Exploring the Impact of Amidation Status in -Diaminopimelic-Acid-Containing Disaccharide Peptidoglycan Fragments on Host Innate Immune Activation.

Bacterial peptidoglycan, the essential cell surface polymer that protects bacterial integrity, also serves as the molecular pattern recognized by the host's innate immune system. Although the minimal motifs of bacterial peptidoglycan fragments (PGNs) that activate mammalian NOD1 and NOD2 sensors are well-known and often represented by small canonical ligands, the immunostimulatory effects of natural PGNs, which are structurally more complex and potentially can simultaneously activate both the NOD1 and NOD2 signaling pathways in hosts, have not been comprehensively investigated. In particular, many bacteria incorporate additional structural modifications in peptidoglycans to evade host immune surveillance, resulting in diverse structural variations among natural PGNs that may influence their biological effects in hosts.

Biochemical Characterization of Recombinant EntV Peptide to Elucidate Its Antihyphal and Antifungal Mechanisms against .

is a common opportunistic fungus in humans, whose morphological switch between yeast and hyphae forms represents a key virulence trait. Developing strategies to inhibit hyphal growth may provide insights into designs of novel antivirulent therapeutics. Importantly, the gut commensal bacterium, , secretes a bacteriocin EntV which has potent antivirulent and antifungal effects against in infection models; however, hampered by the challenges to access large quantities of bioactive EntV, the detailed understanding of its mechanisms on has remained elusive.

Correction: A closer look at ligand specificity for cellular activation of NOD2 with synthetic muramyl dipeptide analogues.

Correction for 'A closer look at ligand specificity for cellular activation of NOD2 with synthetic muramyl dipeptide analogues' by Christopher Adamson , , 2024, , 2212-2215, https://doi.org/10.1039/D3CC05807G.

A closer look at ligand specificity for cellular activation of NOD2 with synthetic muramyl dipeptide analogues.

To further understand the specificity of muramyl dipeptide (MDP) sensing by NOD2, we evaluated the compatibility of synthetic MDP analogues for cellular uptake and NAGK phosphorylation, the pre-requisite steps of intracellular NOD2 activation. Our results revealed that these two prior steps do not confer ligand stereoselectivity; yet NAGK strictly discriminates against the disaccharide NOD2 agonists for phosphorylation , despite it being indispensable for the cellular NOD2-stimulating effects of these analogues, implying potential glycosidase cleavage as a novel intermediate step for cellular activation of NOD2.

Chemoenzymatic Probes Reveal Peptidoglycan Recognition and Uptake Mechanisms in .

, the major fungal pathogen in humans, is under the strong influence of bacterial peptidoglycan fragments to undergo the yeast-to-hyphae transition, a key virulent step in pathogenesis and infections. However, due to the synthetic difficulties of obtaining peptidoglycan fragments for biological studies, mechanistic details of how recognizes and uptakes these peptidoglycan fragments have not been well elucidated. Notably, previous works have solely focused on the synthetic peptidoglycan ligand, muramyl dipeptide (MDP), despite its poor hyphal-inducing activity in .

Association of Prenatal Exposure to Early-Life Adversity With Neonatal Brain Volumes at Birth.

Importance: Exposure to early-life adversity alters the structural development of key brain regions underlying neurodevelopmental impairments. The association between prenatal exposure to adversity and brain structure at birth remains poorly understood.

Objective: To examine whether prenatal exposure to maternal social disadvantage and psychosocial stress is associated with neonatal global and regional brain volumes and cortical folding.

Brain White Matter Development Over the First 13 Years in Very Preterm and Typically Developing Children Based on the -w/ -w Ratio.

Background And Objectives: To investigate brain regional white matter development in full-term (FT) and very preterm (VP) children at term equivalent and 7 and 13 years of age based on the ratio of - and -weighted MRI ( -w/ -w), including (1) whether longitudinal changes differ between birth groups or sexes, (2) associations with perinatal risk factors in VP children, and (3) relationships with neurodevelopmental outcomes at 13 years.

Methods: Prospective longitudinal cohort study of VP (born <30 weeks' gestation or <1,250 g) and FT infants born between 2001 and 2004 and followed up at term equivalent and 7 and 13 years of age, including MRI studies and neurodevelopmental assessments. -w/ -w images were parcellated into 48 white matter regions of interest.

The Structural Connectome and Internalizing and Externalizing Symptoms at 7 and 13 Years in Individuals Born Very Preterm and Full Term.

Background: Children born very preterm (VP) are at higher risk of emotional and behavioral problems compared with full-term (FT) children. We investigated the neurobiological basis of internalizing and externalizing symptoms in individuals born VP and FT by applying a graph theory approach.

Methods: Structural and diffusion magnetic resonance imaging data were combined to generate structural connectomes and calculate measures of network integration and segregation at 7 (VP: 72; FT: 17) and 13 (VP: 125; FT: 44) years.

Live-Cell Protein Modification by Boronate-Assisted Hydroxamic Acid Catalysis.

Selective methods for introducing protein post-translational modifications (PTMs) within living cells have proven valuable for interrogating their biological function. In contrast to enzymatic methods, abiotic catalysis should offer access to diverse and new-to-nature PTMs. Herein, we report the boronate-assisted hydroxamic acid (BAHA) catalyst system, which comprises a protein ligand, a hydroxamic acid Lewis base, and a diol moiety.

Diversity-oriented synthesis of glycomimetics.

Glycomimetics are structural mimics of naturally occurring carbohydrates and represent important therapeutic leads in several disease treatments. However, the structural and stereochemical complexity inherent to glycomimetics often challenges medicinal chemistry efforts and is incompatible with diversity-oriented synthesis approaches. Here, we describe a one-pot proline-catalyzed aldehyde α-functionalization/aldol reaction that produces an array of stereochemically well-defined glycomimetic building blocks containing fluoro, chloro, bromo, trifluoromethylthio and azodicarboxylate functional groups.

Integrating abiotic chemical catalysis and enzymatic catalysis in living cells.

Life emerges from networks of multiple chemical reactions mediated by enzymes. If abiotic chemical catalysis is implanted into the reaction network of life, such an integration would produce organisms generating unique secondary metabolites and value-added materials from feedstocks or even air, or new diagnostics and therapeutics against diseases. In this review, we introduce selected papers in this emerging field of catalysis research.

Cortisol is not associated with pre-treatment medial temporal lobe volume or volume changes after electroconvulsive therapy in patients with late-life depression.

Accumulating evidence suggests that late-life depression is associated with reduced hippocampal volume and that cortisol might be related to this volumetric reduction. We explored whether cortisol awaking response (CAR), which is the increase in cortisol after awakening, was associated with volumetric changes in the medial temporal lobe (MTL) after electroconvulsive therapy (ECT) in 41 patients (age ≥ 55) treated for major depressive disorder (MDD) with ECT. Cortisol was measured before the start of the ECT treatment and was related to MTL volumes derived from structural T1-weighted images.

Marker-based watershed transform method for fully automatic mandibular segmentation from CBCT images.

Objectives:: To propose a reliable and practical method for automatically segmenting the mandible from CBCT images.

Methods:: The marker-based watershed transform is a region-growing approach that dilates or "floods" predefined markers onto a height map whose ridges denote object boundaries. We applied this method to segment the mandible from the rest of the CBCT image.

Corpus callosum macro and microstructure in late-life depression.

Background: Differences in corpus callosum (CC) morphology and microstructure have been implicated in late-life depression and may distinguish between late and early-onset forms of the illness. However, a multimodal approach using complementary imaging techniques is required to disentangle microstructural alterations from macrostructural partial volume effects.

Methods: 107 older adults were assessed: 55 currently-depressed patients without dementia and 52 controls without cognitive impairment.

Brain connectivity networks and longitudinal trajectories of depression symptoms in adolescence.

High levels of depression during adolescence may contribute to the risk for future depression later in life. This study examined the relationship between the developmental timing of depressive symptoms, and brain structural outcomes in late adolescence. In a prior work, we examined longitudinal trajectories of depressive symptoms in 243 adolescents (121 males and 122 females), and identified four subgroups: a normative group with stable low levels of depression, two groups with declining symptoms, and one group with increasing symptoms.

Structural Snapshots for Mechanism-Based Inactivation of a Glycoside Hydrolase by Cyclopropyl Carbasugars.

Glycoside hydrolases (GHs) have attracted considerable attention as targets for therapeutic agents, and thus mechanism-based inhibitors are of great interest. We report the first structural analysis of a carbocyclic mechanism-based GH inactivator, the results of which show that the two Michaelis complexes are in H conformations. We also report the synthesis and reactivity of a fluorinated analogue and the structure of its covalently linked intermediate (flattened H half-chair).

Axon density and axon orientation dispersion in children born preterm.

Background: Very preterm birth (VPT, <32 weeks' gestation) is associated with altered white matter fractional anisotropy (FA), the biological basis of which is uncertain but may relate to changes in axon density and/or dispersion, which can be measured using Neurite Orientation Dispersion and Density Imaging (NODDI). This study aimed to compare whole brain white matter FA, axon dispersion, and axon density between VPT children and controls (born ≥37 weeks' gestation), and to investigate associations with perinatal factors and neurodevelopmental outcomes.

Methods: FA, neurite dispersion, and neurite density were estimated from multishell diffusion magnetic resonance images for 145 VPT and 33 control 7-year-olds.

Structural connectivity relates to perinatal factors and functional impairment at 7years in children born very preterm.

Objective: To use structural connectivity to (1) compare brain networks between typically and atypically developing (very preterm) children, (2) explore associations between potential perinatal developmental disturbances and brain networks, and (3) describe associations between brain networks and functional impairments in very preterm children.

Methods: 26 full-term and 107 very preterm 7-year-old children (born <30weeks' gestational age and/or <1250g) underwent T1- and diffusion-weighted imaging. Global white matter fibre networks were produced using 80 cortical and subcortical nodes, and edges were created using constrained spherical deconvolution-based tractography.

A New MRI-Based Pediatric Subcortical Segmentation Technique (PSST).

Volumetric and morphometric neuroimaging studies of the basal ganglia and thalamus in pediatric populations have utilized existing automated segmentation tools including FIRST (Functional Magnetic Resonance Imaging of the Brain's Integrated Registration and Segmentation Tool) and FreeSurfer. These segmentation packages, however, are mostly based on adult training data. Given that there are marked differences between the pediatric and adult brain, it is likely an age-specific segmentation technique will produce more accurate segmentation results.

Longitudinal growth and morphology of the hippocampus through childhood: Impact of prematurity and implications for memory and learning.

The effects of prematurity on hippocampal development through early childhood are largely unknown. The aims of this study were to (1) compare the shape of the very preterm (VPT) hippocampus to that of full-term (FT) children at 7 years of age, and determine if hippocampal shape is associated with memory and learning impairment in VPT children, (2) compare change in shape and volume of the hippocampi from term-equivalent to 7 years of age between VPT and FT children, and determine if development of the hippocampi over time predicts memory and learning impairment in VPT children. T1 and T2 magnetic resonance images were acquired at both term equivalent and 7 years of age in 125 VPT and 25 FT children.

Brain extraction using the watershed transform from markers.

Isolation of the brain from other tissue types in magnetic resonance (MR) images is an important step in many types of neuro-imaging research using both humans and animal subjects. The importance of brain extraction is well appreciated-numerous approaches have been published and the benefits of good extraction methods to subsequent processing are well known. We describe a tool-the marker based watershed scalper (MBWSS)-for isolating the brain in T1-weighted MR images built using filtering and segmentation components from the Insight Toolkit (ITK) framework.

Hippocampal shape variations at term equivalent age in very preterm infants compared with term controls: perinatal predictors and functional significance at age 7.

The hippocampus undergoes rapid growth and development in the perinatal months. Infants born very preterm (VPT) are vulnerable to hippocampal alterations, and can provide a model of disturbed early hippocampal development. Hippocampal shape alterations have previously been associated with memory impairment, but have never been investigated in infants.

Saccadic eye movement characteristics in adult Niemann-Pick Type C disease: relationships with disease severity and brain structural measures.

Niemann-Pick Type C disease (NPC) is a rare genetic disorder of lipid metabolism. A parameter related to horizontal saccadic peak velocity was one of the primary outcome measures in the clinical trial assessing miglustat as a treatment for NPC. Neuropathology is widespread in NPC, however, and could be expected to affect other saccadic parameters.

Thickness profile generation for the corpus callosum using Laplace's equation.

The corpus callosum facilitates communication between the cerebral hemispheres. Morphological abnormalities of the corpus callosum have been identified in numerous psychiatric and neurological disorders. To quantitatively analyze the thickness profile of the corpus callosum, we adapted an automatic thickness measurement method, which was originally used on magnetic resonance (MR) images of the cerebral cortex (Hutton et al.