OPPRESSION IN THE LIVES OF HOMELESS MOTHERS WITH MENTAL ILLNESS

Individuals with mental illness are overrepresented in the homeless population. However, within this group, the increasingly growing subpopulation of homeless mothers with mental illness face a unique set of challenges. The experiences of homeless mothers with mental illness were examined from the critical perspective of feminist f j intersectionality. The purpose of this study was to unveil experiences of oppression and | resistance in the lives of homeless mothers with mental illness, while learning from them [■ I what is conducive to their health. A qualitative secondary analysis was done using focus 1 group transcripts from a study examining issues related to diversity and homelessness for psychiatric survivors and a study on mental health and housing. A purposive sample of 7 focus groups comprised of 67 participants was used for this study. Findings revealed three overarching themes: (a) discrimination based on intersecting social identities, (b) being stuck: the cycle of oppression, and (c) we \u27re not giving up: resistance through perseverance. The complexity and contextual influences of mothering while homeless with a mental illness was emphasized in the results. The findings revealed the sociopolitical nature of health in the lives of homeless mothers with mental illness and illuminated the need for increased and ongoing advocacy. Nurses can advocate for the unique needs of this population by increasing awareness of the social injustices these women face and by supporting system-wide policies such as universal screening for abuse, discharge protocols that prevent homelessness, and enforcement of human rights legislation

Potential migration of buoyant LNAPL from Intermediate Level Waste (ILW) emplaced in a geological disposal facility (GDF) for UK radioactive waste

A safety case for the disposal of Intermediate Level (radioactive) Waste (ILW) in a deep geological disposal facility (GDF) requires consideration of the potential for waste-derived light non-aqueous phase liquid (LNAPL) to migrate under positive buoyancy from disposed waste packages. Were entrainment of waste-derived radionuclides in LNAPL to occur, such migration could result in a shorter overall travel time to environmental or human receptors than radionuclide migration solely associated with the movement of groundwater. This paper provides a contribution to the assessment of this issue through multiphase-flow numerical modelling underpinned by a review of the UK's ILW inventory and literature to define the nature of the associated ILW LNAPL source term. Examination has been at the waste package-local GDF environment scale to determine whether proposed disposal of ILW would lead to significant likelihood of LNAPL migration, both from waste packages and from a GDF vault into the local host rock. Our review and numerical modelling support the proposition that the release of a discrete free phase LNAPL from ILW would not present a significant challenge to the safety case even with conservative approximations. 'As-disposed' LNAPL emplaced with the waste is not expected to pose a significant issue. 'Secondary LNAPL' generated in situ within the disposed ILW, arising from the decomposition of plastics, in particular PVC (polyvinyl chloride), could form the predominant LNAPL source term. Released high molecular weight phthalate plasticizers are judged to be the primary LNAPL potentially generated. These are expected to have low buoyancy-based mobility due to their very low density contrast with water and high viscosity. Due to the inherent uncertainties, significant conservatisms were adopted within the numerical modelling approach, including: the simulation of a deliberately high organic material - PVC content wastestream (2D03) within an annular grouted waste package vulnerable to LNAPL release; upper bound inventory estimates of LNAPLs; incorporating the lack of any hydraulic resistance of the package vent; the lack of any degradation of dissolved LNAPL; and, significantly, the small threshold displacement pressure assumed at which LNAPL is able to enter initially water-saturated pores. Initial scoping calculations on the latter suggested that the rate at which LNAPL is able to migrate from a waste package is likely to be very small and insignificant for likely representative displacement pressure data: this represents a key result. Adopting a conservative displacement pressure, however, allowed the effect of other features and processes in the system to be assessed. High LNAPL viscosity together with low density contrast with water reduces LNAPL migration potential. Migration to the host rock is less likely if waste package vent fluxes are small, solubility limits are high and path lengths through the backfill are short. The capacity of the system to dissolve all of the free LNAPL will, however, depend on groundwater availability. Even with the conservatisms invoked, the overall conclusion of model simulations of intact and compromised (cracked or corroded) waste packages, for a range of realistic ILW LNAPL scenarios, is that it is unlikely that significant LNAPL would be able to migrate from the waste packages and even more unlikely it would be sufficiently persistent to reach the host rock immediately beyond the GDF

Wheat germ cell-free expression system as a pathway to improve protein yield and solubility for the SSGCID pipeline

A set of 44 protein targets was used to test expression in the wheat germ cell-free system, the vast majority of which were expressed and soluble in this system; further increases in solubility were achieved by addition of the NVoy polymer

Defining an ageing-related pathology, disease or syndrome: International Consensus Statement

Around the world, individuals are living longer, but an increased average lifespan does not always equate to an increased health span. With advancing age, the increased prevalence of ageing-related diseases can have a significant impact on health status, functional capacity and quality of life. It is therefore vital to develop comprehensive classification and staging systems for ageing-related pathologies, diseases and syndromes. This will allow societies to better identify, quantify, understand and meet the healthcare, workforce, well-being and socioeconomic needs of ageing populations, whilst supporting the development and utilisation of interventions to prevent or to slow, halt or reverse the progression of ageing-related pathologies. The foundation for developing such classification and staging systems is to define the scope of what constitutes an ageing-related pathology, disease or syndrome. To this end, a consensus meeting was hosted by the International Consortium to Classify Ageing-Related Pathologies (ICCARP), on February 19, 2024, in Cardiff, UK, and was attended by 150 recognised experts. Discussions and voting were centred on provisional criteria that had been distributed prior to the meeting. The participants debated and voted on these. Each criterion required a consensus agreement of ≥ 70% for approval. The accepted criteria for an ageing-related pathology, disease or syndrome were (1) develops and/or progresses with increasing chronological age; (2) should be associated with, or contribute to, functional decline or an increased susceptibility to functional decline and (3) evidenced by studies in humans. Criteria for an ageing-related pathology, disease or syndrome have been agreed by an international consortium of subject experts. These criteria will now be used by the ICCARP for the classification and ultimately staging of ageing-related pathologies, diseases and syndromes

Microtubule-Targeting Agents Eribulin and Paclitaxel Differentially Affect Neuronal Cell Bodies in Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of anticancer treatment with microtubule-targeted agents (MTAs). The frequency of severe CIPN, which can be dose limiting and even life threatening, varies widely among different MTAs. For example, paclitaxel induces a higher frequency of severe CIPN than does eribulin. Different MTAs also possess distinct mechanisms of microtubule-targeted action. Recently, we demonstrated that paclitaxel and eribulin differentially affect sciatic nerve axons, with paclitaxel inducing more pronounced neurodegenerative effects and eribulin inducing greater microtubule stabilizing biochemical effects. Here, we complement and extend these axonal studies by assessing the effects of paclitaxel and eribulin in the cell bodies of sciatic nerve axons, housed in the dorsal root ganglia (DRG). Importantly, the microtubule network in cell bodies is known to be significantly more dynamic than in axons. Paclitaxel induced activating transcription factor 3 expression, a marker of neuronal stress/injury. Paclitaxel also increased expression levels of acetylated tubulin and end binding protein 1, markers of microtubule stability and growth, respectively. These effects are hypothesized to be detrimental to the dynamic microtubule network within the cell bodies. In contrast, eribulin had no significant effect on any of these parameters in the cell bodies. Taken together, DRG cell bodies and their axons, two distinct neuronal cell compartments, contain functionally distinct microtubule networks that exhibit unique biochemical responses to different MTA treatments. We hypothesize that these distinct mechanistic actions may underlie the variability seen in the initiation, progression, persistence, and recovery from CIPN

Oligomerization of the microtubule-associated protein tau is mediated by its N-terminal sequences: implications for normal and pathological tau action.

Despite extensive structure-function analyses, the molecular mechanisms of normal and pathological tau action remain poorly understood. How does the C-terminal microtubule-binding region regulate microtubule dynamics and bundling? In what biophysical form does tau transfer trans-synaptically from one neuron to another, promoting neurodegeneration and dementia? Previous biochemical/biophysical work led to the hypothesis that tau can dimerize via electrostatic interactions between two N-terminal 'projection domains' aligned in an anti-parallel fashion, generating a multivalent complex capable of interacting with multiple tubulin subunits. We sought to test this dimerization model directly. Native gel analyses of full-length tau and deletion constructs demonstrate that the N-terminal region leads to multiple bands, consistent with oligomerization. Ferguson analyses of native gels indicate that an N-terminal fragment (tau(45-230) ) assembles into heptamers/octamers. Ferguson analyses of denaturing gels demonstrates that tau(45-230) can dimerize even in sodium dodecyl sulfate. Atomic force microscopy reveals multiple levels of oligomerization by both full-length tau and tau(45-230) . Finally, ion mobility-mass spectrometric analyses of tau(106-144) , a small peptide containing the core of the hypothesized dimerization region, also demonstrate oligomerization. Thus, multiple independent strategies demonstrate that the N-terminal region of tau can mediate higher order oligomerization, which may have important implications for both normal and pathological tau action. The microtubule-associated protein tau is essential for neuronal development and maintenance, but is also central to Alzheimer's and related dementias. Unfortunately, the molecular mechanisms underlying normal and pathological tau action remain poorly understood. Here, we demonstrate that tau can homo-oligomerize, providing novel mechanistic models for normal tau action (promoting microtubule growth and bundling, suppressing microtubule shortening) and pathological tau action (poisoning of oligomeric complexes)

Oligomerization of the microtubule-associated protein tau is mediated by its N-terminal sequences: implications for normal and pathological tau action.

Despite extensive structure-function analyses, the molecular mechanisms of normal and pathological tau action remain poorly understood. How does the C-terminal microtubule-binding region regulate microtubule dynamics and bundling? In what biophysical form does tau transfer trans-synaptically from one neuron to another, promoting neurodegeneration and dementia? Previous biochemical/biophysical work led to the hypothesis that tau can dimerize via electrostatic interactions between two N-terminal 'projection domains' aligned in an anti-parallel fashion, generating a multivalent complex capable of interacting with multiple tubulin subunits. We sought to test this dimerization model directly. Native gel analyses of full-length tau and deletion constructs demonstrate that the N-terminal region leads to multiple bands, consistent with oligomerization. Ferguson analyses of native gels indicate that an N-terminal fragment (tau(45-230) ) assembles into heptamers/octamers. Ferguson analyses of denaturing gels demonstrates that tau(45-230) can dimerize even in sodium dodecyl sulfate. Atomic force microscopy reveals multiple levels of oligomerization by both full-length tau and tau(45-230) . Finally, ion mobility-mass spectrometric analyses of tau(106-144) , a small peptide containing the core of the hypothesized dimerization region, also demonstrate oligomerization. Thus, multiple independent strategies demonstrate that the N-terminal region of tau can mediate higher order oligomerization, which may have important implications for both normal and pathological tau action. The microtubule-associated protein tau is essential for neuronal development and maintenance, but is also central to Alzheimer's and related dementias. Unfortunately, the molecular mechanisms underlying normal and pathological tau action remain poorly understood. Here, we demonstrate that tau can homo-oligomerize, providing novel mechanistic models for normal tau action (promoting microtubule growth and bundling, suppressing microtubule shortening) and pathological tau action (poisoning of oligomeric complexes)