Inhibitors of alpha-synuclein oligomerization and toxicity: a future therapeutic strategy for Parkinson's disease and related disorders.

An abundance of genetic, histopathological, and biochemical evidence has implicated the neuronal protein, alpha-synuclein (alpha-syn) as a key player in the development of several neurodegenerative diseases, the so-called synucleinopathies, of which Parkinson's disease (PD) is the most prevalent. Development of disease appears to be linked to events that increase the intracellular concentration of alpha-syn or cause its chemical modification, either of which can accelerate the rate at which it forms aggregates. Examples of such events include increased copy number of genes, decreased rate of degradation via the proteasome or other proteases, or altered forms of alpha-syn, such as truncations, missense mutations, or chemical modifications by oxidative reactions. Aggregated forms of the protein, especially newly formed soluble aggregates, are toxic to cells, so that one therapeutic strategy would be to reduce the rate at which such oligomerization occurs. We have therefore designed several peptides and also identified small molecules that can inhibit alpha-syn oligomerization and toxicity in vitro. These compounds could serve as lead compounds for the design of new drugs for the treatment of PD and related disorders in the future.

A Bacterial Enrichment Study and Overview of the Extractable Lipids from Paleosols in the Dry Valleys, Antarctica: Implications for Future Mars Reconnaissance

The Dry Valleys of Antarctica are one of the coldest and driest environments on Earth with paleosols in selected areas that date to the emplacement of tills by warm-based ice during the Early Miocene. Cited as an analogue to the martian surface, the ability of the Antarctic environment to support microbial life-forms is a matter of special interest, particularly with the upcoming NASA/ESA 2018 ExoMars mission. Lipid biomarkers were extracted and analyzed by gas chromatography-mass spectrometry to assess sources of organic carbon and evaluate the contribution of microbial species to the organic matter of the paleosols. Paleosol samples from the ice-free Dry Valleys were also subsampled and cultivated in a growth medium from which DNA was extracted with the explicit purpose of the positive identification of bacteria. Several species of bacteria were grown in solution and the genus identified. A similar match of the data to sequenced DNA showed that Alphaproteobacteria, Gamma-proteobacteria, Bacteriodetes, and Actinobacteridae species were cultivated. The results confirm the presence of bacteria within some paleosols, but no assumptions have been made with regard to in situ activity at present. These results underscore the need not only to further investigate Dry Valley cryosols but also to develop reconnaissance strategies to determine whether such likely Earth-like environments on the Red Planet also contain life.

Family Caregivers and Palliative Care: Current Status and Agenda for the Future

The quality of life of the person confronting the end stages of their life may be severely compromised without the support of family caregivers. Indeed, most people requiring palliative care would not be able to fulfill their preferences, such as care at home, without significant family caregiver input. As a consequence, health services are mandated to support the family alongside the person diagnosed with a life-threatening illness. In short, palliative care is supposed to be family centred. However, the quality and type of support made available to family caregivers has been questioned. The purpose of this review is to outline a succinct and empirically informed account of family caregiving within the context of palliative care and to propose an agenda for the future. The appraisal is underpinned by several systematic reviews, and other seminal publications from the last decade.

Responsive homes of old Cairo: Learning from the past, feeding in the future

By investigating the social dynamics of home in one of the enduring communities of Cairo, this paper reveals the way ordinary people construct and consume their private and public domains on a daily basis. It reveals what is central and what is marginal in the cognitive idea of home. This paper adopts an interdisciplinary strategy of investigation, utilizing sociological and anthropological data to read and visit spatial practices in the home. Building on historical as well as contemporary accounts of residents and families, the concept of home is envisioned as a spectrum of social spheres that is liberated from the physical determinants of space, hence revealing a new domain of part-time spaces and dynamic spatiality. The emergent idea of home intertwines work, domesticity, recreation and hospitality in interplay of space-activity-time relationships. Homes of old Cairo have proved to be responsive to continuous change, and have evolved dynamic forms of the temporal settings required for accommodation of emerging home-based professional activities such as hospitality, home-workers, and care-homes.

Using smart people to form future mobile wireless networks

The concept of a body-to-body network, where smart communicating devices carried or worn by a person are used to form a wireless network with devices situated on other nearby persons. New innovations in this area will see the form factor of smart devices being modified, so that they may be worn on the human body or integrated into clothing, in the process creating a new generation of smart people. Applications of body-to-body networking will extend well beyond the support of cellular and Wi-Fi networks. They will also be used in short-range covert military applications, first responder applications, team sports and used to interconnect body area networks (BAN). Security will be a major issue as routing between multiple nodes will increase the risk of unauthorized access and compromise sensitive data. This will add complexity to the medium access layer (MAC) and network management. Antennas designed to operate in body centric communications systems may be broadly categorized as on- or off-body radiators, according to their radiation pattern characteristics when mounted on the human body.

Engendering Hope: A person-centred reflection on technology and gender

This paper examines instances of recent musical and artistic works and asks to what extent it makes sense to regard certain practices and technologies as gendered. It looks at a number of strategies for making, suggesting that male gender stereotypes are as prevalent and unhelpful (to practitioners) as female ones. It looks at aspects of the working environments of practitioners to determine whether changes in such conditions might alleviate the gender mismatch in enrolment in higher education courses featuring ubiquitous technologies. The paper identifies historical precedents for technology gendering in which readings of such gendering have shifted radically, suggesting they offer scope for optimism in our longer-term reading of the gendered-ness of current practices. The paper also touches on the extent to which a ‘research’ ethos––the foregrounding of the essential human attributes of inquisitiveness and empathy––may contribute to our capacity to tell better, less binary stories of otherness in all its forms.

Data-Augmentation for Reducing Dataset Bias in Person Re-identification

In this paper we explore ways to address the issue of dataset bias in person re-identification by using data augmentation to increase the variability of the available datasets, and we introduce a novel data augmentation method for re-identification based on changing the image background. We show that use of data augmentation can improve the cross-dataset generalisation of convolutional network based re-identification systems, and that changing the image background yields further improvements.

The molecular basis of galactosemia - Past, present and future

Galactosemia, an inborn error of galactose metabolism, was first described in the 1900s by von Ruess. The subsequent 100years has seen considerable progress in understanding the underlying genetics and biochemistry of this condition. Initial studies concentrated on increasing the understanding of the clinical manifestations of the disease. However, Leloir's discovery of the pathway of galactose catabolism in the 1940s and 1950s enabled other scientists, notably Kalckar, to link the disease to a specific enzymatic step in the pathway. Kalckar's work established that defects in galactose 1-phosphate uridylyltransferase (GALT) were responsible for the majority of cases of galactosemia. However, over the next three decades it became clear that there were two other forms of galactosemia: type II resulting from deficiencies in galactokinase (GALK1) and type III where the affected enzyme is UDP-galactose 4'-epimerase (GALE). From the 1970s, molecular biology approaches were applied to galactosemia. The chromosomal locations and DNA sequences of the three genes were determined. These studies enabled modern biochemical studies. Structures of the proteins have been determined and biochemical studies have shown that enzymatic impairment often results from misfolding and consequent protein instability. Cellular and model organism studies have demonstrated that reduced GALT or GALE activity results in increased oxidative stress. Thus, after a century of progress, it is possible to conceive of improved therapies including drugs to manipulate the pathway to reduce potentially toxic intermediates, antioxidants to reduce the oxidative stress of cells or use of "pharmacological chaperones" to stabilise the affected proteins.

Remembering forwards: or how to live together in the future with divided memories

Memory is thought to be about the past. The past is a problem in conflict transformation. This lecture suggests memory can also be about the future. It introduces the notion of remembering forwards, which is contrasted with remembering backwards. The distinction between these two forms of remembering defines the burden of memory in post-conflict societies generally and specifically in Ireland. In societies emerging out of conflict, where divided memories in part constituted the conflict, social memory privileges remembering backward. Collective and personal memories elide within social memory to perpetuate divided group identities and contested personal narratives. Above all, social memory works to arbitrate the future, by predisposing an extreme memory culture that locks people into the past. Forgetting the past is impossible and undesirable. What is needed in societies emerging out of conflict is to be released from the hold that oppressive and haunting memories have over people. This lecture will suggest that this is found in the idea of remembering forwards. This is not the same as forgetting. It is remembering to cease to remember oppressive and haunting memories. It does not involve non-remembrance but active remembering: remembering to cease to remember the past. While the past lives in us always, remembering forwards assists us in not living in the past. Remembering forwards thus allows us to live in tolerance in the future despite the reality that divided memories endure and live on. The lecture further argues that these enduring divided memories need to be reimagined by the application of truth, tolerance, togetherness and trajectory. The lecture suggests that it is through remembering forwards with truth, tolerance, togetherness and trajectory that people in post-conflict societies can inherit the future despite their divided pasts and live in tolerance in the midst of contested memories.