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ASAIO Journal (American Society For... Jul 2024
PubMed: 38941486
DOI: 10.1097/MAT.0000000000002261 -
ELife Jun 2024Genetic diversity is a hallmark of RNA viruses and the basis for their evolutionary success. Taking advantage of the uniquely large genomic database of SARS-CoV-2, we...
Genetic diversity is a hallmark of RNA viruses and the basis for their evolutionary success. Taking advantage of the uniquely large genomic database of SARS-CoV-2, we examine the impact of mutations across the spectrum of viable amino acid sequences on the biophysical phenotypes of the highly expressed and multifunctional nucleocapsid protein. We find variation in the physicochemical parameters of its extended intrinsically disordered regions (IDRs) sufficient to allow local plasticity, but also observe functional constraints that similarly occur in related coronaviruses. In biophysical experiments with several N-protein species carrying mutations associated with major variants, we find that point mutations in the IDRs can have nonlocal impact and modulate thermodynamic stability, secondary structure, protein oligomeric state, particle formation, and liquid-liquid phase separation. In the Omicron variant, distant mutations in different IDRs have compensatory effects in shifting a delicate balance of interactions controlling protein assembly properties, and include the creation of a new protein-protein interaction interface in the N-terminal IDR through the defining P13L mutation. A picture emerges where genetic diversity is accompanied by significant variation in biophysical characteristics of functional N-protein species, in particular in the IDRs.
Topics: SARS-CoV-2; Coronavirus Nucleocapsid Proteins; Mutation; COVID-19; Humans; Intrinsically Disordered Proteins; Phosphoproteins; Nucleocapsid Proteins; Thermodynamics; Protein Stability
PubMed: 38941236
DOI: 10.7554/eLife.94836 -
Supportive Care in Cancer : Official... Jun 2024Fear of progression (FoP) leads to poor clinical outcomes in colorectal cancer patients. The study aimed to clarify the profiles and influencing factors of FoP among...
PURPOSE
Fear of progression (FoP) leads to poor clinical outcomes in colorectal cancer patients. The study aimed to clarify the profiles and influencing factors of FoP among colorectal cancer patients.
METHODS
A cross-sectional study was conducted with 409 colorectal cancer patients. Convenience sampling method was used to select colorectal cancer patients hospitalized in a tertiary-level hospital in Nanjing as the survey subjects. General information questionnaire, Fear of Progression Questionnaire-Short Form, Distress Disclosure Index, and Social Support Rating Scale were used to collect the data. Latent profile analysis was used to explore the latent profiles of FoP in colorectal cancer patients. Additionally, the influencing factors of profiles were explored by Univariate Analysis and Binomial Logistic Regression Analysis.
RESULTS
Latent profile analysis identified two subgroups of fear of disease progression: the "fear low-risk profile (83%)", and the "severe fear profile (17%)." Patients with low age, low social support utilization, first hospital admission, severe healthcare burden, and preoperative bowel symptoms were prone to severe fear of disease progression.
CONCLUSIONS
There is some heterogeneity in the level of postoperative fear of disease progression in colorectal cancer patients. Doctors and nurses should focus on patients with severe fear and take targeted preventive and psychological care for patients' fear of disease progression as early as possible according to the distribution characteristics of different categories.
Topics: Humans; Colorectal Neoplasms; Male; Female; Cross-Sectional Studies; Fear; Middle Aged; Disease Progression; Aged; Surveys and Questionnaires; Social Support; Adult; China
PubMed: 38940963
DOI: 10.1007/s00520-024-08660-7 -
Journal of Radiation Research Jun 2024The ionizing radiation with high linear energy transfer (LET), such as a heavy ion beam, induces more serious biological effects than low LET ones, such as gamma- and...
The ionizing radiation with high linear energy transfer (LET), such as a heavy ion beam, induces more serious biological effects than low LET ones, such as gamma- and X-rays. This indicates a difference in the DNA damage produced by low and high LET radiations and their biological effects. We have been studying the differences in DNA damage produced by gamma-rays and carbon ion beams. Therefore, we analyze mutations induced by both ionizing radiations to discuss the differences in their biological effects in this study. pUC19 plasmid DNA was irradiated by carbon ion beams in the solution containing 1M dimethyl sulfoxide to mimic a cellular condition. The irradiated DNA was cloned in competent cells of Escherichia coli. The clones harboring some mutations in the region of lacZα were selected, and the sequence alterations were analyzed. A one-deletion mutation is significant in the carbon-irradiated DNA, and the C:G↔T:A transition is minor. On the other hand, the gamma-irradiated DNA shows mainly G:C↔T:A transversion. These results suggest that carbon ion beams produce complex DNA damage, and gamma-rays are prone to single oxidative base damage, such as 8-oxoguanine. Carbon ion beams can also introduce oxidative base damage, and the damage species is 5-hydroxycytosine. This was consistent with our previous results of DNA damage caused by heavy ion beams. We confirmed the causal DNA damage by mass spectrometry for these mutations.
PubMed: 38940734
DOI: 10.1093/jrr/rrae050 -
Microbiology Spectrum Jun 2024Despite the first-line recommendation of fosfomycin for uncomplicated urinary tract infections (UTIs), there are pressing barriers for optimizing its use for the...
Skipped wells and scientific error during fosfomycin agar dilution and broth microdilution lead to inconsistent minimal inhibitory concentrations and may be cause for reevaluating testing methods for .
Despite the first-line recommendation of fosfomycin for uncomplicated urinary tract infections (UTIs), there are pressing barriers for optimizing its use for the treatment of non- Enterobacterales UTI. There are no approved breakpoints for oral use against other Enterobacterales, and the recommended agar dilution (AD) reference method for minimal inhibitory concentration (MIC) determination is largely impractical. Using 160 clinical isolates, we sought to understand rates of skipped wells and MIC imprecision in broth microdilution (BMD) and how that compares to rates of error using AD. Though the Clinical and Laboratory Standards Institute refers to the skipped well phenomena in their recommendation against the use of BMD, there is a paucity of data on its frequency. While AD and BMD produced similar MIC values (32/256 µg/mL for AD and 64/256 µg/mL for BMD), essential agreement was poor. No-growth wells at concentrations below the MIC occurred in up to 10.9% of wells at a given concentration, as the most frequent scientific error. Growth in concentrations above the measured MIC occurred in up to 3.3% of wells and was seen within three dilutions of the MIC for BMD. Observation of single colonies either at or beyond the measured MIC for AD was also common and occurred up to 8.3% and 2.5% of the time, respectively. The frequent scientific error in both testing methods should prompt re-evaluation of AD guidelines and expansion of MIC testing methods for fosfomycin susceptibility testing, as poor agreement with another method prone to scientific error should not be the main detractor from BMD use.IMPORTANCEDespite the recommendation of fosfomycin for uncomplicated urinary tract infections (UTIs), there are barriers for optimizing its use. There are no approved breakpoints for oral use against other Enterobacterales, and the recommended agar dilution (AD) reference method for MIC determination is largely impractical. The use of broth microdilution (BMD) for fosfomycin testing is not recommended by the Clinical and Laboratory Standards Institute due to unsatisfactory precision and skipped wells-occurrence of no-growth in a single well before the minimal inhibitory concentration (MIC)-and trailing endpoints. We sought to understand rates of skipped wells and growth at concentrations above measured MICs in BMD and how that compares to scientific error using AD. No-growth wells at concentrations below the MIC occurred in up to 10.9% of wells for BMD and single colonies at or beyond measured MICs for AD were also common. Frequent scientific error in both methods should prompt re-evaluation of both AD and BMD for fosfomycin susceptibility testing.
PubMed: 38940588
DOI: 10.1128/spectrum.04205-23 -
Journal of Child Psychology and... Jun 2024Climate anxiety is increasingly prevalent among adolescents worldwide. Are climate-anxious adolescents prone to engage in pro-environmental behavior? Or might the...
BACKGROUND
Climate anxiety is increasingly prevalent among adolescents worldwide. Are climate-anxious adolescents prone to engage in pro-environmental behavior? Or might the association between climate anxiety and pro-environmental be curvilinear, such that high levels of climate anxiety become 'paralyzing'? And do these associations depend on whether adolescents believe that, with effort, the worst impacts of climate change can still be prevented?
METHODS
We addressed these questions in three studies (two preregistered; combined N = 2,211), conducted across two countries. We used cross-sectional and longitudinal methods, and various measures of climate anxiety and pro-environmental behavior. We performed Bayesian regression analyses comparing two models that tested competing hypotheses. The first model included a linear effect of climate anxiety on pro-environmental behavior, and the second model included both a linear and a curvilinear (i.e. inverted U-shaped) effect of climate anxiety on pro-environmental behavior. Next, we added environmental efficacy to the best fitting model and explored its moderating effects.
RESULTS
Adolescents reported low-to-moderate levels of climate anxiety. Across the board, we found evidence for a small, positive, and mostly linear (rather than curvilinear) association between climate anxiety and pro-environmental behavior. While Study 1 supported a curvilinear association (Bayes Factor (BF) = 18.87), Studies 2 and 3 mostly supported a linear model (BFs range 6.86-12.71), except for weak support (BF = 1.62) for a curvilinear association between climate anxiety symptoms and public sphere pro-environmental behavior. Adolescents' environmental efficacy moderated this link for public sphere (e.g. activism), but not private sphere (e.g. recycling), pro-environmental behavior.
CONCLUSIONS
Climate-anxious adolescents are prone to engage in pro-environmental behavior. We found limited evidence for 'eco-paralysis' (i.e. a passive state of pro-environmental behavioral stasis) at high levels of climate anxiety. Our results are consistent with the possibility that supporting adolescents' environmental efficacy will help climate-anxious adolescents engage in public sphere pro-environmental behavior.
PubMed: 38940197
DOI: 10.1111/jcpp.14035 -
Bioinformatics (Oxford, England) Jun 2024Eukaryotic cells contain organelles called mitochondria that have their own genome. Most cells contain thousands of mitochondria which replicate, even in nondividing...
MOTIVATION
Eukaryotic cells contain organelles called mitochondria that have their own genome. Most cells contain thousands of mitochondria which replicate, even in nondividing cells, by means of a relatively error-prone process resulting in somatic mutations in their genome. Because of the higher mutation rate compared to the nuclear genome, mitochondrial mutations have been used to track cellular lineage, particularly using single-cell sequencing that measures mitochondrial mutations in individual cells. However, existing methods to infer the cell lineage tree from mitochondrial mutations do not model "heteroplasmy," which is the presence of multiple mitochondrial clones with distinct sets of mutations in an individual cell. Single-cell sequencing data thus provide a mixture of the mitochondrial clones in individual cells, with the ancestral relationships between these clones described by a mitochondrial clone tree. While deconvolution of somatic mutations from a mixture of evolutionarily related genomes has been extensively studied in the context of bulk sequencing of cancer tumor samples, the problem of mitochondrial deconvolution has the additional constraint that the mitochondrial clone tree must be concordant with the cell lineage tree.
RESULTS
We formalize the problem of inferring a concordant pair of a mitochondrial clone tree and a cell lineage tree from single-cell sequencing data as the Nested Perfect Phylogeny Mixture (NPPM) problem. We derive a combinatorial characterization of the solutions to the NPPM problem, and formulate an algorithm, MERLIN, to solve this problem exactly using a mixed integer linear program. We show on simulated data that MERLIN outperforms existing methods that do not model mitochondrial heteroplasmy nor the concordance between the mitochondrial clone tree and the cell lineage tree. We use MERLIN to analyze single-cell whole-genome sequencing data of 5220 cells of a gastric cancer cell line and show that MERLIN infers a more biologically plausible cell lineage tree and mitochondrial clone tree compared to existing methods.
AVAILABILITY AND IMPLEMENTATION
https://github.com/raphael-group/MERLIN.
Topics: Single-Cell Analysis; Humans; Cell Lineage; Mitochondria; Mutation; Genome, Mitochondrial; Algorithms; Evolution, Molecular
PubMed: 38940122
DOI: 10.1093/bioinformatics/btae231 -
Plant Biology (Stuttgart, Germany) Jun 2024In fire-prone ecosystems, plant traits are influenced by the fire regime, thus reproduction and establishment can be altered by this disturbance. Changes in fire...
In fire-prone ecosystems, plant traits are influenced by the fire regime, thus reproduction and establishment can be altered by this disturbance. Changes in fire frequency and history can therefore influence seed and germination traits. We investigated the effects of short-term fire exclusion on seed and germination traits of species from tropical open savannas. Seeds from 27 species were collected from two areas with distinct fire histories: recently and frequently burned (RB) or unburned for 5 to 7 years (E). Seeds from both areas underwent germination trials under optimal conditions for 30 days. Also, 10 species were exposed to high temperature treatments (100 or 200 °C) and seed and germination traits measured. Comparisons were then made for each trait, analysing each species separately, between the two areas. Approximately 85% of species studied had at least one of their germination traits altered in the RB area compared to the E area. Clear differences included lower viability and faster germination in seeds from RB areas. Seed traits of 70% of measured species differed between the two areas. Our results show species-specific trait response to different fire histories. For example, faster germination and lower viability of seeds from RB plots suggest selection for faster maturing individuals and differences in resourcing, respectively, under a regime of frequent fire. This study provides insights into fire effects on regeneration responses of tropical savanna species and also points to the need for more studies evaluating the effects of fire history on seed traits.
PubMed: 38940062
DOI: 10.1111/plb.13678 -
Annals of Ibadan Postgraduate Medicine Apr 2024A number of challenges are being faced by children in orphanages, a major one being their oral health as a common unmet need. Studies have shown high prevalence of...
BACKGROUND
A number of challenges are being faced by children in orphanages, a major one being their oral health as a common unmet need. Studies have shown high prevalence of dental caries and oro-facial trauma. This has been attributed to overcrowding, lack of adequate staff, poor oral hygiene, improper dietary habits, inadequacies in the orphanage system, as well as inadequacies in the healthcare system.This study aimed at assessing the prevalence and factors affecting dental caries and trauma among children in orphanages in Ibadan.
MATERIALS AND METHOD
All the children within the age group (7 - 15 years) in all the 18 registered orphanages in the 5 Local Government Areas within Ibadan metropolis were recruited into the study. Intra-oral examination was done under natural light and caries detection was done using tactile and visual method. Sterile mouth mirrors and CPI probes were used for this purpose. Dental caries status and the predisposing factors in each child were assessed. Presence of dental trauma and the predisposing factors were also assessed. Data processing was carried out with the aid of SPSS version 21.
RESULTS
One hundred and forty-six children participated in the study, 51.4% of them were males while 48.6% were females. The age range and the mean age of the children were 7 - 15 years 9. 69 ± 3.78 respectively. The prevalence of dental caries among the children was 17.8% while that of dental trauma was 7.5%. The mean DMFT/dmft was found to be 0.42 ± 1.06. Gender and the presence of deep pits and fissures were the statistically significant predictors of dental caries.
CONCLUSION
Oral health is of utmost importance across all ages, much more pertinent among institutionalized children who are prone to dental caries and trauma as revealed by this study. An average child in an orphanage may be affected by both dental caries and trauma, but appears to be more prone to dental caries in this environment.
PubMed: 38939878
DOI: No ID Found -
Gynecologic Oncology Reports Aug 2024Endometrial large cell neuroendocrine carcinoma (LCNEC) is a highly malignant tumor that presents with neuroendocrine function. It is difficult to diagnose at an early...
Endometrial large cell neuroendocrine carcinoma (LCNEC) is a highly malignant tumor that presents with neuroendocrine function. It is difficult to diagnose at an early stage. Moreover, the diagnosis depends on the pathological and immunohistochemical findings. It is also prone to distant metastasis, but is difficult to treat and shows poor prognosis. Presently, there exists no unified treatment plan, and the prognosis of this disease is also poor. We reported here an analysis and literature review of a case of endometrial LCNEC to facilitate the comprehension of this disease and provide help toward clinical diagnosis and treatment.
PubMed: 38939507
DOI: 10.1016/j.gore.2024.101429