Acta Neuropathologica | Year: 2016
Vascular dementia (VaD) is recognised as a neurocognitive disorder, which is explained by numerous vascular causes in the general absence of other pathologies. The heterogeneity of cerebrovascular disease makes it challenging to elucidate the neuropathological substrates and mechanisms of VaD as well as vascular cognitive impairment (VCI). Consensus and accurate diagnosis of VaD relies on wide-ranging clinical, neuropsychometric and neuroimaging measures with subsequent pathological confirmation. Pathological diagnosis of suspected clinical VaD requires adequate postmortem brain sampling and rigorous assessment methods to identify important substrates. Factors that define the subtypes of VaD include the nature and extent of vascular pathologies, degree of involvement of extra and intracranial vessels and the anatomical location of tissue changes. Atherosclerotic and cardioembolic diseases appear the most common substrates of vascular brain injury or infarction. Small vessel disease characterised by arteriolosclerosis and lacunar infarcts also causes cortical and subcortical microinfarcts, which appear to be the most robust substrates of cognitive impairment. Diffuse WM changes with loss of myelin and axonal abnormalities are common to almost all subtypes of VaD. Medial temporal lobe and hippocampal atrophy accompanied by variable hippocampal sclerosis are also features of VaD as they are of Alzheimer’s disease. Recent observations suggest that there is a vascular basis for neuronal atrophy in both the temporal and frontal lobes in VaD that is entirely independent of any Alzheimer pathology. Further knowledge on specific neuronal and dendro-synaptic changes in key regions resulting in executive dysfunction and other cognitive deficits, which define VCI and VaD, needs to be gathered. Hereditary arteriopathies such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy or CADASIL have provided insights into the mechanisms of dementia associated with cerebral small vessel disease. Greater understanding of the neurochemical and molecular investigations is needed to better define microvascular disease and vascular substrates of dementia. The investigation of relevant animal models would be valuable in exploring the pathogenesis as well as prevention of the vascular causes of cognitive impairment. © 2016, The Author(s).
Dalle Pezze P.,Vitality
Science signaling | Year: 2012
The kinase mammalian target of rapamycin (mTOR) exists in two multiprotein complexes (mTORC1 and mTORC2) and is a central regulator of growth and metabolism. Insulin activation of mTORC1, mediated by phosphoinositide 3-kinase (PI3K), Akt, and the inhibitory tuberous sclerosis complex 1/2 (TSC1-TSC2), initiates a negative feedback loop that ultimately inhibits PI3K. We present a data-driven dynamic insulin-mTOR network model that integrates the entire core network and used this model to investigate the less well understood mechanisms by which insulin regulates mTORC2. By analyzing the effects of perturbations targeting several levels within the network in silico and experimentally, we found that, in contrast to current hypotheses, the TSC1-TSC2 complex was not a direct or indirect (acting through the negative feedback loop) regulator of mTORC2. Although mTORC2 activation required active PI3K, this was not affected by the negative feedback loop. Therefore, we propose an mTORC2 activation pathway through a PI3K variant that is insensitive to the negative feedback loop that regulates mTORC1. This putative pathway predicts that mTORC2 would be refractory to Akt, which inhibits TSC1-TSC2, and, indeed, we found that mTORC2 was insensitive to constitutive Akt activation in several cell types. Our results suggest that a previously unknown network structure connects mTORC2 to its upstream cues and clarifies which molecular connectors contribute to mTORC2 activation.
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2011
Ageing is intrinsically complex, being driven by multiple causal mechanisms. Each mechanism tends to be partially supported by data indicating that it has a role in the overall cellular and molecular pathways underlying the ageing process. However, the magnitude of this role is usually modest. The systems biology approach combines (i) data-driven modelling, often using the large volumes of data generated by functional genomics technologies, and (ii) hypothesis-driven experimental studies to investigate causal pathways and identify their parameter values in an unusually quantitative manner, which enables the contributions of individual mechanisms and their interactions to be better understood, and allows for the design of experiments explicitly to test the complex predictions arising from such models. A clear example of the success of the systems biology approach in unravelling the complexity of ageing can be seen in recent studies on cell replicative senescence, revealing interactions between mitochondrial dysfunction, telomere erosion and DNA damage. An important challenge also exists in connecting the network of (random) damage-driven proximate mechanisms of ageing with the higher level (genetically specified) signalling pathways that influence longevity. This connection is informed by actions of natural selection on the determinants of ageing and longevity. © 2011 The Royal Society.
Nutrition Reviews | Year: 2010
The integrity of the vascular system is essential for the efficient functioning of the brain. Aging-related structural and functional disturbances in the macro- or microcirculation of the brain make it vulnerable to cognitive dysfunction, leading to brain degeneration and dementing illness. Several faltering controls, including impairment in autoregulation, neurovascular coupling, blood-brain barrier leakage, decreased cerebrospinal fluid, and reduced vascular tone, appear to be responsible for varying degrees of neurodegeneration in old age. There is ample evidence to indicate vascular risk factors are also linked to neurodegenerative processes preceding cognitive decline and dementia. The strongest risk factor for brain degeneration, whether it results from vascular or neurodegenerative mechanisms or both, is age. However, several modifiable risks such as cardiovascular disease, hypertension, dyslipidemia, diabetes, and obesity enhance the rate of cognitive decline and increase the risk of Alzheimer's disease in particular. The ultimate accumulation of brain pathological lesions may be modified by genetic influences, such as the apolipoprotein E ε4 allele and the environment. Lifestyle measures that maintain or improve cardiovascular health, including consumption of healthy diets, moderate use of alcohol, and implementation of regular physical exercise are important factors for brain protection. © 2010 International Life Sciences Institute.
Obesity Reviews | Year: 2014
Summary: Open discourse and tolerance between the food industry and public sector is limited. As a result, the public and private sectors are reluctant to collaborate on pressing nutritional issues. Those in the public sector have never heard what they could do to encourage a food company's transition towards healthier foods and beverages, whereas many in the private sector dismissed policies and actions initiated within the public sector. During my career, I have sought to engage the broadest possible stakeholder groups required to develop evidence-based policies and with the aim of improving public health. My recent experience in industry confirmed my view about the need for scientific exchange regardless of the disagreements about policy. Open discourse and partnering is essential if we are to tackle complex food and health issues and improve the global food system. Private-public engagement can provide faster and more sustainable results than government alone without impacting profits. Moreover, a high-quality product in smaller portions will have higher profit margins than a bargain-sized product of lower quality. The food industry and private sector must come together to implement innovative strategies to address urgent nutritional needs. © 2013 International Association for the Study of Obesity.
Current Pharmaceutical Design | Year: 2014
In addition, TERT has been detected in non-nuclear locations such as the cytoplasm and mitochondria. Within mitochondria TERT has been shown to decrease ROS generation, improve respiration, bind to mitochondrial DNA, increase mitochondrial membrane potential and interact with mitochondrial tRNAs. All these different non-telomere-related mechanisms might contribute towards the higher resistance of cancer cells against DNA damaging treatments and promote cellular survival. Understanding these different mechanisms and their complexity in cancer cells might help to design more effective cancer therapies in the future.Telomerase activity is essential for human cancer cells in order to maintain telomeres and provide unlimited proliferation potential and cellular immortality. However, additional non-telomeric roles emerge for the telomerase protein TERT that can impact tumourigenesis and cancer cell properties. This review summarises our current knowledge of non-telomeric functions of telomerase in human cells, with a special emphasis on cancer cells.Non-canonical functions of telomerase can be performed within the nucleus as well as in other cellular compartments. These telomereindependent activities of TERT influence various essential cellular processes, such as gene expression, signalling pathways, mitochondrial function as well as cell survival and stress resistance. Emerging data show the interaction of telomerase with intracellular signalling pathways such as NF-κB and WNT/β-catenin; thereby contributing to inflammation, epithelial to mesenchymal transition (EMT) and cancer invasiveness. All these different functions might contribute to tumourigenesis, and have serious consequences for cancer therapies due to increased resistance against damaging agents and prevention of cell death. © 2014 Bentham Science Publishers.
The Lancet | Year: 2014
Worldwide, more than 1 billion people use tobacco, resulting in about 6 million deaths per year. The tobacco industry's documented history of subverting control efforts required innovative approaches by WHO - led by Gro Harlem Brundtland - including invocation of its constitutional authority to develop treaties. In 2003, WHO member states adopted the WHO Framework Convention on Tobacco Control (WHO FCTC). In the decade since, 177 countries have ratified and started to implement its full provisions. Success has been tempered by new challenges. Tobacco use has fallen in countries that are members of the Organisation for Economic Co-operation and Development but increased in low-income and middle-income countries, a result in no small part of illicit trade and cheap products from China and other unregulated state monopolies. This review of 50 years of policy development aimed at reducing the burden of disease attributable to tobacco reviews the origins and strategies used in forging the WHO FCTC, from the perspective of one who was there.
Vitality | Date: 2014-07-11
Device for removing moisture and/or another substance from ambient air or from a gas, the device being configured to operate alternately in an adsorption phase and a desorption phase. The device comprises a vessel comprising an entry and an exit which comprise valves allowing the exit and entry to be opened and closed and a body of adsorption material positioned inside the vessel dividing the inside of the vessel in an upstream region and a downstream region. The device further comprises a condenser loop comprising a condenser located outside the vessel, a branch conduit which extends from the vessel to the condenser and which allows a branch flow of air or gas to flow from the downstream region to the condenser, and a condenser return conduit which extends from the condenser to the vessel and which allows the branch flow to return from the condenser to the upstream region of the vessel. The device further comprises at least one main return conduit for returning a main return flow of air or gas from the downstream region to the upstream region while bypassing the condenser.
Vitality and Laksa Andrejs | Date: 2016-09-28
A cavitation device (1) comprising a rotor (7) arranged to rotate about a rotation axis (5) and a stator (6), wherein the rotor comprises at least two circular rows of radially outwardly protruding teeth (15), the at least two circular rows of the rotor being arranged concentrically having the same radius and arranged at an axial distance from each other so that an annular cavity is formed between each two adjacent rows, wherein the stator comprises at least one circular row of radially inwardly protruding teeth, wherein the teeth of each row are arranged at a circumferential distance to each other so that a chamber is formed between each two subsequent teeth in a row, wherein the teeth of the stator are arranged to protrude into the annular cavity between the at least two rows of the rotor, so that the chambers of the at least two rows of the rotor and the chambers of the at least one stator, when axially aligned with each other, form channels extending parallel to the rotation axis of the rotor.
Agency: European Commission | Branch: H2020 | Program: SME-1 | Phase: SMEInst-09-2016-2017 | Award Amount: 71.43K | Year: 2016
Vitality Vector creates efficient applications of solid desiccants in thermodynamic processes. The main company focus is towards developing and commercialization of high-efficient desiccant based technology for a variety of HVAC and atmospheric water recovery applications. Vitality Vector has been recognized by the panel of experts (venture capital and industry insiders) at the global H2O challenge, which evaluates the innovation and uniqueness, sustainability and economic viability. As well as, the management team and the value proposition ECOOL technologies comprise two novel (patent WO2015005791 A1) evaporative cooling systems: the RIDEC for dry climates and DEC for semi-humid and humid atmospheric conditions. The RIDEC and DEC systems can generate cooling energy as effective as than any commercial model of MVC, consuming 5-10 times less of electrical energy. The RIDEC (Regenerative indirect direct evaporative cooler) outperform traditional AC consuming 90% less electricity. Moreover, compared to existing regenerative cooling technologies, higher efficiency (20%) and a fraction of the cost, position the RIDEC at an advantage position in the path to displace inefficient vapor compressor technology. The DEC (Desiccant Evaporative Cooling) overcomes the humidity barrier for the applicability of evaporative cooling technologies. The DEC provides 70% energy savings in humid regions, that where reserved exclusively for vapor compressor technology. ECOOL covers the need to reduce energy costs, displaces consumption at peak demand and increases its cooling efficiency when outside temperature is high. The expected market price of the RIDEC (50% less than equivalent AC unit) and DEC (similar price), on top of yearly energy savings, provide a winning value proposition. Vitallity Vector is in a position to build a healthy business model (19.96 cumulative revenue after 5 years) and job creation (expected to grow up to 35 employees in that period).