Vascular Care in Patients With Alzheimer Disease With Cerebrovascular Lesions Slows Progression of White Matter Lesions on MRI The Evaluation of Vascular Care in Alzheimer's Disease (EVA) Study

Background and Purpose-White matter lesions (WMLs) and cerebral infarcts are common findings in Alzheimer disease and may contribute to dementia severity. WMLs and lacunar infarcts may provide a potential target for intervention strategies. This study assessed whether multicomponent vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs and prevents occurrence of new infarcts. Methods-A randomized controlled clinical trial, including 123 subjects, compared vascular care with standard care in patients with Alzheimer disease with cerebrovascular lesions on MRI. Progression of WMLs, lacunes, medial temporal lobe atrophy, and global cortical atrophy were semiquantitatively scored after 2-year follow-up. Results-Sixty-five subjects (36 vascular care, 29 standard care) had a baseline and a follow-up MRI and in 58 subjects, a follow-up scan could not be obtained due to advanced dementia or death. Subjects in the vascular care group had less progression of WMLs as measured with the WML change score (1.4 versus 2.3, P = 0.03). There was no difference in the number of new lacunes or change in global cortical atrophy or medial temporal lobe atrophy between the 2 groups. Conclusions-Vascular care in patients with Alzheimer disease with cerebrovascular lesions slows progression of WMLs. Treatment aimed at vascular risk factors in patients with early Alzheimer disease may be beneficial, possibly in an even earlier stage of the disease. (Stroke. 2010;41:554-556.

Video Task Decathlon: Unifying Image and Video Tasks in Autonomous Driving

Performing multiple heterogeneous visual tasks in dynamic scenes is a hallmark of human perception capability. Despite remarkable progress in image and video recognition via representation learning, current research still focuses on designing specialized networks for singular, homogeneous, or simple combination of tasks. We instead explore the construction of a unified model for major image and video recognition tasks in autonomous driving with diverse input and output structures. To enable such an investigation, we design a new challenge, Video Task Decathlon (VTD), which includes ten representative image and video tasks spanning classification, segmentation, localization, and association of objects and pixels. On VTD, we develop our unified network, VTDNet, that uses a single structure and a single set of weights for all ten tasks. VTDNet groups similar tasks and employs task interaction stages to exchange information within and between task groups. Given the impracticality of labeling all tasks on all frames, and the performance degradation associated with joint training of many tasks, we design a Curriculum training, Pseudo-labeling, and Fine-tuning (CPF) scheme to successfully train VTDNet on all tasks and mitigate performance loss. Armed with CPF, VTDNet significantly outperforms its single-task counterparts on most tasks with only 20% overall computations. VTD is a promising new direction for exploring the unification of perception tasks in autonomous driving.Comment: ICCV 2023, project page at https://www.vis.xyz/pub/vt

Whether, when and how chronic inflammation increases the risk of developing late-onset Alzheimer's disease

Neuropathological studies have revealed the presence of a broad variety of inflammation-related proteins (complement factors, acute-phase proteins, pro-inflammatory cytokines) in Alzheimer's disease (AD) brains. These constituents of innate immunity are involved in several crucial pathogenic events of the underlying pathological cascade in AD, and recent studies have shown that innate immunity is involved in the etiology of late-onset AD. Genome-wide association studies have demonstrated gene loci that are linked to the complement system. Neuropathological and experimental studies indicate that fibrillar amyloid-beta (A beta) can activate the innate immunity-related CD14 and Toll-like receptor signaling pathways of glial cells for pro-inflammatory cytokine production. The production capacity of this pathway is under genetic control and off spring with a parental history of late-onset AD have a higher production capacity for pro-inflammatory cytokines. The activation of microglia by fibrillar A beta deposits in the early preclinical stages of AD can make the brain susceptible later on for a second immune challenge leading to enhanced production of pro-inflammatory cytokines. An example of a second immune challenge could be systemic inflammation in patients with preclinical AD. Prospective epidemiological studies show that elevated serum levels of acute phase reactants can be considered as a risk factor for AD. Clinical studies suggest that peripheral inflammation increases the risk of dementia, especially in patients with preexistent cognitive impairment, and accelerates further deterioration in demented patients. The view that peripheral inflammation can increase the risk of dementia in older people provides scope for preventio

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PARADISEC (Pacific And Regional Archive for Digital Sources in Endangered Cultures), Australian Partnership for Sustainable Repositories, Ethnographic E-Research Project and Sydney Object Repositories for Research and Teaching

LRP1 Has a Predominant Role in Production over Clearance of Aβ in a Mouse Model of Alzheimer's Disease.

The low-density lipoprotein receptor-related protein-1 (LRP1) has a dual role in the metabolism of the amyloid precursor protein (APP). In cellular models, LRP1 enhances amyloid-β (Aβ) generation via APP internalization and thus its amyloidogenic processing. However, conditional knock-out studies in mice define LRP1 as an important mediator for the clearance of extracellular Aβ from brain via cellular degradation or transcytosis across the blood-brain barrier (BBB). In order to analyze the net effect of LRP1 on production and clearance of Aβ in vivo, we crossed mice with impaired LRP1 function with a mouse model of Alzheimer's disease (AD). Analysis of Aβ metabolism showed that, despite reduced Aβ clearance due to LRP1 inactivation in vivo, less Aβ was found in cerebrospinal fluid (CSF) and brain interstitial fluid (ISF). Further analysis of APP metabolism revealed that impairment of LRP1 in vivo shifted APP processing from the Aβ-generating amyloidogenic cleavage by beta-secretase to the non-amyloidogenic processing by alpha-secretase as shown by a decrease in extracellular Aβ and an increase of soluble APP-α (sAPP-α). This shift in APP processing resulted in overall lower Aβ levels and a reduction in plaque burden. Here, we present for the first time clear in vivo evidence that global impairment of LRP1's endocytosis function favors non-amyloidogenic processing of APP due to its reduced internalization and subsequently, reduced amyloidogenic processing. By inactivation of LRP1, the inhibitory effect on Aβ generation overrules the simultaneous impaired Aβ clearance, resulting in less extracellular Aβ and reduced plaque deposition in a mouse model of AD

De relatie tussen waterkwaliteit en welzijn bij Afrikaanse meerval en tong op Nederlandse viskwekerijen

Het doel van deze literatuurstudie is het beschrijven van de mogelijke knelpunten in de relatie tussen het welzijn van vissen en de waterkwaliteit in recirculatiesystemen (RAS), gespecificeerd op de Afrikaanse meerval (Clarias gariepinus) en tong (Solea solea). Hiernaast is bij een tongkwekerij en bij twee meervalkwekerijen een studie uitgevoerd naar de waterkwaliteit. De resultaten tonen aan dat de temperatuur, pH en zuurstofconcentratie van het water constant zijn. Het TAN-niveau (Total Ammonia Nitrogen) laat een variabel beeld zien bij de meervalkwekerijen, bij de tongkwekerij is het TAN-niveau constant laag

Lysine blockage of milk proteins in infant formula impairs overall protein digestibility and peptide release

During heat processing of milk and dairy products, for example infant formula, the Maillard reaction occurs. In vitro and animal studies suggest that Maillard reaction induced lysine blockage impairs protein digestibility. Most studies that investigate the effect of glycation on protein digestion use a mixture of isolated milk protein with reducing sugars. In this study, infant formulas with 6.5%, 8.4%, 11.2%, 14.8%, 20.8%, and 44.5% of blocked lysine (BL) were digested in an in vitro infant digestion model and tested for protein hydrolysis and peptide release. OPA (o-phthalaldehyde) assay was used to assess the degree of protein hydrolysis. SDS-PAGE was conducted to monitor the hydrolysis of specific proteins. Peptides formed after gastric and intestinal digestion were identified by LC/MS. Protein hydrolysis of the 6.5% BL sample was significantly higher after 10 minutes of intestinal digestion compared to all other samples. Most differences were observed after intestinal digestion. A significant change in peptide patterns was observed for the 45% BL sample resulting in a relatively higher number of peptides with more than 14 amino acids. Mainly casein-derived peptides were affected. Overall, the average peptide length was significantly increased for the 44.5% BL glycated product (on average 10.2 amino acids for 6-21% BL vs. 11.4 amino acids for 45% BL; p < 0.001). In conclusion, glycation of milk proteins in an infant formula product can impair overall protein digestibility. These findings emphasize the importance of mild processing and having low BL levels in infant formula to ensure optimal digestion of proteins.</p

Biochemical and biological characterization of wild-type and ATPase-deficient Cockayne syndrome B repair protein

Cockayne syndrome (CS) is a nucleotide excision repair disorder characterized by sun (UV) sensitivity and severe developmental problems. Two genes have been shown to be involved: CSA and CSB. Both proteins play an essential role in preferential repair of transcription-blocking lesions from active genes. In this study we report the purification and characterization of baculovirus-produced HA-His6-tagged CSB protein (dtCSB), using a highly efficient three-step purification protocol. Microinjection of dtCSB protein in CS-B fibroblasts shows that it is biologically functional in vivo. dtCSB exhibits DNA-dependent ATPase activity, stimulated by naked as well as nucleosomal DNA. Using structurally defined DNA oligonucleotides, we show that double-stranded DNA and double-stranded DNA with partial single-stranded character but not true single-stranded DNA act as efficient cofactors for CSB ATPase activity. Using a variety of substrates, no overt DNA unwinding by dtCSB could be detected, as found with other SNF2/SWI2 family proteins. By site-directed mutagenesis the invariant lysine residue in the NTP-binding motif of CSB was substituted with a physicochemically related arginine. As expected, this mutation abolished ATPase activity. Surprisingly, the mutant protein was nevertheless able to partially rescue the defect in recovery of RNA synthesis after UV upon microinjection in CS-B fibroblasts. These results indicate that integrity of the conserved nucleotide-binding domain is important for the in vivo function of CSB but that also other properties independent from ATP hydrolysis may contribute to CSB biological functions