Proximal CA3 is the primary locus of age-related pattern separation deficits in rats

Age-related deficits in pattern separation have been postulated to bias the output of hippocampal memory processing toward pattern completion, which can cause deficits in accurate memory retrieval. While the CA3 region of the hippocampus is often conceptualized as a homogeneous network involved in pattern completion, growing evidence demonstrates a functional gradient in CA3 along the transverse axis, with proximal CA3 supporting pattern separation and distal CA3 supporting pattern completion. We examined the neural representations along the CA3 transverse axis in young (Y), aged memory-unimpaired (AU), and aged memory-impaired (AI) rats when different changes were made to the environment. When the environmental similarity was high (e.g., altered cues or altered environment shapes in the same room), Y and AU rats showed more orthogonalized representations in proximal CA3 than in distal CA3, consistent with prior studies showing a functional dissociation along the transverse axis of CA3. In contrast, AI rats showed less orthogonalization in proximal CA3 than Y and AU rats but showed more normal (i.e., generalized) representations in distal CA3, with little evidence of a functional gradient. When the environmental similarity was low (e.g., recordings were done in different rooms), representations in proximal and distal CA3 remapped in all rats, showing that AI rats are able to dissociate representations when inputs show greater dissimilarity. These results provide evidence that the aged-related bias towards pattern completion is due to the loss in AI rats of the normal transition from pattern separation to pattern completion along the CA3 transverse axis and, furthermore, that proximal CA3 is the primary locus of this age-related dysfunction in neural coding.

Developmental adaptations of neonatal neutrophils (review)

Neutrophils are crucial components of the innate immunity. Differences exist in the physiological, phenotypic, and functional characteristics between neonatal and adult neutrophils. The severity of these changes is inversely proportional to gestational age, which indicates the dynamic development of these cells throughout pregnancy. Therefore, functional insufficiency of neonatal neutrophils is associated with an extremely high risk of developing neonatal infections and sepsis in infants born premature. Neonatal neutrophils are adapted to conditions that prevent unwanted triggering of proinflammatory factors. In addition, suppression of neutrophil functions is necessary to create a healthy microbiome in the postpartum period; however, it can be inhibit the development of a response to pathogenic organisms. Mechanisms underlying the normal transition of functionally limited neutrophils, capable of fully resisting pathogenic microorganisms, have not been established. This review presents features of neutrophil ontogenetic adaptation to intrauterine conditions and early neonatal period and their potential role in neonatal pathology.

IKM DAN DIAGRAM KARTESIUS : KUALITAS PELAYANAN PDAM KOTA PONTIANAK PADA MASA PANDEMI COVID-19

The research objective was to analyze the community satisfaction index (IKM) regarding the service quality of PDAM Pontianak City including the service standards carried out during the new normal transition based on Law no. 19 of 2020. The qualitative descriptive research method uses primary data in the form of 100 customers taken purposively. Research indicators based on Law no. 25 of 2009. The analysis tool uses the IKM analysis and Cartesian diagrams. The results of the study found that based on the IKM analysis, the indicators that were not optimal were the speed of service, service procedures and implementation schedule. Based on Cartesian analysis found major improvements in service procedures and clarity of officers, as well as additional improvements in the form of service speed, fairness of service costs and certainty of service schedules

Edge surface supercurrent and transport anomalies in Hall effect measurements in Nb

We report an experimental study of the edge surface superconductivity and the Hall effect in a Nb thin film Hall device. We show that the previously reported anomalous sign reversal of the Hall resistance across the superconducting-normal transition is due to the edge supercurrent. Large anomalous oscillations between the transverse voltage probes are observed in the field range between Hc2 and Hc3, in both the anti-symmetric (Hall) and symmetric (resistive) channels. These oscillations are extremely sensitive to a small tilting of the edge surface relative to the external magnetic field. We suggest that these oscillations may arise from the Aharonov-Bohm interference of the edge supercurrents.

Youth of the Global South and Why They Are Worth Studying

While real place-based differences exist between groups of youth, the simple global North-South binary is problematic. This essay explores this paradox arguing that differences and the binary itself are the result of historical processes that are continually in flux. These histories-in-the-present are illuminated with descriptive statistics (wealth, violence, human development, inequality) that illustrate empirical differences between Southern and Northern youth. Unpacking the concept of Southern youth using Southern theory shows that material conditions in the Global South mean that many more Southern youth diverge from what is considered a normal transition into adulthood in industrialized nations in late modernity, with implications for the category or life-phase of ‘youth.’ The concepts of ‘precarity’ and the practice of ‘the hustle’ are then used to suggest how a Global South youth studies agenda might simultaneously center issues like livelihoods, struggle, and the formation of sociopolitical consciousness. Southern youth as maestros of the hustle simultaneously assert a form of being young that is not based on deficit or romanticism, is thoroughly modern, and which foreground material realities.

SUN-747 Steroid Hormone Metabolism Mediated Racial Disparity in Men with Benign Prostatic Hyperplasia

Introduction and Objective: Racial disparity in prostate cancer has been well established, with African American (AA) men having higher rates of diagnoses and death from the disease compared to Caucasian American (CA) men. AA men also have a high incidence of benign prostatic hyperplasia (BPH), a disease associated with lower urinary tract symptoms (LUTS) that affect >210 million men worldwide. Furthermore, AA men with BPH have an increased incidence of non-surgical treatment failure, larger prostates at time of surgery, and surgery occurring at a younger age. The use of selective estrogen receptor modulators (SERMs) in the treatment of BPH has been proposed, as an increase in ERα has been associated with disease progression. AA men have higher levels of circulating estrogens as compared to CA leading to an increased prenatal exposure to estrogens. Estrogen exposure has been shown to alter the epigenetic landscape of genes, and this prenatal exposure to estrogens could sensitize the AA men to altered steroid homeostasis leading to an increase susceptibility to BPH and an altered response to treatment. In this study, we examine the prostate expression and localization changes in estrogen receptors (ERα, ERβ) as well as steroid metabolism genes in AA and CA with or without BPH. Methods: To examine the impact of race on BPH, we examined prostate tissue from 66 men. We utilized 21 normal transition zone controls from radical prostatectomies, 8 normal transition zone controls from organ donors, and 37 BPH samples divided between CA and AA men. Using multispectral quantitative multiplex IHC, we examined the steroid hormone related protein expression of ERα, ERβ, CYP7B1, and AKR1C1 on each FFPE tissue section. We quantified the optical density of each protein of interest as well as examined colocalization and coexpression through cell and tissue segmentation. Results: In CA men, there is a dysregulation of ERα:ERβ homeostasis with BPH relative to normal as an increase in ERα and a decrease in ERβ expression was observed. Furthermore, an increase in CYP7B1, an enzyme that degrades ERβ ligands, was also observed. In AA men, we observed no difference between normal and BPH states, however in both normal and BPH prostate tissues, ERα and ERβ were increased relative to CA men. In addition, there is a decrease in AKR1C1, the enzyme that metabolizes DHT to an ERβ ligand. Conclusions: Our study supports the concept that differences in hormone pathways exist between AA and CA men. Understanding how these racial difference in steroid metabolism enzymes as well as ERs between CA and AA men with BPH could enhance treatment strategies for men with BPH.

Analysis of non-reversible Markov chains via similarity orbits

In this paper we develop an in-depth analysis of non-reversible Markov chains on denumerable state space from a similarity orbit perspective. In particular, we study the class of Markov chains whose transition kernel is in the similarity orbit of a normal transition kernel, such as that of birth–death chains or reversible Markov chains. We start by identifying a set of sufficient conditions for a Markov chain to belong to the similarity orbit of a birth–death chain. As by-products, we obtain a spectral representation in terms of non-self-adjoint resolutions of identity in the sense of Dunford [21] and offer a detailed analysis on the convergence rate, separation cutoff and L2-cutoff of this class of non-reversible Markov chains. We also look into the problem of estimating the integral functionals from discrete observations for this class. In the last part of this paper we investigate a particular similarity orbit of reversible Markov kernels, which we call the pure birth orbit, and analyse various possibly non-reversible variants of classical birth–death processes in this orbit.