells to the altered physiology of kidney cells of LS patients has not been completely determined. Here we model the kidney phenotypes of LS using aDrosophilanephrocyte model. Using this model system, we demonstrate that OCRL plays a cell-autonomous role in nephrocyte function. Deletion of the only OCRL ortholog inDrosophila(dOCRL) leads to cell-autonomous defects in larval nephrocyte structure and function. Null mutants ofdOCRL(dOCRLKO) show defects in the endolysosomal system of larval nephrocytes that are associated with physiological defects in nephrocyte function. These defects could be rescued by reconstitution with a humanOCRLtransgene but not with a phosphatase dead version or a human LS patient derived mutation. Overall, this work provides a model system to understand the mechanisms by which the sub-cellular changes from loss of OCRL leads to defects in kidney function in human patients.
Variation in the response to antibiotics and life-history across the majorPseudomonas aeruginosaclone type (mPact) panel
Authors: Tueffers Leif , Batra Aditi , Zimmermann Johannes , Botelho João , Buchholz Florian , Liao Junqi , Mejía Nicolás Mendoza , Munder Antje , Klockgether Jens , Tümmler Burkhard , Rupp Jan , Schulenburg Hinrich 
Published: January 2024

AbstractPseudomonas aeruginosais a ubiquitous, opportunistic human pathogen. Since it often expresses multidrug resistance, it is ranked by the World Health Organization among the top 3 high priority pathogens, for which new treatment options are urgently required. An evaluation of new treatments is usually performed experimentally with one of the canonical laboratory strains (e.g., PAO1 or PA14). However, these two strains are unlikely representative of the strains infecting patients, because they have adapted to laboratory conditions and do not capture the enormous genomic diversity of the species. Here, we characterized the majorP. aeruginosaclone type (mPact) panel. This panel consists of 20 strains, which reflect the genomic diversity of the species, cover all major clone types, and have both patient and environmental origins. We found significant strain variation in distinct responses towards antibiotics and general growth characteristics. Only few of the measured traits are related, and if so, only for specific antibiotics. Moreover, high levels of resistance were only identified for clinical mPact isolates and could be linked to known AMR (antimicrobial resistance) genes in the sequenced genomes. One strain also produced highly unstable AMR, indicating an evolutionary cost to resistance expression. By linking isolation source, growth, and virulence to life history traits, we further identified specific adaptive strategies for individual mPact strains towards either host processes or degradation pathways. Overall, the mPact panel provides a reasonably sized set of distinct strains, enabling in-depth analysis of new treatment designs or evolutionary dynamics in consideration of the species’ genomic diversity.ImportanceNew treatment strategies are urgently needed for high risk pathogens such as the opportunistic and often multidrug resistant pathogenPseudomonas aeruginosa. Here, we characterize the majorP. aeruginosaclone type (mPact) panel. It consists of 20 strains with different origins that cover the major clone types of the species as well as its genomic diversity. This mPact panel shows significant variation in (i) resistance against distinct antibiotics, including several last resort antibiotics, (ii) related traits associated with the response to antibiotics, and (iii) general growth characteristics. We further developed a novel approach that integrates information on resistance, growth, virulence, and life-history characteristics, allowing us to demonstrate the presence of distinct adaptive strategies of the strains that focus either on host interaction or resource processing. In conclusion, the mPact panel provides a manageable number of representative strains for this important pathogen for further in-depth analyses of treatment options and evolutionary dynamics.
Senolytic Treatment for Low Back Pain
Authors: Mannarino Matthew , Cherif Hosni , Ghazizadeh Saber , Martinez Oliver Wu , Sheng Kai , Cousineau Elsa , Lee Seunghwan , Millecamps Magali , Gao Chan , Ouellet Jean A. , Stone Laura , Haglund Lisbet 
Published: January 2024

AbstractSenescent cells (SnCs) accumulate due to aging and external cellular stress throughout the body. They adopt a senescence-associated secretory phenotype (SASP) and release inflammatory, and degenerative factors that actively contribute to age-related diseases such as low back pain (LBP). The senolytics, o-Vanillin and RG-7112, remove senescent human intervertebral (IVD) cells and reduce SASP release, but it is not known if they can treat LBP.sparc-/-mice, with LBP, were treated orally with o-Vanillin and RG-7112 as single or combination treatments. Treatment reduced LBP and SASP factor release and removed SnCs from the IVD and spinal cord. Treatment also lowered degeneration score in the IVDs, improved vertebral bone quality, and reduced the expression of pain markers in the spinal cord. The result indicates that RG-7112 and o-Vanillin with the combination treatment providing the strongest effect are potential disease-modifying drugs for LBP and other painful disorders where cell senescence is implicated.One Sentence Summary:Senolytics drugs can reduce back pain
A spatiotemporally resolved atlas of mRNA decay in theC. elegansembryo reveals differential regulation of mRNA stability across stages and cell types
Authors: Peng Felicia , Nordgren C Erik , Murray John Isaac 
Published: January 2024

AbstractDuring embryonic development, cells undergo dynamic changes in gene expression that are required for appropriate cell fate specification. Although both transcription and mRNA degradation contribute to gene expression dynamics, patterns of mRNA decay are less well-understood. Here we directly measured spatiotemporally resolved mRNA decay rates transcriptome-wide throughoutC. elegansembryogenesis by transcription inhibition followed by bulk and single-cell RNA-sequencing. This allowed us to calculate mRNA half-lives within specific cell types and developmental stages and identify differentially regulated mRNA decay throughout embryonic development. We identified transcript features that are correlated with mRNA stability and found that mRNA decay rates are associated with distinct peaks in gene expression over time. Moreover, we provide evidence that, on average, mRNA is more stable in the germline compared to in the soma and in later embryonic stages compared to in earlier stages. This work suggests that differential mRNA decay across cell states and time helps to shape developmental gene expression, and it provides a valuable resource for studies of mRNA turnover regulatory mechanisms.
Recruitment of the m6A/Am demethylase FTO to target RNAs by the telomeric zinc finger protein ZBTB48
Authors: Nabeel-Shah Syed , Pu Shuye , Burke Giovanni L. , Ahmed Nujhat , Braunschweig Ulrich , Farhangmehr Shaghayegh , Lee Hyunmin , Wu Mingkun , Ni Zuyao , Tang Hua , Zhong Guoqing , Marcon Edyta , Zhang Zhaolei , Blencowe Benjamin J. , Greenblatt Jack F. 
Published: January 2024

AbstractN6-methyladenosine (m6A), the most abundant internal modification on eukaryotic mRNA, and N6, 2′-O-dimethyladenosine (m6Am), are epitranscriptomic marks that function in multiple aspects of posttranscriptional regulation. Fat mass and obesity-associated protein (FTO) can remove both m6A and m6Am; however, little is known about how FTO achieves its substrate selectivity. Here, we demonstrate that ZBTB48, a C2H2-zinc finger protein that functions in telomere maintenance, associates with FTO and binds both mRNA and the telomere-associated regulatory RNA TERRA to regulate the functional interactions of FTO with target transcripts. Specifically, depletion of ZBTB48 affects targeting of FTO to sites of m6A/m6Am modification, changes cellular m6A/m6Am levels and, consequently, alters decay rates of target RNAs. ZBTB48 ablation also accelerates growth of HCT-116 colorectal cancer cells and modulates FTO- dependent regulation of Metastasis-associated protein 1 (MTA1) transcripts by controlling the binding to MTA1 mRNA of the m6A reader IGF2BP2. Our findings thus uncover a previously unknown mechanism of posttranscriptional regulation in which ZBTB48 co-ordinates RNA- binding of the m6A/m6Am demethylase FTO to control expression of its target RNAs.
Multi-state kinetics of the syringe-like injection mechanism of Tc toxins
Authors: Ng’ang’a Peter Njenga , Folz Julian , Kucher Svetlana , Roderer Daniel , Xu Ying , Sitsel Oleg , Belyy Alexander , Prumbaum Daniel , Kühnemuth Ralf , Assafa Tufa E. , Dong Min , Seidel Claus A. M. , Bordignon Enrica , Raunser Stefan 
Published: January 2024

AbstractTc toxins are virulence factors of many insects and human pathogenic bacteria. They attach as soluble prepores to receptors on host cells and following acidification in the late endosome, perforate the cell membrane like a syringe to translocate toxic enzymes into the host cell through their pore-forming channel. Although this complex transformation has been structurally well studied, the functional aspects of this large-scale rearrangement, such as the reaction pathway with possible intermediate states and the resulting temporal evolution have remained elusive. Here, we used an integrated biophysical approach to monitor the prepore-to-pore transition and found that it takes ∼28 h when induced by high pH in the absence of other factors. In the presence of liposomes, an increasingly high pH or receptors, such as heparin or Vsg, the probability to transform prepores to pores increases by a factor of up to 4. This effect can also be mimicked by biotinylation or site-directed mutagenesis of the shell, demonstrating that shell destabilization is a crucial step in prepore-to-pore transition. We show that shell opening is a heterogeneous process with transition times ranging from 60 ms to 1.6 s and resolve three sequential intermediate states: an initial transient intermediate during shell destabilization, a first stable intermediate where the receptor-binding domains on the shell rearrange and a second stable intermediate with an open shell. In contrast, the ejection of the pore-forming channel from the open shell is highly cooperative with a transition time of < 60 ms. This detailed knowledge of the Tc toxin mechanism of action, even in the absence of receptors, is important for the future application of Tc toxins as biomedical devices or biopesticides.
Long wave infrared signature of swept back leading edges in aircraft frontal aspect
Authors: Vinayak Kajal , Mahulikar Shripad P. 
Published: January 2024

Purpose
In recent years, increased use of all-aspect infrared (IR)-guided missiles based on the long-wave infrared (LWIR; 8–12 µm) band has lowered the probability of aircraft survival in warfare. The lock-on of these highly sensitive missiles is difficult to break, especially from the front. Aerodynamically heated swept-back leading edges (SBLE), because of their high temperature and large area, serve as a prominent LWIR source for aircraft detection from the front. This study aims to report the influence of sweep-back angle (Λ, based on the Mach number [M∞]) on aerodynamic heating and the LWIR signature of SBLE.

Design/methodology/approach
The temperature along SBLE is obtained numerically as radiation equilibrium temperature (Tw) by discretizing the SBLE length into “n” number of segments, and for each segment, emission based on Tw is evaluated. IR radiance due to reflected external sources (sky-shine and Earthshine) and radiance due to Tw are collectively used to determine the IR contrast between SBLE and its replaced background in the LWIR band (icont-SBLE,LWIR).

Findings
The results are obtained for low subsonic turboprop aircraft (Λ = 3°, M∞ = 0.44); high subsonic strategic bombers (Λ = 35°, M∞ = 0.8); fifth-generation stealth aircraft (Λ = 40°, M∞ = 1.6); and aircraft with supercruise/supersonic capability (Λ = 50°, M∞ = 2.5). The aircraft with supersonic capability (Λ = 50°, M∞ = 2.5) reports the maximum LWIR signatures and hence the highest visibility from the front. The results obtained are compared with values at Λ = 0° for all cases, which shows that increasing Λ significantly reduces aerodynamic heating and LWIR signatures.

Originality/value
The novelty of this study comes from its report on the influence of Λ on the LWIR signatures of aircraft SBLE in the frontal aspect for the first time.
Driving forces behind service innovation in knowledge-intensive services with different knowledge bases
Authors: Krupskaya Anastasia 
Published: January 2024

Purpose
The purpose of this paper is to identify and describe the influence of the knowledge base (KB) of the company on driving forces of innovation processes in knowledge-intensive services (KIS) and to compare the level of innovativeness of the final services.

Design/methodology/approach
The paper investigates through qualitative research 11 KIS organisations with different KB.

Findings
The research results identified and described the influence of the KB on driving forces of innovations processes and its results in companies with four newly identified KBs (analytical, synthetic, symbolic and compliance).

Research limitations/implications
Further research, based on a larger number of companies, is needed to confirm the results of this research and to complement the effect of the KB on driving forces of innovation.

Practical implications
This research can help organisations understand how to develop strategic plans and new ideas for innovative services depending on the KB of the organisation.

Social implications
The description of successful innovation processes and results in several leading companies presented in the study may help other companies in identifying knowledge-integration practices to improve performance and innovation processes that support multiplicity, productivity and creativity.

Originality/value
The study systemised the sources of new ideas for innovation in companies with different KB, several driving forces of innovation were identified and how these forces are affected by each KB; lastly, innovation results were compared in companies with different KB.
Assessing the effect of housing attributes and green certification on Malaysian house price
Authors: Chuweni Nor Nazihah , Fauzi Nurul Sahida , Che Kasim Asmma , Mayangsari Sekar , Wardhani Nurhastuty Kesumo 
Published: January 2024

Purpose
Sustainability represents innovative elements in determining the profitability of real estate investments, among other factors, including the green component in real estate. Evidence from the literature has pointed out that incorporating green features into residential buildings can reduce operational costs and increase the building’s value. Although green real estate is considered the future trend of choice, it is still being determined whether prospective buyers are willing to accept the extra cost of green residential investment. Therefore, this study aims to investigate the effect of housing attributes and green certification on residential real estate prices.

Design/methodology/approach
The impact of the housing attribute and green certification in the residential sectors was assessed using a transaction data set comprising approximately 861 residential units sold in Selangor, Malaysia, between 2014 and 2022. Linear and quantile regression were used in this study by using SPSS software for a robust result.

Findings
The findings indicate that the market price of residential properties in Malaysia is influenced by housing attributes, transaction types and Green Building Index certification. The empirical evidence from this study suggests that green certification significantly affects the sales price of residential properties in Malaysia. The findings of this research will help investors identify measurable factors that affect the transaction prices of green-certified residential real estate. These identifications will facilitate the development of strategic plans aimed at achieving sustainable rates of return in the sustainable residential real estate market.

Practical implications
Specifically, this research will contribute to achieving area 4 of the 11th Malaysia Plan, which pertains to pursuing green growth for sustainability and resilience. This will be achieved by enhancing awareness among investors and homebuyers regarding the importance of green residential buildings in contributing to the environment, the economy and society.

Originality/value
The regression model for housing attributes and green certification on house price developed in this study could offer valuable benefits to support and advance Malaysia in realising its medium and long-term goals for green technology.
Selection of Industry 4.0 technologies for Lean Six Sigma integration using fuzzy DEMATEL approach
Authors: Ibrahim Arish , Kumar Gulshan 
Published: January 2024

Purpose
This study aims to explore the integration of Industry 4.0 technologies with lean six sigma practices in the manufacturing sector for enhanced process improvement.

Design/methodology/approach
This study used a fuzzy decision-making trial and evaluation laboratory approach to identify critical Industry 4.0 technologies that can be harmonized with Lean Six Sigma methodologies for achieving improved processes in manufacturing.

Findings
The research reveals that key technologies such as modeling and simulation, artificial intelligence (AI) and machine learning, big data analytics, automation and industrial robots and smart sensors are paramount for achieving operational excellence when integrated with Lean Six Sigma.

Research limitations/implications
The study is limited to the identification of pivotal Industry 4.0 technologies for Lean Six Sigma integration in manufacturing. Further studies can explore the implementation challenges and the quantifiable benefits of such integrations.

Practical implications
Integrating Industry 4.0 technologies with Lean Six Sigma enhances manufacturing efficiency. This approach leverages AI for predictive analysis, uses smart sensors for energy efficiency and adaptable robots for flexible production. It is vital for competitive advantage, significantly improving decision-making, reducing costs and streamlining operations in the manufacturing sector.

Social implications
The integration of Industry 4.0 technologies with Lean Six Sigma in manufacturing has significant social implications. It promotes job creation in high-tech sectors, necessitating advanced skill development and continuous learning among the workforce. This shift fosters an innovative, knowledge-based economy, potentially reducing the skills gap. Additionally, it enhances workplace safety through automation, reduces hazardous tasks for workers and contributes to environmental sustainability by optimizing resource use and reducing waste in manufacturing processes.

Originality/value
This study offers a novel perspective on synergizing advanced Industry 4.0 technologies with established Lean Six Sigma practices for enhanced process improvement in manufacturing. The findings can guide industries in prioritizing their technological adoptions for continuous improvement.