Are heat shock proteins an important link between type 2 diabetes and Alzheimer disease?

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Type 2 diabetes (T2D) and Alzheimer’s disease (AD) are growing in prevalence worldwide. The development of T2D increases the risk of AD disease, while AD patients can show glucose imbalance due to an increased insulin resistance. T2D and AD share similar pathological features and underlying mechanisms, including the deposition of amyloidogenic peptides in pancreatic islets (i.e., islet amyloid polypeptide; IAPP) and brain (β-Amyloid; Aβ). Both IAPP and Aβ can undergo misfolding and aggregation and accumulate in the extracellular space of their respective tissues of origin. As a main response to protein misfolding, there is evidence of the role of heat shock proteins (HSPs) in moderating T2D and AD. HSPs play a pivotal role in cell homeostasis by providing cytoprotection during acute and chronic metabolic stresses. In T2D and AD, intracellular HSP (iHSP) levels are reduced, potentially due to the ability of the cell to export HSPs to the extracellular space (eHSP). The increase in eHSPs can contribute to oxidative damage and is associated with various pro-inflammatory pathways in T2D and AD. Here, we review the role of HSP in moderating T2D and AD, as well as propose that these chaperone proteins are an important link in the relationship between T2D and AD

Teachers as knowledge creators

Explore how teachers are connecting with each other through use of online learning technologies. • Demonstrate how teachers are creating learning artefacts for use in their own practice contexts. • Show how teachers are integrating their educational values in practice by asking, researching and answering the question, 'how can I improve my practice?

Living with a diagnosis of behavioural-variant frontotemporal dementia: The person’s experience.

YesResearch investigating behavioural-variant frontotemporal dementia has concentrated on identifying and quantifying people’s difficulties; yet few studies have considered how people with behavioural-variant frontotemporal dementia make sense of their difficulties. Five participants were interviewed and interpretive phenomenological analysis used to analyse the data. Two superordinate themes emerged: ‘Bewilderment’ and ‘Relationships with others’. ‘Bewilderment’ reflected the feelings of the participants from the start of their dementia, and was divided into two main themes (1) ‘Awareness of change: What’s the problem? and (2) Threats to self: This is not me. The superordinate theme, ‘Relationships with others’, reflected difficulties with social relationships and comprised two main themes (1) ‘Family and friends: Things haven’t changed… but do I say anything wrong?’ and (2) Coping with threats to self: Blame others or just avoid them. The themes were discussed in relation to literature evaluating the difficulties associated with behavioural-variant frontotemporal dementia together with implications for clinical practice

Spectro-electrochemical studies on [Ru(TAP)2(dppz)]2+ - insights into the mechanism of its photosensitized oxidation of oligonucleotides

[Ru(TAP)2(dppz)]2+ (TAP = 1,4,5,8-tetraazaphenanthrene; dppz = dipyrido[3,2-a:2′,3′-c]phenazine) is known to photo-oxidize guanine in DNA. Whether this oxidation proceeds by direct photoelectron transfer or by proton-coupled electron transfer is still unknown. To help distinguish between these mechanisms, spectro-electrochemical experiments have been carried out with [Ru(TAP)2(dppz)]2+ in acetonitrile. The UV–vis and mid-IR spectra obtained for the one-electron reduced product were compared to those obtained by picosecond transient absorption and time-resolved infrared experiments of [Ru(TAP)2(dppz)]2+ bound to guanine-containing DNA. An interesting feature of the singly reduced species is an electronic transition in the near-IR region (with λmax at 1970 and 2820 nm). Density functional and time-dependent density functional theory simulations of the vibrational and electronic spectra of [Ru(TAP)2(dppz)]2+, the reduced complex [Ru(TAP)2(dppz)]+, and four isomers of [Ru(TAP)(TAPH)(dppz)]2+ (a possible product of proton-coupled electron transfer) were performed. Significantly, these predict absorption bands at λ > 1900 nm (attributed to a ligand-to-metal charge-transfer transition) for [Ru(TAP)2(dppz)]+ but not for [Ru(TAP)(TAPH)(dppz)]2+. Both the UV–vis and mid-IR difference absorption spectra of the electrochemically generated singly reduced species [Ru(TAP)2(dppz)]+ agree well with the transient absorption and time-resolved infrared spectra previously determined for the transient species formed by photoexcitation of [Ru(TAP)2(dppz)]2+ intercalated in guanine-containing DNA. This suggests that the photochemical process in DNA proceeds by photoelectron transfer and not by a proton-coupled electron transfer process involving formation of [Ru(TAP)(TAPH)(dppz)]2+, as is proposed for the reaction with 5′-guanosine monophosphate. Additional infrared spectro-electrochemical measurements and density functional calculations have also been carried out on the free TAP ligand. These show that the TAP radical anion in acetonitrile also exhibits strong broad near-IR electronic absorption (λmax at 1750 and 2360 nm)

Inflamation and oxidative stress : The molecular connectivity between insulin resistance, obesity and Alzheimer\u27s disease

Type 2 diabetes (T 2 DM), Alzheimer’s disease (AD), and insulin resistance are age-related conditions and increased prevalence is of public concern. Recent research has provided evidence that insulin resistance and impaired insulin signalling may be a contributory factor to the progression of diabetes, dementia, and other neurological disorders. Alzheimer’s disease (AD) is the most common subtype of dementia. Reduced release (for T 2 DM) and decreased action of insulin are central to the development and progression of both T 2 DM and AD. A literature search was conducted to identify molecular commonalities between obesity, diabetes, and AD. Insulin resistance affects many tissues and organs, either through impaired insulin signalling or through aberrant changes in both glucose and lipid (cholesterol and triacylglycerol) metabolism and concentrations in the blood. Although epidemiological and biological evidence has highlighted an increased incidence of cognitive decline and AD in patients with T 2 DM, the common molecular basis of cell and tissue dysfunction is rapidly gaining recognition. As a cause or consequence, the chronic in flammatory response and oxidative stress associated with T 2 DM, amyloid- ! (A ! ) protein accumulation, and mitochondrial dysfunction link T 2 DM and AD

Manganese tricarbonyl complexes with asymmetric 2 2‑iminopyridine ligands: toward decoupling steric and electronic 3 factors in electrocatalytic CO2 reduction

Manganese tricarbonyl bromide complexes incorporating IP (2-(phenylimino)pyridine) derivatives, [MnBr(CO)3(IP)], are demonstrated as a new group of catalysts for CO2 reduction, which represent the first example of utilization of (phenylimino)pyridine ligands on manganese centers for this purpose. The key feature is the asymmetric structure of the redox-noninnocent ligand that permits independent tuning of its steric and electronic properties. The α-diimine ligands and five new Mn(I) compounds have been synthesized, isolated in high yields, and fully characterized, including X-ray crystallography. Their electrochemical and electrocatalytic behavior was investigated using cyclic voltammetry and UV−vis−IR spectroelectrochemistry within an OTTLE cell. Mechanistic investigations under an inert atmosphere have revealed differences in the nature of the reduction products as a function of steric bulk of the ligand. The direct ECE (electrochemical−chemical−electrochemical) formation of a five-coordinate anion [Mn(CO)3(IP)]−, a product of two-electron reduction of the parent complex, is observed in the case of the bulky DIPIMP (2-[((2,6-diisopropylphenyl)imino)methyl]pyridine), TBIMP (2-[((2-tert-butylphenyl)imino)methyl]-pyridine), and TBIEP (2-[((2-tert-butylphenyl)imino)ethyl]pyridine) derivatives. This process is replaced for the least sterically demanding IP ligand in [MnBr(CO)3(IMP)] (2-[(phenylimino)methyl]pyridine) by the stepwise formation of such a monoanion via an ECEC(E) mechanism involving also the intermediate Mn−Mn dimer [Mn(CO)3(IMP)]2. The complex [MnBr(CO)3(IPIMP)] (2-[((2-diisopropylphenyl)imino)methyl]pyridine), which carries a moderately electron donating, moderately bulky IP ligand, shows an intermediate behavior where both the five-coordinate anion and its dimeric precursor are jointly detected on the time scale of the spectroelectrochemical experiments. Under an atmosphere of CO2 the studied complexes, except for the DIPIMP derivative, rapidly coordinate CO2, forming stable bicarbonate intermediates, with no dimer being observed. Such behavior indicates that the CO2 binding is outcompeting another pathway: viz., the dimerization reaction between the five-coordinate anion and the neutral parent complex. The bicarbonate intermediate species undergo reduction at more negative potentials (ca. −2.2 V vs Fc/Fc+ ), recovering [Mn(CO)3(IP)]− and triggering the catalytic production of CO

Identifying and Understanding the Non-clinical Impacts of Delayed or Cancelled Surgery in Order to Inform Prioritisation Processes: A Scoping Review

The COVID-19 pandemic has resulted in significant delays to non-urgent elective surgery. Decision making regarding prioritisation for surgery is currently informed primarily by clinical urgency. The ways in which decision making should also consider potential social and economic harm arising from surgical delay are currently unclear. This scoping review aimed to identify evidence related to (i) the nature and prevalence of social and economic harm experienced by patients associated with delayed surgery, and (ii) any patient assessment tools that could measure the extent of, or predict, such social and economic harm. A rapid scoping review was undertaken following JBI methodological guidance. The following databases were searched in October 2020: AMED; BNI; CINAHL; EMBASE; EMCARE; HMIC; Medline; PsychINFO, Cochrane, and the JBI. A total of 21 publications were included. The findings were categorised into five themes: (i) employment, (ii) social function and leisure, (iii) finances, (iv) patients’ experiences of waiting, and (v) assessment tools that could inform decision making. The findings suggest that, for some patients, waiting for surgery can include significant social, economic, and emotional hardship. Few validated assessment tools exist. There is an urgent need for more research on patients’ experiences of surgical delay in order to inform a more holistic process of prioritising people on surgical waiting lists in the COVID- 19 pandemic recovery stages

The powers in PowerPoint: Embedded authorities, documentary tastes, and institutional (second) orders in corporate Korea

Microsoft PowerPoint is both the bane and banality of contemporary South Korean office work. Corporate workers spend countless hours refining and crafting plans, proposals, and reports in PowerPoint that often lead to conflicts with coworkers and overtime work. This article theorizes the excessive attention to documents in modern office contexts. Where scholars have been under the impression that institutional documents align with institutional purposes, I describe a context in which making documents for individual purposes and making them for work exist under a basic tension. Based on fieldwork in corporate Korea between 2013 and 2015, I describe how Korean office workers calibrate documents to the tastes of superiors who populate the managerial chain. These practices leave little trace of real "work" on paper, but they are productive for navigating complex internal labor markets and demonstrating a higher order value of attention toward others. These findings suggest that institutional and individual authorities are not competing projects inside organizations but become entangled in increasingly complex participatory encounters, even as they are channeled through a seemingly simple software like PowerPoint. [documents, expertise, authority, technology, South Korea

A review of abnormalities in the perception of visual illusions in schizophrenia

Specific abnormalities of vision in schizophrenia have been observed to affect high-level and some low-level integration mechanisms, suggesting that people with schizophrenia may experience anomalies across different stages in the visual system affecting either early or late processing or both. Here, we review the research into visual illusion perception in schizophrenia and the issues which previous research has faced. One general finding that emerged from the literature is that those with schizophrenia are mostly immune to the effects of high-level illusory displays, but this effect is not consistent across all low-level illusions. The present review suggests that this resistance is due to the weakening of top–down perceptual mechanisms and may be relevant to the understanding of symptoms of visual distortion rather than hallucinations as previously thought

Communication and cross-examination in court for children and adults with intellectual disabilities: A systematic review

Courts in England, Wales and Northern Ireland have identified children and adults with intellectual disabilities (ID) as vulnerable witnesses. The call from the English Court of Appeal is for advocates to adjust questioning during cross-examination according to individual needs. This review systematically examined previous empirical studies with the aim of delineating the particular communication needs of children and adults with ID during cross-examination. Studies utilising experimental methodology similar to examination/cross-examination processes, or which assessed the communication of actual cross-examinations in court were included. A range of communication challenges were highlighted including: suggestibility to leading questions and negative feedback; acquiescence; accuracy; and understanding of court language. In addition, a number of influencing factors were identified, including: age; IQ level; question styles used; recall memory; and delays. This review highlights the need for further research using cross-examination methodology and live practice, that take into consideration the impact on communication of the unique environment and situation of the cross-examination process