bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic centromere identity is precisely maintained through DNA replication but is uniquely specified among human cells
Authors: Mahlke Megan A. , Lumerman Lior , Ly Peter , Nechemia-Arbely Yael 
Published: September 2022

AbstractCentromere identity is defined and maintained epigenetically by the presence of the histone variant CENP-A. How centromeric CENP-A position is specified and precisely maintained through DNA replication is not fully understood. The recently released Telomere-to-Telomere (T2T-CHM13) genome assembly containing the first complete human centromere sequences provides a new resource for examining CENP-A position. Mapping CENP-A position in clones of the same cell line to T2T-CHM13 identified highly similar CENP-A position following multiple cell divisions. In contrast, centromeric CENP-A epialleles were evident at several centromeres of different human cell lines, demonstrating the location of CENP-A enrichment and site of kinetochore recruitment varies among human cells. Across the cell cycle, CENP-A molecules deposited in G1 phase are maintained at their precise position through DNA replication. Thus, despite CENP-A dilution during DNA replication, CENP-A is precisely reloaded onto the same sequences within the daughter centromeres, maintaining unique centromere identity among human cells.
Actin-driven protrusions generate rapid long-range membrane tension propagation in cells
Authors: De Belly Henry , Yan Shannon , da Rocha Hudson Borja , Ichbiah Sacha , Town Jason P. , Turlier Hervé , Bustamante Carlos , Weiner Orion D. 
Published: September 2022

Membrane tension is thought to be a long-range integrator of cell physiology. This role necessitates effective tension transmission across the cell. However, the field remains strongly divided as to whether cell membranes support or resist tension propagation, in part due to a lack of adequate tools for locally manipulating membrane tension. We overcome these limitations by leveraging optogenetics to generate localized actinbased protrusions while concurrently monitoring the propagation of membrane tension using dual-trap optical tweezers. Surprisingly, actin-driven protrusions elicit rapid global membrane tension propagation with little to no attenuation, while forces applied to the cell membrane only do not. We present a simple unifying mechanical model in which mechanical forces that act on both the membrane and actin cortex drive rapid, robust membrane tension propagation.SummaryMechanical perturbations acting on both actin cortex and plasma membrane drive global membrane tension increase within seconds
Oncogenic signals prime cancer cells for toxic cell growth during a G1 cell cycle arrest
Authors: Foy Reece , Crozier Lisa , Pareri Aanchal U , Park Ben Ho , Saurin Adrian T 
Published: September 2022

SUMMARYA long-term goal in cancer research has been to inhibit the cell cycle in tumour cells without causing toxicity in proliferative healthy tissues. The best evidence that this is achievable is provided by CDK4/6 inhibitors, which arrest the cell cycle in G1, are well-tolerated in patients, and are effective in treating ER+/HER2-breast cancer. CDK4/6 inhibitors are effective because they arrest tumour cells more efficiently than some healthy cell types and, in addition, they affect the tumour microenvironment to enhance anti-tumour immunity. We demonstrate here another reason to explain their efficacy. Tumour cells are specifically vulnerable to CDK4/6 inhibition because during the G1 arrest, oncogenic signals drive toxic cell overgrowth. This overgrowth causes permanent cell cycle withdrawal by either preventing exit from G1 or by inducing replication stress and genotoxic damage during the subsequent S-phase and mitosis. Inhibiting or reverting oncogenic signals that converge onto mTOR can rescue this excessive growth, DNA damage and cell cycle exit in cancer cells. Conversely, inducing oncogenic signals in non-transformed cells can drive these toxic phenotypes and sensitize cells to CDK4/6 inhibition. Together, this demonstrates how oncogenic signals that have evolved to stimulate constitutive tumour growth and proliferation can be driven to cause toxic cell growth and irreversible cell cycle exit when proliferation is halted in G1.
The genetics of cortical organisation and development: a study of 2,347 neuroimaging phenotypes
Authors: Warrier Varun , Stauffer Eva-Maria , Huang Qin Qin , Wigdor Emilie M. , Slob Eric A.W. , Seidlitz Jakob , Ronan Lisa , Valk Sofie , Mallard Travis T. , Grotzinger Andrew D. , Romero-Garcia Rafael , Baron-Cohen Simon , Geschwind Daniel H. , Lancaster Madeline , Murray Graham K. , Gandal Michael J. , Alexander-Bloch Aaron , Won Hyejung , Martin Hilary C. , Bullmore Edward T. , Bethlehem Richard A.I. 
Published: September 2022

AbstractOur understanding of the genetic architecture of the human cerebral cortex is limited both in terms of the diversity of brain structural phenotypes and the anatomical granularity of their associations with genetic variants. Here, we conducted genome-wide association meta-analysis of 13 structural and diffusion magnetic resonance imaging derived cortical phenotypes, measured globally and at 180 bilaterally averaged regions in 36,843 individuals from the UK Biobank and the ABCD cohorts. These phenotypes include cortical thickness, surface area, grey matter volume, and measures of folding, neurite density, and water diffusion. We identified 4,349 experiment-wide significant loci associated with global and regional phenotypes. Multiple lines of analyses identified four genetic latent structures and causal relationships between surface area and some measures of cortical folding. These latent structures partly relate to different underlying gene expression trajectories during development and are enriched for different cell types. We also identified differential enrichment for neurodevelopmental and constrained genes and demonstrate that common genetic variants associated with surface area and volume specifically are associated with cephalic disorders. Finally, we identified complex inter-phenotype and inter-regional genetic relationships among the 13 phenotypes which reflect developmental differences among them. These analyses help refine the role of common genetic variants in human cortical development and organisation.One sentence summaryGWAS of 2,347 neuroimaging phenotypes shed light on the global and regional genetic organisation of the cortex, underlying cellular and developmental processes, and links to neurodevelopmental and cephalic disorders.
To what extent have street-level bureaucrats used their discretionary powers during the COVID-19 pandemic in Indonesia?
Authors: Hadna Agus Heruanto , Listyaningsih Umi , Ihwanudin Idris 
Published: September 2022

PurposeThe objective of this research is to analyze the extent to which street-level bureaucrats (SLBs) have exercised discretion (low, medium and high) and the contributing factors involved (i.e. the influence of personal, work environment and demographic factors on the exercise of discretion).Design/methodology/approachThe mixed-methods research uses the embedded design approach. Data were collected during the COVID-19 pandemic through a survey of 2,867 Official Certifier of Title Deeds (Pejabat Pembuat Akta Tanah/PPAT) as SLBs spread across fifty regencies/cities in ten provinces in Indonesia.FindingsThis field study found a significant and positive correlation between SLBs' economic motive and the client's knowledge of land issues with the exercise of discretion. In addition, the study found a significant correlation between the age and gender of SLBs and their practice of discretion.Practical implicationsThis study provides insights into that new policies should not further complicate the system but reduce face-to-face interactions between SLBs and their clients by allowing digital technology.Originality/valueThe novelty of this research is the paradox of SLB service during the COVID-19 pandemic differed from the paradoxes identified in earlier studies. SLBs commonly cope with service paradox by limiting their services or focusing solely on the most profitable clientele. However, this study shows that some SLBs actively reach out to clients using a “friendly” service model.
Human herpesvirus 6A and 6B and polyomavirus JC and BK infections in renal cell carcinoma and their relationship with p53, p16INK4a, Ki‐67, and nuclear factor‐kappa B expression
Authors: Namdari Sepide , Chong Pei Pei , Behzad‐Behbahani Abbas , Geramizadeh Bita , Nazhvani Ali Dehghani , Sekawi Zamberi , Farhadi Ali 
Published: September 2022

AbstractThere are a limited number of studies regarding the involvement of viruses in the development and pathogenesis of renal cell carcinoma (RCC). In this study, we aimed to discover whether human herpesvirus 6A (HHV‐6A) and 6B (HHV‐6B) and human polyomavirus JC (JCV) and BK (BKV) are associated with RCC and the expression of p53, p16INK4a, Ki‐67, and nuclear factor‐κB (NF‐κB) in patients with RCC. A total of 122 histologically confirmed RCC tissue specimens and 96 specimens of their corresponding peritumoral tissues were included in this prospective study. Nested PCR was performed to amplify viral DNA sequences. Restriction endonuclease analysis was carried out to discriminate between HHV‐6A and HHV‐6B. p53, p16INK4a, Ki‐67, and NF‐κB immunostaining data of the studied tissue specimens were available from our previous study. Statistical analysis was performed to demonstrate the potential associations. HHV‐6B and JCV were detected in 10.7% and 13.9% of patients with RCC, respectively. We did not detect HHV‐6A and BKV in any of RCC tissue specimens. Moreover, no association was found between either of these viruses and RCC. Our study revealed a significant association between HHV‐6B and p53 overexpression. No other associations were found between cellular biomarkers p53, p16INK4a, Ki‐67, and NF‐κB and the studied viruses. The data of this study, though very limited, disprove the involvement of HHV‐6A, HHV‐6B, BKV, and JCV in the initiation or progression of RCC.
Conserved age‐related increases in hippocampal PDE11A4 cause unexpected proteinopathies and cognitive decline of social associative memories
Authors: Pilarzyk Katy , Porcher Latarsha , Capell William R. , Burbano Steven D. , Davis Jeff , Fisher Janet L. , Gorny Nicole , Petrolle Siena , Kelly Michy P. 
Published: September 2022

AbstractIn humans, associative memories are more susceptible to age‐related cognitive decline (ARCD) than are recognition memories. Reduced cAMP/cGMP signaling in the hippocampus may contribute to ARCD. Here, we found that both aging and traumatic brain injury‐associated dementia increased the expression of the cAMP/cGMP‐degrading enzyme phosphodiesterase 11A (PDE11A) in the human hippocampus. Further, age‐related increases in hippocampal PDE11A4 mRNA and protein were conserved in mice, as was the increased vulnerability of associative versus recognition memories to ARCD. Interestingly, mouse PDE11A4 protein in the aged ventral hippocampus (VHIPP) ectopically accumulated in the membrane fraction and filamentous structures we term “ghost axons.” These age‐related increases in expression were driven by reduced exoribonuclease‐mediated degradation of PDE11A mRNA and increased PDE11A4‐pS117/pS124, the latter of which also drove the punctate accumulation of PDE11A4. In contrast, PDE11A4‐pS162 caused dispersal. Importantly, preventing age‐related increases in PDE11 expression via genetic deletion protected mice from ARCD of short‐term and remote long‐term associative memory (aLTM) in the social transmission of food preference assay, albeit at the expense of recent aLTM. Further, mimicking age‐related overexpression of PDE11A4 in CA1 of old KO mice caused aging‐like impairments in CREB function and remote social—but not non‐social—LTMs. RNA sequencing and phosphoproteomic analyses of VHIPP identified cGMP‐PKG—as opposed to cAMP‐PKA—as well as circadian entrainment, glutamatergic/cholinergic synapses, calcium signaling, oxytocin, and retrograde endocannabinoid signaling as mechanisms by which PDE11A deletion protects against ARCD. Together, these data suggest that PDE11A4 proteinopathies acutely impair signaling in the aged brain and contribute to ARCD of social memories.
In vitro bactericidal efficacy of a new triple antibiotic paste formulation against Enterococcus faecalis biofilm
Authors: Smittiset Benjaporn , Banomyong Danuchit , Ruangsawasdi Nisarat , Kaewprag Jittranan 
Published: September 2022

AbstractThe aim of this study was to evaluate the bactericidal efficacy on Enterococcus faecalis biofilm of a novel, low‐concentration triple‐antibiotic paste (TAP‐L2) in propylene glycol/carboxymethylcellulose vehicle (VEH‐2), a ready‐to‐use prototype, compared with two currently used products; a low‐concentration (TAP‐L1) and a high‐concentration paste (TAP‐H1) mixed in macrogol/propylene glycol vehicle (VEH‐1). Sixty‐two root canals were infected with E. faecalis biofilm, medicated with (a) TAP‐L1, (b) TAP‐L2, (c) TAP‐H1, (d) VEH‐1 or (e) VEH‐2 (n = 10) and incubated for 21 days. Live/dead assays were performed using confocal laser scanning microscopy (CLSM), and dead bacteria (%) were calculated. The TAP‐H1 group demonstrated the highest dead bacteria (67.54 ± 2.38%), which was significantly higher than the TAP‐L2 and TAP‐L1 groups (56.85 ± 7.11% and 54.23 ± 10.19%) (p < 0.05). The TAP groups demonstrated significantly higher dead bacteria than the VEH‐1 and VEH‐2 groups (47.51 ± 6.41% and 45.14 ± 8.28%) (p < 0.05). The ready‐to‐use TAP‐L2 had antibacterial activity comparable to TAP‐L1, both of which were lower than TAP‐H1.
Real‐world evidence for the long‐term effect of allergen immunotherapy: Current status on database‐derived European studies
Authors: Vogelberg Christian , Klimek Ludger , Brüggenjürgen Bernd , Jutel Marek 
Published: September 2022

AbstractRandomized controlled trials (RCTs) are the gold‐standard for benefit–risk assessments during drug approval processes. Real‐word data (RWD) and the resulting real‐world evidence (RWE) are becoming increasingly important for assessing the effectiveness of drug products after marketing authorization showing how RCT results are transferred into real life care. The effectiveness of allergen immunotherapy (AIT) has been assessed in several RWE studies based on large prescription databases. We performed a literature search for retrospective cohort assessments of prescription databases in Europe to provide an overview on the methodology, long‐term effectiveness outcomes, and adherence to AIT. Thirteen respective publications were selected. AIT was more effective in reducing the progression of allergic rhinitis (AR) compared to a non‐AIT control group receiving only symptomatic treatment for AR for up to 6 years. The development and progression of asthma were hampered for most endpoints in patients treated with most preparations compared to the non‐AIT group, receiving only anti‐asthmatic medication. The results for “time to onset” of asthma were inconsistent. Adherence to AIT decreased during the recommended 3‐year treatment period, however, in most studies higher adherence to subcutaneous than to sublingual AIT was shown. The analysis of long‐term effectiveness outcomes of the RWE studies based on prescription databases confirms the long‐term efficacy of AIT demonstrated in RCTs. Progression of rhinitis and asthma symptoms as well as delayed onset of asthma triggered by different allergens, real life adherence to the treatment shows differences in particular application routes.
Caring Housing Futures: A Radical Care Framework for Understanding Rent Control Politics in Seattle, USA
Authors: Thompson Samantha 
Published: September 2022

AbstractHegemonic responses to housing crises overwhelmingly rely on liberal economic logics, which preclude understandings of housing inequalities as produced by intersecting structures of racial capitalism and settler colonialism. This creates housing futures that replicate housing injustice, through the reproduction of housing crises that uphold racial capitalism, the settler state, and white property ownership. To address this gap, I develop a radical care framework for analysing responses to housing crises as an approach that emphasises relationality, challenges the commodification of housing, and renders different housing futures possible. Radical care is a collective response to immediate crises and precarious futures. I apply this framework to rent control debates in Seattle, USA, which highlight the complex intersections between care and housing politics in responses to housing crises. I argue that analysing housing politics through a radical care framework helps us to account for more expansive sociopolitical imaginaries and actions that point to housing futures beyond the limits of what is deemed possible in a colonial, racial capitalist housing system.
Molecular physiology of Arc/Arg3.1: The oligomeric state hypothesis of synaptic plasticity
Authors: Eriksen Maria Steene , Bramham Clive R. 
Published: September 2022

AbstractThe immediate early gene, Arc, is a pivotal regulator of synaptic plasticity, memory, and cognitive flexibility. But what is Arc protein? How does it work? Inside the neuron, Arc is a protein interaction hub and dynamic regulator of intra‐cellular signaling in synaptic plasticity. In remarkable contrast, Arc can also self‐assemble into retrovirus‐like capsids that are released in extracellular vesicles and capable of intercellular transfer of RNA. Elucidation of the molecular basis of Arc hub and capsid functions, and the relationship between them, is vital for progress. Here, we discuss recent findings on Arc structure–function and regulation of oligomerization that are giving insight into the molecular physiology of Arc. The unique features of mammalian Arc are emphasized, while drawing comparisons with Drosophila Arc and retroviral Gag. The Arc N‐terminal domain, found only in mammals, is proposed to play a key role in regulating Arc hub signaling, oligomerization, and formation of capsids. Bringing together several lines of evidence, we hypothesize that Arc function in synaptic plasticity—long‐term potentiation (LTP) and long‐term depression (LTD)—are dictated by different oligomeric forms of Arc. Specifically, monomer/dimer function in LTP, tetramer function in basic LTD, and 32‐unit oligomer function in enhanced LTD. The role of mammalian Arc capsids is unclear but likely depends on the cross‐section of captured neuronal activity‐induced RNAs. As the functional states of Arc are revealed, it may be possible to selectively manipulate specific forms of Arc‐dependent plasticity and intercellular communication involved in brain function and dysfunction.
“They really care about you, they really build relationships”: Care and justice in a community organization
Authors: Dutt Anjali , Toolis Erin , Shi Christine , Moore Claire 
Published: September 2022

AbstractContemporary United States society is marked by exacerbated economic inequity and deep sociopolitical polarization, which increases a sense of precarity among marginalized communities. There is growing need to develop and foster practices that promote care and justice for marginalized communities. Organizational settings designed with the intent of supporting marginalized communities may possess unique knowledge related to actualizing care and promoting justice. Through analysis of ethnographic field notes and qualitative interviews conducted with 22 participants at the organization, this study examines organizational policies and practices of everyday decision‐making at a drop‐in center for women and gender non‐conforming people in Washington State, USA. Findings document how policies and practices at the center promote care and justice for diverse marginalized groups. Implications for promoting equitable values in social settings more broadly are discussed.
A closer look at the domain‐specific associations of openness with language achievement: Evidence on the role of intrinsic value from two large‐scale longitudinal studies
Authors: Meyer Jennifer , Schmidt Fabian T. C. , Fleckenstein Johanna , Köller Olaf 
Published: September 2022

AbstractBackgroundMany empirical investigations focus on how personality traits and academic motivation are related to academic achievement. Regarding the personality traits described in the five‐factor model, prior research has shown associations between openness to experience and language achievement in particular. Following the principle of trait activation, associations with intrinsic value can explain these domain‐specific relationships of openness with achievement.AimsThis study investigated whether intrinsic value mediates the associations of openness to experience with language achievement to understand these associations more closely. Based on the principle of trait activation, we combined openness to experience with intrinsic value as a motivational construct more proximal to behaviour.SamplesWe capitalized on two large‐scale longitudinal data sets (N = 1994; M = 16.8 years; 51% female; and N = 2722; M = 17.34 years; 58% female) of German‐speaking students in upper secondary education with two points of measurement, respectively.MethodsWe assessed achievement using report card grades and standardized test scores, capturing three language subskills: reading and listening, measured by standardized tests, and writing competencies, measured by essay assignments. We conducted mediation analysis using bootstrapped confidence intervals and robust standard errors to account for dependencies in the data due to students clustered within classrooms.Results and ConclusionsOverall, our results show that intrinsic value mediated the relationship between openness and achievement in English as a foreign language. The results remained stable when controlling for prior achievement, predicting achievement gains. Our investigation provides empirical insights into the manifestations of personality in academic contexts. We discuss the limitations of our approach, with a focus on the use of a mediation analysis in this research design.