Alzheimer’s disease (AD) is characterized by memory loss, cognitive decline, and devastating neurodegeneration, not only as a result of the extracellular accumulation of beta-amyloid peptide (Aβ) and ...intracellular accumulation of tau, but also as a consequence of the dysfunction and loss of synapses. Although significant advances have been made in our understanding of the relationship of the pathological role of Aβ and tau in synapse dysfunction, several questions remain as to how Aβ and tau interdependently cause impairments in synaptic function in AD. Overall, more insight into these questions should enable researchers in this field to develop novel therapeutic targets to mitigate or delay the cognitive deficits associated with this devastating disease.
The postharvest phase has been considered an environment for successful application of biological control agents (BCAs). However, the interactions between fungal pathogen, host (fruit), and ...antagonist are influenced by several parameters such as temperature, oxidative stresses, oxygen composition and water activity that could determine the success of biocontrol. Knowledge of the modes of action of BCAs is essential in order to enhance their viability and increase their potential in disease control. The antagonists display a wide range of modes of action: antibiosis, competition for nutrients and space, parasitism and induction of resistance are considered the main ones. Their efficacy, however, is related to the host and the pathogen; sometimes, these mechanisms could act simultaneously, and it is therefore difficult to establish which is related to a specific antifungal action. The current review presents a brief summary of the research that has led to a better understanding of the mode of action of BCAs with particular emphasis on the most recent literature.
Ascribing mental states to non-human agents has been shown to increase their likeability and lead to better joint-task performance in human-robot interaction (HRI). However, it is currently unclear ...what physical features non-human agents need to possess in order to trigger mind attribution and whether different aspects of having a mind (e.g., feeling pain, being able to move) need different levels of human-likeness before they are readily ascribed to non-human agents. The current study addresses this issue by modeling how increasing the degree of human-like appearance (on a spectrum from mechanistic to humanoid to human) changes the likelihood by which mind is attributed towards non-human agents. We also test whether different internal states (e.g., being hungry, being alive) need different degrees of humanness before they are ascribed to non-human agents. The results suggest that the relationship between physical appearance and the degree to which mind is attributed to non-human agents is best described as a two-linear model with no change in mind attribution on the spectrum from mechanistic to humanoid robot, but a significant increase in mind attribution as soon as human features are included in the image. There seems to be a qualitative difference in the perception of mindful versus mindless agents given that increasing human-like appearance alone does not increase mind attribution until a certain threshold is reached, that is: agents need to be classified as having a mind first before the addition of more human-like features significantly increases the degree to which mind is attributed to that agent.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The impact of apolipoprotein E ε4 (APOE4), the strongest genetic risk factor for Alzheimer's disease (AD), on human brain cellular function remains unclear. Here, we investigated the effects of APOE4 ...on brain cell types derived from population and isogenic human induced pluripotent stem cells, post-mortem brain, and APOE targeted replacement mice. Population and isogenic models demonstrate that APOE4 local haplotype, rather than a single risk allele, contributes to risk. Global transcriptomic analyses reveal human-specific, APOE4-driven lipid metabolic dysregulation in astrocytes and microglia. APOE4 enhances de novo cholesterol synthesis despite elevated intracellular cholesterol due to lysosomal cholesterol sequestration in astrocytes. Further, matrisome dysregulation is associated with upregulated chemotaxis, glial activation, and lipid biosynthesis in astrocytes co-cultured with neurons, which recapitulates altered astrocyte matrisome signaling in human brain. Thus, APOE4 initiates glia-specific cell and non-cell autonomous dysregulation that may contribute to increased AD risk.
The role of specific gut microbes in shaping body composition remains unclear. We transplanted fecal microbiota from adult female twin pairs discordant for obesity into germ-free mice fed low-fat ...mouse chow, as well as diets representing different levels of saturated fat and fruit and vegetable consumption typical of the U.S. diet. Increased total body and fat mass, as well as obesity-associated metabolic phenotypes, were transmissible with uncultured fecal communities and with their corresponding fecal bacterial culture collections. Cohousing mice harboring an obese twin's microbiota (Ob) with mice containing the lean co-twin's microbiota (Ln) prevented the development of increased body mass and obesity-associated metabolic phenotypes in Ob cage mates. Rescue correlated with invasion of specific members of Bacteroidetes from the Ln microbiota into Ob microbiota and was diet-dependent. These findings reveal transmissible, rapid, and modifiable effects of diet-by-microbiota interactions.
The routine use of neuromuscular blocking agents reduces the occurrence of unacceptable surgical conditions. In some surgeries, such as retroperitoneal laparoscopies, deep neuromuscular block (NMB) ...may further improve surgical conditions compared with moderate NMB. In this study, the effect of deep NMB on surgical conditions was assessed.
Twenty-four patients undergoing elective laparoscopic surgery for prostatectomy or nephrectomy were randomized to receive moderate NMB (train-of-four 1–2) using the combination of atracurium/mivacurium, or deep NMB (post-tetanic count 1–2) using high-dose rocuronium. After surgery, NMB was antagonized with neostigmine (moderate NMB), or sugammadex (deep NMB). During all surgeries, one surgeon scored the quality of surgical conditions using a five-point surgical rating scale (SRS) ranging from 1 (extremely poor conditions) to 5 (optimal conditions). Video images were obtained and 12 anaesthetists rated a random selection of images.
Mean (standard deviation) SRS was 4.0 (0.4) during moderate and 4.7 (0.4) during deep NMB (P<0.001). Moderate block resulted in 18% of scores at the low end of the scale (Scores 1–3); deep block resulted in 99% of scores at the high end of the scale (Scores 4 and 5). Cardiorespiratory conditions were similar during and after surgery in both groups. Between anaesthetists and surgeon, there was poor agreement between scores of individual images (average κ statistic 0.05).
Application of the five-point SRS showed that deep NMB results in an improved quality of surgical conditions compared with moderate block in retroperitoneal laparoscopies, without compromise to the patients’ peri- and postoperative cardiorespiratory conditions.
The study was registered at clinicaltrials.gov under number NCT01361149.
•New Schiff bases tested as bronze corrosion inhibitors in concentrated acid rain.•2-(Salicylideneimino) thiophenol (SITP) afforded η = 100% after 480 h immersion.•Duplex protective film formed: ...adsorbed SITP molecules over a Cu(I)-SITP layer.•Phosphates (P) added to SITP produced higher resistance against localized attack.•SITP and SITP + P hindered bronze decuprification in concentrated acid rain.
In this research, different Schiff bases were synthesized and tested as bronze corrosion inhibitors in concentrated synthetic acid rain at pH 3.3. Some of them showed good inhibiting effects, as detected by EIS and polarization curve recording. The most efficient inhibitor (2-(salicylideneimino) thiophenol, SITP) was also tested with addition of sodium dihydrogen phosphate (P). P improved the surface film resistance against breakdown phenomena. XPS and SEM investigations showed that SITP and SITP + P significantly hinder decuprification. Moreover, SITP forms a protective layer on bronze, composed of both Cu(I)-SITP complexes and adsorbed inhibitor molecules. Cu(II) phosphates were also detected with P addition.
This work focuses on the tribological behaviour of PVD coated Ti-6Al-4V. Commercially available single layer CrN, CrN/NbN superlattice and multilayer WC/C coatings were taken into consideration. The ...dry sliding behaviour of the coated systems was studied by a flat-on-cylinder tribometer (load range 30–60
N). A critical load, corresponding to the end of coating life, was identified for each coated system. The highest critical loads were observed for CrN- and WC/C-coated Ti-6Al-4V. However, only WC/C also led to a significant decrease of the coefficient of friction. The good performance of WC/C-coated Ti-6Al-4V was ascribed to both the high
H/
E ratio of the coating and to the best match of elastic modulus with the substrate.
► Evaluation of dry sliding behaviour of CrN, CrN/NbN and WC/C-coated Ti-6Al-4V. ► All the PVD coatings improved the wear resistance of the Ti-6Al-4V alloy. ► Critical load identified for each coated system: highest for CrN and WC/C. ► Only multilayer WC/C coating improved wear resistance and decreased friction.
Microglia are strongly implicated in the development and progression of Alzheimer’s disease (AD), yet their impact on pathology and lifespan remains unclear. Here we utilize a CSF1R hypomorphic mouse ...to generate a model of AD that genetically lacks microglia. The resulting microglial-deficient mice exhibit a profound shift from parenchymal amyloid plaques to cerebral amyloid angiopathy (CAA), which is accompanied by numerous transcriptional changes, greatly increased brain calcification and hemorrhages, and premature lethality. Remarkably, a single injection of wild-type microglia into adult mice repopulates the microglial niche and prevents each of these pathological changes. Taken together, these results indicate the protective functions of microglia in reducing CAA, blood-brain barrier dysfunction, and brain calcification. To further understand the clinical implications of these findings, human AD tissue and iPSC-microglia were examined, providing evidence that microglia phagocytose calcium crystals, and this process is impaired by loss of the AD risk gene, TREM2.
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•Absence of microglia in Alzheimer’s disease mice promotes cerebral amyloid angiopathy•Increased vascular amyloid is accompanied by hemorrhages, calcification, and lethality•Adult transplantation of microglia prevents these diverse pathological changes•snRNA-seq reveals the impact of microglial absence and replacement on other cell types
Kiani Shabestari et al. show that genetic absence of microglia in Alzheimer’s disease mice causes a shift from parenchymal amyloid plaques to cerebral amyloid angiopathy, brain calcification and hemorrhages, and premature lethality. Adult microglial transplantation rescues these pathological changes, demonstrating that microglia protect the brain against detrimental Alzheimer’s disease co-pathologies.
In this work, Plasma Electrolytic Oxidation (PEO) coatings were produced on AZ91D Mg alloy, using as electrolyte an aqueous solution containing both silicates and phosphates. SiC particles, or ...borosilicate glass particles or a combination of them (SiC + borosilicate glass) were suspended into the electrolyte.
The PEO-treated samples were characterized through Scanning Electron Microscope (SEM) (both on the surface and in cross section), X-Ray Diffraction (XRD) and X-Ray Photoelectron Spectroscopy (XPS) in order to study the morphology, thickness, adhesion, structure and composition of the coating as well as particle distribution. The corrosion behavior was analyzed by potentiodynamic polarization and electrochemical impedance spectroscopy (EIS). The wear resistance was evaluated by dry sliding tests vs. AISI 52100 bearing steel (block-on-ring contact geometry).
The results showed that both SiC and borosilicate glass particles were incorporated into the PEO layers. Glass particles contributed to enhance corrosion resistance, whereas SiC particles decreased it. On the other hand, SiC particles improved the wear resistance (due to enhanced load support), leading to an increase of the friction coefficient (due to an increase of the abrasive component of friction). The best combination of properties was obtained with the addition of glass particles for 3 min treatment time. In this way, both the corrosion and wear resistance were increased, minimizing the detrimental effects of SiC particles on the corrosion properties and the friction coefficient.
•SiC and borosilicate glass particles successfully incorporated into PEO coatings•SiC particles enter through inert incorporation, instead glass particles are melted and solidified during the treatment.•-Corrosion resistance is decreased by SiC particles and increased by glass particles.•-Wear resistance resulted increased by the combination of SiC and glass particles•The best combination of corrosion and wear resistance is obtained with the presence of both SiC and glass particles.
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