bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioelectronic Zeitgebers: targeted neuromodulation to re-establish circadian rhythms
Authors: Deli Alceste , Zamora Mayela , Fleming John E. , Zand Amir Divanbeighi , Benjaber Moaad , Green Alexander L. , Denison Timothy 
Published: May 2023

AbstractExisting neurostimulation systems implanted for the treatment of neurodegenerative disorders generally deliver invariable therapy parameters, regardless of phase of the sleep/wake cycle. However, there is considerable evidence that brain activity in these conditions varies according to this cycle, with discrete patterns of dysfunction linked to loss of circadian rhythmicity, worse clinical outcomes and impaired patient quality of life. We present a targeted concept of circadian neuromodulation using a novel device platform. This system utilises stimulation of circuits important in sleep and wake regulation, delivering bioelectronic cues (Zeitgebers) aimed at entraining rhythms to more physiological patterns in a personalised and fully configurable manner. Preliminary evidence from its first use in a clinical trial setting, with brainstem arousal circuits as a surgical target, further supports its promising impact on sleep/wake pathology. Data included in this paper highlight its versatility and effectiveness on two different patient phenotypes. In addition to exploring acute and long-term electrophysiological and behavioural effects, we also discuss current caveats and future feature improvements of our proposed system, as well as its potential applicability in modifying disease progression in future therapies.
Uncoupling the distinct functions of HP1 proteins during heterochromatin establishment and maintenance
Authors: Seman Melissa , Levashkevich Alexander , Larkin Ajay , Huang Fengting , Ragunathan Kaushik 
Published: May 2023

SUMMARYH3K9 methylation (H3K9me) marks transcriptionally silent genomic regions called heterochromatin. HP1 proteins are required to establish and maintain heterochromatin. HP1 proteins bind to H3K9me, recruit factors that promote heterochromatin formation, and oligomerize to form phase-separated condensates. We do not understand how HP1 protein binding to heterochromatin establishes and maintains transcriptional silencing. Here, we demonstrate that theS.pombeHP1 homolog, Swi6, can be completely bypassed to establish silencing at ectopic and endogenous loci when an H3K4 methyltransferase, Set1 and an H3K14 acetyltransferase, Mst2 are deleted. Deleting Set1 and Mst2 enhances Clr4 enzymatic activity, leading to higher H3K9me levels and spreading. In contrast, Swi6 and its capacity to oligomerize were indispensable during epigenetic maintenance. Our results demonstrate the role of HP1 proteins in regulating histone modification crosstalk during establishment and identifies a genetically separable function in maintaining epigenetic memory.
Transcriptomic Characterization Reveals Disrupted Medium Spiny Neuron Trajectories in Huntington’s Disease and Possible Therapeutic Avenues
Authors: Aguirre Carlos Galicia , Tshilenge Kizito-Tshitoko , Battistoni Elena , Lopez-Ramirez Alejandro , Naphade Swati , Perez Kevin , Song Sicheng , Mooney Sean D. , Melov Simon , Ehrlich Michelle E. , Ellerby Lisa M. 
Published: May 2023

SUMMARYHuntington’s disease (HD) is a neurodegenerative disorder caused by an expansion of CAG repeats in exon 1 of theHTTgene, ultimately resulting in the generation of a mutant HTT (mHTT) protein. Although mHTT is expressed in various tissues, it significantly affects medium spiny neurons (MSNs) in the striatum, resulting in their loss and the subsequent motor function impairment in HD. While HD symptoms typically emerge in midlife, disrupted MSN neurodevelopment has an important role. To explore the effects of mHTT on MSN development, we differentiated HD induced pluripotent stem cells (iPSC) and isogenic controls into neuronal stem cells, and then generated a developing MSN population encompassing early, intermediate progenitors, and mature MSNs. Single-cell RNA sequencing revealed that the developmental trajectory of MSNs in our model closely emulated the trajectory of fetal striatal neurons. However, in the HD MSN cultures, the differentiation process downregulated several crucial genes required for proper MSN maturation, including Achaete-scute homolog 1 and members of the DLX family of transcription factors. Our analysis also uncovered a progressive dysregulation of multiple HD-related pathways as the MSNs matured, including the NRF2-mediated oxidative stress response and mitogen-activated protein kinase signaling. Using the transcriptional profile of developing HD MSNs, we searched the L1000 dataset for small molecules that induce the opposite gene expression pattern. Our analysis pinpointed numerous small molecules with known benefits in HD models, as well as previously untested novel molecules. A top novel candidate, Cerulenin, partially restored the DARPP-32 levels and electrical activity in HD MSNs, and also modulated genes involved in multiple HD-related pathways.
The highly developed symbiotic system between the solar-powered nudibranchPteraeolidia semperiand Symbiodiniacean algae
Authors: Mizobata Hideaki , Tomita Kenji , Yonezawa Ryo , Hayashi Kentaro , Kinoshita Shigeharu , Yoshitake Kazutoshi , Asakawa Shuichi 
Published: May 2023

AbstractThe intricate coexistence of Symbiodiniacean algae with a diverse range of marine invertebrates underpins the flourishing biodiversity observed within coral reef ecosystems. However, the phenomenon of coral bleaching—precipitated by the dissolution of symbiotic relationships with Symbiodiniaceae—poses a significant threat to these ecosystems, thereby necessitating an urgent investigation into the underlying symbiotic mechanisms. The symbiosis between nudibranchs and Symbiodiniaceae has been identified as an efficacious model for examining these mechanisms, yet a comprehensive understanding of their histological structures and cellular processes remains elusive. In this study, we concentrate on the nudibranch hostPteraeolidia semperi, renowned for its exceptional symbiotic capabilities, and we elucidate its sophisticated symbiotic architecture. Furthermore, we delineate the bleaching process within the nudibranch, uncovering the associated cellular processes. Collectively, these findings furnish invaluable insights into the intricate relationship between nudibranchs and Symbiodiniaceae, thereby contributing to our understanding of the symbiosis that sustains these critical marine ecosystems.
Exploring the Role of Spatial Confinement in Immune Cell Recruitment and Regeneration of Skin Wounds
Authors: Liu Yining , Suarez-Arnedo Alejandra , Caston Eleanor , Riley Lindsay , Schneider Michelle , Segura Tatiana 
Published: May 2023

AbstractMicroporous annealed particle (MAP) scaffolds are injectable granular materials comprised of micron sized hydrogel particles (microgels). The diameter of these microgels directly determines the size of the interconnected void space between particles where infiltrating or encapsulated cells reside. This tunable porosity allows us to use MAP scaffolds to study the impact of spatial confinement (SC) on both cellular behaviors and the host response to biomaterials. Despite previous studies showing that pore size and SC influence cellular phenotypes, including mitigating the macrophage inflammatory response, there is still a gap in knowledge regarding how SC within a biomaterial modulates immune cell recruitmentin vivoin wounds and implants. Thus, we studied the immune cell profile within confined and unconfined biomaterials using small (40 μm), medium (70 μm), and large (130 μm) diameter spherical microgels, respectively. We discovered that MAP scaffolds imparted regenerative wound healing with an IgG1-biased Th2 response. MAP scaffolds generated from 130 μm diameter microgels have a median pore size that can accommodate ∼40 µm diameter spheres induced a more balanced pro-regenerative macrophage response and better wound healing outcomes with more mature collagen regeneration and reduced levels of inflammation.
A cryo-EM structure of KTF1-bound polymerase V transcription elongation complex
Authors: Zhang Hong-Wei , Huang Kun , Gu Zhan-Xi , Wu Xiao-Xian , Wang Jia-Wei , Zhang Yu 
Published: May 2023

AbstractDe novoDNA methylation in plants relies on transcription elongation of RNA polymerase V (Pol V) along with KTF1 and SPT4, which produces long non-coding RNAs for recruitment and assembly of DNA methylation machinery. Here, we report a cryo-EM structure of the KTF1-bound Pol V transcription elongation complex. The structure reveals conformation of the structure motifs in the active site of Pol V that accounts for its inferior RNA-extension ability. The structure further reveals structural features of Pol V that prevent it from interacting with the general transcription factors of Pol II and Pol IV. The KOW5 domain of KTF1 binds near the RNA exit channel of Pol V, where it provides a scaffold for the proposed recruitment of Argonaute proteins to initiate the assembly of DNA methylation machinery. The structure provides insight into the Pol V transcription elongation and the role of KTF1 during Pol V transcription-coupled DNA methylation.
Structural Insights into γH2Ax containing Nucleosomes
Authors: Panigrahi Rashmi , Edwards Ross , Islam Md Touhidul (Apu) , Lu Jun , Kulepa Ayodeji , Kim Tae Hwan , Glover J. N. Mark 
Published: May 2023

AbstractMDC1 is a key mediator of DNA-damage signaling. When DNA double-strand breaks (DSB) occur, the histone variant H2AX on the nucleosome is phosphorylated on its C-terminus at residue Ser139 to form the γH2AX nucleosome. This phosphorylated form is specifically recognized by the tandem BRCT repeats of MDC1. The MDC1-bound nucleosome serves as a docking platform to promote the localization of other DNA repair factors. To further characterize the nucleosome-BRCT interaction, we developed a time efficient two-step modified native chemical ligation protocol to prepare phosphorylated nucleosomes. Our binding studies show that BRCT interacts with the nucleosome with a higher affinity than the phosphorylated peptide. Using cryogenic electron microscopy (cryo-EM), we obtained structures of the γH2AX nucleosome revealing the structural basis for nucleosome-nucleosome stacking promoted by interactions of the H4 N-terminal of one nucleosome with its stacked partner. In contrast, we show that binding of the MDC1 BRCT domain disrupts this stacking, suggesting that histone/DNA dynamics are integral to DNA damage signaling.
Piezo1-dependent regulation of pericyte proliferation by blood flow during brain vascular development
Authors: Zi Huaxing , Peng Xiaolan , Cao Jianbin , Bu Jiwen , Du Jiulin , Li Jia 
Published: May 2023

AbstractBlood flow is known to regulate cerebrovascular development through acting on vascular endothelial cells (ECs). As an indispensable component of the cerebrovascular unit, brain pericytes physically couple with ECs with the highest density in the body and play vital roles in blood-brain barrier integrity maintenance and neurovascular coupling. However, it remains unclear whether blood flow affects the development of brain pericytes. Here, we report that blood flow can promote brain pericyte proliferation, which depends on the mechanosensitive ion channel Piezo1. Usingin vivotime-lapse imaging of larval zebrafish, we monitored the developmental dynamics of brain pericytes and found that they proliferated to expand their population and increase their coverage on brain vessels. In combination with pharmacological and genetic approaches, we demonstrate that the proliferation of brain pericytes can be enhanced by increased blood flow through Piezo1 expressed in ECs. Furthermore, EC-intrinsic Notch signaling was found to be downstream of Piezo1 for the blood flow regulation of brain pericyte proliferation. Thus, our findings reveal an important role of blood flow for pericyte proliferation, extending the functional spectrum of hemodynamics on the development of cerebral vasculature.
Robust differentiation in a synthetic stem-cell circuit
Authors: Glass David S. , Bren Anat , Vaisbourd Elizabeth , Mayo Avi , Alon Uri 
Published: May 2023

AbstractDifferentiation is a process fundamental to multicellularity. In its simplest form, differentiation converts self-renewing stem cells into non-proliferative cells with specified function. This process is inherently susceptible to mutant takeover — mutant stem cells that never differentiate produce excess proliferative daughter cells, driving cancer-like expansion and decreasing the availability of differentiated cells to the organism. It has been proposed that coupling differentiation to an essential trait can select against these mutants by producing a biphasic fitness curve. This would provide mutant stem cells that do not differentiate with a selective disadvantage. However, this theory has yet to be tested experimentally. Here we use “fitness landscape engineering” to design and construct a synthetic biological model of stem cell differentiation inEscherichia coliwith biphasic fitness. We find that this circuit is robust to mutations as predicted. Surprisingly, its optimal differentiation rate is robust to a wide range of environmental pressures. This environmental robustness is driven by transit-amplifying cells that differentiate and proliferate irrespective of environment. These results provide new interpretations for natural differentiation mechanisms and suggest strategies for engineering robust, complex multicellular consortia.
Distinct Social Behavior and Inter-Brain Connectivity in Dyads with autistic individuals
Authors: Moreau Quentin , Brun Florence , Ayrolles Anaël , Nadel Jacqueline , Dumas Guillaume 
Published: May 2023

AbstractAutism Spectrum Disorder (ASD) is defined by distinctive socio-cognitive behaviors that deviate from typical patterns. Notably, social imitation skills appear to be particularly impacted, manifesting early on in development. This paper compared the behavior and inter-brain dynamics of dyads made up of two typically developing (TD) participants with mixed dyads made up of ASD and TD participants during social imitation tasks. By combining kinematics and EEG-hyperscanning, we show that individuals with ASD exhibited a preference for the follower rather than the lead role in imitating scenarios. Moreover, the study revealed inter-brain synchrony differences, with low-alpha inter-brain synchrony differentiating control and mixed dyads. The study’s findings suggest the importance of studying interpersonal phenomena in dynamic and ecological settings and using hyperscanning methods to capture inter-brain dynamics during actual social interactions.
“When the baby sleeps, I work” – neoliberal motherhood in Latin America during the Covid-19 lockdown
Authors: Paludi Mariana I. , Krysa Isabella , Kivijärvi Marke 
Published: May 2023

PurposeThis paper explores working mothers’ coping strategies concerning paid and unpaid work in Chile and Argentina during the Covid-19 pandemic. The paper aimed to understand the influence of cultural norms on motherhood and neoliberal workplace practices on mothers’ sensemaking processes and coping strategies. This study focuses on mothers living in Chile and Argentina where governments established mandatory lockdowns between March and September 2020. Drawing on the notion of neoliberal motherhood, women’s demands were analyzed when paid work and mothering duties collide in time and space.Design/methodology/approachOpen-ended interviews were conducted with 17 women in Chile and Argentina. All interviewees had at least 1 child below the age of 6 and were working from home during the lockdown.FindingsNeoliberal workplace demands, and disadvantageous government policies greatly heightened the dual burdens of working mothers. Women were expected to fulfill the discourses of the neoliberal worker and the good mother, while also adopting additional strategies in the wake of the lockdown. The data highlights mothers’ strategies to cope with care and work duties by adjusting to new routines involving their partners, relatives and the wider community.Research limitations/implicationsThe generalizability of the results is limited by the small sample of 17 interviewees, all from middle to middle-upper class. The changing scenario due to Covid-19 makes the collected data not sufficient to grasp the impact of the pandemic, as during the interviews (December 2020 and January 2021) the process was still ongoing.Practical implicationsOrganizations should assess their role in the management of paid and unpaid work for both genders, as the neoliberal discourse views the worker as masculine, full-time, always available and productive, ignoring women’s additional care duties outside of the workplace.Originality/valueThe Covid-19 pandemic provides a unique opportunity to reflect on care work and gender, collective versus individual responses to care and work demands and the idea of organizing.
Fuzzy active disturbance rejection control method for an omnidirectional mobile robot with MY3 wheel
Authors: Ye Changlong , Shao Jingru , Liu Yong , Yu Suyang 
Published: May 2023

Purpose
Omnidirectional mobile robots with a special type of wheel structure can realize flexible motion with all three degrees of freedom in a plane. But the driving method brings large disturbance, which affects motion accuracy and stability. This study aims to improve the motion control accuracy of the omnidirectional mobile platform with MY3 wheels (MY3-OMR), a new fuzzy active disturbance rejection control (FADRC) method with adaptivity is proposed.

Design/methodology/approach
Based on the basic mechanical structure and drive characteristics of MY3-OMR, the dynamics model of the system is established. The linear active disturbance rejection control (LADRC) system is designed to reduce the interference of nonlinear factors in this dynamics model. A fuzzy controller is introduced to realize the online adjustment of the parameters of the LADRC, which further improves the anti-disturbance performance of the system.

Findings
The control method proposed in this paper is compared and analyzed with other methods by simulation and experiment. Results show that the proposed method has better tracking and robustness, which effectively improves the control accuracy of trajectory tracking of MY3-OMR.

Originality/value
A FADRC method with adaptivity is proposed by combining fuzzy control and LADRC. The motion accuracy and anti-interference ability of the MY3-OMR are improved by this control method, which lays a foundation for the subsequent application of MY3-OMR.
Comparison of different reinforcement methods on crack monitoring characteristics of eddy current array sensor
Authors: Fan Xianghong , Chen Tao , He Yuting 
Published: May 2023

Purpose
This paper aims to study the influence of different reinforcement methods on crack monitoring characteristics of eddy current array sensors, and the sensors with two different reinforcement methods, SUS304 reinforcement and permalloy reinforcement, are proposed.

Design/methodology/approach
First, the finite element model of the sensor is established to analyze the influence of the reinforcement plate’s electromagnetic parameters on the crack identification sensitivity. Then, the crack monitoring accuracy test of sensors with two reinforcement methods is carried out. Finally, the fatigue crack monitoring experiments with bolt tightening torques of 45 and 63 N · m are carried out, respectively.

Findings
In this study, it is found that the crack identification sensitivity of the sensor can be improved by increasing the relative permeability of the reinforcement plate. The crack monitoring accuracy of the sensors with two different reinforcement methods is about 1 mm. And the crack identification sensitivity of the sensor reinforced by permalloy reinforcement plate is significantly higher than that of the sensor reinforced by SUS304 reinforcement plate.

Originality/value
The sensor reinforced by reinforcement plate can work normally under the squeezing action of the bolt, and the crack monitoring sensitivity of the sensor can be significantly improved by using the reinforcement plate with high relative permeability.
Employees’ proactive customer service performance in hospitality: impacts of customer mistreatment and team performance pressure
Authors: Jiang Jing , Yuan Yuan , Dong Yanan , Dong Huijuan 
Published: May 2023

Purpose
This study aims to examine the joint impact of customer mistreatment (external stressor) and team performance pressure (internal stressor) on employees’ proactive customer service performance (PCSP) using the stressor-emotion model.

Design/methodology/approach
The sample consisted of 220 employees and 54 branch leaders from a large restaurant chain in China. This study conducted a multi-time and multi-source design study using Mplus 7.4 to examine the hypotheses.

Findings
Customer mistreatment has a positive effect on employees’ emotional exhaustion, which further reduces PCSP. Team performance pressure strengthens the dysfunctional effect of customer mistreatment on emotional exhaustion, whereas leaders’ positive affective presence mitigates the negative relationship between emotional exhaustion and PCSP.

Originality/value
This study investigates how internal and external stressors jointly affect employees’ PCSP. Thus, it provides a comprehensive perspective of employee stress management and active service management for organization managers.
A case of bullous pemphigoid developing under treatment with benralizumab for bronchial asthma
Authors: Tanaka Arisa , Fujimura Yu , Fuke Satoshi , Izumi Kentaro , Ujiie Hideyuki 
Published: May 2023

AbstractBullous pemphigoid (BP) is an autoimmune disease characterized by itchy erythema and tense blisters on the whole body. Recent reports have unveiled the pathogenic roles of eosinophils in BP (e.g., dermal‐epidermal separation, generation of pruritus). Thus, eosinophils are considered a therapeutic target. Benralizumab is an anti‐IL‐5 receptor alpha (IL‐5Rα) monoclonal antibody (mAb) that is widely used to treat severe eosinophilic asthma. By affecting IL‐5Rα, benralizumab depletes eosinophils and basophils due to apoptosis through antibody‐dependent cell‐mediated cytotoxicity. The efficacies of benralizumab and other biologics, including bertilimumab (anti‐eotaxin‐1 mAb) and mepolizumab (anti‐IL‐5 mAb), were evaluated in several clinical trials. Also, reslizumab, an anti‐IL‐5 mAb, was reported as a successful treatment option in a case of BP. We present a case of severe asthma treated with benralizumab at 8‐week intervals for 3 years before BP developed. Histologically, subepidermal blisters without eosinophilic infiltration were observed. Methylprednisolone pulse therapy followed by 40 mg/day (1 mg/kg/day) of oral prednisolone (PSL) was initiated, but the skin lesions worsened. Additional intravenous immunoglobulin and oral azathioprine enabled the oral PSL to be tapered. The benralizumab was discontinued after the onset of BP because the asthma did not worsen. To the best of our knowledge, there have been no reports of BP developing during anti‐eosinophil therapy. BP may occur paradoxically via various pathways during treatment with drugs that are typically effective against BP.