Signal transduction through tyrosine-phosphorylated C-terminal fragments of amyloid precursor protein via an enhanced interaction with Shc/Grb2 adaptor proteins in reactive astrocytes of Alzheimer's disease brain.

The proteolytic processing of amyloid precursor protein (APP) through the formation of membrane-bound C-terminal fragments (CTFs) and of soluble beta-amyloid peptides likely influences the development of Alzheimer's disease (AD). We show that in human brain a subset of CTFs are tyrosine-phosphorylated and form stable complexes with the adaptor protein ShcA. Grb2 is also part of these complexes, which are present in higher amounts in AD than in control brains. ShcA immunoreactivity is also greatly enhanced in patients with AD and occurs at reactive astrocytes surrounding cerebral vessels and amyloid plaques. A higher amount of phospho-ERK1,2, likely as result of the ShcA activation, is present in AD brains. In vitro experiments show that the ShcA-CTFs interaction is strictly confined to glial cells when treated with thrombin, which is a well known ShcA and ERK1,2 activator and a regulator of APP cleavage. In untreated cells ShcA does not interact with either APP or CTFs, although they are normally generated. Altogether these data suggest that CTFs are implicated in cell signaling via Shc transduction machinery, likely influencing MAPK activity and glial reaction in AD patients

Diagnosis, treatment, and follow-up of patients with cerebral amyloid angiopathy-related inflammation

Purpose Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare potentially reversible encephalopathy associated with an autoimmune process against proteins deposited in the walls of cortical and leptomeningeal brain vessels. Definite diagnosis requires histopathological features of vascular inflammation and amyloid deposition from brain biopsy. Clinical-neuroradiological criteria have been recently introduced and validated to reduce the need for biopsy. The purpose of this paper is to report a historical retrospective review of clinical-neuroradiological follow-up of two patients with probable CAA-ri and five patients with a reasonably probable suspect of CAA-ri (4 females, 3 males, patient's age at admission: 66-79 years) seen at our institution between 2007 and 2021, focusing on clinical and neuroradiological awareness to this entity and variable response to immunotherapy. Materials and methods Clinical features at presentation included subacute to acute confusion (6/7), seizures (4/7), cognitive impairment (5/7), and focal neurological signs (3/7). Neuroradiology included braincomputed tomography followed by magnetic resonance imaging. Infectious diseases and autoimmune workups were then performed. Results CSF analysis was performed in two patients. Cerebral angiography was performed in two patients, to rule out vascular malformations. Hemorrhagic posterior reversible encephalopathy syndrome has been suspected in two patients. Four patients underwent immunotherapy with corticosteroids followed by reduction of brain dysfunctions. Three patients did not undergo immunotherapy but underwent clinical and/or neuroradiological remission. Conclusions Patients with CAA-ri present a rare steroid-responsive acute to subacute brain dysfunction. Thus, it has to be known and recognized both clinically and neuroradiologically. Spontaneous clinical and/or neuroradiological improvement is possible in patients with mild symptoms

Detailed thermal, fire, and mechanical study of silicon-modified epoxy resin containing humic acid and other additives

Following a waste-to-wealth approach, humic acid (HA) was exploited as a flame retardant additive. The effect of its addition alone and in combination with urea (UR) and ammonium polyphosphate (APP) on the thermal, fire, and mechanical performances of a bisphenol A diglycidyl ether (DGEBA)-based epoxy resin modified with (3-aminopropyl)-triethoxysilane (AP) and cured with aliphatic isophoronediamine (IDA) has been investigated. Unlike in previous studies, a UL 94-V-0 classification was achieved for epoxy resin containing HA at 6 wt % and APP at only 1 wt % phosphorus (P) loading. The presence of silicon-modified epoxy chains ameliorated the distribution of the biowaste within the resin, and the addition of HA alone avoided melt dripping. Besides, APP and UR promoted a remarkable reduction (up to 52%) of the peak heat release rate (pHRR) values and a significant delay (up to 21%) of the time to ignition in cone calorimetry tests, and hence an increase (up to 1.8 min) of the time to flashover, without any detrimental effect on the overall mechanical behavior. The evolved gas, thermal, and fire analysis was used to propose the combined mode of action of HA, UR, APP, and silicon in the fire performance improvement of the hybrid epoxy system

Worldwide Diversity of Klebsiella pneumoniae That Produce β-Lactamase blaKPC-2 Gene1

TOC summary: Clones harboring different plasmids with identical genetic structure could be the origin of worldwide spread

FORUM:Remote testing for psychological and physiological acoustics

Acoustics research involving human participants typically takes place in specialized laboratory settings. Listening studies, for example, may present controlled sounds using calibrated transducers in sound-attenuating or anechoic chambers. In contrast, remote testing takes place outside of the laboratory in everyday settings (e.g., participants' homes). Remote testing could provide greater access to participants, larger sample sizes, and opportunities to characterize performance in typical listening environments at the cost of reduced control of environmental conditions, less precise calibration, and inconsistency in attentional state and/or response behaviors from relatively smaller sample sizes and unintuitive experimental tasks. The Acoustical Society of America Technical Committee on Psychological and Physiological Acoustics launched the Task Force on Remote Testing (https://tcppasa.org/remotetesting/) in May 2020 with goals of surveying approaches and platforms available to support remote testing and identifying challenges and considerations for prospective investigators. The results of this task force survey were made available online in the form of a set of Wiki pages and summarized in this report. This report outlines the state-of-the-art of remote testing in auditory-related research as of August 2021, which is based on the Wiki and a literature search of papers published in this area since 2020, and provides three case studies to demonstrate feasibility during practice

Hierarchy of speech-driven spectrotemporal receptive fields in human auditory cortex

Existing data indicate that cortical speech processing is hierarchically organized. Numerous studies have shown that early auditory areas encode fine acoustic details while later areas encode abstracted speech patterns. However, it remains unclear precisely what speech information is encoded across these hierarchical levels. Estimation of speech-driven spectrotemporal receptive fields (STRFs) provides a means to explore cortical speech processing in terms of acoustic or linguistic information associated with characteristic spectrotemporal patterns. Here, we estimate STRFs from cortical responses to continuous speech in fMRI. Using a novel approach based on filtering randomly-selected spectrotemporal modulations (STMs) from aurally-presented sentences, STRFs were estimated for a group of listeners and categorized using a data-driven clustering algorithm. ‘Behavioral STRFs’ highlighting STMs crucial for speech recognition were derived from intelligibility judgments. Clustering revealed that STRFs in the supratemporal plane represented a broad range of STMs, while STRFs in the lateral temporal lobe represented circumscribed STM patterns important to intelligibility. Detailed analysis recovered a bilateral organization with posterior-lateral regions preferentially processing STMs associated with phonological information and anterior-lateral regions preferentially processing STMs associated with word- and phrase-level information. Regions in lateral Heschl’s gyrus preferentially processed STMs associated with vocalic information (pitch)

Tailoring Structure: Current Design Strategies and Emerging Trends to Hierarchical Catalysts

Nature mimicking implies the design of nanostructured materials, which can be assembled into a hierarchical structure, thus outperforming the features of the neat components because of their multiple length scale organization. This approach can be effectively exploited for the design of advanced photocatalysts with superior catalytic activity for energy and environment applications with considerable development in the recent six years. In this context, we propose a review on the state of the art for hierarchical photocatalyst production. Particularly, different synthesis strategies are presented, including template-free structuring, and organic, inorganic, and hybrid templating. Furthermore, emerging approaches based on hybrid and bio-waste templating are also highlighted. Finally, a critical comparison among available methods is carried out based on the envisaged application

Tailoring Structure: Current Design Strategies and Emerging Trends to Hierarchical Catalysts

Nature mimicking implies the design of nanostructured materials, which can be assembled into a hierarchical structure, thus outperforming the features of the neat components because of their multiple length scale organization. This approach can be effectively exploited for the design of advanced photocatalysts with superior catalytic activity for energy and environment applications with considerable development in the recent six years. In this context, we propose a review on the state of the art for hierarchical photocatalyst production. Particularly, different synthesis strategies are presented, including template-free structuring, and organic, inorganic, and hybrid templating. Furthermore, emerging approaches based on hybrid and bio-waste templating are also highlighted. Finally, a critical comparison among available methods is carried out based on the envisaged application

Humic acids on fire? Physico-chemical, thermal, flammability features and extraction process of different humic acids in support of their possible applications

: Humic acids (HA) consist in a multitude of heterogeneous organic molecules surviving the biological and chemical degradation of both vegetal and animal biomasses. The great abundance and chemical richness of these residues make their valorisation one of the most promising approaches to move towards a circular economy. However, the heterogeneity of the biomass from which HA are extracted, as well as the production process, significantly affects the nature and the relative content of functional groups (i.e. quinones, phenols and carboxylic and hydroxyl moieties), eventually changing HA reactivity and ultimately determining their application field. Indeed, depending on their properties, these substances can be used as flame retardants in the case of pronounced resilience degree (i.e., absent or low reactivity), or as antioxidant or antimicrobial agents in the case of pronounced reactivity, thanks to their redox behaviour. In this work we investigated the flammable, the thermal and the physico-chemical features of HA extracted from different composted biomasses to identify the reactivity or the resiliency of these moieties. Several techniques, including flammability characterization (LIT and MIE), laser diffraction granulometry, TG, XRD analyses, FTIR spectroscopy on both solid and gaseous phases, and Raman spectroscopy were integrated to investigate the correlation among the safety parameters, the distributions of particle sizes, as well as the thermal, the chemical properties of HA powders and the influence of post-extraction processes on HA final properties