“How Can I Stay Silent?”: One Woman’s Struggles for Environmental Justice in Lesotho

This article explores one woman’s activism in the context of a large scale dam and infrastructure project in Southern Africa. Since 1986, Lesotho and South Africa are building one of the largest multi-dam water schemes in the world, the Lesotho Highlands Water Project (LHWP). Local communities impacted by the LHWP face resettlement, increased risk of impoverishment, and changed access to natural resources. Much like with other projects of this type and scale (Scudder, 2006), the multidimensional costs of the $8 billion dollar World Bank funded water scheme will fall hardest on rural women. Rural Basotho women are at the front lines in negotiating a changed landscape, and lead the struggle to speak out about their experiences and organize impacted people against transnational environmental injustice. This paper privileges one woman’s activist experiences as a way to explore in depth the diversity of actions and choices that activism might entail and the contexts in which activism can take place in the everyday lives of women in Lesotho, specifically, but also throughout the world

Challenges and Pitfalls for Implementing Digital Health Solutions in Clinical Studies in Europe

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Tetrahydrodipicolinate N-Succinyltransferase and Dihydrodipicolinate Synthase from Pseudomonas aeruginosa: Structure Analysis and Gene Deletion

The diaminopimelic acid pathway of lysine biosynthesis has been suggested to provide attractive targets for the development of novel antibacterial drugs. Here we report the characterization of two enzymes from this pathway in the human pathogen Pseudomonas aeruginosa, utilizing structural biology, biochemistry and genetics. We show that tetrahydrodipicolinate N-succinyltransferase (DapD) from P. aeruginosa is specific for the L-stereoisomer of the amino substrate L-2-aminopimelate, and its D-enantiomer acts as a weak inhibitor. The crystal structures of this enzyme with L-2-aminopimelate and D-2-aminopimelate, respectively, reveal that both compounds bind at the same site of the enzyme. Comparison of the binding interactions of these ligands in the enzyme active site suggests misalignment of the amino group of D-2-aminopimelate for nucleophilic attack on the succinate moiety of the co-substrate succinyl-CoA as the structural basis of specificity and inhibition. P. aeruginosa mutants where the dapA gene had been deleted were viable and able to grow in a mouse lung infection model, suggesting that DapA is not an optimal target for drug development against this organism. Structure-based sequence alignments, based on the DapA crystal structure determined to 1.6 Å resolution revealed the presence of two homologues, PA0223 and PA4188, in P. aeruginosa that could substitute for DapA in the P. aeruginosa PAO1ΔdapA mutant. In vitro experiments using recombinant PA0223 protein could however not detect any DapA activity

Association of telomerase activity with radio- and chemosensitivity of neuroblastomas

<p>Abstract</p> <p>Background</p> <p>Telomerase activity compensates shortening of telomeres during cell division and enables cancer cells to escape senescent processes. It is also supposed, that telomerase is associated with radio- and chemoresistance. In the here described study we systematically investigated the influence of telomerase activity (TA) and telomere length on the outcome of radio- and chemotherapy in neuroblastoma.</p> <p>Methods</p> <p>We studied the effects on dominant negative (DN) mutant, wild type (WT) of the telomerase catalytic unit (hTERT) using neuroblastoma cell lines. The cells were irradiated with ⁶⁰Co and treated with doxorubicin, etoposide, cisplatin and ifosfamide, respectively. Viability was determined by MTS/MTT-test and the GI₅₀was calculated. Telomere length was measured by southernblot analysis and TA by Trap-Assay.</p> <p>Results</p> <p>Compared to the hTERT expressing cells the dominant negative cells showed increased radiosensitivity with decreased telomere length. Independent of telomere length, telomerase negative cells are significantly more sensitive to irradiation. The effect of TA knock-down or overexpression on chemosensitivity were dependent on TA, the anticancer drug, and the chemosensitivity of the maternal cell line.</p> <p>Conclusions</p> <p>Our results supported the concept of telomerase inhibition as an antiproliferative treatment approach in neuroblastomas. Telomerase inhibition increases the outcome of radiotherapy while in combination with chemotherapy the outcome depends on drug- and cell line and can be additive/synergistic or antagonistic. High telomerase activity is one distinct cancer stem cell feature and the here described cellular constructs in combination with stem cell markers like CD133, Aldehyddehydrogenase-1 (ALDH-1) or Side population (SP) may help to investigate the impact of telomerase activity on cancer stem cell survival under therapy.</p

Geschlechterunterschiede im Bildungskontext. Von wissenschaftlichen Studien zu Impulsen für die Unterrichtspraxis

Sind Mädchen motivierter im Lesen? Zeigen Jungen mehr Interesse in Mathematik? Immer wieder zeigen Studien Geschlechterunterschiede bei Interesse, Motivation und Berufsplänen von Schüler*innen – und das hat gesellschaftliche Tragweite: mehr Männer als Frauen in MINT-Berufen, ungenutztes Potential, Lohnungleichheit. Doch wie entstehen diese Unterschiede, die so große Auswirkungen auf wichtige Lebensentscheidungen haben? Und was können Lehrkräfte, Schulleitungen und andere Akteure der Bildungspraxis beitragen, um Geschlechterunterschiede abzubauen? Diesen und weiteren Fragen geht das Themenheft nach. Zum Einstieg geben die Autor*innen ausführliche theoretische Hintergrundinformationen mit Blick auf Ursachen von Geschlechterunterschieden und deren Auftreten in Schülermerkmalen wie Interesse und Motivation. Das Herzstück des Themenhefts bildet eine Forschungssynthese, die sich mit der Förderung dieser Merkmale beschäftigt. Die Autor*innen analysieren hier, inwiefern sich die Wirkung der Fördermaßnahmen für Mädchen und Jungen unterscheidet und wovon Schüler*innen auch insgesamt am meisten profitieren. Abschließend gibt das Themenheft in Form von Beispielen und Reflexionsfragen wertvolle Impulse für die Praxis. (DIPF/Orig.

Burnout em professores: diferença e análise de gênero

The teaching profession is target of numerous psychosocial stressors, which when persistent, can lead to Burnout Syndrome (BS). The present study aimed to determine if there are differences between men and women in dimensions and profiles of the SB. The non-probability sample consisted of 474 teachers working at different levels of education in Porto Alegre, metropolitan region of Rio Grande do Sul State, Brazil. This study used the Cuestionario para la Evaluación del Syndrome de Quemarse por el Trabajo (CESQT) and a questionnaire to survey sociodemographic and professional data. Results obtained through Student’s t test show that male participants have higher averages in the dimension of Indolence, Guilt and Profile 2. Female participants have higher averages in the dimension of Enthusiasm toward the job. The results of the study point to the need to consider the differences in the social construction of gender in the illness process of the teaching category.Keywords: Burnout Syndrome, occupational stress, gender, teachers.A profissão docente é alvo de inúmeros estressores psicossociais que, quando persistentes, podem levar à Síndrome de Burnout (SB). O presente estudo objetivou verificar se existe diferença entre homens e mulheres nas dimensões e perfis da SB. A amostra não probabilística se constituiu de 474 professores atuantes em diferentes níveis de ensino de Porto Alegre e região metropolitana do Rio Grande do Sul, Brasil. Como instrumentos de pesquisa foram utilizados o Cuestionario para la Evaluación del Síndrome de Quemarse por el Trabajo (CESQT) e um questionário para levantamento de dados sociodemográficos e laborais. Os dados foram analisados por meio da prova t de student. Evidenciou-se que participantes do sexo masculino apresentaram maior índice médio nas dimensões de Indolência, Culpa e Perfil 2. Participantes do sexo feminino revelaram maior índice médio na dimensão de Ilusão pelo Trabalho. Os resultados do estudo apontam para a necessidade de se considerar as diferenças de construção social de gênero no processo de adoecimento da categoria docente.Palavras-chave: Síndrome de Burnout, estresse ocupacional, gênero, professores

Prominent microglial inclusions in transgenic mouse models of α-synucleinopathy that are distinct from neuronal lesions.

Alpha-synucleinopathies are a group of progressive neurodegenerative disorders, characterized by intracellular deposits of aggregated α-synuclein (αS). The clinical heterogeneity of these diseases is thought to be attributed to conformers (or strains) of αS but the contribution of inclusions in various cell types is unclear. The aim of the present work was to study αS conformers among different transgenic (TG) mouse models of α-synucleinopathies. To this end, four different TG mouse models were studied (Prnp-h[A53T]αS; Thy1-h[A53T]αS; Thy1-h[A30P]αS; Thy1-mαS) that overexpress human or murine αS and differed in their age-of-symptom onset and subsequent disease progression. Postmortem analysis of end-stage brains revealed robust neuronal αS pathology as evidenced by accumulation of αS serine 129 (p-αS) phosphorylation in the brainstem of all four TG mouse lines. Overall appearance of the pathology was similar and only modest differences were observed among additionally affected brain regions. To study αS conformers in these mice, we used pentameric formyl thiophene acetic acid (pFTAA), a fluorescent dye with amyloid conformation-dependent spectral properties. Unexpectedly, besides the neuronal αS pathology, we also found abundant pFTAA-positive inclusions in microglia of all four TG mouse lines. These microglial inclusions were also positive for Thioflavin S and showed immunoreactivity with antibodies recognizing the N-terminus of αS, but were largely p-αS-negative. In all four lines, spectral pFTAA analysis revealed conformational differences between microglia and neuronal inclusions but not among the different mouse models. Concomitant with neuronal lesions, microglial inclusions were already present at presymptomatic stages and could also be induced by seeded αS aggregation. Although nature and significance of microglial inclusions for human α-synucleinopathies remain to be clarified, the previously overlooked abundance of microglial inclusions in TG mouse models of α-synucleinopathy bears importance for mechanistic and preclinical-translational studies

omega-3 fatty acids contribute to the asthma-protective effect of unprocessed cow's milk

Background: Living on a farm has repeatedly been shown to protect children from asthma and allergies. A major factor involved in this effect is consumption of unprocessed cow's milk obtained directly from a farm. However, this phenomenon has never been shown in a longitudinal design, and the responsible milk components are still unknown. Objectives: We sought to assess the asthma-protective effect of unprocessed cow's milk consumption in a birth cohort and to determine whether the differences in the fatty acid (FA) composition of unprocessed farm milk and industrially processed milk contributed to this effect. Methods: The Protection Against Allergy-Study in Rural Environments (PASTURE) study followed 1133 children living in rural areas in 5 European countries from birth to age 6 years. In 934 children milk consumption was assessed by using yearly questionnaires, and samples of the ``usually'' consumed milk and serum samples of the children were collected at age 4 years. Doctor-diagnosed asthma was parent reported at age 6 years. In a nested case-control study of 35 asthmatic and 49 nonasthmatic children, 42 FAs were quantified in milk samples. Results: The risk of asthma at 6 years of age was reduced by previous consumption of unprocessed farm milk compared with shop milk (adjusted odds ratio for consumption at 4 years, 0.26; 95% CI,0.10-0.67). Part of the effect was explained by the higher fat content of farm milk, particularly the higher levels of omega-3 polyunsaturated FAs (adjusted odds ratio, 0.29; 95% CI,0.11-0.81). Conclusion: Continuous farm milk consumption in childhood protects against asthma at school age partially by means of higher intake of omega-3 polyunsaturated FAs, which are precursors of anti-inflammatory mediators.Peer reviewe