Presenilins as hub proteins controlling the endocytic and autophagic pathways and small extracellular vesicle secretion.

Emerging evidence indicates that autophagy is tightly connected to the endocytic pathway. Here, we questioned the role of presenilins (PSENs 1 and 2), previously shown to be involved in autophagy regulation, in the secretion of small endocytic-originating extracellular vesicles known as exosomes. Indeed, while wild-type cells responded to stimuli promoting both multivesicular endosome (MVE) formation and secretion of small extracellular vesicles (sEVs) enriched in canonical exosomal proteins, PSEN-deficient cells were almost unaffected to these stimuli.

Impact of Sodium Glucose Cotransporter 2 Inhibitors (SGLT2i) Therapy on Dementia and Cognitive Decline.

Dementia is an age-related syndrome characterized by the progressive deterioration of cognition and capacity for independent living. Diabetes is often associated with cognitive decline and shares similar pathophysiological mechanisms with dementia, such as systemic inflammation, oxidative stress, insulin resistance, and advanced glycation end-products formation. Therefore, adequate diabetes management may reduce the risk of cognitive decline, especially in patients with other comorbidities and risk factors.

Unsupervised Single-Cell Clustering with Asymmetric Within-Sample Transformation and Per-Cluster Supervised Features Selection.

This chapter shows applying the Asymmetric Within-Sample Transformation to single-cell RNA-Seq data matched with a previous dropout imputation. The asymmetric transformation is a special winsorization that flattens low-expressed intensities and preserves highly expressed gene levels. Before a standard hierarchical clustering algorithm, an intermediate step removes noninformative genes according to a threshold applied to a per-gene entropy estimate.

The Phytophthora parasitica effector AVH195 interacts with ATG8, attenuates host autophagy, and promotes biotrophic infection.

Background: Plant pathogens secrete effector proteins into host cells to suppress immune responses and manipulate fundamental cellular processes. One of these processes is autophagy, an essential recycling mechanism in eukaryotic cells that coordinates the turnover of cellular components and contributes to the decision on cell death or survival.

Results: We report the characterization of AVH195, an effector from the broad-spectrum oomycete plant pathogen, Phytophthora parasitica.

Uranium contamination of bivalve Mytilus galloprovincialis, speciation and localization.

Uranium is a natural radioelement (also a model for heavier actinides), but may be released through anthropogenic activities. In order to assess its environmental impact in a given ecosystem, such as the marine system, it is essential to understand its distribution and speciation, and also to quantify its bioaccumulation. Our objective was to improve our understanding of the transfer and accumulation of uranium in marine biota with mussels taken here as sentinel species because of their sedentary nature and ability to filter seawater.

A mechanical wave travels along a genetic guide to drive the formation of an epithelial furrow during Drosophila gastrulation.

Epithelial furrowing is a fundamental morphogenetic process during gastrulation, neurulation, and body shaping. A furrow often results from a fold that propagates along a line. How fold formation and propagation are controlled and driven is poorly understood.

Medial Patellofemoral Ligament Reconstruction Using Gracilis Tendon Graft and "All Suture" Knotless Anchors for Patellar Fixation.

Patellar dislocation is a frequent sports-related knee injury. The primary restraint to lateral translation of patella is medial patellofemoral ligament. Several treatments for patella dislocation have been described in the literature.

GLUT-1 changes in paediatric Huntington disease brain cortex and fibroblasts: an observational case-control study.

Background: Paediatric Huntington disease with highly expanded mutations (HE-PHD; >80 CAG repeats) presents atypically, compared to adult-onset Huntington disease (AOHD), with neurodevelopmental delay, epilepsy, abnormal brain glucose metabolism, early striatal damage, and reduced lifespan. Since genetic GLUT-1 deficiency syndrome shows a symptom spectrum similar to HE-PHD, we investigated the potential role of the two main glucose transporters, GLUT-1 and GLUT-3, in HE-PHD.

Methods: We compared GLUT-1 and GLUT-3 protein expression in HE-PHD, juvenile-onset (JOHD), and AOHD brains (n = 2; n = 3; n = 6) and periphery (n = 3; n = 2; n = 2) versus healthy adult controls (n = 6; n = 6).

Intraoperative navigation system use increases accuracy of glenoid component inclination but not functional outcomes in reverse total shoulder arthroplasty: a prospective comparative study.

Background: While the use of computer-assisted navigation systems in prosthetic implantation is steadily increasing, its utility in reverse shoulder arthroplasty (RSA) remains unclear. The purpose of this study was to evaluate the clinical utility of an intraoperative navigation system in patients undergoing RSA.

Materials And Methods: Patients undergoing navigated or standard RSA at a single institution between September 2020 and December 2021 were prospectively enrolled.

Conserved meiotic mechanisms in the cnidarian revealed by knockout.

During meiosis, DNA recombination allows the shuffling of genetic information between the maternal and paternal chromosomes. Recombination is initiated by double-strand breaks (DSBs) catalyzed by the conserved enzyme Spo11. How this crucial event is connected to other meiotic processes is unexpectedly variable depending on the species.

A Review of Current Research on the Use of Geopolymer Recycled Aggregate Concrete for Structural Members.

Geopolymer cement (GPC) is a sustainable alternative to ordinary Portland cement (OPC) that considerably cuts the emission of carbon dioxide linked to the building of concrete structures. Over the last few decades, while a large number of papers have been written concerning the use of GPC with natural aggregates and OPC with recycled aggregates, few papers have been devoted to investigating the use of Geopolymer Recycled Aggregate Concrete (GRAC) in structural members. Most of them show more interest in the mechanical strength of the material, rather than the structural behavior of RC members.

Influence of Cross-Section Shape and FRP Reinforcement Layout on Shear Capacity of Strengthened RC Beams.

The evaluation of the shear capacity of an FRP-strengthened reinforced-concrete beam is challenging due to the complex interaction between different contributions provided by the concrete, steel stirrup and FRP reinforcement. The shape of the beam and the FRP inclination can have paramount importance that is not often recognized by the models that are suggested by codes. The interaction among different resisting mechanisms has a significant effect on the shear capacity of beams, since it can cause a reduction in the efficiency of some resisting mechanisms.

Unravelling the sex-specific diversity and functions of adrenal gland macrophages.

Despite the ubiquitous function of macrophages across the body, the diversity, origin, and function of adrenal gland macrophages remain largely unknown. We define the heterogeneity of adrenal gland immune cells using single-cell RNA sequencing and use genetic models to explore the developmental mechanisms yielding macrophage diversity. We define populations of monocyte-derived and embryonically seeded adrenal gland macrophages and identify a female-specific subset with low major histocompatibility complex (MHC) class II expression.

The Cultural Heritage of "Black Stones" (/) of Leopardi's Child Home (Recanati, Italy).

A macroscopic lithological study and physical (hardness, size, weight) investigations, coupled with laser-induced breakdown spectroscopy (LIBS) and X-ray fluorescence (XRF) chemical analyses of three egg- and one pear-shaped polished black stones, exposed in the library of the child home of the famous poet Giacomo Leopardi, at Recanati (Italy), were carried out. They are characterized by different sizes: two with the same weight of 16.9 kg and the two smaller ones of 5.

massiveGST: A Mann-Whitney-Wilcoxon Gene-Set Test Tool That Gives Meaning to Gene-Set Enrichment Analysis.

Gene-set enrichment analysis is the key methodology for obtaining biological information from transcriptomic space's statistical result. Since its introduction, Gene-set Enrichment analysis methods have obtained more reliable results and a wider range of application. Great attention has been devoted to global tests, in contrast to competitive methods that have been largely ignored, although they appear more flexible because they are independent from the source of gene-profiles.

CAPE and its synthetic derivative VP961 restore BACH1/NRF2 axis in Down Syndrome.

The cells possess several mechanisms to counteract the over-production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), including enzymes such as superoxide dismutase, catalase and glutathione peroxidase. Moreover, an important sensor involved in the anti-oxidant response is KEAP1-NRF2-ARE signaling complex. Under oxidative stress (OS), the transcription factor NRF2 can dissociate from the KEAP1-complex in the cytosol and translocate into the nucleus to promote the transcriptional activation of anti-oxidant genes, such as heme oxygenase 1 and NADPH quinone oxidoreductase.

It is really time to retire laparoscopic gastric banding? Positive outcomes after long-term follow-up: the management is the key.

After the initial widespread diffusion, laparoscopic adjustable gastric banding (LAGB) has been progressively abandoned and laparoscopic sleeve gastrectomy (LSG) has become the worldwide most adopted procedure. Nevertheless, recent reports raised concerns about the long-term weight regain after different bariatric techniques. Considering the large LAGB series recorded in our multicentric bariatric database, we analysed the anthropometric and surgical outcomes of obese patients underwent LAGB at a long-term follow-up, focusing on LAGB management.

Combined ACL and Segond Repair in Combined Acute Proximal ACL Tears and Segond Fracture.

A renewed interest in anterior cruciate ligament preservation has been noted using arthroscopic primary repair in patients with proximal tears, but the main concern remained the control of the rotational instability. Segond fracture occurs in less than 10% of cases of acute anterolateral instability, but it can result in continued rotation instability. The aim of this study is to describe the surgical technique to acutely repair both the anterior cruciate ligament and Segond fracture in the acute setting.

Analysis of Diagnostic Images of Artworks and Feature Extraction: Design of a Methodology.

Digital images represent the primary tool for diagnostics and documentation of the state of preservation of artifacts. Today the interpretive filters that allow one to characterize information and communicate it are extremely subjective. Our research goal is to study a quantitative analysis methodology to facilitate and semi-automate the recognition and polygonization of areas corresponding to the characteristics searched.