Improving Conversations about Parkinson's Dementia.

Background: People with Parkinson's disease (PD) have an increased risk of dementia, yet patients and clinicians frequently avoid talking about it due to associated stigma, and the perception that "nothing can be done about it". However, open conversations about PD dementia may allow people with the condition to access treatment and support, and may increase participation in research aimed at understanding PD dementia.

Objectives: To co-produce information resources for patients and healthcare professionals to improve conversations about PD dementia.

A neuroimaging measure to capture heterogeneous patterns of atrophy in Parkinson's disease and dementia with Lewy bodies.

Introduction: Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) show heterogeneous brain atrophy patterns which group-average analyses fail to capture. Neuroanatomical normative modelling overcomes this by comparing individuals to a large reference cohort. Patient-specific atrophy patterns are measured objectively and summarised to index overall neurodegeneration (the 'total outlier count').

Which components of the Mediterranean diet are associated with dementia? A UK Biobank cohort study.

Cohort studies suggest that the Mediterranean diet is associated with better global cognition in older adults, slower cognitive decline and lower risk of dementia. However, little is known about the relative contribution of each component of the Mediterranean diet to dementia risk or whether the diet's effects are due to one or more specific food components. We aimed to examine whether Mediterranean diet components are associated with all-cause dementia risk in the UK BioBank cohort.

Drug-induced Bile Duct Injury - A Short Review.

The liver represents the major site of drug metabolism, i.e. the key organ in the processes of detoxification and elimination of drugs from the organism.

A critical role of integrin-linked kinase, ch-TOG and TACC3 in centrosome clustering in cancer cells.

Many cancer cells contain more than two centrosomes, which imposes a potential for multipolar mitoses, leading to cell death. To circumvent this, cancer cells develop mechanisms to cluster supernumerary centrosomes to form bipolar spindles, enabling successful mitosis. Disruption of centrosome clustering thus provides a selective means of killing supernumerary centrosome-harboring cancer cells.

Beyond focal adhesions: integrin-linked kinase associates with tubulin and regulates mitotic spindle organization.

Integrin-linked kinase (ILK) is a member of a multiprotein complex at focal adhesions which interacts with actin. Here, it functions as a kinase and adapter protein to regulate diverse cellular processes. Gene knockout studies have demonstrated critical roles for ILK in embryonic development and in organ and tissue homeostasis.

Rictor and integrin-linked kinase interact and regulate Akt phosphorylation and cancer cell survival.

An unbiased proteomic screen to identify integrin-linked kinase (ILK) interactors revealed rictor as an ILK-binding protein. This finding was interesting because rictor, originally identified as a regulator of cytoskeletal dynamics, is also a component of mammalian target of rapamycin complex 2 (mTORC2), a complex implicated in Akt phosphorylation. These functions overlap with known ILK functions.

Mapping the integrin-linked kinase interactome using SILAC.

Protein-protein interactions play an essential role in the regulation of vital biological functions. Through a network of interactions, integrin-linked kinase (ILK) functions downstream of integrin receptors to control cell spreading, migration, growth, survival, and cell cycle progression. Despite many reports on the role of ILK in the regulation of multiple signaling pathways, it is still not understood how ILK integrates and controls complex cellular signals.

Integrin-linked kinase localizes to the centrosome and regulates mitotic spindle organization.

Integrin-linked kinase (ILK) is a serine-threonine kinase and scaffold protein with well defined roles in focal adhesions in integrin-mediated cell adhesion, spreading, migration, and signaling. Using mass spectrometry-based proteomic approaches, we identify centrosomal and mitotic spindle proteins as interactors of ILK. alpha- and beta-tubulin, ch-TOG (XMAP215), and RUVBL1 associate with ILK and colocalize with it to mitotic centrosomes.

[The use of 1H-NMR spectroscopy for the prognosis of overall survival of breast cancer patients].

The pool of low-molecular metabolites in untreated breast cancer patients was investigated by high-resolution 1H-NMR spectrometry. It was found that the delta = 1.75 m.

Lipoproteins and mitogen-activated protein kinase signaling: a role in atherogenesis?

Purpose Of Review: Lipoproteins play a critical role in the development of atherosclerosis, which might result partly from their capacity to induce specific intracellular signaling pathways. The goal of this review is to summarize the signaling properties of lipoproteins, in particular, their capacity to induce activation of mitogen-activated protein kinase pathways and the resulting modulation of cellular responses in blood vessel cells.

Recent Findings: Lipoproteins activate the extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways in all blood vessel cell types.

Interleukin-8 secretion by fibroblasts induced by low density lipoproteins is p38 MAPK-dependent and leads to cell spreading and wound closure.

We have previously reported (Dobreva, I., Waeber, G., Mooser, V.

Cholesterol is the major component of native lipoproteins activating the p38 mitogen-activated protein kinases.

Elevated low-density lipoprotein (LDL) levels induce activation of the p38 mitogen-activated protein kinase (MAPK), a stress-activated protein kinase potentially participating in the development of atherosclerosis. The nature of the lipoprotein components inducing p38 MAPK activation has remained unclear however. We show here that both LDLs and high-density lipoproteins (HDLs) have the ability to stimulate the p38 MAPKs with potencies that correlate with their cholesterol content.

LDLs induce fibroblast spreading independently of the LDL receptor via activation of the p38 MAPK pathway.

Because adventitial fibroblasts play an important role in the repair of blood vessels, we assessed whether elevation in LDL concentrations would affect fibroblast function and whether this depended on activation of intracellular signaling pathways. We show here that in primary human fibroblasts, LDLs induced transient activation of the p38 mitogen-activated protein kinase (MAPK) pathway, but not the c-Jun N-terminal kinase MAPK pathway. This activation did not require the recruitment of the LDL receptor (LDLR), because LDLs efficiently stimulated the p38 MAPK pathway in human and mouse fibroblasts lacking functional LDLR, and because receptor-associated protein, an LDLR family antagonist, did not block the LDL-induced p38 activation.