bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydrocinnamic acid and perillyl alcohol are effective against Escherichia coli biofilms when used alone and combined with antibiotics
Authors: Sousa Mariana , Afonso Ana Cristina , Saavedra Maria José , Simões Lúcia Chaves , Simões Manuel 
Published: October 2023

Abstract

Aims
The use of phytochemicals to improve the effectiveness of antibiotics is a promising strategy for the development of novel antimicrobials. In this study, the antibiofilm activity of perillyl alcohol and hydrocinnamic acid, both phytochemicals present in several plants, and two antibiotics from different classes (amoxicillin and chloramphenicol) was tested, alone and in combination, against Escherichia coli.

Methods and results
Each molecule was tested at the minimum inhibitory concentration (MIC), 5 × MIC, and 10 × MIC, and characterized concerning biomass removal, metabolic inactivation, and cellular culturability. The highest percentages of metabolic inactivation (88.5% for 10 × MIC) and biomass reduction (61.7% for 10 × MIC) were obtained with amoxicillin. Interestingly, for 5 × MIC and 10 × MIC, phytochemicals provided a total reduction of colony-forming units (CFUs). Dual and triple combinations of phytochemicals and antibiotics (at MIC and 5 × MIC) demonstrated high efficacy in metabolic inactivation, moderate efficacy in terms of biomass reduction, and total reduction of cellular culturability for 5 × MIC.

Conclusions
The results demonstrated the antibiofilm potential of phytochemicals, highlighting the advantage of phytochemical/antibiotic combinations for biofilm control.
The decentralization of public employment services and local governments’ responses to incentives
Authors: Nieminen Jeremias , Kanninen Ohto , Karhunen Hannu 
Published: October 2023

Abstract
We examine how the decentralization of public employment services (PES) affects the behavior and service provision of PES offices and the labor market outcomes of job seekers. We use difference-in-differences, utilizing a Finnish temporary reform during which PES were decentralized for specific groups of job seekers in treated municipalities and remained centralized for others. The reform presented the treated municipalities with the possibility of shifting costs to the central government. We find no evidence of better labor market outcomes and find evidence consistent with municipalities being able to shift 10% of their unemployment benefit costs to the central government.
Biomarkers of immunotherapy for non-small cell lung cancer
Authors: Shirasawa Masayuki , Yoshida Tatsuya , Ohe Yuichiro 
Published: October 2023

Abstract
Immunotherapy is revolutionizing the treatment of non-small cell lung cancer by targeting immune checkpoint proteins, including programmed death-1, programmed death ligand 1 and cytotoxic T-lymphocyte-associated antigen 4. Several immune checkpoint inhibitors, including programmed death ligand 1 inhibitors, programmed death-1 inhibitors and cytotoxic T-lymphocyte-associated antigen 4 inhibitors, were approved for the treatment of patients with advanced non-small cell lung cancer. Programmed death ligand 1 expression is currently the only predictive biomarker for immune checkpoint inhibitors to guide the treatment strategy in these patients. However, programmed death ligand 1 expression is not a perfect biomarker for predicting the efficacy of immunotherapy. Therefore, various biomarkers such as tumour mutation burden, tumour microenvironment, gut microbiome and T-cell receptor repertoire have been proposed to predict the efficacy of immunotherapy more accurately. Additionally, combining different biomarkers may provide a more accurate prediction of response to immunotherapy. This article reports the review of the latest evidence of the predictive marker of immunotherapy in patients with advanced non-small cell lung cancer.
G-CSF reshapes the cytosolic PCNA scaffold and modulates glycolysis in neutrophils
Authors: Aymonnier Karen , Bosetta Enzo , Leborgne Nathan G F , Ullmer Audrey , Le Gall Morgane , De Chiara Alessia , Salnot Virginie , Many Souganya , Scapini Patrizia , Wicks Ian , Chatfield Simon , Martin Katherine R , Witko-Sarsat Véronique 
Published: October 2023

Abstract
Cytosolic proliferating cell nuclear antigen (PCNA) is involved in neutrophil survival and function, in which it acts as a scaffold and associates with proteins involved in apoptosis, NADPH oxidase activation, cytoskeletal dynamics, and metabolism. While the PCNA interactome has been characterized in neutrophils under homeostatic conditions, less is known about neutrophil PCNA in pathophysiological contexts. Granulocyte colony-stimulating factor (G-CSF) is a cytokine produced in response to inflammatory stimuli that regulates many aspects of neutrophil biology. Here, we used isolated normal-density neutrophils from G-CSF–treated haemopoietic stem cell donors (GDs) as a model to understand the role of PCNA during inflammation. Proteomic analysis of the neutrophil cytosol revealed significant differences between GDs and healthy donors (HDs). PCNA was one of the most upregulated proteins in GDs, and the PCNA interactome was significantly different in GDs compared with HDs. Importantly, while PCNA associated with almost all enzymes involved in glycolysis in HDs, these associations were decreased in GDs. Functionally, neutrophils from GDs had a significant increase in glycolysis compared with HDs. Using p21 competitor peptides, we showed that PCNA negatively regulates neutrophil glycolysis in HDs but had no effect on GD neutrophils. These data demonstrate that G-CSF alters the PCNA scaffold, affecting interactions with key glycolytic enzymes, and thus regulates glycolysis, the main energy pathway utilized by neutrophils. By this selective control of glycolysis, PCNA can organize neutrophils functionality in parallel with other PCNA mechanisms of prolonged survival. PCNA may therefore be instrumental in the reprogramming that neutrophils undergo in inflammatory or tumoral settings.
Later Is aCis-HeteroPatriarchal Time Zone: Narratives of Resistance to LGBTQI+ Inclusion amongst Humanitarian Practitioners
Authors: Michelis Ilaria 
Published: October 2023

AbstractThe plight of forcibly displaced LGBTQI+ people has become increasingly visible in Western media and scholarship within the past 10 years. Yet, despite increasing commitments and an expanding number of dedicated reports and initiatives, LGBTQI+ individuals remain discriminated against, exposed to violence, and excluded from humanitarian assistance. This article investigates the disconnect between global rhetoric and the persistent exclusion of LGBTQI+ people from most humanitarian relief programmes by conducting a critical discourse analysis of narratives deployed by humanitarian protection actors regarding LGBTQI+ inclusion. Drawing from interviews with humanitarian workers and humanitarian guidance documents, it argues that several mutually reinforcing discourses are currently at play within the humanitarian system to endlessly delay the meaningful inclusion of forcibly displaced LGBTQI+ people. These narratives not only uphold the cis-heteronormative and racist structures upon which the humanitarian system is constructed but also contribute to further stigmatization and anti-LGBTQI+ violence in an increasingly polarized world.
The power spectrum of extended [C ii] haloes around high redshift galaxies
Authors: Zhang Meng , Ferrara Andrea , Yue Bin 
Published: October 2023

ABSTRACT
Atacama Large Millimeter/sub-millimeter Array (ALMA) observations have detected extended (≃10 kpc) [C$\scriptstyle \rm II$] haloes around high-redshift (z ≳ 5) star-forming galaxies. If such extended structures are common, they may have an impact on the line intensity mapping (LIM) signal. We compute the LIM power spectrum including both the central galaxy and the [C $\scriptstyle \rm II$] halo, and study the detectability of such signal in an ALMA LIM survey. We model the central galaxy and the [C $\scriptstyle \rm II$] halo brightness with a $\rm S\acute{e}rsic$ + exponential profile. The model has two free parameters: the effective radius ratio $f_{R_{\rm e}}$, and the central surface brightness ratio, fΣ, between the two components. [C $\scriptstyle \rm II$] haloes can significantly boost the LIM power spectrum signal. For example, for relatively compact [C $\scriptstyle \rm II$] haloes ($f_\Sigma =0.4$, $f_{R_{\rm e}}=2.0$), the signal is boosted by ≃20 times; for more extended and diffuse haloes ($f_\Sigma =0.1, f_{R_{\rm e}}=6.0$), the signal is boosted by ≃100 times. For the ALMA ASPECS survey (resolution θbeam = 1.13 arcsec, survey area $\Omega _{\rm survey}=2.9\, \rm arcmin^{2}$) the [C $\scriptstyle \rm II$] power spectrum is detectable only if the deL14d [C $\scriptstyle \rm II$]–SFR relation holds. However, with an optimized survey (θbeam = 0.232 arcsec, $\Omega _{\rm survey}=2.0\, \rm deg^{2}$), the power spectrum is detectable for all the [C $\scriptstyle \rm II$]–SFR relations considered in this paper. Such a survey can constrain $f_\Sigma$ ($f_{R_{\rm e}}$) with a relative uncertainty of $\sim 15~{{\ \rm per\ cent}}$ ($\sim 10~{{\ \rm per\ cent}}$). A successful LIM experiment will provide unique constraints on the nature, origin, and frequency of extended [C $\scriptstyle \rm II$] haloes, and the [C $\scriptstyle \rm II$]–SFR relation at early times.
ZNF432 stimulates PARylation and inhibits DNA resection to balance PARPi sensitivity and resistance
Authors: O’Sullivan Julia , Kothari Charu , Caron Marie-Christine , Gagné Jean-Philippe , Jin Zhigang , Nonfoux Louis , Beneyton Adèle , Coulombe Yan , Thomas Mélissa , Atalay Nurgul , Meng X Wei , Milano Larissa , Jean Dominique , Boisvert François-Michel , Kaufmann Scott H , Hendzel Michael J , Masson Jean-Yves , Poirier Guy G 
Published: October 2023

Abstract
Zinc finger (ZNF) motifs are some of the most frequently occurring domains in the human genome. It was only recently that ZNF proteins emerged as key regulators of genome integrity in mammalian cells. In this study, we report a new role for the Krüppel-type ZNF-containing protein ZNF432 as a novel poly(ADP-ribose) (PAR) reader that regulates the DNA damage response. We show that ZNF432 is recruited to DNA lesions via DNA- and PAR-dependent mechanisms. Remarkably, ZNF432 stimulates PARP-1 activity in vitro and in cellulo. Knockdown of ZNF432 inhibits phospho-DNA-PKcs and increases RAD51 foci formation following irradiation. Moreover, purified ZNF432 preferentially binds single-stranded DNA and impairs EXO1-mediated DNA resection. Consequently, the loss of ZNF432 in a cellular system leads to resistance to PARP inhibitors while its overexpression results in sensitivity. Taken together, our results support the emerging concept that ZNF-containing proteins can modulate PARylation, which can be embodied by the pivotal role of ZNF432 to finely balance the outcome of PARPi response by regulating homologous recombination.
PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer
Authors: Fracassi Cristina , Ugge' Martina , Abdelhalim Mohamed , Zapparoli Ettore , Simoni Matilde , Magliulo Daniela , Mazza Davide , Lazarevic Dejan , Morelli Marco J , Collas Philippe , Bernardi Rosa 
Published: October 2023

Abstract
The promyelocytic leukemia (PML) protein organizes nuclear aggregates known as PML nuclear bodies (PML-NBs), where many transcription factors localize to be regulated. In addition, associations of PML and PML-NBs with chromatin are described in various cell types, further implicating PML in transcriptional regulation. However, a complete understanding of the functional consequences of PML association to DNA in cellular contexts where it promotes relevant phenotypes is still lacking. We examined PML chromatin association in triple-negative breast cancer (TNBC) cell lines, where it exerts important oncogenic functions. We find that PML associates discontinuously with large heterochromatic PML-associated domains (PADs) that contain discrete gene-rich euchromatic sub-domains locally depleted of PML. PML promotes heterochromatic organization in PADs and expression of pro-metastatic genes embedded in these sub-domains. Importantly, this occurs outside PML-NBs, suggesting that nucleoplasmic PML exerts a relevant gene regulatory function. We also find that PML plays indirect regulatory roles in TNBC cells by promoting the expression of pro-metastatic genes outside PADs. Our findings suggest that PML is an important transcriptional regulator of pro-oncogenic metagenes in TNBC cells, via transcriptional regulation and epigenetic organization of heterochromatin domains that embed regions of local transcriptional activity.
BOLA3 and NFU1 link mitoribosome iron–sulfur cluster assembly to multiple mitochondrial dysfunctions syndrome
Authors: Zhong Hui , Janer Alexandre , Khalimonchuk Oleh , Antonicka Hana , Shoubridge Eric A , Barrientos Antoni 
Published: October 2023

Abstract
The human mitochondrial ribosome contains three [2Fe–2S] clusters whose assembly pathway, role, and implications for mitochondrial and metabolic diseases are unknown. Here, structure-function correlation studies show that the clusters play a structural role during mitoribosome assembly. To uncover the assembly pathway, we have examined the effect of silencing the expression of Fe–S cluster biosynthetic and delivery factors on mitoribosome stability. We find that the mitoribosome receives its [2Fe–2S] clusters from the GLRX5-BOLA3 node. Additionally, the assembly of the small subunit depends on the mitoribosome biogenesis factor METTL17, recently reported containing a [4Fe–4S] cluster, which we propose is inserted via the ISCA1-NFU1 node. Consistently, fibroblasts from subjects suffering from ‘multiple mitochondrial dysfunction’ syndrome due to mutations in BOLA3 or NFU1 display previously unrecognized attenuation of mitochondrial protein synthesis that contributes to their cellular and pathophysiological phenotypes. Finally, we report that, in addition to their structural role, one of the mitoribosomal [2Fe–2S] clusters and the [4Fe–4S] cluster in mitoribosome assembly factor METTL17 sense changes in the redox environment, thus providing a way to regulate organellar protein synthesis accordingly.
XYLEM CYSTEINE PEPTIDASE 1 and its inhibitor CYSTATIN 6 regulate pattern-triggered immunity by modulating the stability of the NADPH oxidase RESPIRATORY BURST OXIDASE HOMOLOG D
Authors: Liu Yang , Gong Tingting , Kong Xiangjiu , Sun Jiaqi , Liu Lijing 
Published: October 2023

Abstract
Plants produce a burst of reactive oxygen species (ROS) after pathogen infection to successfully activate immune responses. During pattern-triggered immunity (PTI), ROS are primarily generated by the NADPH oxidase RESPIRATORY BURST OXIDASE HOMOLOG D (RBOHD). RBOHD is degraded in the resting state to avoid inappropriate ROS production; however, the enzyme mediating RBOHD degradation and how to prevent RBOHD degradation after pathogen infection is unclear. In this study, we identified an Arabidopsis (Arabidopsis thaliana) vacuole-localized papain-like cysteine protease, XYLEM CYSTEINE PEPTIDASE 1 (XCP1), and its inhibitor CYSTATIN 6 (CYS6). Pathogen-associated molecular pattern-induced ROS burst and resistance were enhanced in the xcp1 mutant but were compromised in the cys6 mutant, indicating that XCP1 and CYS6 oppositely regulate PTI responses. Genetic and biochemical analyses revealed that CYS6 interacts with XCP1 and depends on XCP1 to enhance PTI. Further experiments showed that XCP1 interacts with RBOHD and accelerates RBOHD degradation in a vacuole-mediated manner. CYS6 inhibited the protease activity of XCP1 toward RBOHD, which is critical for RBOHD accumulation upon pathogen infection. As CYS6, XCP1, and RBOHD are conserved in all plant species tested, our findings suggest the existence of a conserved strategy to precisely regulate ROS production under different conditions by modulating the stability of RBOHD.
The micro-dynamics of scientific choice: research project motivations among public affairs academics
Authors: Nelson John P 
Published: October 2023

Abstract
Academic researchers’ choices about research projects to pursue are an important mechanism in societal allocation of research effort. It is unclear whether researchers’ criteria for project choice align with those articulated by policy scholars and philosophers. Many potential criteria for project choice are commonly discussed in scholarly and popular literature, but they have been little studied on the individual level. I review and catalog such potential criteria and then empirically explore researcher motivations for project choice through factor analysis of survey data from 409 authors of research articles in major public administration and public policy journals. I find empirical support for personal gain, societal importance, and intellectual interest as research motivations. These motivations do not neatly align with proposed ideal criteria for scientific choice. Thus, such criteria must be translated to speak to researchers’ personal interests to achieve expression in individual scientific choice.
Bringing technology to market: National Heart, Lung, and Blood Institute SBIR Phase IIB projects
Authors: Nienow Sara , Leonchuk Olena , O’Connor Alan C , Link Albert N 
Published: October 2023

Abstract
The National Heart, Lung, and Blood Institute (NHLBI) is the fourth largest institute in the US National Institutes of Health (NIH). Surprisingly, there is a conspicuous void of policy studies related to the research activities of NHLBI in comparison to NIH or the National Cancer Institute. This paper investigates the likelihood that a business funded through NHLBI’s Small Business Innovation Research (SBIR) program will commercialize from its Phase IIB translational support. Commercialization is one performance metric that quantifies a policy dimension of the success of the funded SBIR project. Based on an empirical analysis of sixty-one Phase IIB projects, we find that the most significant covariate with the likelihood of commercialization is the growth in human capital within the business since the Phase IIB award.
Targeting phospholipid remodeling pathway improves insulin resistance in diabetic mouse models
Authors: Tian Ye , Lu Wei , Shi Ruicheng , McGuffee Reagan , Lee Richard , Ford David A. , Wang Bo 
Published: October 2023

AbstractPrevious studies have revealed that membrane phospholipid composition controlled by lysophosphatidylcholine acyltransferase 3 (LPCAT3) is involved in the development of insulin resistance in type 2 diabetes. In this study, we aimed to investigate the therapeutic potential of targeting Lpcat3 in the treatment of insulin resistance in diabetic mouse models. Lpcat3 expression was suppressed in the whole body by antisense oligonucleotides (ASO) injection or in the liver by adeno‐associated virus (AAV)‐encoded Cre in high‐fat diet (HFD)‐induced and genetic ob/ob type 2 diabetic mouse models. Glucose tolerance test (GTT), insulin tolerance test (ITT), fasting blood glucose, and insulin levels were used to assess insulin sensitivity. Lipid levels in the liver and serum were measured. The expression of genes involved in de novo lipogenesis was analyzed by real‐time RT‐PCR. Metabolic rates were measured by indirect calorimetry using the Comprehensive Lab Animal Monitoring System (CLAMS). Our data demonstrate that acute knockout of hepatic Lpcat3 by AAV‐Cre improves both hyperglycemia and hypertriglyceridemia in HFD‐fed mice. Similarly, whole‐body ablation of Lpcat3 by ASO administration improves obesity and insulin resistance in both HFD‐fed and ob/ob mice. These findings demonstrate that targeting LPCAT3 could be a novel therapy for insulin resistance.
Identification of the novel role of sterol regulatory element binding proteins (SREBPs) in mechanotransduction and intraocular pressure regulation
Authors: Wang Ting , Soundararajan Avinash , Rabinowitz Jeffrey , Jaiswal Anant , Osborne Timothy , Pattabiraman Padmanabhan Paranji 
Published: October 2023

AbstractTrabecular meshwork (TM) cells are contractile and mechanosensitive, and they aid in maintaining intraocular pressure (IOP) homeostasis. Lipids are attributed to modulating TM contractility, with poor mechanistic understanding. In this study using human TM cells, we identify the mechanosensing role of the transcription factors sterol regulatory element binding proteins (SREBPs) involved in lipogenesis. By constitutively activating SREBPs and pharmacologically inactivating SREBPs, we have mechanistically deciphered the attributes of SREBPs in regulating the contractile properties of TM. The pharmacological inhibition of SREBPs by fatostatin and molecular inactivation of SREBPs ex vivo and in vivo, respectively, results in significant IOP lowering. As a proof of concept, fatostatin significantly decreased the SREBPs responsive genes and enzymes involved in lipogenic pathways as well as the levels of the phospholipid, cholesterol, and triglyceride. Further, we show that fatostatin mitigated actin polymerization machinery and stabilization, and decreased ECM synthesis and secretion. We thus postulate that lowering lipogenesis in the TM outflow pathway can hold the key to lowering IOP by modifying the TM biomechanics.
Impaired electrical activity of the brain explains the onset of dementia in aging people
Authors: Marchesi Vincent T. 
Published: October 2023

AbstractAging brains that share many cognitive deficits with the early stages of Alzheimer's‐type dementias are not caused by toxic protein deposits but by somatic mutations that impair synaptic signaling. These mutant proteins that contribute to neuronal action potentials could be biomarkers of functional defects that offer new approaches to diagnosis and treatment.
Seek to Understand: Cultural Humility in Undergraduate Nursing Students and Faculty
Authors: Compton-McBride Sheri , Andrews Angela , Reed Amy 
Published: October 2023

Abstract
There exists a critical knowledge deficit in undergraduate nursing students when caring for multiculturally diverse clients. A mixed-methods study was conducted with a sample of undergraduate nursing faculty and students. Foronda’s Cultural Humility Scale was used, along with a survey about cultural experiences in undergraduate nursing education. The study found that to provide opportunities for psychologically safe conversations and simulated cultural encounters, concepts related to cultural humility should be considered when redesigning nursing curricula.