bluuebunny/crossref_metadata_2025 huggingface dataset:
Anaplastic Thyroid Cancer Cells Upregulate Mitochondrial One-Carbon Metabolism To Meet Purine Demand, Eliciting A Critical Targetable Vulnerability
Authors: Sugarman Adam J. , Huynh Luong Do , Shabro Aidin , Di Cristofano Antonio
Published: May 2023

Anaplastic thyroid cancer (ATC) is one of the most aggressive and lethal tumor types, characterized by loss of differentiation, epithelial-to-mesenchymal transition, extremely high proliferation rate, and generalized resistance to therapy. To identify novel relevant, targetable molecular alterations, we analyzed gene expression profiles from a genetically engineered ATC mouse model and from human patient datasets, and found consistent upregulation of genes encoding enzymes involved in the one-carbon metabolic pathway, which uses serine and folates to generate both nucleotides and glycine.

Genetic and pharmacological inhibition ofSHMT2, a key enzyme of the mitochondrial arm of the one-carbon pathway, rendered ATC cells glycine auxotroph and led to significant inhibition of cell proliferation and colony forming ability, which was primarily caused by depletion of the purine pool. Notably, these growth-suppressive effects were significantly amplified when cells were grown in the presence of physiological types and levels of folates. Genetic depletion ofSHMT2dramatically impaired tumor growth in vivo, both in xenograft models and in an immunocompetent allograft model of ATC.

Together, these data establish the upregulation of the one-carbon metabolic pathway as a novel and targetable vulnerability of ATC cells, which can be exploited for therapeutic purposes.
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

Existing 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

H3K9 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

Huntington’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

The 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

Microporous 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

De 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

MDC1 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

Blood 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

Differentiation 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

Autism 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.
Highly complete long-read genomes reveal pangenomic variation underlying yeast phenotypic diversity
Authors: Weller Cory A. , Andreev Ilya , Chambers Michael J. , Park Morgan ,   NISC Comparative Sequencing Program, Bloom Joshua S. , Sadhu Meru J.
Published: May 2023

Understanding the genetic causes of trait variation is a primary goal of genetic research. One way that individuals can vary genetically is through variable pangenomic genes: genes that are only present in some individuals in a population. The presence or absence of entire genes could have large effects on trait variation. However, variable pangenomic genes can be missed in standard genotyping workflows, owing to reliance on aligning short-read sequencing to reference genomes. A popular method for studying the genetic basis of trait variation is linkage mapping, which identifies quantitative trait loci (QTLs), regions of the genome that harbor causative genetic variants. Large-scale linkage mapping in the budding yeastSaccharomyces cerevisiaehas found thousands of QTLs affecting myriad yeast phenotypes. To enable the resolution of QTLs caused by variable pangenomic genes, we used long-read sequencing to generate highly complete de novo genome assemblies of 16 diverse yeast isolates. With these assemblies, we resolved QTLs for growth on maltose, sucrose, raffinose, and oxidative stress to specific genes that are absent from the reference genome but present in the broader yeast population at appreciable frequency. Copies of genes also duplicate onto chromosomes where they are absent in the reference genome, and we found that these copies generate additional QTLs whose resolution requires pangenome characterization. Our findings show the need for highly complete genome assemblies to identify the genetic basis of trait variation.
A novel quantitative trait locus implicatesMsh3in the propensity for genome-wide short tandem repeat expansions in mice
Authors: Maksimov Mikhail O. , Wu Cynthia , Ashbrook David G. , Villani Flavia , Colonna Vincenza , Mousavi Nima , Ma Nichole , Lu Lu , Pritchard Jonathan K. , Goren Alon , Williams Robert W. , Palmer Abraham A. , Gymrek Melissa
Published: May 2023

Short tandem repeats (STRs) are a class of rapidly mutating genetic elements typically characterized by repeated units of 1–6 bp. We leveraged whole-genome sequencing data for 152 recombinant inbred (RI) strains from the BXD family of mice to map loci that modulate genome-wide patterns of new mutations arising during parent-to-offspring transmission at STRs. We defined quantitative phenotypes describing the numbers and types of germline STR mutations in each strain and performed quantitative trait locus (QTL) analyses for each of these phenotypes. We identified a locus on Chromosome 13 at which strains inheriting the C57BL/6J (B) haplotype have a higher rate of STR expansions than those inheriting the DBA/2J (D) haplotype. The strongest candidate gene in this locus isMsh3, a known modifier of STR stability in cancer and at pathogenic repeat expansions in mice and humans, as well as a current drug target against Huntington's disease. TheDhaplotype at this locus harbors a cluster of variants near the 5′ end ofMsh3, including multiple missense variants near the DNA mismatch recognition domain. In contrast, theBhaplotype contains a unique retrotransposon insertion. The rate of expansion covaries positively withMsh3expression—with higher expression from theBhaplotype. Finally, detailed analysis of mutation patterns showed that strains carrying theBallele have higher expansion rates, but slightly lower overall total mutation rates, compared with those with theDallele, particularly at tetranucleotide repeats. Our results suggest an important role for inherited variants inMsh3in modulating genome-wide patterns of germline mutations at STRs.
“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

Purpose

This 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/approach

Open-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.

Findings

Neoliberal 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/implications

The 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 implications

Organizations 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/value

The 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

Bullous 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.
Pre‐pandemic autonomic function as a predictor of the COVID clinical course in young adults
Authors: Sharma Vagisha , Pattnaik Sanghamitra , Ahluwalia Himani , Kaur Manpreet
Published: May 2023

Long coronavirus disease (COVID) is emerging as a common clinical entity in the current era. Autonomic dysfunction is one of the frequently reported post‐COVID complications. We hypothesize a bi‐directional relationship between the autonomic function and the COVID course. This postulation has been inadequately addressed in the literature. A retrospective cohort (pre and post‐comparison) study was conducted on 30 young adults whose pre‐COVID autonomic function test results were available. They were divided into case and control groups based on whether they tested reverse transcription polymerase chain reaction positive for COVID‐19. Autonomic function tests were performed in both the case and control groups. COVID infection in healthy young adults shifts the sympatho–vagal balance from the pre‐disease state. Postural orthostatic tachycardia syndrome was present in 35% of the COVID‐affected group. COVID course parameters were found to be associated with parasympathetic reactivity and the baroreflex function. Baseline autonomic function (parasympathetic reactivity represented by Δ heart rate changes during deep breathing and 30:15 ratio during lying‐to‐standing test) was also associated with the COVID course, the post‐COVID symptoms and the post‐COVID autonomic function profile. Additionally, multiple regression analysis found that the baseline parasympathetic reactivity was a very important determinant of the clinical course of COVID, the post‐COVID symptoms and the post‐COVID autonomic profile. Sympatho–vagal balance shifts to parasympathetic withdrawal with sympathetic predominance due to COVID infection in healthy young adults. There is a bi‐directional relationship between the autonomic function and the COVID course.
Women and the Labour Party: Gender and the Writing of British Political History
Authors: Jenkins Lyndsey , Ward Stephanie
Published: May 2023

This article takes stock of the state of women's political history in the twentieth century and suggests new lines of enquiry, drawing on the authors’ own work on the Labour Party. It identifies a number of key themes which have enriched histories of women and gender in the nineteenth and early twentieth century and considers how these might be developed. Firstly, it examines the significance of the local, and more particularly, the neighbourhood, in women's political lives. Secondly, it asserts the value of focussing on the membership, including the economic, social and cultural shifts that shaped their lives, the intersection of gender with factors such as age or ethnicity, and their own political identities. Finally, it stresses the importance of interrogating masculine cultures to understand how gendered dynamics played out. It concludes with a reminder that inserting women into established political narratives is insufficient: the point is to transform those narratives.
Effects of activated earth, activated alumina, and chitosan adsorption processes on thermal and rheological and chemical characteristics of menhaden oil
Authors: Yin Huaixia , Bechtel Peter. J. , Sathivel Subramaniam
Published: May 2023

The objective of this study was the effectiveness of using activated earth, activated alumina, and/or chitosan, either separately or in combination, as adsorbents to remove free fatty acids (FFA) and peroxides from unpurified menhaden oil (MO). Thermal and rheological properties of MO were also evaluated. Five different combinations of absorbents were used to purify MO: Processes 1–3 involved purifications of MO by 5% chitosan (wt/wt of oil), 5% activated earth, and 5% activated alumina, respectively, process 4 involved MO purification with a combination of 6.5% chitosan, 3.5% activated earth, and 5% activated alumina, and process 5 involved MO purification process with a combination of adsorbents of 9% chitosan, 1% activated earth, and 5% activated alumina. All the adsorption processes were conducted at 25°C. Purified MO and MO were evaluated for their fatty acid profile, FFA, peroxide value (PV), moisture content (MC), minerals, and color. Triplicate experiments were conducted, and data were statistically analyzed using α = 0.05. Processes 4 and 5 were effective in reducing PV, FFA, and MC in MO. Thermal properties indicated processes 4 and 5 produced purer MO than processes 1–3. All the oil samples became less viscous, and the flow behavior index of MO was close to 1 after the adsorption processes. This study demonstrated that adsorption processes that include chitosan, activated earth, and activated alumina could effectively improve MO quality.
Enhancing perspectives on lake impairments using satellite observations: A case study on High Rock Lake, North Carolina
Authors: Di Vittorio Courtney A. , Moerk Michael , Kreutzberger William
Published: May 2023

Stakeholders developing water quality improvement plans for lakes and reservoirs are challenged by the sparsity of in‐situ data and the uncertainty ingrained in management decisions. This study explores how satellite images can fill gaps in water quality databases and provide more holistic assessments of impairments. The study site is an impaired water body that is serving as a pilot for improving state‐wide nutrient management planning processes. An existing in‐situ database was used to calibrate semi‐analytical models that relate satellite reflectance values to turbidity and total suspended solids (TSS). Landsat‐7 images from 1999 to 2020 that overpass High Rock Lake, North Carolina were downloaded and processed, providing 42 turbidity and 39 TSS satellite and in‐situ match‐ups for model calibration and validation. Model r‐squared values for the fitted turbidity and TSS models are 0.72 and 0.74, and the mean absolute errors are 14.6 NTU and 3.2 mg/L. The satellite estimates were compared to the in‐situ data and simulated TSS values produced by a calibrated hydrologic‐hydrodynamic model. The process‐based model is considered less accurate than the satellite model based on statistical performance metrics. Comparisons between data sources are illustrated with time series plots, frequency curves, and aggregate decision metrics to highlight the dependence of lake impairment assessments on the spatial and temporal frequency of available data and model accuracy.
Sequence capture: Obsolete or irreplaceable? A thorough validation across phylogenetic distances and its applicability to hybrids and allopolyploids
Authors: Bartoš Oldřich , Bohlen Jörg , Šlechtová Vendula Bohlen , Kočí Jan , Röslein Jan , Janko Karel
Published: May 2023

As whole‐genome sequencing has become pervasive, some have suggested that reduced genomic representation approaches, for example, sequence capture, are becoming obsolete. In the present study, we argue that these techniques still provide excellent tools in terms of price and quality of data as well as in their ability to provide markers with specific features, as required, for example, in phylogenomics. A potential drawback of the wide‐scale application of reduced representation approaches could be their drop in efficiency with increasing phylogenetic distance from the reference species. While some studies have focused on the degree and performance of reduced representation techniques in such situations, to our knowledge, none of them evaluated their applicability to inter‐specific hybrids and polyploids. This highlights a significant gap in current knowledge since there is increasing evidence for the frequent occurrence of natural hybrids and polyploids, as well as for the major importance of both phenomena in evolution. The main aim of the present study was to carry out a thorough validation of SEQcap applicability to (1) a set of non‐model taxa with a wide range of phylogenetic relatedness and (2) inter‐specific hybrids of various ploidies and genomic compositions. Considering the latter point, we especially focused on mechanisms causing allelic bias and consequent allelic dropout, as these could have confounding effects with respect to the evolutionary genomic dynamics of hybrids, especially in asexuals, which virtually reproduce as a frozen F1 generation.
Burial offerings in intramural tombs at Middle Bronze Age Megiddo
Authors: Amir Ayala , Kalisher Rachel , Cradic Melissa S. , Adams Matthew J. , Martin Mario A. S. , Neumann Ronny , Gadot Yuval , Finkelstein Israel
Published: May 2023

Tel Megiddo is a major type‐site for the Middle Bronze in the Levant. During this period a new burial custom appeared in which the dead were interred beneath occupied houses. This tradition is well attested in Area K at the site. Area H, near the palatial complex, revealed a monumental masonry‐constructed chamber tomb. This article presents the results of residue analysis conducted on ceramic vessels placed in these tombs as burial offerings. Hundreds of intramural Middle Bronze tombs with ceramic offerings were excavated in the Levant, but this is the first time the content of the vessels is revealed.
Expanding the phenotype of PIGP deficiency to multiple congenital anomalies‐hypotonia‐seizures syndrome
Authors: Martín‐Grau Carla , Orellana Alonso Carmen , Roselló Piera Mónica , Pedrola Vidal Laia , Llorens‐Salvador Roberto , Quiroga Ramiro , Marín Reina Purificación , Rubio Moll Juan Salvador , Gómez Portero Rosa , Martínez‐Castellano Francisco
Published: May 2023

Glycosylphosphatidylinositol‐anchored proteins are involved in multiple physiological processes and the initial stage of their biosynthesis is mediated by PIGA, PIGC, PIGH, PIGP, PIGQ, PIGY, and DMP2 genes, which have been linked to a wide spectrum of phenotypes depending on the gene damaged. To date, the PIGP gene has only been related to Developmental and Epileptic Encephalopathy 55 (MIM#617599) in just seven patients. A detailed medical history was performed in two affected siblings with a multiple malformation syndrome. Genetic testing was performed using whole‐exome sequencing. One patient presented dysmorphic features, congenital anomalies, hypotonia and epileptic encephalopathy as described in PIGA, PIGQ and PIGY deficiencies. The other one was a fetus with a severe malformation disorder at 17 weeks of gestation whose pregnancy was interrupted. Both were compound heterozygous of pathogenic variants in PIGP gene: NM_153682.3:c.2 T > C(p.?) and a 136 Kb deletion (GRCh37/hg19 21q22.13(chr21:38329939‐38 466 066)×1) affecting the entire PIGP gene. Our results extend the clinical phenotype associated to PIGP gene and propose to include it as a novel cause of Multiple Congenital Anomalies‐Hypotonia‐Seizures syndrome.
Evolution of clinical and radiological presentations of spondyloepimetaphyseal dysplasia, RPL13‐related: Description of 11 further cases
Authors: Díaz‐González Francisca , Parrón‐Pajares Manuel , Lucas‐Castro Elsa , Modamio‐Høybjør Silvia , Sentchordi‐Montané Lucia , Seidel Verónica , Prieto Pablo , Tarraso‐Urios Guillermo , Codina‐Sola Marta , Cueto‐González Anna M. , Ballesta‐Martínez Mary J. , Santos‐Simarro Fernando , Sousa Sergio B. , Heath Karen E.
Published: May 2023

Spondyloepimetaphyseal dysplasia (SEMD), RPL13‐related is caused by heterozygous variants in RPL13, which encodes the ribosomal protein eL13, a component of the 60S human ribosomal subunit. Here, we describe the clinical and radiological evolution of 11 individuals, 7 children and 4 adults, from 6 families. Some of the skeletal features improved during the course of this condition, whilst others worsened. We describe for the first time “corner fractures” as a feature of this dysplasia which as with other dysplasias disappear with age. In addition, we review the heights and skeletal anomalies of these reported here and previously in a total of 25 individuals from 15 families. In this study, six different RPL13 variants were identified, five of which were novel. All were located in the apparently hotspot region, located in intron 5 and exon 6. Splicing assays were performed for two of the three previously undescribed splicing variants. Until now, all splice variants have occurred in the intron 5 splice donor site, incorporating an additional 18 amino acids to the mutant protein. Here, we report the first variant in intron 5 splice acceptor site which generates two aberrant transcripts, deleting the first three and four amino acids encoded by exon 6. Thus, this study doubles the number of SEMD‐RPL13‐related cases and variants reported to date and describes unreported age‐related clinical and radiological features.
Picture books for young children of incarcerated parents: Through the lens of bibliotherapy
Authors: Spates Kamesha , Monobe Gumiko , James Tierra
Published: May 2023

Research suggests that bibliotherapy can help children cope with life's challenges through age‐appropriate reading and storytelling. Bibliotherapy has been employed to assist children in dealing with grief, divorce, adoption and other stressors. However, limited studies have investigated how this approach can support young children with incarcerated parents. Utilizing bibliotherapy as a framework, this study conducts a thematic analysis of children's picture books published between 1977 and 2014, featuring children of incarcerated parents as main characters to better understand the challenges they face. The study aims to explore the challenges depicted among child characters in picture books addressing parental incarceration for a young reading audience over almost 50 years. Our findings reveal that child characters grapple with various emotional, psychological and social challenges related to the sudden separation from their loved ones. We discuss the implications of each finding in greater detail.
Influence of bisphosphonate treatment on bone substitute performance in osteoporotic conditions
Authors: Camargo Winston Adam , Hoekstra Jan Willem , Jansen John A. , van den Beucken Jeroen J. J. P.
Published: May 2023

Objective

Considering the elevated number of osteoporotic patients in need of bone graft procedures, we here evaluated the effect of alendronate (ALN) treatment on the regeneration of bone defects in osteoporotic rats. Bone formation was histologically and histomorphometrically assessed in rat femoral condyle bone defects filled with bone graft (Bio‐Oss®) or left empty.

Methods

Male Wistar rats were induced osteoporotic through orchidectomy (ORX) and SHAM‐operated. The animals were divided into three groups: osteoporotic (ORX), osteoporotic treated with ALN (ORX + ALN) and healthy (SHAM). Six weeks after ORX or SHAM surgeries, bone defects were created bilaterally in femoral condyles; one defect was filled with Bio‐Oss® and the other one left empty. Bone regeneration within the defects was analyzed by histology and histomorphometry after 4 and 12 weeks.

Results

Histological samples showed new bone surrounding Bio‐Oss® particles from week 4 onward in all three groups. At week 12, the data further showed that ALN treatment of osteoporotic animals enhanced bone formation to a 10‐fold increase compared to non‐treated osteoporotic control. Bio‐Oss® filling of the defects promoted bone formation at both implantation periods compared to empty controls.

Conclusion

Our histological and histomorphometric results demonstrate that the enteral administration of alendronate under osteoporotic bone conditions leverages bone defect regeneration to a level comparable to that in healthy bone. Additionally, Bio‐Oss® is an effective bone substitute, increasing bone formation, and acting as an osteoconductive scaffold guiding bone growth in both healthy and osteoporotic bone conditions.

Significance

Based on the results of this study, enteral use of ALN mitigates adverse effects of an osteoporotic condition on bone defect regeneration.
Inhibiting leukocyte‐endothelial cell interactions by Chinese medicine Tongxinluo capsule alleviates no‐reflow after arterial recanalization in ischemic stroke
Authors: Liu Shen , Zhang Zhaoxu , He Yannan , Kong Lingbo , Jin Qiushuo , Qi Xiangjia , Qi Dahe , Gao Ying
Published: May 2023

Aims

Despite successful vascular recanalization in stroke, one‐fourth of patients have an unfavorable outcome due to no‐reflow. The pathogenesis of no‐reflow is fully unclear, and therapeutic strategies are lacking. Upon traditional Chinese medicine, Tongxinluo capsule (TXL) is a potential therapeutic agent for no‐reflow. Thus, this study is aimed to investigate the pathogenesis of no‐reflow in stroke, and whether TXL could alleviate no‐reflow as well as its potential mechanisms of action.

Methods

Mice were orally administered with TXL (3.0 g/kg/d) after transient middle cerebral artery occlusion. We examined the following parameters: neurological function, no‐reflow, leukocyte‐endothelial cell interactions, HE staining, leukocyte subtypes, adhesion molecules, and chemokines.

Results

Our results showed stroke caused neurological deficits, neuron death, and no‐reflow. Adherent and aggregated leukocytes obstructed microvessels as well as leukocyte infiltration in ischemic brain. Leukocyte subtypes changed after stroke mainly including neutrophils, lymphocytes, regulatory T cells, suppressor T cells, helper T type 1 (Th1) cells, Th2 cells, B cells, macrophages, natural killer cells, and dendritic cells. Stroke resulted in upregulated expression of adhesion molecules (P‐selectin, E‐selectin, and ICAM‐1) and chemokines (CC‐chemokine ligand (CCL)‐2, CCL‐3, CCL‐4, CCL‐5, and chemokine C‐X‐C ligand 1 (CXCL‐1)). Notably, TXL improved neurological deficits, protected neurons, alleviated no‐reflow and leukocyte‐endothelial cell interactions, regulated multiple leukocyte subtypes, and inhibited the expression of various inflammatory mediators.

Conclusion

Leukocyte‐endothelial cell interactions mediated by multiple inflammatory factors are an important cause of no‐reflow in stroke. Accordingly, TXL could alleviate no‐reflow via suppressing the interactions through modulating various leukocyte subtypes and inhibiting the expression of multiple inflammatory mediators.
Bilateral inferior venae cava combined with the persistent left superior vena cava and hemiazygos continuation of left inferior vena cava with drainage into right atrium: A case report
Authors: Jia Yongmei , Gao Junxia
Published: May 2023

The persistent left superior vena cava (PLSVC) is a common venous abnormality. However, malformation of the bilateral inferior venae cava (IVC) is extremely rare, with an incidence rate of .3%. IVC malformation is associated most frequently with heart defects and isomerism and often has a poor prognosis. We presented a case of vascular malformations in the fetus of bilateral caval veins with the interruption of the left‐sided venous return with hemiazygos continuation in presence of a right‐sided inferior caval vein. Also noted were the PLSVC and a dilated right heart with a widened pulmonary trunk. In this case, there were no heart defects or chromosomal abnormalities, and the newborn postpartum was in a good condition.