bluuebunny/crossref_metadata_2025_split huggingface dataset:
Holo-chromodulin: competition between the native Cr3+ and other biogenic cations (Fe3+, Fe2+, Mg2+, and Zn2+) for the binding sites
Authors: Kircheva Nikoleta , Toshev Nikolay , Dudev Todor 
Published: October 2022

Abstract
Chromodulin is an oligopeptide that has an essential role for the flawless functioning of insulin. Although the precise sequence of the constituent amino acid residues and the 3D structure of the molecule has not yet been deciphered, it is known that chromodulin contains only four amino acids in the ratio of Glu–: Gly: Cys: Asp– = 4: 2: 2: 2. An indispensable part for the integrity of the molecule in its active (holo-) form are four chromium cations (hence the name) in the oxidation state of 3+, positioned in two metal binding sites containing one and three Cr3+ ions. Experimental works provide some hints/clues concerning the structure of the metal centers, although their exact composition, type, and arrangement of metal ligating entities remain enigmatic. In the current study, we endeavor to unveil possible structure(s) of the Cr3+ loaded binding sites by strictly following the evidence provided by the experimental data. Well-calibrated in silico methodology for optimization and evaluation of Gibbs free energies is applied and gives strong premises for reliably deciphering the composition/structure of chromodulin metal binding sites. Additional computations reveal the advantage of choosing Cr3+ over other tri- (Fe3+) and divalent (Fe2+, Mg2+, and Zn2+) biogenic ions for securing maximum stability of the metal-occupied binding sites.
Male and Female Sprague Dawley Rats Exhibit Equivalent Natural Reward, Nicotine Self-Administration, Extinction, and Reinstatement During Adolescent-Initiated Behaviors
Authors: Carreño Diana , Lotfipour Shahrdad 
Published: October 2022

AbstractIntroductionThe initiation of nicotine and tobacco use peaks during adolescence. How adolescent males and females differ based on the acquisition of nicotine use and nicotine-seeking behavior is less understood. Our current studies develop a preclinical intravenous self-administration and reinstatement paradigm in male and female Sprague Dawley rats to evaluate how sex impacts the acquisition of nicotine self-administration and nicotine-seeking, when behavior is initiated during adolescence.Aims and MethodsMale and female adolescent rats were food trained under a fixed-ratio one (FR1) schedule of reinforcement and progressively increased to FR5. Animals were implanted with catheters and began nicotine self-administration (0.015 mg/kg/infusion) at FR5 during adolescence on postnatal day 34. Upon reaching stable reinforced responding, animals were tested for progressive ratio (PR) schedules of reinforcement followed by extinction via the removal of drug and associated cues for a minimum of 5 days or until responding was reduced to ≤25% of baseline. Reinstatement testing began for cue only, nicotine only, and a combination of nicotine plus cues using a Latin square design. Animals returned to extinction conditions for 2 days minimum between testing.ResultsNo sex differences were observed for natural rewards, acquisition, and PR schedules of nicotine self-administration, days to extinction, and reinstatement condition.ConclusionsOur findings provide evidence that sex does not impact natural rewards, nicotine reinforcement, reward, and reinstatement, when behavior is initiated during adolescence. Our study offers a feasible approach for assessing nicotine-seeking in male and female Sprague Dawley rats during the unique developmental window of adolescence.ImplicationsThis study demonstrates the impact of nicotine and associated cues in the reinstatement of nicotine-seeking in male and female rats when behavior is initiated during adolescence. Findings support the equivalent impact of nicotine and the nonpharmacological stimuli of cues between male and female adolescent rats that began nicotine self-administration during adolescence.
Too hot! Preventing, recognizing and managing heat injury in children
Authors: Hicks Anne , Komar Lindsay 
Published: October 2022

Abstract
Climate change-related extreme heat events leading to public health emergencies are increasing in Canada and expected to affect more regions, more frequently and for longer time periods. Children, city dwellers and marginalized populations are amongst the most vulnerable to morbidity and mortality related to extreme heat. Paediatricians can provide caregivers and families with advice to minimize risks as well as advocate for safer city planning and harm mitigation strategies.
Daniel Defoe on Naturalization
Authors: Mierowsky Marc 
Published: October 2022

Abstract
This essay explores the connection in Daniel Defoe’s writing between naturalization as a civic concept and naturalization as an epistemological or literary-critical process. For Defoe, the incorporation of new subjects was a moral project that entailed the literary interpellation of a more productive, tolerant and empowered populace. A history of his efforts to encourage immigration by broadening access to legal citizenship provides, then, not just crucial insight into his view of the national political community but points to the role his satire, journalism and novels might play in bringing subjects together in its formation. In pursuit of this history, I trace Defoe’s approach to naturalization to The True-born Englishman (1700), the poem that established his reputation as an advocate for immigration reform. I then track Defoe’s activism in favour of The Foreign Protestants Naturalization Act (7 Anne c. 5) before its passage in March 1709 and after its repeal in 1711 (10 Anne c. 9), as debate turned to the fate of successive alien populations: Huguenot and Palatine refugees and England’s Jews. These debates provide an important new context for Defoe’s final novel, The Fortunate Mistress [Roxana] (1724). Attention to the ways Defoe deployed poetry and prose fiction during them reveals how questions of admission and assimilation underpinned his polemical strategy as a popular author and signalled the importance of his work to the history of modern citizenship.
COMPARISON OF GAMMA ABSORBED DOSE RATES IN THE AIR MEASURED WITH A PORTABLE SURVEY METER AND THE SOIL RADIOACTIVITY MEASUREMENTS
Authors: Lee Hae Young , Maeng Seongjin , Park Seong Jin , Lee Sang Hoon 
Published: October 2022

Abstract
To compare the measurement results of a portable survey meter with a soil-based dose rate assessment method, the gamma absorbed dose rates in the air were measured at 27 sites. The soil-based gamma absorbed dose rates in the air were calculated using established conversion factors and the activity concentrations of 226Ra, 232Th and 40K of the soil at the sites. The gamma absorbed dose rate averages of the portable survey meter, and computing from the activity concentrations in the soil were 65.8 ± 4.26 and 64.8 ± 3.68 nGy⋅h−1, respectively. A significant positive correlation was found in the comparison between the evaluated gamma absorbed dose rates from soil radioactivity and in the air. Conversion factors based on the local soils converting to the absorbed dose rate were computed from the portable survey meter data and the soil activity concentrations, and it was compared with others.
“Bring Your Straight Friends”: Anti-Gay Religious Stigma and Black and White LGB-Affirming Church Members
Authors: Lee Austin Colby Guy 
Published: October 2022

Abstract
This comparative study of Black and white members of LGB-affirming churches finds that race plays a major role in shaping the socio-temporal contexts in which American Protestants come to understand anti-gay religious stigma and make meaning of their affiliation to LGB-affirming churches. Through interviews with 13 Black and 14 white members of churches that actively describe themselves as affirming and inclusive of LGB people, I find that Black church members made efforts to distinguish their churches from “gay churches” and that LGB inclusion functions as a potential source of stigma for Black-affirming church members. Conversely, white respondents articulated a valuing of LGB inclusion tied to broader conceptions of inclusion and social progress. These findings suggest that Black and white Protestants encounter distinct cultural landscapes when evaluating the legitimacy and status of their religious institutions and that Black LGB-affirming church members internalize stigma related to their religious affiliations.
Mucilaginibacter rivuli sp. nov., isolated from a water rivulet
Authors: Bae Seokhyeon , Kang Heeyoung , Kim Haneul , Joh Kiseong 
Published: October 2022

Strain HMF5004T was isolated from a rivulet located in Yongin, Republic of Korea. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain HMF5004T belonged to the genus

Mucilaginibacter

. Strain HMF5004T was closely related to

Mucilaginibacter paludis

(97.7%) and

Mucilaginibacter gracilis

(97.2%). The values of average nucleotide identity and digital DNA–DNA hybridization between strain HMF5004T and

M. paludis

were 72.8 and 19.2 %, respectively. Cells of strain HMF5004T were Gram-stain-negative, rod-shaped, non-motile, catalase-positive and oxidase-positive. The DNA G+C content of strain HMF5004T was 42.4 mol%. Strain HMF5004T had menaquinone-7 as a major quinone. The major cellular fatty acids included iso-C15 : 0, summed feature 3 (C16 : 1
ω7c and/or C16 : 1
ω6c) and anteiso-C15 : 0. The polar lipids of strain HMF5004T contained phosphatidylethanolamine, five unidentified aminolipids, one unidentified aminophospholipid and four unidentified polar lipids. On the basis of the evidence presented in this polyphasic taxonomic study, strain HMF5004T is considered to represent a novel species for which the name Mucilaginibacter rivuli sp. nov. is proposed. The type strain is HMF5004T (=KCTC 82633T=NBRC 115091T).
Nimbolide Targets RNF114 to Induce the Trapping of PARP1 and Poly-ADP-Ribosylation-Dependent DNA Repair Factors
Authors: Li Peng , Zhen Yuanli , Kim Chiho , Deng Heping , Deng Hejun , Wang Xu-Dong , Qin Tian , Yu Yonghao 
Published: October 2022

AbstractPARP1 is an abundant nuclear enzyme that is critically involved in DNA damage response. Its main enzymatic function is to catalyze a protein post-translational modification known as poly-ADP-ribosylation (PARylation). Despite the tremendous progresses of PARP1 inhibitors (PARPi) in the clinic, the basic mechanism of action of PARPi is poorly understood. Recent studies point to PARP1 trapping as a key factor driving the cytotoxic and immunomodulatory functions of PARPi. However, the molecular underpinnings of PARP1 trapping remain elusive. Here, using an unbiased, quantitative proteomic screen, we identified RING finger protein 114 (RNF114), as a PARylation-dependent, ubiquitin E3 ligase involved in DNA damage response. Upon sensing DNA damage, RNF114 was recruited, in a PAR-dependent manner, to the DNA lesions, where it specifically targeted PARylated-PARP1 for ubiquitin-proteasomal degradation. The blockade of this pathway interfered with the removal of PARP1 from the DNA damage site, leading to profound PARP1 trapping. We show that a natural product, Nimbolide, targeted RNF114 to block the degradation and removal of PARylated-PARP1 from DNA lesions. Unlike conventional PARPi, nimbolide treatment induced the trapping of both PARP1 and PARylation-dependent DNA repair factors. This unique mechanism of action of nimbolide translated into its superior cytotoxic effects against BRCA-deficient cancers. Furthermore, we demonstrated that, as a super trapper of both PARylated-PARP1 and PARylation-dependent DNA repair factors, nimbolide was able to overcome the intrinsic and acquired resistance to PARPi. Finally, we showed that nimbolide treatment activated innate immune signaling and was able to synergize with various cytotoxic agents. These results point to the exciting possibility of targeting homologous recombination-deficient cancers using nimbolide and its analogs.
Treatment of pancreatic cancer with irreversible electroporation and intratumoral CD40 antibody stimulates systemic immune responses that inhibit liver metastasis in an orthotopic model
Authors: Narayanan Jayanth S. Shankara , Hayashi Tomoko , Erdem Suna , McArdle Sara , Tiriac Herve , Ray Partha , Pu Minya , Mikulski Zbigniew , Miller Aaron , Messer Karen , Carson Dennis , Schoenberger Stephen P. , White Rebekah R. 
Published: October 2022

ABSTRACTBackgroundPancreatic cancer (PC) has a poor prognosis, and most patients present with either locally advanced or distant metastatic disease. Irreversible Electroporation (IRE) is a non-thermal method of ablation used clinically in locally advanced PC, but most patients eventually develop distant recurrence. We have previously shown that IRE alone is capable of generating protective, neoantigen-specific immunity. Here we aim to generate meaningful therapeutic immune effects by combining IRE with local (intratumoral) delivery of a CD40 agonistic antibody (CD40Ab).MethodsKPC46 organoids were generated from a tumor-bearing male KrasLSL-G12D-p53LSL-R172H-Pdx-1-Cre (KPC) mouse. Orthotopic tumors were established in the pancreatic tail of B6/129 F1J mice via laparotomy. Mice were randomized to treatment with either sham laparotomy, IRE alone, CD40Ab alone, or IRE followed immediately by CD40Ab injection. Metastatic disease and immune infiltration in the liver were analyzed 14 days post-procedure using flow cytometry and multiplex immunofluorescence imaging with spatial analysis. Candidate neoantigens were identified by mutanome profiling of tumor tissue for ex vivo functional analyses.ResultsThe combination of IRE+CD40Ab improved median survival to greater than 35 days, significantly longer than IRE (21 days) or CD40Ab (24 days) alone (p<0.01). CD40Ab decreased metastatic disease burden, with less disease in the combination group than in the sham group or IRE alone. Immunohistochemistry of liver metastases revealed a more than two-fold higher infiltration of CD8+ T-cells in the IRE+CD40Ab group than in any other group (p<0.01). Multiplex immunofluorescence imaging revealed a 4-6-fold increase in the density of CD80+CD11c+ activated dendritic cells (p<0.05), which were spatially distributed throughout the tumor unlike the sham group, where they were restricted to the periphery. In contrast, CD4+FoxP3+ T-regulatory cells (p<0.05) and Ly6G+ MDSCs (P<0.01) were reduced and restricted to the tumor periphery in the IRE+CD40Ab group. T-cells from the IRE+CD40Ab group recognized significantly more peptides representing candidate neoantigens than did T-cells from the IRE or untreated control groups.ConclusionsIRE can induce local tumor regression and neoantigen-specific immune responses. Addition of CD40Ab to IRE improved dendritic cell activation and neoantigen recognition, while generating a strong systemic anti-tumor T-cell response that inhibited metastatic disease progression.Abstract Figure
Unified and standardized mass spectrometry data processing in Python using spectrum_utils
Authors: Bittremieux Wout , Levitsky Lev , Pilz Matteo , Sachsenberg Timo , Huber Florian , Wang Mingxun , Dorrestein Pieter C. 
Published: October 2022

Abstractspectrum_utils is a Python package for mass spectrometry data processing and visualization. Since its introduction, spectrum_utils has grown into a fundamental software solution that powers various applications in proteomics and metabolomics, ranging from spectrum preprocessing prior to spectrum identification and machine learning applications, to spectrum plotting from online data repositories, and assisting data analysis tasks for dozens of other projects. Here we present updates to spectrum_utils, which include new functionality to integrate mass spectrometry community data standards, enhanced mass spectral data processing, and unified mass spectral data visualization in Python. spectrum_utils is freely available as open source at https://github.com/bittremieux/spectrum_utils.
Auditory biases in cognitive assessment – Insights from hearing-loss simulation for dementia screening
Authors: Füllgrabe Christian 
Published: October 2022

AbstractCognitive-screening tests are used to detect pathological changes in mental abilities. Many use orally presented instructions and test items. Hence, hearing loss (HL), whose prevalence increases with age, may bias cognitive-test performance in the target population for dementia screening. To study the effect of the test format, an impairment-simulation approach was used in normal-hearing listeners to compare performance on the Hopkins Verbal Learning Test when test items were unprocessed and processed to simulate age-related HL. Immediate verbal recall declined with simulated HL, suggesting that auditory factors are confounding variables in cognitive assessment and result in the underestimation of cognitive functioning.
Defining the in vivo mechanism of air pollutant toxicity using murine stress response biomarkers
Authors: Inesta-Vaquera Francisco , Miyasita Lisa , Grigg Jonathan , Henderson Colin J. , Wolf C. Roland 
Published: October 2022

AbstractBackgroundAir pollution can cause a wide range of serious human diseases. For the informed instigation of interventions which prevent these outcomes there is an urgent need to develop robust in vivo biomarkers which provide insights into mechanisms of toxicity and relate pollutants to specific adverse outcomes.ObjectiveTo exemplify the application of in vivo stress response reporters in establishing mechanisms of air pollution toxicity and the application of this knowledge in epidemiological studies and potentially in disease prevention.MethodsMurine stress-reporter models (oxidative stress/inflammation, DNA damage and Ah receptor -AhR-activity) and primary mouse and primary human nasal cells were exposed to chemicals present in diesel exhaust emissions, particulate matter (PM) standards (PM2.5-SRM2975, PM10-SRM1648b) or fresh roadside PM10. Stress reporter activity was analysed by luminescence assays and histochemical approaches in a panel of murine tissues. Biochemical, genetic and pharmacological approaches were used to establish the mechanism of the stress responses observed. Pneumococcal adhesion was assessed in exposed primary human nasal epithelial cells (HPNEpC).ResultsNitro-PAHs induced Hmox1 and CYP1a1 reporters in a time- and dose-dependent, cell- and tissue-specific manner. NRF2 pathway mediated this Hmox1-reporter induction. SRM1658b, but not SRM2975, was a potent inducer of NRF2-dependent Hmox1 reporter activity in lung macrophages. Combined use of HPNEpC and in vivo reporters demonstrated that London roadside PM10 particles induced pneumococcal infection in HPNEpC mediated by oxidative stress responses.DiscussionThe combined use of in vivo reporter models with HPNEpC provides a robust approach to define the relationship between air pollutant exposure and health risks. These models can be used to hazard ranking environmental pollutants by considering the complexity of mechanisms of toxicity. These data will facilitate the relationship between toxic potential and the level of pollutant exposure in populations to be established and potentially extremely valuable tools for intervention studies.
Guitarfishes are plucked: undermanaged in global fisheries despite declining populations and high volume of unreported international trade
Authors: Sherman C. Samantha , Simpfendorfer Colin A. , Haque Alifa B. , Digel Eric D. , Zubick Patrick , Eged Jonathan , Matsushiba Jay H. , Sant Glenn , Dulvy Nicholas K. 
Published: October 2022

AbstractSome sharks and rays are subject to fisheries catch and international trade regulations. However, the Guitarfishes (family Rhinobatidae) are a highly threatened group with minimal regulations. Substantial underreporting of catch and broad commodity codes for traded products are masking the true volume of Guitarfishes included in international trade. Here, we collate international trade information for Guitarfishes that have not readily been documented in trade, possibly due to poor resolution of molecular genetic markers, to begin to document the extent of trade. We assess the shortfall in fisheries management (M-Risk) for all species of Guitarfish based on 99 assessments across 28 countries. Globally, Guitarfishes are inadequately managed, with an average M-Risk of 45% of an ideal score, resulting in 76% of species being threatened globally. The high and unregulated catch and trade volume, paired with the management shortfalls, require global integrated improvement in fisheries management, supported by regulating international trade to sustainable levels.
Revaluation of old data with new techniques reveals novel insights into the celiac microbiome
Authors: Colgan John J , Burns Michael B 
Published: October 2022

ABSTRACTCeliac disease is an autoimmune disorder of the small intestine in which gluten, an energy-storage protein expressed by wheat and other cereals, elicits an immune response leading to villous atrophy. Despite a strong genetic component, the disease arises sporadically throughout life, leading us to hypothesize the the microbiome might be a trigger for celiac disease. Here, we took microbiome data from 3 prior studies examining celiac disease and the microbiome and analyzed this data with newer computational tools and databases: the dada2 and PICRUSt2 pipelines and the SILVA database. Our results both confirmed findings of previous studies and generated new data regarding the celiac microbiome of India and Mexico. Our results showed that, while some aspects of prior reports are robust, older datasets must be reanalyzed with new tools to ascertain which findings remain accurate while also uncovering new findings.IMPORTANCEBioinformatics is a rapidly developing field, with new computational tools released yearly. It is thus important to revisit results generated using older tools to determine whether they are also revealed by currently available technology. Celiac disease is an autoimmune disorder that affects up to 2% of the world’s population. While the ultimate cause of celiac disease is unknown, many researchers hypothesize that changes to the intestinal microbiome play a role in the disease’s progression. Here, we have re-analyzed 16S rRNA data from several previous celiac studies to determine whether previous results are also uncovered using new computational tools.
Patterns of Ongoing Thought in the Real-World
Authors: Mulholland Bridget , Goodall-Halliwell Ian , Wallace Raven , Chitiz Louis , Mckeown Brontë , Rastan Aryanna , Poerio Giulia , Leech Robert , Turnbull Adam , Klein Arno , Van Auken Wil , Milham Michael , Wammes Jeffrey , Jefferies Elizabeth , Smallwood Jonathan 
Published: October 2022

AbstractPrevious research has indicated that health and well-being are impacted on by both the way we think, and the things we do. In the laboratory, studies suggest that specific task contexts affect this process because the people we are with, the places we are in, and the activities we perform may influence our thought patterns. In our study participants completed multi-dimensional experience-sampling surveys eight times per day for 5 days to generate thought data across a variety of dimensions in daily life. Principal component analysis was used to decompose the experience sampling data, and linear mixed modelling related these patterns to the activity in daily life in which they emerged. Our study replicated the influence of socializing on patterns of ongoing thought observed in our prior study and established that this is part of a broader set of relationship that links our current activities to how our thoughts are organised in daily life. We also found that factors such as time of day and the physical location are associated with reported patterns of thought, factors that are important for future studies to explore. Our study suggests that sampling thinking in the real world may be able to provide a set of comprehensive thinking-activity mappings that will be useful to researchers and health care professionals interested in health and well-being.