Dynamic Formation of Imidazolidino Boronate Enables Design of Cysteine-Responsive Peptides

We describe the dynamic and chemoselective conjugation between 2-formylphenylboronic acid and l-2,3-diaminopropionic acid yielding an imidazolidino boronate (IzB) complex. The IzB complex formation readily proceeds in biological milieu with little interference by common biomolecules except cysteine. We demonstrate the potential of this reversible conjugation for biological applications by creating “smart” peptides that specifically respond to cysteine in complex biological media. Specifically, the design and characterization of a fluorogenic sensor of cysteine is described

Phage Display of Dynamic Covalent Binding Motifs Enables Facile Development of Targeted Antibiotics

Antibiotic resistance of bacterial pathogens poses an increasing threat to the wellbeing of our society and urgently calls for new strategies for infection diagnosis and antibiotic discovery. The antibiotic resistance problem at least partially arises from extensive use of broad-spectrum antibiotics. Ideally, for the treatment of infection, one would like to use a narrow-spectrum antibiotic that specifically targets and kills the disease-causing strain. This is particularly important considering the commensal bacterial species that are beneficial and sometimes even critical to the health of a human being. In this contribution, we describe a phage display platform that enables rapid identification of peptide probes for specific bacterial strains. The phage library described herein incorporates 2-acetylphenylboronic acid moieties to elicit dynamic covalent binding to the bacterial cell surface. Screening of the library against live bacterial cells yields submicromolar and highly specific binders for clinical strains of <i>Staphylococcus aureus</i> and <i>Acinetobacter baumannii</i> that display antibiotic resistance. We further show that the identified peptide probes can be readily converted to bactericidal agents that deliver generic toxins to kill the targeted bacterial strain with high specificity. The phage display platform described here is applicable to a wide array of bacterial strains, paving the way to facile diagnosis and development of strain-specific antibiotics

Presentation_1_Decreased Bilateral FDG-PET Uptake and Inter-Hemispheric Connectivity in Multi-Domain Amnestic Mild Cognitive Impairment Patients: A Preliminary Study.PDF

<p>Background: Amnestic mild cognitive impairment (aMCI) is a heterogeneous condition. Based on clinical symptoms, aMCI could be categorized into single-domain aMCI (SD-aMCI, only memory deficit) and multi-domain aMCI (MD-aMCI, one or more cognitive domain deficit). As core intrinsic functional architecture, inter-hemispheric connectivity maintains many cognitive abilities. However, few studies investigated whether SD-aMCI and MD-aMCI have different inter-hemispheric connectivity pattern.</p><p>Methods: We evaluated inter-hemispheric connection pattern using fluorine-18 positron emission tomography – fluorodeoxyglucose (¹⁸F PET-FDG), resting-state functional MRI and structural T1 in 49 controls, 32 SD-aMCI, and 32 MD-aMCI patients. Specifically, we analyzed the 18^F PET-FDG (intensity normalized by cerebellar vermis) in a voxel-wise manner. Then, we estimated inter-hemispheric functional and structural connectivity by calculating the voxel-mirrored homotopic connectivity (VMHC) and corpus callosum (CC) subregions volume. Further, we correlated inter-hemispheric indices with the behavioral score and pathological biomarkers.</p><p>Results: We found that MD-aMCI exhibited more several inter-hemispheric connectivity damages than SD-aMCI. Specifically, MD-aMCI displayed hypometabolism in the bilateral middle temporal gyrus (MTG), inferior parietal lobe, and left precuneus (PCu) (p < 0.001, corrected). Correspondingly, MD-aMCI showed decreased VMHC in MTG, PCu, calcarine gyrus, and postcentral gyrus, as well as smaller mid-posterior CC than the SD-aMCI and controls (p < 0.05, corrected). Contrary to MD-aMCI, there were no neuroimaging indices with significant differences between SD-aMCI and controls, except reduced hypometabolism in bilateral MTG. Within aMCI patients, hypometabolism and reduced inter-hemispheric connectivity correlated with worse executive ability. Moreover, hypometabolism indices correlated to increased amyloid deposition.</p><p>Conclusion: In conclusion, patients with MD-aMCI exhibited the more severe deficit in inter-hemispheric communication than SD-aMCI. This long-range connectivity deficit may contribute to cognitive profiles and potentially serve as a biomarker to estimate disease progression of aMCI patients.</p

Additional file 1 of The relationship between amyloid pathology, cerebral small vessel disease, glymphatic dysfunction, and cognition: a study based on Alzheimer’s disease continuum participants

Additional file 1: Supplementary Material 1. Demographics of participants with and without chin-up. Supplementary Material 2. Methods. Supplementary Material 3. Supplementary Material 4. Comparison of DTI-ALPS among different locations. Supplementary Material 5. The correlations between different locations DTI-ALPS. Supplementary Material 6. The association of DTI-ALPS and Choroid Plexus volume with WMH burden and Aβ in amyloid positive participants with at least one vascular risk factor. Supplementary Material 7. The association of DTI-ALPS and Choroid Plexus volume with WMH burden and Aβ in amyloid positive participants corrected for vascular risk factor score. Supplementary Material 8. Glymphatic markers comparison between participants with and without each vascular risk factor in amyloid positive participants