Facile one-pot synthesis of amoxicillin-coated gold nanoparticles and their antimicrobial activity

Nanomaterials have been the object of intense study due to promising applications in a number of different disciplines. In particular, medicine and biology have seen the potential of these novel materials with their nanoscale properties for use in diverse areas such as imaging, sensing and drug vectorisation. Gold nanoparticles (GNPs) are considered a very useful platform to create a valid and efficient drug delivery/carrier system due to their facile and well-studied synthesis, easy surface functionalization and biocompatibility. In the present study, stable antibiotic conjugated GNPs were synthesised by a one-step reaction using a poorly water soluble antibiotic, amoxicillin. Amoxicillin, a member of the penicillin family, reduces the chloroauric acid to form nanoparticles and at the same time coats them to afford the functionalised nanomaterial. A range of techniques including UV-vis spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM) and thermogravimetric analysis (TGA) were used to ascertain the gold/drug molar ratio and the optimum temperature for synthesis of uniform monodisperse particles in the ca. 30-40 nm size range. Amoxicillin-conjugated gold showed an enhancement of antibacterial activity against Escherichia coli compared to the antibiotic alone

Towards Subject and Diagnostic Identifiability in the Alzheimer’s Disease Spectrum Based on Functional Connectomes

Alzheimer’s disease (AD) is the only major cause of mortality in the world without an effective disease modifying treatment. Evidence supporting the so called “disconnection hypothesis” suggests that functional connectivity biomarkers may have clinical potential for early detection of AD. However, known issues with low test-retest reliability and signal to noise in functional connectivity may prevent accuracy and subsequent predictive capacity. We validate the utility of a novel principal component based diagnostic identifiability framework to increase separation in functional connectivity across the Alzheimer’s spectrum by identifying and reconstructing FC using only AD sensitive components or connectivity modes. We show that this framework (1) increases test-retest correspondence and (2) allows for better separation, in functional connectivity, of diagnostic groups both at the whole brain and individual resting state network level. Finally, we evaluate a posteriori the association between connectivity mode weights with longitudinal neurocognitive outcomes

Ultra-high field imaging, plasma markers and autopsy data uncover a specific rostral locus coeruleus vulnerability to hyperphosphorylated tau

Autopsy data indicate that the locus coeruleus (LC) is one of the first sites in the brain to accumulate hyperphosphorylated tau pathology, with the rostral part possibly being more vulnerable in the earlier stages of the disease. Taking advantage of recent developments in ultra-high field (7 T) imaging, we investigated whether imaging measures of the LC also reveal a specific anatomic correlation with tau using novel plasma biomarkers of different species of hyperphosphorylated tau, how early in adulthood these associations can be detected and if are associated with worse cognitive performance. To validate the anatomic correlations, we tested if a rostro-caudal gradient in tau pathology is also detected at autopsy in data from the Rush Memory and Aging Project (MAP). We found that higher plasma measures of phosphorylated tau, in particular ptau231, correlated negatively with dorso-rostral LC integrity, whereas correlations for neurodegenerative plasma markers (neurofilament light, total tau) were scattered throughout the LC including middle to caudal sections. In contrast, the plasma Aβ42/40 ratio, associated with brain amyloidosis, did not correlate with LC integrity. These findings were specific to the rostral LC and not observed when using the entire LC or the hippocampus. Furthermore, in the MAP data, we observed higher rostral than caudal tangle density in the LC, independent of the disease stage. The in vivo LC-phosphorylated tau correlations became significant from midlife, with the earliest effect for ptau231, starting at about age 55. Finally, interactions between lower rostral LC integrity and higher ptau231 concentrations predicted lower cognitive performance. Together, these findings demonstrate a specific rostral vulnerability to early phosphorylated tau species that can be detected with dedicated magnetic resonance imaging measures, highlighting the promise of LC imaging as an early marker of AD-related processes

Associations between plasma neurofilament light, in vivo brain pathology, and cognition in non-demented individuals with autosomal-dominant Alzheimer's disease

BACKGROUND: Neurofilament light (NfL) is a promising biomarker of early neurodegeneration in Alzheimer's disease (AD). We examined whether plasma NfL was associated with in vivo amyloid beta and tau, and cognitive performance in non-demented presenilin-1 (PSEN1) E280A mutation carriers. METHODS: Twenty-five mutation carriers and 19 non-carriers (age range: 28 to 49 years) were included in this study. Participants underwent 11C Pittsburgh compound B (PiB)-PET (positron emission tomography), flortaucipir-PET, blood sampling, and cognitive testing. RESULTS: Mutation carriers exhibited higher plasma NfL levels than non-carriers. In carriers, higher NfL levels were related to greater regional tau burden and worse cognition, but not amyloid beta load. When we adjusted for age, a proxy of disease progression, elevated plasma NfL levels were only correlated with worse memory recall. CONCLUSIONS: Findings support an association between plasma NfL, cognition, and tau pathology in non-demented individuals at genetic risk for developing AD dementia. Plasma NfL may be useful for selecting individuals at increased risk and tracking disease progression in AD

CD33 Alzheimer’s disease locus: Altered monocyte function and amyloid biology

In our functional dissection of the CD33 Alzheimer’s disease susceptibility locus, we find that the rs3865444C risk allele is associated with greater cell surface expression of CD33 in monocytes (t50 = 10.06, pjoint=1.3×10–13) of young and older individuals. It is also associated with (1) diminished internalization of Aβ42) (2) accumulation of neuritic amyloid pathology and fibrillar amyloid on in vivo imaging and (3), increased numbers of activated human microglia

Alternative preparation of size-controlled thiol-capped gold colloids

Colloidal nanoparticles find application in chemistry, biology, and life science. We report an alternative preparation method for thiol-capped gold colloids by leaching of premade particles on a support. Via this method, monodispersed particles in the size of 2 to 2.5 nm can be obtained whereas the occurrence of bigger particles is restricted.ISSN:0017-155

Low-oxygen waters limited habitable space for early animals

The oceans at the start of the Neoproterozoic Era (1,000–541 million years ago, Ma) were dominantly anoxic, but may have become progressively oxygenated, coincident with the rise of animal life. However, the control that oxygen exerted on the development of early animal ecosystems remains unclear, as previous research has focussed on the identification of fully anoxic or oxic conditions, rather than intermediate redox levels. Here we report anomalous cerium enrichments preserved in carbonate rocks across bathymetric basin transects from nine localities of the Nama Group, Namibia (~550–541 Ma). In combination with Fe-based redox proxies, these data suggest that low-oxygen conditions occurred in a narrow zone between well-oxygenated surface waters and fully anoxic deep waters. Although abundant in well-oxygenated environments, early skeletal animals did not occupy oxygen impoverished regions of the shelf, demonstrating that oxygen availability (probably >10 μM) was a key requirement for the development of early animal-based ecosystems