Natural forgetting reversibly modulates engram expression.

Memories are stored as ensembles of engram neurons and their successful recall involves the reactivation of these cellular networks. However, significant gaps remain in connecting these cell ensembles with the process of forgetting. Here, we utilized a mouse model of object memory and investigated the conditions in which a memory could be preserved, retrieved, or forgotten.

A new silicon phthalocyanine dye induces pyroptosis in prostate cancer cells during photoimmunotherapy.

Photoimmunotherapy (PIT) combines the specificity of antibodies with the cytotoxicity of light activatable photosensitizers (PS) and is a promising new cancer therapy. We designed and synthesized, in a highly convergent manner, the silicon phthalocyanine dye WB692-CB2, which is novel for being the first light-activatable PS that can be directly conjugated via a maleimide linker to cysteines. In the present study we conjugated WB692-CB2 to a humanized antibody with engineered cysteines in the heavy chains that specifically targets the prostate-specific membrane antigen (PSMA).

Influence of surprise on reinforcement learning in younger and older adults.

Surprise is a key component of many learning experiences, and yet its precise computational role, and how it changes with age, remain debated. One major challenge is that surprise often occurs jointly with other variables, such as uncertainty and outcome probability. To assess how humans learn from surprising events, and whether aging affects this process, we studied choices while participants learned from bandits with either Gaussian or bi-modal outcome distributions, which decoupled outcome probability, uncertainty, and surprise.

Photoimmunotherapy of HER2-expressing Breast Cancer Cells.

Background/aim: Breast cancer (BC) is the most common malignant disease worldwide. Localized stages of BC can be successfully treated by surgery. However, local recurrence occurs in about 4-10% of patients, requiring systemic treatments that impair the patients' quality of life and shortens life expectancy.

Photoimmunotherapy of Prostate Cancer With Antibody and Fab Fragments Targeting the Prostate Specific Membrane Antigen.

Background/aim: The standard treatment for localized prostate cancer involves surgical removal of the prostate with curative intent. However, when tumor cells persist in the operation site, there is high risk of local recurrence and tumor spread, leading to stressful follow-up treatments, impaired quality of life, and reduced overall survival. This study examined photoimmunotherapy (PIT) as a new treatment option for prostate cancer cells.

Antibody-dye Conjugates Targeting EGFR and HER2 for the Photoimmunotherapy of Bladder Cancer.

Background/aim: Although there are curative treatment options for non-muscle-invasive bladder cancer, the recurrence of this tumor is high. Therefore, novel targeted therapies are needed for the complete removal of bladder cancer cells in stages of localized disease, in order to avoid local recurrence, to spare bladder cancer patients from stressful and expensive treatment procedures and to increase their quality of life and life expectancy. This study tested a new approach for the photoimmunotherapy (PIT) of bladder cancer.

Instruments for measuring self-management and self-care in geriatric patients - a scoping review.

Introduction: With demographic changes, prioritizing effective care for geriatric patients to maintain functionality, independence, and quality of life is crucial. Well-developed self-management or self-care abilities, which can be maintained and improved through interventions, are of the utmost importance. To implement these interventions tailored and effectively, a thorough assessment of the individual's self-management and self-care abilities is required.

Exploring factors associated with self-rated health in individuals with diabetes and its impact on quality of life: Evidence from the Survey of Health, Ageing, and Retirement in Europe.

Background: Self-rated health (SRH), a measure of self-reported general health, is a robust predictor of morbidity and mortality in various populations, including people with diabetes. Diabetes is negatively associated with SRH and quality of life (QoL). Little is known about how people with diabetes rate their health and which aspects influence the rating.

Signed and unsigned effects of prediction error on memory: Is it a matter of choice?

Adaptive decision-making is governed by at least two types of memory processes. On the one hand, learned predictions through integrating multiple experiences, and on the other hand, one-shot episodic memories. These two processes interact, and predictions - particularly prediction errors - influence how episodic memories are encoded.

The dorsomedial prefrontal cortex represents subjective value across effort-based and risky decision-making.

Decisions that require taking effort costs into account are ubiquitous in real life. The neural common currency theory hypothesizes that a particular neural network integrates different costs (e.g.

The effect of prediction error on episodic memory encoding is modulated by the outcome of the predictions.

Expectations can lead to prediction errors of varying degrees depending on the extent to which the information encountered in the environment conforms with prior knowledge. While there is strong evidence on the computationally specific effects of such prediction errors on learning, relatively less evidence is available regarding their effects on episodic memory. Here, we had participants work on a task in which they learned context/object-category associations of different strengths based on the outcomes of their predictions.

Syntheses of 6,7-Benzotropolones by a Sequence of Acylation (or α-Hydroxyalkylation/Oxidation), Ring-Closing Metathesis, and Hydrolysis/β-Elimination.

Starting from -bromostyrenes, 12 6,7-benzotropolones were synthesized in 3 or 4 steps. Br/Li exchanges provided the respective -lithiostyrenes. The latter were acylated by a Weinreb amide, if unhindered, or hydroxyalkylated by an aldehyde, if hindered (an oxidation ensuing thereafter).

Force-induced changes of α-catenin conformation stabilize vascular junctions independently of vinculin.

Cadherin-mediated cell adhesion requires anchoring via the β-catenin-α-catenin complex to the actin cytoskeleton, yet, α-catenin only binds F-actin weakly. A covalent fusion of VE-cadherin to α-catenin enhances actin anchorage in endothelial cells and strongly stabilizes endothelial junctions in vivo, blocking inflammatory responses. Here, we have analyzed the underlying mechanism.

MMP9 expression in intestinal fistula from patients with fistulizing CD and from human xenograft mouse model.

Fistula treatment represents a major unmet medical need in the therapy of Crohn's disease (CD). Current medical therapies, such as anti-TNF antibody treatments, are often insufficient and do not achieve permanent fistula closure. Previously published data point toward a critical role for metalloproteinase-9 (MMP-9)/gelatinase B in fistula pathogenesis.

Stereostructure Clarifying Total Synthesis of the (Polyenoyl)tetramic Acid Militarinone B. A Highly Acid-Labile -Protecting Group for Amides†.

The 5, 8', and 10' configurations of militarinone B (), which is a natural product from , should equal those in its biosynthetic precursor, militarinone C. The configuration at C-1' emerged from syntheses of the militarinone B candidates 1''- and 1''-(5,8',10')- from the building blocks , , , and while introducing TMB as a more acid-labile -protecting group for β-ketoamides than DMB. Comparisons of 1''- and 1''-(5,8',10')- with natural militarinone B (; reisolated from Nature) revealed identity versus distinctness.

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

Thousands of interactions assemble proteins into modules that impart spatial and functional organization to the cellular proteome. Through affinity-purification mass spectrometry, we have created two proteome-scale, cell-line-specific interaction networks. The first, BioPlex 3.

Response-based outcome predictions and confidence regulate feedback processing and learning.

Influential theories emphasize the importance of predictions in learning: we learn from feedback to the extent that it is surprising, and thus conveys new information. Here, we explore the hypothesis that surprise depends not only on comparing current events to past experience, but also on online evaluation of performance via internal monitoring. Specifically, we propose that people leverage insights from response-based performance monitoring - outcome predictions and confidence - to control learning from feedback.

PECAM-1 supports leukocyte diapedesis by tension-dependent dephosphorylation of VE-cadherin.

Leukocyte extravasation is an essential step during the immune response and requires the destabilization of endothelial junctions. We have shown previously that this process depends in vivo on the dephosphorylation of VE-cadherin-Y731. Here, we reveal the underlying mechanism.

Contribution of CD3+CD8- and CD3+CD8+ T Cells to TNF-α Overexpression in Crohn Disease-Associated Perianal Fistulas and Induction of Epithelial-Mesenchymal Transition in HT-29 Cells.

Background: Fistulas represent a frequent and severe complication in patients with Crohn disease (CD). Tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta, and interleukin (IL)-13 are known to trigger epithelial-mesenchymal transition (EMT), promoting fistula formation. Here, we investigated the role of T-lymphocytes (T cells) in fistula pathogenesis.

Control of acetyl phosphate-dependent phosphorylation of the response regulator CiaR by acetate kinase in .

The two-component regulatory system CiaRH of affects a large variety of physiological processes including ß-lactam resistance, competence development, maintenance of cell integrity, bacteriocin production, but also host colonization and virulence. The response regulator CiaR is active under a wide variety of conditions and the cognate CiaH kinase is not always needed to maintain CiaR activity. Using tetracycline-controlled expression of and variants, acetyl phosphate was identified as the alternative source of CiaR phosphorylation in the absence of CiaH.

Stereoselective Total Synthesis of the Dimeric Naphthoquinonopyrano-γ-lactone (-)-Crisamicin A: Introducing the Dimerization Site by a Late-Stage Hartwig Borylation.

The first stereoselective total synthesis of the dimeric naphthoquinonopyrano-γ-lactone (-)-crisamicin A was realized (13 steps, 5% overall yield). 1,4,5-Trimethoxynaphthalene, reached in five known steps, was brominated at C-3 to install a but-3-enoic ester by an ensuing Heck coupling. An asymmetric Sharpless dihydroxylation followed and gave a β-hydroxy-γ-lactone with >99.

Structure-Elucidating Total Synthesis of the (Polyenoyl)tetramic Acid Militarinone C§.

The (polyenoyl)tetramic acid militarinone C () heads a family of seven members. Before our work, the configuration of C-5 was unknown whereas the configurations of C-8' and C-10' were either (,) or (,). We synthesized the four stereoisomers of constitution , which conform with these insights.

Stromal Cells in the Pathogenesis of Inflammatory Bowel Disease.

Up till now, research on inflammatory bowel disease [IBD] has mainly been focused on the immune cells present in the gastrointestinal tract. However, recent insights indicate that stromal cells also play an important and significant role in IBD pathogenesis. Stromal cells in the intestines regulate both intestinal epithelial and immune cell homeostasis.

Atropselective Synthesis of -Bis(diphenylphosphanes) from Bridged 2-Arylindoles Based on Effective Point-to-Axial Asymmetric Inductions after an Unusual Dilithiation ⊥.

An asymmetric methanolysis of glutaric anhydride and 6 ensuing steps gave veratrol-annulated dimethylcyclo-heptenone diastereomers with 99% ; ring closures occurred by Friedel-Crafts acylations of carboxylic acids obtained by stereospecific hydrogenolyses of a pair of diastereomeric δ-lactones. The mentioned cycloheptenones and Ph-NH-NH underwent Fischer indole syntheses providing the tetracyclic indoles - and -, respectively. Double lithiations with BuLi and quenchings with ClPPh furnished the diphosphanes - and - with perfect ()- and ()-atropselectivity, respectively.