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Nature Feb 2024HIV can infect non-dividing cells because the viral capsid can overcome the selective barrier of the nuclear pore complex and deliver the genome directly into the...
HIV can infect non-dividing cells because the viral capsid can overcome the selective barrier of the nuclear pore complex and deliver the genome directly into the nucleus. Remarkably, the intact HIV capsid is more than 1,000 times larger than the size limit prescribed by the diffusion barrier of the nuclear pore. This barrier in the central channel of the nuclear pore is composed of intrinsically disordered nucleoporin domains enriched in phenylalanine-glycine (FG) dipeptides. Through multivalent FG interactions, cellular karyopherins and their bound cargoes solubilize in this phase to drive nucleocytoplasmic transport. By performing an in vitro dissection of the nuclear pore complex, we show that a pocket on the surface of the HIV capsid similarly interacts with FG motifs from multiple nucleoporins and that this interaction licences capsids to penetrate FG-nucleoporin condensates. This karyopherin mimicry model addresses a key conceptual challenge for the role of the HIV capsid in nuclear entry and offers an explanation as to how an exogenous entity much larger than any known cellular cargo may be able to non-destructively breach the nuclear envelope.
Topics: Humans; Active Transport, Cell Nucleus; Capsid Proteins; Diffusion; Dipeptides; Glycine; HIV; In Vitro Techniques; Intrinsically Disordered Proteins; Karyopherins; Molecular Mimicry; Nuclear Pore; Nuclear Pore Complex Proteins; Permeability; Phenylalanine; Solubility; Virus Internalization; Capsid
PubMed: 38267582
DOI: 10.1038/s41586-023-06969-7 -
Materials (Basel, Switzerland) Feb 2024Hydrogen embrittlement (HE) is a broadly recognized phenomenon in metallic materials. If not well understood and managed, HE may lead to catastrophic environmental... (Review)
Review
Hydrogen embrittlement (HE) is a broadly recognized phenomenon in metallic materials. If not well understood and managed, HE may lead to catastrophic environmental failures in vessels containing hydrogen, such as pipelines and storage tanks. HE can affect the mechanical properties of materials such as ductility, toughness, and strength, mainly through the interaction between metal defects and hydrogen. Various phenomena such as hydrogen adsorption, hydrogen diffusion, and hydrogen interactions with intrinsic trapping sites like dislocations, voids, grain boundaries, and oxide/matrix interfaces are involved in this process. It is important to understand HE mechanisms to develop effective hydrogen resistant strategies. Tensile, double cantilever beam, bent beam, and fatigue tests are among the most common techniques employed to study HE. This article reviews hydrogen diffusion behavior, mechanisms, and characterization techniques.
PubMed: 38399215
DOI: 10.3390/ma17040965 -
Sleep Medicine Sep 2023This study aimed to explore the characteristics of sleep disorders and their relationship with abnormal white-matter integrity in patients with sporadic amyotrophic...
This study aimed to explore the characteristics of sleep disorders and their relationship with abnormal white-matter integrity in patients with sporadic amyotrophic lateral sclerosis. One hundred and thirty-six patients and 80 healthy controls were screened consecutively, and 56 patients and 43 healthy controls were ultimately analyzed. Sleep disorders were confirmed using the Pittsburgh sleep quality index, the Epworth sleepiness scale, and polysomnography; patients were classified into those with poor and good sleep quality. White-matter integrity was assessed using diffusion tensor imaging and compared between groups to identify the white-matter tracts associated with sleep disorders. The relationship between scores on the Pittsburgh sleep quality index and impaired white-matter tracts was analyzed using multiple regression. Poor sleep quality was more common in patients (adjusted odds ratio, 4.26; p = 0.005). Compared to patients with good sleep quality (n = 30), patients with poor sleep quality (n = 26; 46.4%) showed decreased fractional anisotropy, increased mean diffusivity, and increased radial diffusivity of projection and commissural fibers, and increased radial diffusivity of the right thalamus. The Pittsburgh score showed the best fit with the mean fractional anisotropy of the right anterior limb of the internal capsule (r = - 0.355, p = 0.011) and the mean radial diffusivity of the right thalamus (r = 0.309, p = 0.028). We conclude that sleep disorders are common in patients with sporadic amyotrophic lateral sclerosis and are associated with reduced white-matter integrity. The pathophysiology of amyotrophic lateral sclerosis may contribute directly to sleep disorders.
Topics: Humans; Amyotrophic Lateral Sclerosis; White Matter; Diffusion Tensor Imaging; Extremities; Sleep Initiation and Maintenance Disorders
PubMed: 37459708
DOI: 10.1016/j.sleep.2023.07.003 -
Scientific Reports Nov 2023MRI scanner hardware, field strengths, and sequence parameters are major variables in diffusion studies of the spinal cord. Reliability between scanners is not well...
MRI scanner hardware, field strengths, and sequence parameters are major variables in diffusion studies of the spinal cord. Reliability between scanners is not well known, particularly for the thoracic cord. DTI data was collected for the entire cervical and thoracic spinal cord in thirty healthy adult subjects with different MR vendors and field strengths. DTI metrics were extracted and averaged for all slices within each vertebral level. Metrics were examined for variability and then harmonized using longitudinal ComBat (longComBat). Four scanners were used: Siemens 3 T Prisma, Siemens 1.5 T Avanto, Philips 3 T Ingenia, Philips 1.5 T Achieva. Average full cord diffusion values/standard deviation for all subjects and scanners were FA: 0.63, σ = 0.10, MD: 1.11, σ = 0.12 × 10 mm/s, AD: 1.98, σ = 0.55 × 10 mm/s, RD: 0.67, σ = 0.31 × 10 mm/s. FA metrics averaged for all subjects by level were relatively consistent across scanners, but large variability was found in diffusivity measures. Coefficients of variation were lowest in the cervical region, and relatively lower for FA than diffusivity measures. Harmonized metrics showed greatly improved agreement between scanners. Variability in DTI of the spinal cord arises from scanner hardware differences, pulse sequence differences, physiological motion, and subject compliance. The use of longComBat resulted in large improvement in agreement of all DTI metrics between scanners. This study shows the importance of harmonization of diffusion data in the spinal cord and potential for longitudinal and multisite clinical research and clinical trials.
Topics: Adult; Humans; Diffusion Tensor Imaging; Reproducibility of Results; Spinal Cord; Diffusion Magnetic Resonance Imaging; Spinal Cord Injuries; Cervical Cord
PubMed: 37957164
DOI: 10.1038/s41598-023-46465-6 -
PNAS Nexus Aug 2023Soluble oligomers produced during protein aggregation have been thought to be toxic species causing various diseases. Characterization of these oligomers is difficult...
Soluble oligomers produced during protein aggregation have been thought to be toxic species causing various diseases. Characterization of these oligomers is difficult because oligomers are a heterogeneous mixture, which is not readily separable, and may appear transiently during aggregation. Single-molecule spectroscopy can provide valuable information by detecting individual oligomers, but there have been various problems in determining the size and concentration of oligomers. In this work, we develop and use a method that analyzes single-molecule fluorescence burst data of freely diffusing molecules in solution based on molecular diffusion theory and maximum likelihood method. We demonstrate that the photon count rate, diffusion time, population, and Förster resonance energy transfer (FRET) efficiency can be accurately determined from simulated data and the experimental data of a known oligomerization system, the tetramerization domain of p53. We used this method to characterize the oligomers of the 42-residue amyloid-β (Aβ42) peptide. Combining peptide incubation in a plate reader and single-molecule free-diffusion experiments allows for the detection of stable oligomers appearing at various stages of aggregation. We find that the average size of these oligomers is 70-mer and their overall population is very low, less than 1 nM, in the early and middle stages of aggregation of 1 µM Aβ42 peptide. Based on their average size and long diffusion time, we predict the oligomers have a highly elongated rod-like shape.
PubMed: 37564361
DOI: 10.1093/pnasnexus/pgad253 -
International Journal of Molecular... Aug 2023The mixed ionic and electronic oxide LaNiFeO (LNF) is a promising ceramic cathode material for solid oxide fuel cells. Since the reaction rate of oxygen interaction with...
The mixed ionic and electronic oxide LaNiFeO (LNF) is a promising ceramic cathode material for solid oxide fuel cells. Since the reaction rate of oxygen interaction with the cathode material is extremely important, the present work considers the oxygen exchange mechanism between O and LNF oxide. The kinetic dependence of the oxygen/oxide interaction has been determined by two isotopic methods using O-labelled oxygen. The application of the isotope exchange with the gas phase equilibrium (IE-GPE) and the pulsed isotope exchange (PIE) has provided information over a wide range of temperatures (350-800 °C) and oxygen pressures (10-200 mbar), as each method has different applicability limits. Applying mathematical models to treat the kinetic relationships, the oxygen exchange rate (, atom × cm × s) and the diffusion coefficient (, cm/s) were calculated. The values of and depend on both temperature and oxygen pressure. The activation energy of the surface exchange rate is 0.73 ± 0.05 eV for the PIE method at 200 mbar, and 0.48 ± 0.02 eV for the IE-GPE method at 10-20 mbar; for the diffusion coefficient, the activation energy equals 0.62 ± 0.01 eV at 10-20 mbar for the IE-GPE method. Differences in the mechanism of oxygen exchange and diffusion on dense and powder samples are observed due to the different microstructure and surface morphology of the samples. The influence of oxygen pressure on the ratio of contributions of different exchange types to the total oxygen exchange rate is demonstrated. For the first time, the rate-determining step in the oxygen exchange process for LNF material has been identified. This paper discusses the reasons for the difference in the mechanisms of oxygen exchange and diffusion.
Topics: Oxygen; Gases; Ceramics; Diffusion; Oxides
PubMed: 37629194
DOI: 10.3390/ijms241613013 -
JTO Clinical and Research Reports Nov 2023Pervious studies reported the association of TTF-1 expression with the efficacy of platinum-doublet chemotherapy in combination with immune checkpoint inhibitors in...
Predictive Impact of Diffuse Positivity for TTF-1 Expression in Patients Treated With Platinum-Doublet Chemotherapy Plus Immune Checkpoint Inhibitors for Advanced Nonsquamous NSCLC.
INTRODUCTION
Pervious studies reported the association of TTF-1 expression with the efficacy of platinum-doublet chemotherapy in combination with immune checkpoint inhibitors in advanced nonsquamous NSCLC. Nevertheless, the predictive value of extent of TTF-1 expression (diffuse or focal TTF-1 positivity) remains unclear.
METHODS
The present study retrospectively reviewed 74 patients with TTF-1-positive recurrent or advanced nonsquamous NSCLC receiving first-line chemoimmunotherapy in a single institution in Japan. TTF-1 expression score in pretreatment tumor specimens was evaluated using immunohistochemistry, and the impact of chemoimmunotherapy response was analyzed.
RESULTS
In the total cohort, ≥50% of the tumor cells were TTF-1 positive (i.e., diffusely TTF-1 positive) in specimens of 61 patients (82.4%), whereas 10% to 49% of the tumor cells were TTF-1 positive (i.e., focally TTF-1 positive) in specimens of the remaining 13 patients (17.6%). In multivariate analysis, the median progression-free survival and overall survival (OS) were significantly longer in patients with diffusely TTF-1-positive tumors than in those with focally TTF-1-positive tumors (14.2 versus 9.2 mo, = 0.01 and 30.2 versus 17.3 mo, = 0.01, respectively). Moreover, the median OS was significantly longer in patients receiving chemoimmunotherapy including pemetrexed than in those receiving chemoimmunotherapy not including pemetrexed among the patients with diffusely TTF-1-positive tumors (not attained versus 23.2 mo, < 0.01).
CONCLUSIONS
The positive extent of diffuse TTF-1 expression associated with patient outcome was an independent predictive factor for better progression-free survival and OS in patients with advanced nonsquamous NSCLC receiving chemoimmunotherapy.
PubMed: 37885809
DOI: 10.1016/j.jtocrr.2023.100578 -
Bioinformatics (Oxford, England) Dec 2023Microbiota data encounters challenges arising from technical noise and the curse of dimensionality, which affect the reliability of scientific findings. Furthermore,...
MOTIVATION
Microbiota data encounters challenges arising from technical noise and the curse of dimensionality, which affect the reliability of scientific findings. Furthermore, abundance matrices exhibit a zero-inflated distribution due to biological and technical influences. Consequently, there is a growing demand for advanced algorithms that can effectively recover missing taxa while also considering the preservation of data structure.
RESULTS
We present mb-PHENIX, an open-source algorithm developed in Python that recovers taxa abundances from the noisy and sparse microbiota data. Our method infers the missing information of count matrix (in 16S microbiota and shotgun studies) by applying imputation via diffusion with supervised Uniform Manifold Approximation Projection (sUMAP) space as initialization. Our hybrid machine learning approach allows to denoise microbiota data, revealing differential abundance microbes among study groups where traditional abundance analysis fails.
AVAILABILITY AND IMPLEMENTATION
The mb-PHENIX algorithm is available at https://github.com/resendislab/mb-PHENIX. An easy-to-use implementation is available on Google Colab (see GitHub).
Topics: Reproducibility of Results; Microbiota; Algorithms; Machine Learning; Diffusion
PubMed: 38015858
DOI: 10.1093/bioinformatics/btad706 -
Materials (Basel, Switzerland) Oct 2023Ni-based superalloys are materials utilized in high-performance services that demand excellent corrosion resistance and mechanical properties. Its usages can include...
Ni-based superalloys are materials utilized in high-performance services that demand excellent corrosion resistance and mechanical properties. Its usages can include fuel storage, gas turbines, petrochemistry, and nuclear reactor components, among others. On the other hand, hydrogen (H), in contact with metallic materials, can cause a phenomenon known as hydrogen embrittlement (HE), and its study related to the superalloys is fundamental. This is related to the analysis of the solubility, diffusivity, and permeability of H and its interaction with the bulk, second-phase particles, grain boundaries, precipitates, and dislocation networks. The aim of this work was mainly to study the effect of chromium (Cr) content on H diffusivity in Ni-based superalloys; additionally, the development of predictive models using artificial intelligence. For this purpose, the permeability test was employed based on the double cell experiment proposed by Devanathan-Stachurski, obtaining the effective diffusion coefficient (D), steady-state flux (J), and the trap density (N) for the commercial and experimentally designed and manufactured Ni-based superalloys. The material was characterized with energy-dispersed X-ray spectroscopy (EDS), atomic absorption, CHNS/O chemical analysis, X-ray diffraction (XRD), brightfield optical microscopy (OM), and scanning electron microscopy (SEM). On the other hand, predictive models were developed employing artificial neural networks (ANNs) using experimental results as a database. Furthermore, the relative importance of the main parameters related to the H diffusion was calculated. The D, J, and N achieved showed relatively higher values considering those reported for Ni alloys and were found in the following orders of magnitude: [1 × 10, 1 × 10 m/s], [1 × 10, 9 × 10 mol/cms], and [7 × 10 traps/m], respectively. Regarding the predictive models, linear correlation coefficients of 0.96 and 0.80 were reached, corresponding to the D and J. Due to the results obtained, it was suitable to dismiss the effect of Cr in solid solution on the H diffusion. Finally, the predictive models developed can be considered for the estimation of D and J as functions of the characterized features.
PubMed: 37895604
DOI: 10.3390/ma16206622 -
Human Brain Mapping Jul 2023This study investigated associations between psychological resilience and characteristics of white matter microstructure in pediatric concussion. This is a case control... (Randomized Controlled Trial)
Randomized Controlled Trial
This study investigated associations between psychological resilience and characteristics of white matter microstructure in pediatric concussion. This is a case control study and a planned substudy of a larger randomized controlled trial. Children with an acute concussion or orthopedic injury were recruited from the emergency department. Participants completed both the Connor-Davidson Resilience Scale 10 and an MRI at 72 h and 4-weeks post-injury. The association between resiliency and fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) at both timepoints were examined. We examined whether these associations were moderated by group. The association between resiliency captured at 72 h and diffusion tensor imaging metrics at 4 weeks was also investigated. Clusters were extracted using a significance threshold of threshold-free cluster enhancement corrected p < .05. A total of 66 children with concussion (median (IQR) age = 12.88 (IQR: 11.80-14.36); 47% female) and 29 children with orthopedic-injury (median (IQR) age = 12.49 (IQR: 11.18-14.01); 41% female) were included. A negative correlation was identified in the concussion group between 72 h resilience and 72 h FA. Meanwhile, positive correlations were identified in the concussion group with concussion between 72 h resilience and both 72 h MD and 72 h RD. These findings suggest that 72 h resilience is associated with white matter microstructure of the forceps minor, superior longitudinal fasciculus, and anterior thalamic radiation at 72 h post-concussion. Resilience seems to be associated with neural integrity only in the acute phase of concussion and thus may be considered when researching concussion recovery.
Topics: Humans; Child; Female; Male; White Matter; Diffusion Tensor Imaging; Brain; Resilience, Psychological; Benchmarking; Case-Control Studies; Brain Concussion; Anisotropy
PubMed: 37126608
DOI: 10.1002/hbm.26321