Browse Articles

Cortical signatures linked to behavior quantitatively track arousal levels

While current arousal level assessments in patients with disorders of consciousness discriminate altered states of consciousness, there are significant limitations in characterizing the transition from one state to another or quantifying the frequent arousal level fluctuations observed in a patient. Here, we identified a repeated, temporally discrete, dynamical pattern evident in the recovery of consciousness from anesthesia and brain injury coma models in rodents. We prospectively validated these features we label “Arousal Units” (AU) in neonatal humans recovering from static hypoxic injuries and senior patients emerging from anesthesia indicating their generalizability. The AUs lawfully link changes in spectral power and breathing frequency and reliably associate with motor changes. Distinctive cortical patterns within AUs can be transformed into arousal indices, determining arousal levels. The reliability of these events is demonstrated across intact and brain-injured states and translates to the human brain; extracting these stereotyped dynamics could aid anesthesia monitoring, tracking coma recovery, and identifying cognitive motor dissociation.

Spinal posture, stiffness and motor control during pushing and pulling in flexion and active extension patterns of chronic nonspecific low back pain

The mediating role of anxiety between child abuse and pain among a sample of Lebanese adults

Exploiting thioether reactivity to label mycobacterial glycans

Mycobacterium tuberculosis ( Mtb ) is a leading cause of death worldwide. Mtb cell envelope glycans are potent virulence factors that play key roles in mediating infection of host tissues and modulating the host immune response. However, there are few ways to site-selectively modify and label these or any glycans to study their functions in disease. This gap arises because glycans generally lack functional groups amenable to bioconjugation strategies. Methylthioxylofuranose (MTX), a rare monosaccharide in select pathogenic mycobacteria, is an exception. MTX is appended to mannose-capped lipoarabinomannan (ManLAM), an antigenic glycolipid in the Mtb cell envelope implicated in downregulating the host immune system during infection. MTX is unique not only in its prevalence but also in its functionality—it contains a thioether not present in other glycans. We envisioned exploiting the MTX thioether to selectively label ManLAM with an oxaziridine probe. Here, we show that MTX-containing glycans can be labeled selectively in the test tube and live cells, highlighting the reactivity and accessibility of this motif. Our approach labels ManLAM efficiently despite the presence of protein methionine residues and can distinguish between different mycobacterial species. Using an oxaziridine equipped with a reporter, we could visualize ManLAM localization in live cells and a macrophage infection model, highlighting the stability of the label and the cell envelope in this environment. These studies will enable investigations of dynamic changes in a critical Mtb cell envelope component during infection. Moreover, the selective reactivity of thioethers can be leveraged to expand the repertoire of glycan bioconjugation strategies.

Computational assessment of blood lipid influence on hemodynamics in human retinal vessels

Response surface optimization reveals monthly total flavonoid peaks in Ginkgo biloba leaves with corresponding DPPH scavenging activity

Single-cell elderly blood–CSF atlas implicates peripherally influenced immune dysregulation in normal pressure hydrocephalus

We have generated a single-cell RNA sequencing atlas of peripheral blood and ventricular CSF in idiopathic normal pressure hydrocephalus (iNPH) patients totaling 140,207 single-cell transcriptomes. We found proinflammatory alterations in peripheral blood and CSF monocytes in iNPH patients with lower baseline cognitive function. We also identified CSF cell populations likely representing periventricular sloughing of degenerating neuroglial cells. Our findings suggest possible immune dysregulation in the blood and CSF of iNPH patients.

Age dependent susceptibility and immune responses to La Crosse virus infection in non-human primates

Abstract La Crosse virus (LACV) is a primary cause of pediatric viral encephalitis in the United States but rarely causes disease in adults. We tested whether cynomolgus macaques displayed a similar age-dependent susceptibility to LACV. Immune responses from naïve or LACV infected weanling (9–15 months), juvenile (19–23 months) or adult (> 6 years) animals were measured and infected animals were monitored for disease. Naïve weanling animals had fewer dendritic cells in their blood and weaker induction of IFN-stimulated genes (ISG) and chemokines when PBMCs were stimulated in vitro. While no infected animals developed disease, the weaker innate response in naive weanlings correlated with increased viral RNA in plasma from 2 of 3 infected weanlings out to 7 days post infection (dpi). Activated CD8 + T cells and neutralizing antibody proportions were similar amongst all ages. However, CD4 + T cells proportions were increased in young animals relative to adults. This suggests the CD4 + adaptive response in young animals may be bolstering an initially weak innate response to clear virus. Finally, because macaques were resistant to disease, we infected 3 common marmosets intranasally with LACV. Marmoset were selected due to their susceptibility to viral encephalitis. Although no animals showed disease signs, one animal had evidence of infection in the nasal mucosa out to 23 days with associated vacuolization, edema and immune cell infiltration.

Activity and structure of human (d)CTP deaminase CDADC1

Vertebrates have evolved an understudied protein termed CDADC1 (NYD-SP15) that contains an inactive N-terminal and active C-terminal DCTD-like domain. Here, we show that human CDADC1 is a (d)CTP-specific deaminase, with a roughly 2-fold in vitro preference for dCTP over CTP. We determined high-resolution cryo-EM structures of CDADC1 in the absence of substrate and in complex with dCTP and 5-methyl-dCTP. The structures show that CDADC1 forms trimers and dimers of trimers in solution. The (d)CTP substrate is selected by a narrow pocket for the cytosine base and multiple lysine and arginine contacts to the triphosphate. Substrate binding promotes the association of trimers into hexamers and the transition of the hexamers from a loose to a tighter arrangement. Genetic experiments in mice show that loss of Cdadc1 is surprisingly well tolerated, even in the absence of the dCMP deaminase Dctd that is considered as the main source of dUMP, the precursor of dTTP.

Embedded feature fusion for multi-label criteria selection via local search strategy and particle swarm optimization

Structure and nucleic acid interactions of the S ^Δ60 domain of the hepatitis delta virus small antigen

Infection with hepatitis delta virus (HDV) causes the most severe form of viral hepatitis, affecting more than 15 million people worldwide. HDV is a small RNA satellite virus of the hepatitis B virus (HBV) that relies on the HBV envelope for viral particle assembly. The only specific HDV component is the ribonucleoprotein (RNP), which consists of viral RNA (vRNA) associated with the small (S) and large (L) delta antigens (HDAg). While the structure of the HDAg N-terminal assembly domain is known, here we address the structure of the remaining S Δ60 protein using NMR. We show that S Δ60 contains two intrinsically disordered regions separated by a helix–loop–helix motif and that this structure is conserved in the full-length protein. Solution NMR analysis revealed that S Δ60 binds to both full-length and truncated vRNA, highlighting the role of the helical regions in submicromolar affinity interactions. The resulting complex contains approximately 120 S Δ60 proteins per RNA. Our results provide a model for the arginine-rich domains in RNP assembly and RNA interactions. In addition, we show that a cluster of acidic residues within the structured region of S Δ60 is critical for HDV replication, possibly mimicking the nucleosome acidic patch involved in the recruitment of chromatin remodelers. Our work thus provides the molecular basis for understanding the role of the C-terminal RNA-binding domain of S-HDAg in HDV infection.

Modelling species distribution of Anopheles gambiae s.l. in Osun state using random forest modeling approach

Incorporation of polylactic acid microplastics into the carbon cycle as a carbon source to remodel the endogenous metabolism of the gut

Biodegradable polylactic acid (PLA) plastics have been praised as an effective solution to the global pollution caused by petroleum-based plastics, and their widespread use in food packaging and disposable tableware has resulted in increased oral exposure to PLA microplastics (PLA-MPs). Despite their eco-friendly and biodegradable reputation, the in vivo behaviors of PLA-MPs concerning fermentation, carbon cycle, and adverse effects remain unknown. Here, we showed that gut microbiota from the colon can effectively degrade the PLA-MPs by secreting esterase FrsA, whereas esterase FrsA-producing bacteria were identified to dominate this behavior in male C57BL/6 mice. Using isotope tracing and multiomics techniques, we uncovered that 13 C-labeled PLA-MPs were incorporated into the carbon cycle of gut microbiota as a carbon source. Meanwhile, these degraded PLA-MPs fragments entered the succinate pathway of the tricarboxylic acid cycle within gut epithelial cells. These processes altered the metabolic phenotype of the gut, resulting in the decreased linear short-chain fatty acids that are primary energy sources of the gut epithelium. Furthermore, we found that exposure of PLA-MPs significantly reduced the appetite and body weight of mice. Our findings present an overall process of biodegradable plastics within hosts, with the focus on the entire double carbon cycle of PLA-MPs in the gut, which offers indispensable insights into the potential impact of exposure to PLA-MPs.

‘Unemat Rubi’, a new spineless pineapple cultivar and resistant to fusariosis for the international market

Abstract Pineapple cultivation worldwide depends on a limited number of cultivars. In Brazil, the cultivar ‘‘Pérola’’ accounts for 85% of the commercial planted area but is susceptible to fusariosis, the most significant disease affecting pineapple crops. This study introduces the cultivar ‘Unemat Rubi’, emphasizing its superior fruit quality and resistance to fusariosis through multivariate analyses, correlation networks, and genetic parameters. Eighteen genotypes were evaluated for qualitative and quantitative traits and resistance to fusariosis, using a randomized block design with five replications and 20 plants per plot. The genotypes were grouped into two main clusters based on their resistance or susceptibility to fusariosis. ‘Unemat Rubi’ was classified in Cluster I, along with its female parent (‘BRS Imperial’), sharing resistance to fusariosis, cylindrical fruits with yellow pulp, and no leaf spines. However, ‘Unemat Rubi’ was superior to ‘BRS Imperial’ in terms of fruit weight and diameter, presenting a mass above 1.5 kg and an average diameter above 10 cm. No correlations were observed between the groups of chemical and physical traits of fruit and resistance to fusariosis, only between the groups of physical and chemical traits. There was a high and positive correlation for FMWOC and FMWC (0.99) and a strong and significant correlation between DLL with FMWOC and FMWC, both with 0.74. Heritability estimates exceeded 90% for most traits, except for fruit diameter. The cultivar ‘Unemat Rubi’, registered at the Brazilian Ministry of Agriculture and Livestock under number 56,622, represents a significant advancement in pineapple breeding by integrating superior fruit quality with fusariosis resistance, making it a promising candidate for commercial expansion.

Peri-coronary adipose tissue attenuation and its association with plaque vulnerability and clinical outcomes in coronary artery disease using combined CCTA and OCT

Recent updates of the MPEXS2.1-DNA Monte Carlo code for simulations of water radiolysis under ion irradiation

Abstract To improve radiotherapy, especially that with ion beams such as proton and carbon ion beams, the mechanisms of interactions induced by ionizing radiation must be understood. MPEXS2.1-DNA is a Monte Carlo simulation code developed for water radiolysis studies and DNA damage simulations that uses GPU devices for fast computation. However, the original chemistry model in MPEXS2.1-DNA did not include detailed chemical reactions for reactive oxygen species (ROS), e.g., O•-, O2, O2 •-, HO2 •, HO2 -. In the present study, drawing the former work on the step-by-step (SBS) model for the RITRACKS code, we implemented an alternative SBS model into MPEXS2.1-DNA to increase the capabilities and computational speed of water radiolysis simulations under ion irradiation. This model is based on the theory of Green’s function of the diffusion equation (GFDE-SBS). Also, we implemented multiple ionization processes which enhance ROS generation under high-LET irradiation. We compared the simulation results obtained by GFDE-SBS with experimental data from previous studies. The validation results demonstrated that the GFDE-SBS model accurately reproduced the measured radiation chemical yields of major species, such as hydroxyl radicals and hydrogen peroxide. Furthermore, the computational speed of GFDE-SBS was increased approximately ten times faster than the original model due to the changes in time stepping. Additionally, simulations using a Fricke dosimeter confirmed that this model is reliable for long-term simulations over seconds. These improvements enable simulations of radiation interactions and can help in the study of DNA damage mechanisms.

Development of a flavour wheel for Coffea canephora using rate-all-that-apply

Modeling the functionalized genistein-hyoscyamine derivatives

Abstract Due to the significant rise in demand for functional foods and health-conscious alternatives, natural extracts present a promising avenue for exploration and application within the food processing sector. For many individuals suffering from monosymptomatic nocturnal enuresis (MNE) and its accompanying complications, supplying the market with a functional food that aids accelerating resolving this problem will be a very valuable addition. Thus, in this study we aimed to validate and functionalize modeled composite of Genistein-Hyoscyamine as to further employ the best match in food processing sector as a novel food-additive for functional-foods serving enuretic patients. In attempts to model the most chemically favorable and experimentally achievable composite structures we thoroughly studied the parent molecules employing various DFT descriptors, selected electronic and thermodynamic parameters that help foresee and assess the structures’ behavior and stability in various conditions that are common during food processing. Afterwards, composites were primarily assessed through selected ADME parameters in regard to their suitability for ingestion, water solubility, GI absorption, bioavailability score, and synthetic accessibility. Based on the screening of modeled structures, composites number 02 and 04 were found to possess the most favorable structures and characteristics where composite number 02 has shown relatively higher band gap energy and dipole moment as well as slightly more heat capacity; while composite number 04 has shown higher lipophilicity as well as lower TPSA value, less enthalpy, free energy, and entropy, suggesting more stability and bioavailability. Highlighting their suitability for being introduced to food matrices as food-additives in the form of composite bioactive materials.

Dynamic interplay between niche variation and flight adaptability drove a hundred million years’ dispersion in iconic lacewings

The form and change of animal biogeography reflects the long-term interplay between organisms and their environment, involving physiological limitation, dispersal capability, and adaptive evolution versus plate tectonics, global climatic shifts, and changing landscapes. This is especially manifest for lineages with extended geological histories, which, therefore, evokes questions as to the associated processes producing such patterns. Insects, as the earliest flying animals, have exceptional abilities for expanding their range and habitats and to avoid detrimental conditions. They are ideal for exploring historical biogeography augmented via adaptation. Here, we employ beaded lacewings as a model to explore such patterns and likely processes, particularly given that they differ notably from the commonly observed pattern of a latitudinal diversity gradient. Furthermore, owing to their good fossil record it can be observed that their distributions varied remarkably through time. Ecological niche modeling and evaluation demonstrate their niche variation and niche breadth expansion intermittently accompanying global climate change. However, different niche relevant variables changed under patterns of either phylogenetic conservatism or evolutionary lability. By assessing wing morphological disparity and modeling flight aerodynamics, we uncovered a continuous improvement of flight efficiency through beaded-lacewing history as well as a Paleogene divergence in strategy, which reveals a long-term associated path with the niche variation. Our results unveil the adaptive evolution and dispersal history of beaded lacewings through 170 My, achieved by dynamic strategies in niche shift and flight adaptation as responses to a changing planet.

Experimental study on energy evolution and damage characteristics of unloading coal under cyclic loading