MINERALIZATION OF TEETH ENAMEL AFTER ERUPTION

The aim: The paper was aimed at the study of the processes of mineralization of the enamel of the permanent tooth after its eruption. Materials and methods: To study the structure of the enamel of permanent teeth has been carried out using light and electron microscopy. The study of the process of the development of the primordia of the permanent teeth involved 10 culled puppies of 30-40 days of age. Microscopic, electron microscopic, immunohistochemical methods of research have been used to study the processes of histogenesis. Results: The studies show that in the postnatal period, the formation of the crown, externally covered with cuticular epithelium, marks the formation of the primordium of the permanent tooth at the follicle stage. After eruption of a tooth, different parts of its crown have three individual structural and functional barriers to enamel biomineralization. The first one is provided by the cuticular epithelium of the pitted areas of the crown, which ensures filtering of the salivary fluid from the protein deposit in the form of a pellicle. The second barrier is defined on the lateral and cuspidate surfaces of the enamel, where the cuticle is erased or poorly expressed. The third structural and functional barrier of enamel biomineralization is located in the cervical portion of teeth of different classes. Conclusions: Different areas of the enamel in the tooth crown have specific filtration barriers, which can be distinguished as follows: pit-and-fissure-and-groove, cuspidateand-approximal, and cervical barriers. The cuticle is poorly expressed or totally absent on the cusps of the tooth crowns in contrast to pitted areas.

FUNCTIONAL CONNECTIVITY IN MILD GNITIVE IMPAIRMENT PATIENTS WITH PIB+ AND – BIOMARKERS

Background: According to the recent NIA-AA, a probable predictor of Alzheimer’s disease convertor in mild cognitive impairment (MCI) is the Aβ protein deposit in PET PIB exam. However, there is a lack of studies investigating functional connectivity in PIB +/- MCI patients. Objectives: to investigate differences in functional connectivity during resting state in MCI patients with PET PIB+ and - biomarkers. Methods: PET PIB+ (N=12 and PIB- (N=12) MCI patients underwent fMRI during resting state using 3 ROIS related to memory (posterior cingulate and bilateral hippocampus). Results: there were significant connectivity differences (p <0.05) between PIB+ and PIB- patients above 80% for right temporal region connectivity regarding left and right temporal region. Conclusions The results suggest that PET PIB+ MCI patients show significant difference in functional connectivity on the right temporal region in relation to left and right hippocampus ROI during the resting state possibly related to functional compensation.

AMPK regulates ESCRT-dependent microautophagy of proteasomes concomitant with proteasome storage granule assembly during glucose starvation

The ubiquitin-proteasome system regulates numerous cellular processes and is central to protein homeostasis. In proliferating yeast and many mammalian cells, proteasomes are highly enriched in the nucleus. In carbon-starved yeast, proteasomes migrate to the cytoplasm and collect in phase-separated proteasome storage granules (PSGs). PSGs dissolve and proteasomes return to the nucleus within minutes of glucose refeeding. The mechanisms by which cells regulate proteasome homeostasis under these conditions remain largely unknown. Here we show that AMP-activated protein kinase (AMPK) together with endosomal sorting complexes required for transport (ESCRTs) drive a glucose starvation-dependent microautophagy pathway that preferentially sorts aberrant proteasomes into the vacuole, thereby biasing accumulation of functional proteasomes in PSGs. The proteasome core particle (CP) and regulatory particle (RP) are regulated differently. Without AMPK, the insoluble protein deposit (IPOD) serves as an alternative site that specifically sequesters CP aggregates. Our findings reveal a novel AMPK-controlled ESCRT-mediated microautophagy mechanism in the regulation of proteasome trafficking and homeostasis under carbon starvation.

The fitness cost and benefit of phase separated protein deposits

ABSTRACTPhase separation of soluble proteins into insoluble deposits is associated with numerous diseases. However, protein deposits can also function as membrane-less compartments for many cellular processes. What are the fitness costs and benefits of forming such deposits in different conditions? Using a model protein that phase separates into deposits, we distinguish and quantify the fitness contribution due to the loss or gain of protein function and deposit formation in yeast. The environmental condition and the cellular demand for the protein function emerge as key determinants of fitness. Protein deposit formation can lead to cell-to-cell differences in free protein abundance between individuals. This results in variable manifestation of protein function and a continuous range of phenotypes in a cell population, favoring survival of some individuals in certain environments. Thus, protein deposit formation by phase separation might be a mechanism to sense protein concentration in cells and to generate phenotypic variability. The selectable phenotypic variability, previously described for prions, could be a general property of proteins that can form phase separated assemblies and may influence cell fitness.Stand-first textUsing a model protein that phase separates into deposits, we distinguish and quantify the fitness contribution due to the loss or gain of protein function and deposit formation in yeast.Bullet pointsThe presented approach identifies and quantifies different fitness effects associated with protein deposit formation due to phase separationThe environmental condition and the cellular demand for the protein function emerge as key determinants of fitness upon protein deposit formationVariability in protein deposit formation can lead to cell-to-cell differences in free protein abundance between individualsProtein phase separation can generate a continuous range of phenotypes in a cell population