bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Population-Specific Novel Protein Biomarkers and Possible Therapeutic Targets in Gliomas by Proteomics Approach
Authors: Kumar S. Devanand Senthil , Periyasamy Anbazhagan
Published: May 2024

Objective To analyze the differential proteomic profile of gliomas in patients from South India and to identify novel protein glioma biomarkers and possible therapeutic targets to tailor the treatment to individual patients.

Material and Methods We have prospectively analyzed the differential proteomic profile of 34 patients with glioma imaging characteristics and compared them with that of normal brain tissue. This research was conducted at the Institute of Neurosurgery, Madras Medical College, in technical collaboration with the Indian Institute of Technology, Madras, over 1 year.

Statistical Analysis Biological variate analysis (I-ANALYSIS OF VARIANCE (ANOVA)) was used, with p-value less than 0.05 being significant.

Results Twenty proteins (10 upregulated and 10 downregulated) were differentially expressed in tumor tissue. The expression of three pro-apoptotic proteins was downregulated and the expression of three anti-apoptotic proteins was upregulated with statistical significance. The cellular functions of the 20 differentially regulated proteins were subjected to pathway analysis revealing significant alterations in heme biosynthesis, deoxyribonucleic acid (DNA) replication, fibroblast growth factor (FGF) signaling, and epidermal growth factor (EGF0 receptor signaling in glioma.

Conclusion KRT18, PRS4, and EF1A2 are anti-apoptotic proteins and are significantly upregulated in gliomas. EARS2, COX5A, and LSM3 are pro-apoptotic proteins, and are significantly downregulated in gliomas. This subverts the apoptotic pathways resulting in prolonged cell survival. This study's statistically significant dysregulation of these six proteins was unique, suggesting that they might be considered population-specific biomarkers and possible therapeutic targets for patients from South India. Abnormalities of heme biosynthesis at the proteomic level were identified in this study, which has not been very well studied previously.
Coronary Artery Bypass Grafting versus Percutaneous Coronary Intervention in Patients with Chronic Total Occlusion
Authors: Kirov Hristo , Fischer Johannes , Caldonazo Tulio , Tasoudis Panagiotis , Runkel Angelique , Soletti Giovanni Jr. , Cancelli Gianmarco , Dell'Aquila Michele , Mukharyamov Murat , Doenst Torsten
Published: May 2024

Objectives Mechanisms of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) differ as CABG provides surgical collateralization and may prolong life by preventing future myocardial infarctions (MIs). However, evidence for CABG in patients with chronic total occlusion (CTO) has not been fully elucidated and the impact of PCI is discussed controversially.

Methods We performed a meta-analysis of studies comparing outcomes in patients with/without multivessel disease undergoing CABG or PCI for CTO. The primary outcome was long-term all-cause mortality (≥5 years). Secondary outcomes were MIs, repeat revascularization, cardiac mortality, major adverse cardiovascular events, and stroke, as well as short-term mortality (30 days/in-hospital) and stroke. A pooled Kaplan–Meier survival curve after reconstruction analysis was generated. Random-effects models were used.

Results Six studies totaling 12,504 patients were included. In the pooled Kaplan–Meier analysis, PCI showed a significantly higher risk of death in the follow-up compared with CABG (hazard ratio [HR]: 2.12, 95% confidence interval [CI]: 1.88–2.38, p < 0.01). During the observation period, PCI was also associated with higher rates of MI (odds ratio [OR]: 2.86, 95% CI: 1.82–4.48, p < 0.01) and more repeat revascularization (OR: 4.88, 95% CI: 1.99–11.91, p = 0.0005). The other outcomes did not show significant differences.

Conclusion CABG is associated with superior survival to PCI over time in patients with CTO who are eligible for both PCI and CABG. This survival advantage is associated with fewer events of MI and repeat revascularization.
Understanding Hepatic Porphyrias: Symptoms, Treatments, and Unmet Needs
Authors: Balogun Oluwashanu , Nejak-Bowen Kari
Published: May 2024

Hepatic porphyrias are a group of metabolic disorders that are characterized by overproduction and accumulation of porphyrin precursors in the liver. These porphyrins cause neurologic symptoms as well as cutaneous photosensitivity, and in some cases patients can experience life-threatening acute neurovisceral attacks. This review describes the acute hepatic porphyrias in detail, including acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, as well as the hepatic porphyrias with cutaneous manifestations such as porphyria cutanea tarda and hepatoerythropoietic porphyria. Each section will cover disease prevalence, clinical manifestations, and current therapies, including strategies to manage symptoms. Finally, we review new and emerging treatment modalities, including gene therapy through use of adeno-associated vectors and chaperone therapies such as lipid nanoparticle and small interfering RNA-based therapeutics.
Interferon signaling in the nasal epithelium distinguishes among lethal and common cold coronaviruses and mediates viral clearance
Authors: Otter Clayton J. , Renner David M. , Fausto Alejandra , Tan Li Hui , Cohen Noam A. , Weiss Susan R.
Published: May 2024

All respiratory viruses establish primary infections in the nasal epithelium, where efficient innate immune induction may prevent dissemination to the lower airway and thus minimize pathogenesis. Human coronaviruses (HCoVs) cause a range of pathologies, but the host and viral determinants of disease during common cold versus lethal HCoV infections are poorly understood. We model the initial site of infection using primary nasal epithelial cells cultured at an air-liquid interface (ALI). HCoV-229E, HCoV-NL63, and human rhinovirus-16 are common cold-associated viruses that exhibit unique features in this model: early induction of antiviral interferon (IFN) signaling, IFN-mediated viral clearance, and preferential replication at nasal airway temperature (33 °C) which confers muted host IFN responses. In contrast, lethal SARS-CoV-2 and MERS-CoV encode antagonist proteins that prevent IFN-mediated clearance in nasal cultures. Our study identifies features shared among common cold-associated viruses, highlighting nasal innate immune responses as predictive of infection outcomes and nasally directed IFNs as potential therapeutics.
Arguing across spaces in an online epistemic community
Authors: Baker Michael J. , Détienne Françoise
Published: May 2024

Wikipedia is the most consulted source of information on the web, on a global level. The collective writing of
articles, open to the participation of all, can give rise to major conflicts between contributors, in texts and debates, given the
high stakes involved in achieving agreement on a public presentation of controversial topics. We present analyses of how
disagreements are managed across socio-technical and dialogical spaces in French Wikipedia, with respect to two case studies, on
Freud and the Turin Shroud. We adopt a mixed methods approach, combining results of analyses of interviews with moderators in
these articles and argumentative discussions underlying them, within a broadly pragma-dialectical framework. We show, on one hand,
that moderators’ attempts to resolve disagreements by requiring participants to cite sources simply displace conflicts to the
nature of those sources, their validity, their authors and the good faith of their proponents. Debates concerning sources
themselves draw on social actors’ perspectives in dialogical spaces, beyond the discussion itself. Disagreements are managed
rather than resolved dialectically by displacing them to alternative socio-technical spaces, such as different sections of the
text itself, or participants’ personal pages.
Information and communication technologies for improving investment readiness of small and medium agribusinesses
Authors:   Commercial Agriculture for Smallholders and Agribusiness (CASA), Valverde Alvaro
Published: May 2024

Information and communication technologies (ICTs) are increasingly seen as an enabler to improve and promote efficiencies in global food market systems, and the high penetration rate of mobile phones is playing a catalytic role in developing countries. Mobile-based agriculture-value-added services (agri-VAS) aim to mitigate the information, financial and market access gaps faced by smallholder farmers and agribusinesses in developing countries. Over the last two decades, the number and variety of agri-VAS has been continuously increasing, and their landscape has been evolving. However, many agri-VAS never reach financial sustainability or scale and are discontinued after a few years. Increasing efforts are being made to map the landscape of agri-VAS targeted at smallholder farmers across Africa and Asia. However, insufficient attention has been paid to exploring successful agri-VAS that have small and medium (SME) agribusinesses as their main clients and that source from smallholder farmers. Areas with potential for further study include the following: (a) agribusinesses operating in value chains that are digitized by others (e.g. mobile network operators); (b) agribusinesses that are developing and deploying agri-VAS in-house; (c) agribusinesses using services provided by third-party agri-VAS providers within their value chains; and (d) agribusinesses that develop partnerships with agri-VAS providers to co-develop solutions. This study aims to address the following question: What are the factors behind successful deployment of mobile technologies to improve agribusiness productivity and investment readiness? It aims to analyse agri-VAS that have SME agribusinesses as their main clients, as they are more likely to positively impact the investment readiness of SME agribusinesses than agri-VAS with smallholder farmers as their only clients, which are also the most evaluated type of agri-VAS. The study consists of a combination of secondary and primary research, resulting in: (a) a set of investment-policy and service-design recommendations, based on high-impact, sustainable agribusiness-focused VAS; (b) recommendations on how to improve the body of impact evidence; and (c) the identification of investment opportunities at the agribusiness and agri-VAS levels.
Optical third-harmonic generation of spherical quantum dots under inversely quadratic Hellmann plus inversely quadratic potential
Authors: Wang Xing , Li Xuechao
Published: May 2024

The third-harmonic generation (THG) coefficient for a spherical quantum dot system with inversely quadratic Hellmann plus inversely quadratic potential is investigated theoretically, considering the regulation of quantum size, confinement potential depth and the external environment. The numerical simulation results indicate that the THG coefficient can reach the order of 10−12 m2 V–2, which strongly relies on the tunable factor, with its resonant peak experiencing a redshift or blueshift. Interestingly, the effect of temperature on the THG coefficient in terms of peak location and size is consistent with the quantum dot radius but contrasts with the hydrostatic pressure. Thus, it is crucial to focus on the influence of internal and external parameters on nonlinear optical effects, and to implement the theory in practical experiments and the manufacture of optoelectronic devices.
Deep-subwavelength single grooves prepared by femtosecond laser direct writing on Si
Authors: Ye 叶 Rui-Xi 瑞熙 , Huang 黄 Min 敏
Published: May 2024

It is well known that femtosecond laser pulses can easily spontaneously induce deep-subwavelength periodic surface structures on transparent dielectrics but not on non-transparent semiconductors. Nevertheless, in this study, we demonstrate that using high-numerical-aperture 800 nm femtosecond laser direct writing with controlled pulse energy and scanning speed in the near-damage-threshold regime, polarization-dependent deep-subwavelength single grooves with linewidths of ∼ 180 nm can be controllably prepared on Si. Generally, the single-groove linewidth increases slightly with increase in the pulse energy and decrease in the scanning speed, whereas the single-groove depth significantly increases from ∼ 300 nm to ∼ 600 nm with decrease in the scanning speed, or even to over 1 μm with multi-processing, indicating the characteristics of transverse clamping and longitudinal growth of such deep-subwavelength single grooves. Energy dispersive spectroscopy composition analysis of the near-groove region confirms that single-groove formation tends to be an ultrafast, non-thermal ablation process, and the oxidized deposits near the grooves are easy to clean up. Furthermore, the results, showing both the strong dependence of groove orientation on laser polarization and the occurrence of double-groove structures due to the interference of pre-formed orthogonal grooves, indicate that the extraordinary field enhancement of strong polarization sensitivity in the deep-subwavelength groove plays an important role in single-groove growth with high stability and collimation.
Dielectric anisotropy in liquid crystal mixtures with nematic and smectic phases
Authors: Tang 汤 Xing-Zhou 星舟 , Ye 叶 Jia-Yao 家耀 , Wang 王 Zi-Ye 子烨 , Jiang 姜 Hao-Yi 皓译 , Shang 尚 Xiao-Hu 小虎 , Yang 杨 Zhao-Yan 朝雁 , Li 李 Bing-Xiang 炳祥
Published: May 2024

The modulation of dielectric anisotropy (Δε) is pivotal for elucidating molecular interactions and directing the alignment of liquid crystals. In this study, we combine liquid crystals with opposing dielectric anisotropies to explore the impact of varying concentrations on their properties. We report the sign-reversal of Δε in both the nematic and smectic A phases of these mixed liquid crystals, alongside a dual-frequency behaviour across a broad temperature spectrum. Our research further quantifies the influence of mixture ratios under various temperatures and electric field frequencies. This exploration may pave the way for the discovery of new physical phenomena.
Quantifying the Impact of Single-Event Upsets on Neural Networks with Uncertainty Analysis
Authors: Yan Jingjing , Gao Zhenbin
Published: May 2024

The Convolutional neural networks have gradually penetrated into various fields of social life, in addition to aerospace devices, neural network chips are also indispensable for target recognition and detection, etc. Due to the complex environment in space, neural network chips are extremely easy to be damaged by cosmic rays, so it is urgent to evaluate and enhance the robustness of neural network chips. However, most of the existing researches are monolithic error injection of neural networks and do not build relevant models for quantitative analysis. The goal of this paper is to analyse the effects of single-event upsets (SEUs) induced by the penetration of SRAM storage areas in a quantized neural network chip by energetic particles from space. Firstly, a SEU probability model as well as an uncertainty assessment model are established, and the effect of SEU on the reliability of CNNs is evaluated by fault injection with the upset rate of four chip types. The results of the error injection experiments show that the Virtex-5 type of rollover rate decreases the average accuracy of VGG-16 by 20%, while the other three types of error injection have an impact of about 11% on the accuracy of the neural network. Quantitative experimental results confirm the hypothesis that SEU increases the uncertainty of neural networks. The quantification of these effects contributes to the study of reinforcement of neural network chips.
A Lightweight Semi-supervised Eye Semantic Segmentation Method Based on Iterative Learning
Authors: Qi Ruochen , Zhang Guanghui , Zhu Dongchen , Shi Wenjun , Zhang Xiaolin
Published: May 2024

Eye semantic segmentation has a significant role in promoting biometric recognition. Most works improve the accuracy through designing complicated feature learning modules that usually require a high computation cost and are prone to over-fit. In this work, we propose a lightweight eye semantic segmentation method based on iterative learning, which only requires a small amount of labeled eye image data under visible light conditions. To be specific, we first propose a pseudo-label filtering strategy for eye semantic segmentation, which leverages a semi-supervised incremental learning technique to solve the problem of label scarcity. Besides, an attention-guided lightweight high-representation module is designed to boost precision while ensuring efficiency. Experiments on the Ubiris dataset show that the proposed method achieves state-of-the-art performance, with a mIoU of 86.18%.
Stability control of single-wheel failure in four-wheel independent drive electric vehicles
Authors: Xu Tao , Liu Tao , Zhao Peng , Qiang Guiyan , Zheng Zheng , Liu Yiqun
Published: May 2024

The integration of the motor and transmission mechanism into the wheels of a four-wheel independent drive electric vehicle with hub motors increases the frequency of failures, especially torque output failures, which seriously affect vehicle stability and jeopardize driving safety. This paper focuses on the perspective of single-wheel torque output failure and studies the vehicle stability control strategy. Firstly, based on the constructed simulation dynamics model, a slip controller is designed to obtain the direct lateral moment. Then, based on the control allocation principle, upper-level lateral moment allocation rules are designed, and torque allocation rules under single-wheel torque output failure are formulated. Finally, simulation experiments are conducted under different operating conditions. The simulation results show that this control strategy can effectively control vehicle stability under single-wheel failure conditions and ensure safe driving.
Research on the vehicle lane-changing decision-making system in complex traffic environments
Authors: Lu Xiaochun , Wei Xikai , Zhang Yongjie
Published: May 2024

In order to ensure the safety of vehicles changing lanes, there should be a certain degree of interaction and dynamics between vehicles on the way. In this paper, the problems of non-interactive road information and imprecise path planning are investigated. Through the research of the road condition decision-making system, autonomous lane-changing assistance system and intelligent traffic system, vehicle wireless networking technology, vehicle-road cooperation technology, and lane-changing decision-making and planning technology are used to increase the frequency of information interaction between vehicles and the external environment in order to realize information interaction between vehicles and collaborative driving. In this paper, simulation experiments of vehicle lane-changing are carried out by using MATLAB Simulink and compared with other research models. The results show that the lane change planning data based on the road condition decision system is more accurate, which leads to fast lane change driving in complex traffic scenarios.
Searching for WIMPs with TREX-DM: achievements and challenges
Authors: Castel J.F. , Cebrián S. , Dafni T. , Díez-Ibáñez D. , Ezquerro A. , Galán J. , García J.A. , Irastorza I.G. , Jiménez M. , Luzón G. , Margalejo C. , de Mira A. , Mirallas H. , Obis L. , Ortiz de Solórzano A. , Pérez O. , Ruz J. , Vogel J.
Published: May 2024

The TREX-DM detector, a low background chamber with microbulk Micromegas readout, was commissioned in the Canfranc Underground Laboratory (LSC) in 2018. Since then, data taking campaigns have been carried out with argon and neon mixtures, at different pressures from 1 to 4 bar. By achieving a low energy threshold of 1 keV
ee
and a background level of 80 counts keV-1 kg-1 day-1 in the region from 1 to 7 keV
ee
, the experiment demonstrates its potential to search for low-mass WIMPs. Two of the most important challenges currently faced are the reduction of both, background level and energy threshold. With respect to the energy threshold, recently a new readout plane is being developed, based on the combination of Micromegas and GEM technologies, aiming to have a pre-amplification stage that would permit very low energy thresholds, close to the single-electron ionization energy. With respect to the background reduction, apart from studies to identify and minimize contamination population, a high sensitivity alpha detector is being developed in order to allow a proper material selection for the TREX-DM detector components. Both challenges, together with the optimization of the gas mixture used as target for the WIMP detection, will take TREX-DM to explore regions of WIMP's mass below 1 GeV c
-2.
Design of a very low power 12 bits, 40 MS/s ADC based on a time-interleaved SAR architecture
Authors: Bontems W. , Dzahini D.
Published: May 2024

The paper describes a new figure of merit reachable in terms of very low power dissipation for a 12 bit, 40 MS/s Analog to Digital Converter in a 65 nm CMOS process with 1 V power supply. A differential time interleaved successive approximations register architecture is used. Each individual ADC channel is optimized with regard to power consumption hence interleaving 28 ADC channels in an analog memory like method, the total power consumption is only 280 μW including all the reference voltage drivers, the clock management and the digital sections. The total layout area of this converter is 0.87 mm2.
Design of multi-channel electronic prototype for 101Sn energy level lifetime measurement
Authors: Wang Z. , Yan J. , An Y. , Liang G. , Zhou X. , Wang C. , Pu T. , She Q. , Fang F. , Qiang Y. , Guo S. , Qian Y. , Kong J.
Published: May 2024

In this study, a 32-channel front-end data acquisition unit
(DAQU) with high temporal resolution and count rate was developed at
the Heavy Ion Research Facility in Lanzhou (HIRFL), China, to
measure the lifetime of 101Sn on the Spectrometer for Heavy
Atoms and Nuclear Structure. The DAQU data analysis module uses a
field programmable gate array (FPGA) to implement and time stamp
extraction through an FPGA-based tapped delay line (TDL)
time-to-digital converter. The energy measurements were implemented
using a trapezoidal algorithm and a sliding baseline averaging
method. The DAQU was tested and calibrated using a pulse generator
and cosmic rays. The results show that the system had a dead time of
less than 500 ns, a dynamic range of “0” to “500” mV, and an
energy resolution of better than 4.8‰ (full width
at the half-maximum, FWHM). In addition, the single-channel temporal
resolution under multi-channel settings surpasses 111.2 ps (FWHM),
satisfying the experiment's requirements for the electronics
system.
Exploiting finite geometries for better quantum advantages in Mermin-like games
Authors: Kelleher Colm , Holweck Frédéric , Lévay Péter
Published: May 2024

Quantum games embody non-intuitive consequences of quantum phenomena, such as entanglement and contextuality. The Mermin-Peres game is a simple example, demonstrating how two players can utilise shared quantum information to win a no—communication game with certainty, where classical players cannot. In this paper we look at the geometric structure behind such classical strategies, and borrow ideas from the geometry of symplectic polar spaces to maximise this quantum advantage. We introduce a new game called the Eloily game with a quantum–classical success gap of

0.2

6
―

, larger than that of the Mermin-Peres and doily games. We simulate this game in the IBM Quantum Experience and obtain a success rate of 1, beating the classical bound of

0.7

3
―

demonstrating the efficiency of the quantum strategy.
Exact time-evolving scattering states in open quantum-dot systems with an interaction: discovery of time-evolving resonant states
Authors: Nishino Akinori , Hatano Naomichi
Published: May 2024

We study exact time-evolving many-electron states of an open double quantum-dot system with an interdot Coulomb interaction. A systematic construction of the time-evolving states for arbitrary initial conditions is proposed. For any initial states of one- and two-electron plane waves on the electrical leads, we obtain exact solutions of the time-evolving scattering states, which converge to known stationary scattering eigenstates in the long-time limit. For any initial states of localized electrons on the quantum dots, we find exact time-evolving states of a new type, which we refer to as time-evolving resonant states. In contrast to stationary resonant states, whose wave functions spatially diverge and not normalizable, the time-evolving resonant states are normalizable since their wave functions are restricted to a finite space interval due to causality. The exact time-evolving resonant states enable us to calculate the time-dependence of the survival probability of electrons on the quantum dots for the system with the linearized dispersions. It decays exponentially in time on one side of an exponential point of resonance energies while, on the other side, it oscillates during the decay as a result of the interference of the two resonance energies.
Actions of some mapping classes on the closed Riemann surfaces of genus two
Authors: Nakamura Gou
Published: May 2024

The Teichmüller space of closed Riemann surfaces of genus two is considered as a subset of

R

7

\mathbb {R}^7

. We present some mapping classes acting on the model of the Teichüller space and investigate its action especially on the extremal surfaces with respect to a certain metric. As a result we estimate the distance between two orbits of distinct extremal surfaces from above.
Multisensory Perception
Authors: Doyon Maxime
Published: May 2024

One of the most debated questions in recent scholarship concerns the proper way of characterizing the phenomenology of multisensory experiences. While some believe that the phenomenal character of multisensory integration is reducible to the co-conscious sum of modality-specific features, this chapter refutes this thesis and shows how a vast array of bodily cues and sensations contribute to the experiential make-up of our conscious lives. Building on this insight, it is argued that the phenomenology of multisensory experience includes various forms of bodily self-experiences and often contains felt possibilities of action and behaviours. While spelling out the details of this claim, the chapter outlines an account of multimodal perception and sensory interaction that shows that all forms of perceptual experiences depend on the interplay of two or more senses. At the same time, it specifies the intrinsic relation between normativity and perception by demonstrating the impact of multisensory integration on agency.
State Responsibility and International Liability
Authors: Bhat B. Sandeepa
Published: May 2024

The Outer Space Treaty 1967 stands as a classic example of an earlier treaty, recognising the distinction between State responsibility and international liability with two separate provisions. While norms on State responsibility under the Outer Space Treaty were not further elaborated on with a separate treaty, the space liability norms were supplemented by the Liability Convention 1972. Unfortunately, the real implications of State responsibility and international liability norms under the space treaties remain unclear due to vagueness in the wording of provisions and consequential varied interpretations. It is a grim fact that not a single successful case has been fought under the Liability Convention since its entry into force five decades ago. Hence, it is pertinent to understand the existing regime of State responsibility and international liability under the United Nations space treaties to discover the present concerns with a view to addressing them effectively.
Meaning Bodies
Authors: Marchesi Ilaria
Published: May 2024

The chapter addresses the question of what it means for a woman to be a sign; that is, her double nature as always already a natural/material as well as a cultural/semiotic object. Martial’s women are (i.e., they are made to be) their bodies, bodies that (are made to) bear value. The body of texts analyzed here is extracted from Book 11, a unit in the collection which display’s Martial’s keen interest in somatology. In the selected epigrams the semiotic double bind of women is presented in its purest, most basic, and most essential form: it is a double-bind which extends to, and is rooted in, their bodies. By studying them as material and cultural tokens, at once physically existing and culturally meaning, Martial presents women as caught in the irreducible paradox of all signs. They are the primary example of the semiotic tension affecting his culture.
Architecture and functions of stomatal cell walls in eudicots and grasses
Authors: Jaafar Leila , Anderson Charles T
Published: May 2024

Background

Like all plant cells, the guard cells of stomatal complexes are encased in cell walls that are composed of diverse, interacting networks of polysaccharide polymers. The properties of these cell walls underpin the dynamic deformations that occur in guard cells as they expand and contract to drive the opening and closing of the stomatal pore, the regulation of which is crucial for photosynthesis and water transport in plants.

Scope

Our understanding of how cell wall mechanics are influenced by the nanoscale assembly of cell wall polymers in guard cell walls, how this architecture changes over stomatal development, maturation and ageing and how the cell walls of stomatal guard cells might be tuned to optimize stomatal responses to dynamic environmental stimuli is still in its infancy.

Conclusion

In this review, we discuss advances in our ability to probe experimentally and to model the structure and dynamics of guard cell walls quantitatively across a range of plant species, highlighting new ideas and exciting opportunities for further research into these actively moving plant cells.
O01 Mapping the cellular and molecular dynamics of mouse and human hair follicles reveals mechanisms of hair growth
Authors: Annusver Karl , Fernandez David , Pereira Diana , Nicolas Jean-François , Kasper Maria , Sequeira Inês
Published: May 2024

Introduction and aims

Tissue homeostasis in continuously renewing organs, such as the skin, rely on orchestrated cellular and molecular dynamics. The hair follicle (HF) is characterized by distinct keratinocytes organized in transcriptionally and functionally distinct concentric HF layers. The anagen progenitor cells (also called germinative layer cells) are located juxtaposed to the dermal papilla and give rise to each of the differentiated layers. Despite this well-known high level of organization and cell-lineage separation, it is still unclear how the germinative layer cells coordinate hair growth and commit to specific lineages.

Methods

Here, we employed single-cell RNA sequencing, single-molecule mRNA fluorescence in situ hybridization and in vivo lineage tracing to show how the matrix progenitor cells commit and contribute to the HF lineages depending on their position. Furthermore, we developed a four-dimensional live imaging system of the human HF to construct a global map of single-cell dynamics.

Results

We show that the HF progenitors dynamically relocate in a conveyor-belt-like movement, switch their lineage fate and gradually restrict their potential. This spatiotemporal cell choreography is characterized by a gradual change of expression from Lgr5 in the lower proximal cup, through Dcn, Id3 and Msx1 in the central part, to distal Lef1 expression where the medulla lineage starts. Detailed in situ mRNA staining and mouse clonal lineage tracing show the transcriptional changes and gradual lineage restriction of matrix progenitors in the spatial context. Combining human HF imaging with fluid dynamics theories, we uncovered a spiral-like downward movement of outer root sheath cells, feeding the germinative layer stem cells, and revealed a pulling force induced by the outer root sheath cells as a critical driver for hair growth.

Conclusions

Taken together, our study uncovered how HF progenitor cells progress in a conveyor-belt-like manner through several transcriptional states and discovered new cellular and molecular mechanisms regulating hair formation.
O10 Tuneable Caf1 protein polymers as an innovative and scalable solution for regenerative wound care
Authors: Nie Yuanjinze , Waller Helen , Peter Daniel , Reynolds Nick , Lakey Jeremy
Published: May 2024

Introduction and aims

Wound healing is a complex process essential for tissue restoration, where the extracellular matrix (ECM) plays a crucial role by providing structural and biochemical support to cells. Laminin 332, a key ECM component, is a promising target for protein-based therapeutics in view of its pathogenic role in junctional epidermolysis bullosa (JEB). Bioengineered capsular antigen F1 protein (Caf1) has emerged as a potential candidate molecule. We have developed the technology to enable bacteria to produce Caf1 polymers with multiple tailored bioactive motifs. Additionally, the unique properties of Caf1 minimize the potential for a host immune response. In this study, we engineered Caf1 proteins to express specific synthetic basement membrane components related to laminin 332 with the aim of restoring ECM equilibrium and achieving effective wound healing.

Methods

To evaluate Caf1 construct effects on human epidermal keratinocytes (HEKs) (CCD 1106) and human dermal fibroblasts (HDFs), scratch assays were performed under different treatment with Caf constructs. The Incucyte® ZOOM system (Sartorius AG, Göttingen, Germany) automated scratch wound and Live-Cell Analysis System screened constructs enhancing wound healing, capturing images every 2 h. Analysis involved quantifying the area under the curve of wound confluence (%) over 72 h to assess wound closure.

Results

The migration of HDFs was enhanced by 10.4% ± 0.95% (P < 0.05 Anova, n = 9 independent experiments) when there was interaction with Caf1-CTB4 (PMQKMRGDVFSP). The migration of CCDs was enhanced by 12.7% ± 1.03% when interacting with Caf1-J3 (KNSFMALYLSKGR) and by 14.4% ± 1.11% when interacting with Caf1-J4 (TALIRATYGEYSTGYI) (P < 0.05 Anova; n = 3 independent experiments). Combining Caf1-J3 and Caf1-J4 synergistically boosts CCD migration by 19.1% ± 1.42% (P < 0.05 Anova; n = 3 independent experiments), yielding better Results compared with individual treatments.

Conclusions

Caf1 exhibits promise as a platform for motif delivery, and the incorporation of cell migration motifs into Caf1 holds the potential to enhance wound healing.
O11 Investigating the genetic basis of the influence of adiposity on psoriasis
Authors: Ramessur Ravi , Saklatvala Jake , Mahil Satveer , Barker Jonathan , Loset Mari , Dand Nick , Simpson Michael , Smith Catherine
Published: May 2024

Introduction and aims

Obesity is a chronic inflammatory state that is highly prevalent in people with psoriasis. There is evidence to suggest that increasing levels of adiposity promotes the risk of psoriasis development and worsens disease severity. The degree to which adiposity influences psoriasis varies between individuals, and it is also unclear which key genetic factors underpin this variation. Identifying this could be mechanistically informative in uncovering immunological pathways connecting adiposity and psoriasis. This project explores the hypothesis that the influence of adiposity on psoriasis has a genetic basis.

Methods

Firstly, we examined the comparative strength of association between a range of measures of adiposity and psoriasis in a population-based study (UK Biobank, n = 336 806). Secondly, we performed a genome-wide by environment interaction study (GWEIS) meta-analysis examining the interaction between key measures of adiposity and psoriasis susceptibility in two large population-based studies [UK Biobank and HUNT (n = 164 753)]. Thirdly, in view of this association between human leucocyte antigen (HLA)-C*06:02 and higher adiposity levels in psoriasis, we wanted to explore whether biological differences existed between HLA-stratified subgroups. To explore this, we performed HLA-C*06:02-stratified Mendelian randomization to establish whether a difference in causal effect of adiposity on psoriasis existed between subgroups.

Results

We found that measures of central obesity (including impedance and dual-energy x-ray absorptiometry/magnetic resonance imaging measures) were most strongly associated with both psoriasis risk and severity. A sexual dimorphism was observed, with a stronger effect in men compared with women. Through GWEIS meta-analysis, we found a significant interaction between HLA-C*06:02-status and waist circumference on psoriasis risk (P = 3.69e−08). No significant difference in causal effect of body mass index or waist circumference on psoriasis risk were found in HLA-C*06:02-stratified subgroups.

Conclusions

These findings underscore the significance of central adiposity in influencing psoriasis risk. This study also emphasizes both the value and limitations of HLA-C*06:02 as a potential biomarker for distinguishing metabolically-driven psoriasis.
O12 Macrophages enhance angiogenesis in an induced pluripotent stem cell-derived skin organoid model
Authors: Foster April Rose , Admane Chloe , Adao Diana , Torabi Fereshteh , Gopee Nusayhah Hudaa , Olabi Bayanne , Winheim Elena , Rowe Victoria , Le Phuong Ahn , Serdy Sara , Kim Jin , Deakin CiCi , Lee Jiyoon , Li Tong , Koehler Karl , Gambardella Laure , Haniffa Muzlifah
Published: May 2024

Introduction and aims

Hair-bearing skin organoids (SkOs) are a complex three-dimensional (3D) model that faithfully recapitulates human skin as a multicellular organ with appendage structures. The development of such models provides unique potential for investigating human skin development and translational dermatology. Although this model answers many demands of an investigative tool, one obvious limitation is the absence of immune cells in SkOs. Our aim is to generate coculture systems of SkOs with macrophages to investigate how macrophages influence skin development.

Methods

Our group, and others, generated single-cell (sc)RNA-Seq and spatial transcriptomic datasets to thoroughly characterize human skin cell populations across the human lifespan. We used these datasets to compare the dynamic tempo of induced pluripotent stem cell (iPSC)-derived SkO (n = 84) differentiation with human prenatal (n = 15) and adult skin. For functional assays, we generated 2D angiogenesis coculture assays with macrophages and endothelial cells (n = 3) and 3D coculture of SkOs with macrophages (n = 3). Macrophages, endothelial cells and SkOs were all derived from the same iPSC line following established protocols. SkO vasculature was analysed after immunowholemount staining of CD31+ endothelial cells.

Results

Analysis of scRNA-Seq data highlighted a paucity in endothelial cell heterogeneity in SkOs compared with prenatal skin. We hypothesized that this could be explained by the absence of immune cells, as spatial transcriptomics microenvironment analysis of prenatal skin demonstrated that endothelial cells collocate with macrophages. With this in mind, we generated functional assays to investigate interactions of macrophages and endothelial cells in skin development. The 2D and 3D assays revealed that presence of macrophages significantly increased endothelial cell sprouting and network formation.

Conclusions

Our findings suggest a vital role of macrophages in skin morphogenesis, specifically in relation to the guidance of tip cells during angiogenesis. In addition, we present the SkO as an excellent complex model for investigating skin development, cell–cell interactions, and disease modelling for translational research in regenerative medicine and beyond.
O15 Transcriptomic profiling reveals regulators of dermal fibroblast state switching
Authors: Kirk Thomas , Ahmed Abubkr , Bensa Tjaša , Tekkala Stavroula , Khan Mohammad , Connelly John , Rognoni Emanuel
Published: May 2024

Introduction and aims

Fibroblasts, the major cell population in connective tissue, are the guardians of the extracellular matrix homeostasis. In adult tissue they exist in a quiescent state that can persist for years, but upon tissue injury, they become rapidly activated and re-enter the cell cycle, followed by deposition and reorganization of the dermal matrix. The fundamental mechanism by which fibroblasts can maintain quiescence and be primed for prompt activation is currently unknown. Deregulations of this process in the skin and other organs is associated with several pathologies including fibrosis or chronic wounds. Notably, rapid fibroblast state switching is also observed during skin development, where a tightly controlled change from a highly proliferative state to a quiescent state promotes extracellular matrix deposition and maturation of the dermal architecture. Understanding the shared mechanisms and differences between development and wound healing will help in the development of tissue regenerative therapies.

Methods

Using dermal development as a model for fibroblast state switching, we integrated several single-cell RNA-Seq and assay for transposase-accessible chromatin-Seq datasets of whole skin during embryonic and postnatal growth. Our novel integrated multiomics single-cell dataset can recapitulate skin developmental changes observed in vivo and reveal the major regulatory networks.

Results

We identified the activating protein (AP)-1 member cJun as the key regulator of fibroblast state switching in skin development and wound repair. Mechanistically, in quiescent adult fibroblasts cJun is highly transcribed, but the protein is constantly ubiquitinated and degraded, priming fibroblasts for rapid activation when needed. Upon injury cJun ubiquitination is reduced, allowing an accumulation of cJun leading to a change in AP-1 dimer composition at the chromatin level, inhibiting fibroblast quiescence and promoting proliferation and activation.

Conclusions

In normal wounds cJun accumulation is inhibited during the advanced (remodelling) wounding phase; however, chronic wounds and fibrotic disease conditions show a continuous and pathological cJun stabilization, which can be targeted through pharmacological intervention.
O20 Dissecting junctional epidermolysis bullosa heterogeneity
Authors: Garcha Priya , Jones Eleri , Ahmed Abubkr Abdelaal , Aumailley Monique , Rognoni Emanuel , Caley Matthew
Published: May 2024

Introduction and aims

Epidermolysis bullosa (EB) is a family of rare, incurable, inherited disorders that are characterized by extreme skin and mucosal fragility. One of the most severe forms is junctional EB (JEB). JEB is caused by mutations in genes encoding the skin basement membrane proteins laminin 332 (α3, β3, γ2), type XVII collagen or integrin α6β4. Despite similarities between the disease pathology of JEB and other forms of EB there is a dramatic reduction in life expectancy for patients with JEB. Patients with JEB rarely survive beyond the first year of life. To investigate this disparity, we have optimized a previously published conditional tamoxifen induced knockout JEB mouse model (Lama3flx/flxK14CreERT). This mouse model recapitulates all key features of JEB, such as thickening of the epidermis and visible blistering owing to the loss of laminin α3 at the basement membrane.

Methods

Single-cell (sc)RNA-Seq analysis was conducted on pooled skin samples from a healthy (control) and JEB mouse model (n = 3 per genotype). Immunofluorescent staining was conducted to confirm scRNA-Seq analysis including markers for skin differentiation (K14, transglutaminase 1, loricrin), proliferation (Ki67), basement membrane (laminin α3, laminin β3, laminin γ2, collagen VII) and immune markers (F4/80, Ly6-G/C, CD3, CD79).

Results

We can see large differences in cellular populations across the two conditions. With increased T- and B-immune-cell subpopulations in the JEB model compared with the healthy control. Utilizing CellChatDB we identified disease-specific signalling pathways that identify activated T- and B-cell populations interacting with JEB macrophage populations via proinflammatory pathways.

Conclusions

We have utilized an in vivo mouse model to gain insight into the molecular and cellular differences in a JEB diseased phenotype. Identifying changes in cellular pathways could be used as a targeted approach to identify a beneficial therapeutic treatment for JEB.
P19 Defining the mechanism of skin barrier restoration by Lactobacillus rhamnosus
Authors: Coppock Lisa , O’Shaughnessy Ryan , O’Neill Catherine
Published: May 2024

Introduction and aims

We aim to investigate the lysate of Lactobacillus rhamnosus GG (LGG), a bacterium previously established as a gut probiotic, and to examine its postulated ability to enhance and restore human skin barrier function. Compromised skin barriers are implicated in various skin conditions including atopic dermatitis. Furthermore, skin barrier function decreases with age leading to dryness and sensitivity. Previous research has shown promising effects of LGG lysates on keratinocytes, including increasing transepidermal electrical resistance, increasing tight junction protein expression, cell migration promotion and mitigation of Staphylococcus aureus toxicity. This study aims to take a closer look at the molecular mechanisms behind the effect of LGG lysates on the skin, including terminal differentiation, lamin dispersal and nuclear degradation in keratinocytes.

Methods

Normal human epithelial keratinocytes and rat epithelial keratinocytes were grown and treated with the LGG lysate. Western blot analysis was used to determine the relative concentrations of tight junction proteins and other differentiation markers. A phosphoproteomic study was performed to identify key pathways activated by the LGG lysate. A Staphylococcus epidermidis lysate control was used to filter out any nonspecific bacterial effects. Immunostaining of nuclear proteins was used to visualize the effects of LGG lysate on lamin dispersal and nuclear degradation. short hairpin RNA filaggrin knockdown normal human keratinocytes were developed to create a ‘barrier impaired’ model to assess ability of the lysate to ‘rescue’ the skin barrier.

Results

The LGG lysate was shown to increase tight junction protein expression in normal human keratinocytes and increase keratinocyte terminal differentiation markers. We present Results that show decreased tight junction protein expression in filaggrin knockdown cells.

Conclusions

These Results show the potential for LGG lysate to enhance and restore skin barrier function and begin to suggest potential mechanisms for this effect.