bluuebunny/crossref_metadata_2025_split huggingface dataset:
Updated Phylogeny and Protein Structure Predictions Revise the Hypothesis on the Origin of MADS-box Transcription Factors in Land Plants
Authors: Qiu Yichun , Li Zhen , Walther Dirk , Köhler Claudia 
Published: August 2023

Abstract
MADS-box transcription factors (TFs), among the first TFs extensively studied, exhibit a wide distribution across eukaryotes and play diverse functional roles. Varying by domain architecture, MADS-box TFs in land plants are categorized into Type I (M-type) and Type II (MIKC-type). Type I and II genes have been considered orthologous to the SRF and MEF2 genes in animals, respectively, presumably originating from a duplication before the divergence of eukaryotes. Here, we exploited the increasing availability of eukaryotic MADS-box sequences and reassessed their evolution. While supporting the ancient duplication giving rise to SRF- and MEF2-types, we found that Type I and II genes originated from the MEF2-type genes through another duplication in the most recent common ancestor (MRCA) of land plants. Protein structures predicted by AlphaFold2 and OmegaFold support our phylogenetic analyses, with plant Type I and II TFs resembling the MEF2-type structure, rather than SRFs. We hypothesize that the ancestral SRF-type TFs were lost in the MRCA of Archaeplastida (the kingdom Plantae sensu lato). The retained MEF2-type TFs acquired a Keratin-like domain and became MIKC-type before the divergence of Streptophyta. Subsequently in the MRCA of land plants, M-type TFs evolved from a duplicated MIKC-type precursor through loss of the Keratin-like domain, leading to the Type I clade. Both Type I and II TFs expanded and functionally differentiated in concert with the increasing complexity of land plant body architecture. The recruitment of these originally stress-responsive TFs into developmental programs, including those underlying reproduction, may have facilitated the adaptation to the terrestrial environment.
Precise genome editing of the Kozak sequence enables bidirectional and quantitative modulation of protein translation to anticipated levels without affecting transcription
Authors: Xie Jingke , Zhuang Zhenpeng , Gou Shixue , Zhang Quanjun , Wang Xia , Lan Ting , Lian Meng , Li Nan , Liang Yanhui , Ouyang Zhen , Ye Yinghua , Wu Han , Lai Liangxue , Wang Kepin 
Published: August 2023

Abstract
None of the existing approaches for regulating gene expression can bidirectionally and quantitatively fine-tune gene expression to desired levels. Here, on the basis of precise manipulations of the Kozak sequence, which has a remarkable influence on translation initiation, we proposed and validated a novel strategy to directly modify the upstream nucleotides of the translation initiation codon of a given gene to flexibly alter the gene translation level by using base editors and prime editors. When the three nucleotides upstream of the translation initiation codon (named KZ3, part of the Kozak sequence), which exhibits the most significant base preference of the Kozak sequence, were selected as the editing region to alter the translation levels of proteins, we confirmed that each of the 64 KZ3 variants had a different translation efficiency, but all had similar transcription levels. Using the ranked KZ3 variants with different translation efficiencies as predictors, base editor- and prime editor-mediated mutations of KZ3 in the local genome could bidirectionally and quantitatively fine-tune gene translation to the anticipated levels without affecting transcription in vitro and in vivo. Notably, this strategy can be extended to the whole Kozak sequence and applied to all protein-coding genes in all eukaryotes.
The Swi-Snf chromatin remodeling complex mediates gene repression through metabolic control
Authors: Church Michael C , Price Andrew , Li Hua , Workman Jerry L 
Published: August 2023

Abstract
In eukaryotes, ATP-dependent chromatin remodelers regulate gene expression in response to nutritional and metabolic stimuli. However, altered transcription of metabolic genes may have significant indirect consequences which are currently poorly understood. In this study, we use genetic and molecular approaches to uncover a role for the remodeler Swi-Snf as a critical regulator of metabolism. We find that snfΔ mutants display a cysteine-deficient phenotype, despite growth in nutrient-rich media. This correlates with widespread perturbations in sulfur metabolic gene transcription, including global redistribution of the sulfur-sensing transcription factor Met4. Our findings show how a chromatin remodeler can have a significant impact on a whole metabolic pathway by directly regulating an important gene subset and demonstrate an emerging role for chromatin remodeling complexes as decisive factors in metabolic control.
A genetic screen identifies BEND3 as a regulator of bivalent gene expression and global DNA methylation
Authors: Yakhou Lounis , Azogui Anaelle , Gupta Nikhil , Richard Albert Julien , Miura Fumihito , Ferry Laure , Yamaguchi Kosuke , Battault Sarah , Therizols Pierre , Bonhomme Frédéric , Bethuel Elouan , Sarkar Arpita , Greenberg Maxim V C , Arimondo Paola B , Cristofari Gael , Kirsh Olivier , Ito Takashi , Defossez Pierre-Antoine 
Published: August 2023

Abstract
Epigenetic mechanisms are essential to establish and safeguard cellular identities in mammals. They dynamically regulate the expression of genes, transposable elements and higher-order chromatin structures. Consequently, these chromatin marks are indispensable for mammalian development and alterations often lead to disease, such as cancer. Bivalent promoters are especially important during differentiation and development. Here we used a genetic screen to identify new regulators of a bivalent repressed gene. We identify BEND3 as a regulator of hundreds of bivalent promoters, some of which it represses, and some of which it activates. We show that BEND3 is recruited to a CpG-containg consensus site that is present in multiple copies in many bivalent promoters. Besides having direct effect on the promoters it binds, the loss of BEND3 leads to genome-wide gains of DNA methylation, which are especially marked at regions normally protected by the TET enzymes. DNA hydroxymethylation is reduced in Bend3 mutant cells, possibly as consequence of altered gene expression leading to diminished alpha-ketoglutarate production, thus lowering TET activity. Our results clarify the direct and indirect roles of an important chromatin regulator, BEND3, and, more broadly, they shed light on the regulation of bivalent promoters.
Arabidopsis membrane protein AMAR1 interaction with type III effector XopAM triggers a hypersensitive response
Authors: Xie Qingbiao , Wei Bingzheng , Zhan Zhaohong , He Qiguang , Wu Kejian , Chen Yu , Liu Shiyao , He Chaozu , Niu Xiaolei , Li Chunxia , Tang Chaorong , Tao Jun 
Published: August 2023

Abstract
The efficient infection of plants by the bacteria Xanthomonas campestris pv. campestris (Xcc) depends on its type III effectors (T3Es). Although the functions of AvrE family T3Es have been reported in some bacteria, the member XopAM in Xcc has not been studied. As XopAM has low sequence similarity to reported AvrE-T3Es and different reports have shown that these T3Es have different targets in hosts, we investigated the functions of XopAM in the Xcc–plant interaction. Deletion of xopAM from Xcc reduced its virulence in cruciferous crops but increased virulence in Arabidopsis (Arabidopsis thaliana) Col-0, indicating that XopAM may perform opposite functions depending on the host species. We further found that XopAM is a lipase that may target the cytomembrane and that this activity might be enhanced by its membrane-targeted protein XOPAM-ACTIVATED RESISTANCE 1 (AMAR1) in Arabidopsis Col-0. The binding of XopAM to AMAR1 induced an intense hypersensitive response that restricted Xcc proliferation. Our results showed that the roles of XopAM in Xcc infection are not the same as those of other AvrE-T3Es, indicating that the functions of this type of T3E have differentiated during long-term bacterium‒host interactions.
Ethical perspectives and police science: Using Social Contract Theory as an analytical framework for evaluating police legitimacy
Authors: Jonathan-Zamir Tal , Perry Gali , Willis James J 
Published: August 2023

Abstract
It has recently been argued that ethical/moral considerations could be better integrated into the science of policing. The present study picks up the gauntlet and examines if a central normative theory of government authority—Social Contract Theory—can contribute to our understanding of police legitimacy. Building on five constraints on police authority derived from Social Contract Theory, the present study examines the relationship between citizen views of police compliance with the social contract while enforcing COVID-19 regulations, and of police legitimacy. A community survey carried out in Israel reveals that public evaluations of the appropriate balance between liberty, safety, and police authority, have a significant, independent correlation with legitimacy, surpassed only by views of procedural justice. These findings have implications for the theory, practice, and future study of police legitimacy, but more generally demonstrate the utility of theoretical–philosophical theories and concepts concerned with ethics for contemporary research questions in policing.
Dealing with the challenges of legitimacy, values, and politics in policy advice
Authors: Capano Giliberto , Howlett Michael , Pal Leslie A , Ramesh M 
Published: August 2023

AbstractPolicy advice has been the subject of ongoing research in the policy sciences as it raises fundamental issues about what constitutes policy knowledge, expertise, and their effects on policymaking. This introduction reviews the existing literature on the subject and introduces the themes motivating the articles in the issue. It highlights the need to consider several key subjects in the topic in the contemporary era: namely the challenge of legitimacy, that of values, and the challenge of politics. The papers in the issue shed light on the ongoing delegitimization of conventional knowledge providers, the problem of the normative basis of experts’ advice, the increasing politicization of expertise in policymaking, and the relevance of political context in influencing not only the role of experts but also whether or not their advice is accepted and implemented. It is argued that these modern challenges, when not addressed, reinforce trends toward the inclusion of antidemocratic values and uninformed ideas in contemporary policymaking.
Glasgow Coma Scale on admission as predictor of neurological sequelae at discharge and acute respiratory failure in patients with heatstroke
Authors: Chen Lan , Lu Liyun , Fang Yuan , Ren Jingnan , Yang Xiaoling , Gong Zhumei , Zhang Yuping , Feng Xiuqin 
Published: August 2023

Abstract

Background
Transient neuronal dysfunction may occur in most brain regions with heatstroke (HS). This study aimed to explore the prognostic significance of initial Glasgow Coma Scale (GCS) scores in HS.

Methods
Retrospective data regarding HS were obtained from six hospitals. The primary outcome was neurological sequelae at discharge. Secondary outcomes included acute respiratory failure (ARF) and intensive care unit (ICU) admission. Logistic regression models and random forest imputation were used to assess the independent association between GCS score and outcomes. Interaction and stratified analyses of body temperature (BT) at 0.5 hours were also conducted. Receiver operating characteristic curves and decision curve analysis were used to estimate prognostic values.

Results
Of 206 patients, 44 (21.36%) had neurological sequelae at discharge. The mean ± standard deviation initial GCS score was 8.17 ± 4.05. After adjustment for confounders, GCS, as a continuous variable, was significantly related to neurological sequelae at discharge [odds ratio (OR): 0.65; 95% confidence interval (CI): 0.50–0.85; P = 0.002], ARF (OR: 0.76; 95% CI: 0.66–0.87; P = 0.001), and ICU admission (OR: 0.68; 95% CI: 0.53–0.87; P = 0.003). These relationships were consistent in the random forest imputation cohort. The OR between GCS and neurological sequelae at discharge was much lower (P = 0.048) in participants with BT at 0.5 hours ≤39°C than in those with BT at 0.5 hours &gt;39°C. The GCS and National Early Warning Score (NEWS) had similar prognostic ability for all outcomes, whereas the net benefits were greater with the GCS compared with the NEWS.

Conclusions
Initial GCS score was an independent prognostic factor for neurological sequelae at discharge in HS. Rapid cooling played a positive role in this relationship.
Key messages What is already known on this topic Brain damage caused by heatstroke (HS) can be transient or result in irreversible injury. Early recognition of those at risk of death or developing neurological complications is very important for improving the outcomes of HS. What this study adds Initial Glasgow Coma Scale (GCS) score was an independent prognostic factor for neurological sequelae at discharge, acute respiratory failure, and intensive care unit (ICU) admission in HS. Rapid cooling played a positive role in this relationship. How this study might affect research, practice, or policy The GCS upon emergency department admission can be a useful predictor of prognosis in patients with HS.
Necessarily Veridical Hallucinations: A New Problem for the Uninstantiated Property View
Authors: Gow Laura 
Published: August 2023

Abstract
Philosophers of perception have a notoriously difficult time trying to account for hallucinatory experiences. One surprisingly quite popular move, and one that cross-cuts the representationalism/relationalism divide, is to say that hallucinations involve an awareness of uninstantiated properties. In this paper, I provide a new argument against this view. Not only are its proponents forced to classify many hallucinations as veridical, such experiences turn out to be necessarily veridical. In addition, I show that representationalists who endorse the uninstantiated property view must reject the common fundamental kind claim and adopt disjunctivism, and naïve realists/relationalists must radically modify their disjunctivism: The distinction between ‘veridical’ and ‘hallucinatory’ will no longer track a metaphysical distinction between the relevant experiences.
Direct optogenetic activation of upper airway muscles in an acute model of upper airway hypotonia mimicking sleep onset
Authors: Knapman Fiona L , Cohen E Myfanwy , Kulaga Tom , Lovell Nigel , Lisowski Leszek , McMullan Simon , Burke Peter G R , Bilston Lynne E 
Published: August 2023

Abstract

Study Objectives
Obstructive sleep apnea (OSA), where the upper airway collapses repeatedly during sleep due to inadequate dilator muscle tone, is challenging to treat as current therapies are poorly tolerated or have variable and unpredictable efficacy. We propose a novel, optogenetics-based therapy, that stimulates upper airway dilator muscle contractions in response to light. To determine the feasibility of a novel optogenetics-based OSA therapy, we developed a rodent model of human sleep-related upper airway muscle atonia. Using this model, we evaluated intralingual delivery of candidate optogenetic constructs, notably a muscle-targeted approach that will likely have a favorable safety profile.

Methods
rAAV serotype 9 viral vectors expressing a channelrhodopsin-2 variant, driven by a muscle-specific or nonspecific promoter were injected into rat tongues to compare strength and specificity of opsin expression. Light-evoked electromyographic responses were recorded in an acute, rodent model of OSA. Airway dilation was captured with ultrasound.

Results
The muscle-specific promoter produced sufficient opsin expression for light stimulation to restore and/or enhance electromyographic signals (linear mixed model, F = 140.0, p &lt; 0.001) and induce visible tongue contraction and airway dilation. The muscle-specific promoter induced stronger (RM-ANOVA, F(1,8) = 10.0, p = 0.013) and more specific opsin expression than the nonspecific promoter in an otherwise equivalent construct. Viral DNA and RNA were robust in the tongue, but low or absent in all other tissues.

Conclusions
Significant functional responses to direct optogenetic muscle activation were achieved following muscle-specific promoter-driven rAAV-mediated transduction, providing proof-of-concept for an optogenetic therapy for patients with inadequate dilator muscle activity during sleep.
Catch-up vaccination and enhanced immunization against hepatitis B, hepatitis A, measles, mumps, rubella and varicella in children with idiopathic thrombocytopenic purpura
Authors: Taşar Serçin , Taşar Medine Ayşin , Saç Rukiye Ünsal , Alioğlu Bülent 
Published: August 2023

Abstract

Background
Limited data exist about the vaccination of children with idiopathic thrombocytopenic purpura (ITP) against vaccine preventable diseases. This study identified the vaccination status of children with ITP against hepatitis A, hepatitis B, measles, mumps, rubella and varicella, completed the immunization of children with inadequate immunization, re-evaluated post-vaccination antibody titers and identified probable vaccination-related complications.

Patients and methods
All of 46 children had chronic ITP were included. Seroconversion of hepatitis A, hepatitis B, varicella, measles, rubella and mumps vaccines was screened. All children with seronegative antibodies against vaccine preventable disease were given a vaccination appointment. Antibody levels were re-measured during a period ranging from 1 to 6 months. Potential complications were detected.

Results
There were 46 children with a mean age of 12.25 years. All children had chronic ITP and received intravenous immunoglobulin at least once previously. Considering the vaccination status, 50% (23 children) had vaccinations appropriate for their age, 47.8% (22 children) did not know their vaccination status and 2.2% (1 patient) did not have vaccinations. Seven children (15.2%) were seropositive for all antibody types and the remaining 39 children were scheduled for vaccination. Post-vaccination antibody titers confirmed that all children became seropositive for each disease. There was no complication in any patient.

Conclusion
Immunization against hepatitis B, hepatitis A, measles, mumps, rubella and varicella is insufficient in a considerable number of children with ITP, Hepatitis B Virus (HBV) and Hepatitis A Virus (HAV) immunization being the most frequently inadequate. After immunization, adequate seroconversion levels were achievable without complications.
Electromagnetic field and cardiovascular diseases: A state‐of‐the‐art review of diagnostic, therapeutic, and predictive values
Authors: Wang Yan , Zhao Zhen‐Gang , Chai Zheng , Fang Jian‐Cheng , Chen Mao 
Published: August 2023

AbstractDespite encouraging advances in early diagnosis and treatment, cardiovascular diseases (CVDs) remained a leading cause of morbidity and mortality worldwide. Increasing evidence has shown that the electromagnetic field (EMF) influences many biological processes, which has attracted much attention for its potential therapeutic and diagnostic modalities in multiple diseases, such as musculoskeletal disorders and neurodegenerative diseases. Nonionizing EMF has been studied as a therapeutic or diagnostic tool in CVDs. In this review, we summarize the current literature ranging from in vitro to clinical studies focusing on the therapeutic potential (external EMF) and diagnostic potential (internal EMF generated from the heart) of EMF in CVDs. First, we provided an overview of the therapeutic potential of EMF and associated mechanisms in the context of CVDs, including cardiac arrhythmia, myocardial ischemia, atherosclerosis, and hypertension. Furthermore, we investigated the diagnostic and predictive value of magnetocardiography in CVDs. Finally, we discussed the critical steps necessary to translate this promising approach into clinical practice.
Pan‐cancer analysis: SPAG5 is an immunological and prognostic biomarker for multiple cancers
Authors: Gao Xiaofeng , Bu Huitong , Gao Xuzheng , Wang Ying , Wang Long , Zhang Zhenwang 
Published: August 2023

AbstractSperm‐associated antigen 5 (SPAG5) is a mitotic spindle protein that regulates the separation of sister chromatids into daughter cells. Recent studies have discovered its overexpression in various cancers, suggesting its oncogenic characteristics and functions. However, a comprehensive analysis of SPAG5 regarding its diagnostic, prognostic, and immune‐related effects across different cancer types is lacking. In this study, we employed bioinformatics methods and integrated multiple public databases to explore the potential oncogenic role of SPAG5. We analyzed its expression, prognosis, related chemicals, enriched pathways, immune infiltration, and its impact on different tumor genetic alterations. The results revealed that SPAG5 is highly expressed in most cancers and significantly correlates with poor patient prognosis. Additionally, SPAG5 expression showed potential for early cancer diagnosis in 15 different cancer types. In terms of tumor immunity, high expression of SPAG5 was associated with an immunosuppressive tumor microenvironment and immune therapy efficacy indicators. SPAG5 expression exhibited a negative correlation with most immune cell infiltrates but demonstrated a significant positive correlation with Th2 cells and MDSC cells. Multicolor fluorescence immunohistochemistry demonstrated that SPAG5 activates immune cell populations within tumors, indicating its significant role in the tumor microenvironment. Enrichment analysis indicated that SPAG5‐related genes are mainly involved in cell cycle, cellular senescence, P53 signaling pathway, and FoxO signaling pathway. Furthermore, we confirmed the high expression of SPAG5 in cancer cells and observed that its knockdown upregulated the expression of the p53 protein. In conclusion, SPAG5 holds value as a diagnostic, prognostic, and immune biomarker in various cancers and may provide a novel target for tumor immunotherapy.