Population Engineering and the Fight against Climate Change

Contrary to political and philosophical consensus, we argue that the threats posed by climate change justify population engineering, the intentional manipulation of the size and structure of human populations. Specifically, we defend three types of policies aimed at reducing fertility rates: choice enhancement, preference adjustment, and incentivization. While few object to the first type of policy, the latter two are generally rejected because of their potential for coercion or morally objectionable manipulation. We argue that forms of each policy type are pragmatically and morally justified tools for preventing the harms of global climate change

The agents of justice

The complexities of how justice comes to be realized, and by which agents, is a relatively neglected element in contemporary theories of justice. This has left several crucial questions about agency and justice undertheorized, such as why some particular agents are responsible for realizing justice, how their contribution towards realizing justice should be understood, and what role agents such as activists and community leaders play in realizing justice. We aim to contribute towards a better understanding of the landscape of these kinds of questions. First, we argue that theorists should distinguish between (i) agents who are responsible for realizing justice, but not committed to it, (ii) agents who are not responsible for realizing justice, but who are committed to it, and (iii) agents who are both responsible for and committed to realizing justice. Second, we discuss how to incorporate agents of justice more robustly into theorizing about justice

Patients' attitudes and perceptions towards treatment of hypothyroidism in general practice: an in-depth qualitative interview study

Background Suboptimal thyroid hormone replacement is common in patients with hypothyroidism and the behavioural factors underlying this are poorly understood. Aim To explore the attitudes and perceptions of patients to thyroid hormone replacement therapy. Design & setting An in-depth qualitative interview study with patients with hypothyroidism residing in Northumberland, and Tyne and Wear, UK. Method Twenty-seven patients participated, of which 15 patients had thyroid stimulating hormone (TSH) levels within the reference range (0.4–4.0 mU/L) and 12 patients had TSH levels outside the reference range. A grounded theory approach was used to explore and develop emerging themes, which were mapped to the health belief model (HBM). Results Patients generally had a low understanding of their condition or of the consequences of suboptimal thyroid hormone replacement. Patients that had experienced hypothyroid symptoms at initial diagnosis had a better perception of disease susceptibility, and this was reflected in excellent adherence to levothyroxine in this group of patients. The main benefits of optimal thyroid replacement were improved wellbeing and performance. However, patients who remained unwell despite a normal serum TSH level felt that their normal result presented a barrier to further evaluation of their symptoms by their GP

Attenuated CSF-1R signalling drives cerebrovascular pathology

Cerebrovascular pathologies occur in up to 80% of cases of Alzheimer's disease; however, the underlying mechanisms that lead to perivascular pathology and accompanying blood-brain barrier (BBB) disruption are still not fully understood. We have identified previously unreported mutations in colony stimulating factor-1 receptor (CSF-1R) in an ultra-rare autosomal dominant condition termed adult-onset leucoencephalopathy with axonal spheroids and pigmented glia (ALSP). Cerebrovascular pathologies such as cerebral amyloid angiopathy (CAA) and perivascular p-Tau were some of the primary neuropathological features of this condition. We have identified two families with different dominant acting alleles with variants located in the kinase region of the CSF-1R gene, which confer a lack of kinase activity and signalling. The protein product of this gene acts as the receptor for 2 cognate ligands, namely colony stimulating factor-1 (CSF-1) and interleukin-34 (IL-34). Here, we show that depletion in CSF-1R signalling induces BBB disruption and decreases the phagocytic capacity of peripheral macrophages but not microglia. CSF-1R signalling appears to be critical for macrophage and microglial activation, and macrophage localisation to amyloid appears reduced following the induction of Csf-1r heterozygosity in macrophages. Finally, we show that endothelial/microglial crosstalk and concomitant attenuation of CSF-1R signalling causes re-modelling of BBB-associated tight junctions and suggest that regulating BBB integrity and systemic macrophage recruitment to the brain may be therapeutically relevant in ALSP and other Alzheimer's-like dementias

The Huntington's disease mutation impairs Huntingtin's role in the transport of NF-κB from the synapse to the nucleus

Expansion of a polyglutamine (polyQ) tract in the Huntingtin (Htt) protein causes Huntington's disease (HD), a fatal inherited neurodegenerative disorder. Loss of the normal function of Htt is thought to be an important pathogenetic component of HD. However, the function of wild-type Htt is not well defined. Htt is thought to be a multifunctional protein that plays distinct roles in several biological processes, including synaptic transmission, intracellular transport and neuronal transcription. Here, we show with biochemical and live cell imaging studies that wild-type Htt stimulates the transport of nuclear factor κ light-chain-enhancer of activated B cells (NF-κB) out of dendritic spines (where NF-κB is activated by excitatory synaptic input) and supports a high level of active NF-κB in neuronal nuclei (where NF-κB stimulates the transcription of target genes). We show that this novel function of Htt is impaired by the polyQ expansion and thus may contribute to the etiology of HD

The Bacterial Species Campylobacter jejuni Induce Diverse Innate Immune Responses in Human and Avian Intestinal Epithelial Cells

Campylobacter remain the major cause of human gastroenteritis in the Developed World causing a significant burden to health services. Campylobacter are pathogens in humans and chickens, although differences in mechanistic understanding are incomplete, in part because phenotypic strain diversity creates inconsistent findings. Here, we took Campylobacter jejuni isolates (n = 100) from multi-locus sequence typed collections to assess their pathogenic diversity, through their inflammatory, cytotoxicity, adhesion, invasion and signaling responses in a high-throughput model using avian and human intestinal epithelial cells. C. jejuni induced IL-8 and CXCLi1/2 in human and avian epithelial cells, respectively, in a MAP kinase-dependent manner. In contrast, IL-10 responses in both cell types were PI 3-kinase/Akt-dependent. C. jejuni strains showed diverse levels of invasion with high invasion dependent on MAP kinase signaling in both cell lines. C. jejuni induced diverse cytotoxic responses in both cell lines with cdt-positive isolates showing significantly higher toxicity. Blockade of endocytic pathways suggested that invasion by C. jejuni was clathrin- and dynamin-dependent but caveolae- independent in both cells. In contrast, IL-8 (and CXCLi1/2) production was dependent on clathrin, dynamin, and caveolae. This study is important because of its scale, and the data produced, suggesting that avian and human epithelial cells use similar innate immune pathways where the magnitude of the response is determined by the phenotypic diversity of the Campylobacter species

Rates of age- and amyloid β-associated cortical atrophy in older adults with superior memory performance

Introduction: Superior cognitive performance in older adults may reflect underlying resistance to age-associated neurodegeneration. While elevated amyloid b (Ab) deposition (Ab1) has been associated with increased cortical atrophy, it remains unknown whether “SuperAgers” may be protected from Ab-associated neurodegeneration. Methods: Neuropsychologically defined SuperAgers (n 5 172) and cognitively normal for age (n 5 172) older adults from the Australian Imaging, Biomarkers and Lifestyle study were case matched. Rates of cortical atrophy over 8 years were examined by SuperAger classification and Ab status. Results: Of the case-matched SuperAgers and cognitively normal for age older adults, 40.7% and 40.1%, respectively, were Ab1. Rates of age- and Ab-associated atrophy did not differ between the groups on any measure. Ab2 individuals displayed the slowest rates of atrophy. Discussion: Maintenance of superior memory in late life does not reflect resistance to age- or Abassociated atrophy. However, those individuals who reached old age without cognitive impairment nor elevated Ab deposition (i.e. Ab2) displayed reduced rates of cortical atrophy