Viral Gene Delivery Selectively Restores Feeding and Prevents Lethality of Dopamine-Deficient Mice

AbstractDopamine-deficient mice (DA−/−), lacking tyrosine hydroxylase (TH) in dopaminergic neurons, become hypoactive and aphagic and die by 4 weeks of age. They are rescued by daily treatment with L-3,4-dihydroxyphenylalanine (L-DOPA); each dose restores dopamine (DA) and feeding for less than 24 hr. Recombinant adeno-associated viruses expressing human TH or GTP cyclohydrolase 1 (GTPCH1) were injected into the striatum of DA−/− mice. Bilateral coinjection of both viruses restored feeding behavior for several months. However, locomotor activity and coordination were partially improved. A virus expressing only TH was less effective, and one expressing GTPCH1 alone was ineffective. TH immunoreactivity and DA were detected in the ventral striatum and adjacent posterior regions of rescued mice, suggesting that these regions mediate a critical DA-dependent aspect of feeding behavior

User guide to the Magellan synthetic aperture radar images

The Magellan radar-mapping mission collected a large amount of science and engineering data. Now available to the general scientific community, this data set can be overwhelming to someone who is unfamiliar with the mission. This user guide outlines the mission operations and data set so that someone working with the data can understand the mapping and data-processing techniques used in the mission. Radar-mapping parameters as well as data acquisition issues are discussed. In addition, this user guide provides information on how the data set is organized and where specific elements of the set can be located

Microbes follow Humboldt: temperature drives plant and soil microbial diversity patterns from the Amazon to the Andes

Soil microbial diversity, by high-throughput sequencing data to characterise the variation in marker gene sequences, for 14 sites along a 3000 m elevation gradient in tropical forest in Peru. For bacterial community composition, the 16S rRNA gene was amplified in triplicate PCR reactions using the 515f and 806r primers. For fungal community composition, the first internal transcribed spacer region (ITS1) of the rRNA gene was amplified using the ITS1-F and ITS2 primer pair

Stakeholder perceptions of mental health stigma and poverty in Uganda

<p>Abstract</p> <p>Background</p> <p>World wide, there is plentiful evidence regarding the role of stigma in mental illness, as well as the association between poverty and mental illness. The experiences of stigma catalyzed by poverty revolve around experiences of devaluation, exclusion, and disadvantage. Although the relationship between poverty, stigma and mental illness has been documented in high income countries, little has been written on this relationship in low and middle income countries.</p> <p>The paper describes the opinions of a range of mental health stakeholders regarding poverty, stigma, mental illness and their relationship in the Ugandan context, as part of a wider study, aimed at exploring policy interventions required to address the vicious cycle of mental ill-health and poverty.</p> <p>Methods</p> <p>Semi-structured interviews and focus group discussions (FGDs) were conducted with purposefully selected mental health stakeholders from various sectors. The interviews and FGDs were audio-recorded, and transcriptions were coded on the basis of a pre-determined coding frame. Thematic analysis of the data was conducted using NVivo7, adopting a framework analysis approach.</p> <p>Results</p> <p>Most participants identified a reciprocal relationship between poverty and mental illness. The stigma attached to mental illness was perceived as a common phenomenon, mostly associated with local belief systems regarding the causes of mental illness. Stigma associated with both poverty and mental illness serves to reinforce the vicious cycle of poverty and mental ill-health. Most participants emphasized a relationship between poverty and internalized stigma among people with mental illness in Uganda.</p> <p>Conclusion</p> <p>According to a range of mental health stakeholders in Uganda, there is a strong interrelationship between poverty, stigma and mental illness. These findings re-affirm the need to recognize material resources as a central element in the fight against stigma of mental illness, and the importance of stigma reduction programmes in protecting the mentally ill from social isolation, particularly in conditions of poverty.</p

Norms of Presentational Force

This is the author's accepted manuscript, made available with permission of the American Forensic Association.Can style or presentational devices reasonably compel us to believe, agree, act? I submit that they can, and that the normative pragmatic project explains how. After describing a normative pragmatic approach to presentational force, I analyze and evaluate presentational force in Susan B. Anthony's "Is it a Crime for a U. S. Citizen to Vote" as it apparently proceeds from logic, emotion, and style. I conclude with reflections on the compatibility of the normative pragmatic approach with the recently-developed pragma-dialectical treatment of presentational devices

Fungal diversity regulates plant-soil feedbacks in temperate grassland

Feedbacks between plants and soil microbial communities play an important role in vegetation dynamics, but the underlying mechanisms remain unresolved. Here, we show that the diversity of putative pathogenic, mycorrhizal, and saprotrophic fungi is a primary regulator of plant-soil feedbacks across a broad range of temperate grassland plant species. We show that plant species with resource-acquisitive traits, such as high shoot nitrogen concentrations and thin roots, attract diverse communities of putative fungal pathogens and specialist saprotrophs, and a lower diversity of mycorrhizal fungi, resulting in strong plant growth suppression on soil occupied by the same species. Moreover, soil properties modulate feedbacks with fertile soils, promoting antagonistic relationships between soil fungi and plants. This study advances our capacity to predict plant-soil feedbacks and vegetation dynamics by revealing fundamental links between soil properties, plant resource acquisition strategies, and the diversity of fungal guilds in soil

Subjectivity in a context of environmental change: opening new dialogues in mental health research

In a period of unstable experimentation with challenges of globalization of associated risks, and disenchantment with ‘enduring injustice’, we bring forward a consideration of subjectivity to the study of environmental change and mental health. We begin by identifying how mainstream climate change and mental health studies are unable to explain the emergent and co-evolutionary pathways of agency. As a means of freeing these studies of their objective dimensions of linear-causation, we argue in favour of a re-positioning of subjectivity within an appreciation of recognition conflicts and beyond the over-deterministic interpretations of power centres—state, market or religion. We draw on one example of scientific research that was conducted in a region undergoing strong environmental, social and cultural changes, in the state of São Paulo/Brazil, with the aim to open mental health research to new dialogues, to which we contribute with the notion of the ‘pluriversal subject’

predictive precision medicine towards the computational challenge

The emerging fields of predictive and precision medicine are changing the traditional medical approach to disease and patient. Current discoveries in medicine enable to deepen the comprehension of diseases, whereas the adoption of high-quality methods such as novel imaging techniques (e.g. MRI, PET) and computational approaches (i.e. machine learning) to analyse data allows researchers to have meaningful clinical and statistical information. Indeed, applications of radiology techniques and machine learning algorithms rose in the last years to study neurology, cardiology and oncology conditions. In this chapter, we will provide an overview on predictive precision medicine that uses artificial intelligence to analyse medical images to enhance diagnosis, prognosis and treatment of diseases. In particular, the chapter will focus on neurodegenerative disorders that are one of the main fields of application. Despite some critical issues of this new approach, adopting a patient-centred approach could bring remarkable improvement on individual, social and business level

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown