The morphology of Dothistroma septospora on Pinus canariensis from South Africa

The morphology of Dothistroma septospora in pure culture and on the host, Pinus canariensis needles, collected from Isidenge State Forest, Stutterheim, South Africa, is described. The variation of dimensions on the conidia excludes assignment of these isolates to any specific variety

The morphology and taxonomy of some fungi selected from a survey of natural Karoo pasture

Ph.D. (Botany)Please refer to full text to view abstrac

Next generation immunotherapy for pancreatic cancer: DNA vaccination is seeking new combo partners

Pancreatic Ductal Adenocarcinoma (PDA) is an almost incurable radio- and chemo-resistant tumor, and its microenvironment is characterized by a strong desmoplastic reaction associated with a significant infiltration of T regulatory lymphocytes and myeloid-derived suppressor cells (Tregs, MDSC). Investigating immunological targets has identified a number of metabolic and cytoskeletal related molecules, which are typically recognized by circulating antibodies. Among these molecules we have investigated alpha-enolase (ENO1), a glycolytic enzyme that also acts a plasminogen receptor. ENO1 is also recognized by T cells in PDA patients, so we developed a DNA vaccine that targets ENO1. This efficiently induces many immunological processes (antibody formation and complement-dependent cytotoxicity (CDC)-mediated tumor killing, infiltration of effector T cells, reduction of infiltration of myeloid and Treg suppressor cells), which significantly increase the survival of genetically engineered mice that spontaneously develop pancreatic cancer. Although promising, the ENO1 DNA vaccine does not completely eradicate the tumor, which, after an initial growth inhibition, returns to proliferate again, especially when Tregs and MDSC ensue in the tumor mass. This led us to develop possible strategies for combinatorial treatments aimed to broaden and sustain the antitumor immune response elicited by DNA vaccination. Based on the data we have obtained in recent years, this review will discuss the biological bases of possible combinatorial treatments (chemotherapy, PI3K inhibitors, tumor-associated macrophages, ENO1 inhibitors) that could be effective in amplifying the response induced by the immune vaccination in PDA

Association of Sleep Duration and Quality With Alterations in the Hypothalamic-Pituitary Adrenocortical Axis: The Multi-Ethnic Study of Atherosclerosis (MESA)

Context: Short sleep duration and poor sleep quality are associated with cardiovascular outcomes. One mechanism proposed to explain this association is altered diurnal cortisol secretion. Objective: The objective of the study was to examine the associations of sleep duration and sleep quality with diurnal salivary cortisol levels. Design: This was a cross-sectional analysis using data from examination 5 (2010–2012) of the Multi-Ethnic Study of Atherosclerosis. Actigraphy-based measures of sleep duration and efficiency were collected over 7 days, and salivary cortisol samples were collected over 2 days from participants aged 54–93 years (n = 600 with analyzable data). Results: Shorter average sleep duration (<6 h/night) was associated with less pronounced late decline in cortisol [2.2% difference in slope; 95% confidence interval (CI) 0.8–3.7; P ≤ .01] and less pronounced wake-to-bed slope (2.2% difference; 95% CI 1.0–3.4; P ≤ .001) compared with longer sleep duration (≥6 h/night). Lower sleep efficiency (<85%) was associated with less pronounced early decline in cortisol (29.0% difference in slope; 95% CI 4.1–59.7; P < .05) compared with higher sleep efficiency (≥85%). Subjects reporting insomnia had a flatter cortisol awakening response (−16.1% difference in slope; 95% CI −34.6 to −0.1; P < .05) compared with those not reporting insomnia. Conclusions: Shorter sleep duration, lower sleep efficiency, and insomnia are associated with alterations in diurnal cortisol levels consistent with changes in hypothalamic-pituitary-adrenal regulation

Endogenous glutamine decrease is associated with pancreatic cancer progression

Abstract Pancreatic ductal adenocarcinoma (PDAC) is becoming the second leading cause of cancer-related death in the Western world. The mortality is very high, which emphasizes the need to identify biomarkers for early detection. As glutamine metabolism alteration is a feature of PDAC, its in vivo evaluation may provide a useful tool for biomarker identification. Our aim was to identify a handy method to evaluate blood glutamine consumption in mouse models of PDAC. We quantified the in vitro glutamine uptake by Mass Spectrometry (MS) in tumor cell supernatants and showed that it was higher in PDAC compared to non-PDAC tumor and pancreatic control human cells. The increased glutamine uptake was paralleled by higher activity of most glutamine pathway-related enzymes supporting nucleotide and ATP production. Free glutamine blood levels were evaluated in orthotopic and \u202

Photosensitivity in South Africa. II. The experimental production of the ovine hepatogenous photosensitivity disease geeldikkop (Tribulosis ovis) by the simultaneous ingestion of Tribulus terrestris plants and cultures of Pithomyces chartarum containing the mycotoxin sporidesmin

The mycoflora of toxic pastures were surveyed during a number of outbreaks of ovine hepatogenous photosensitivity in South Africa. Pure cultures of several isolates were dosed to sheep, but only those of Pithomyces chartarum and Myrothecium verrucaria proved to be toxic. Photosensitization was induced in sheep by dosing them with cultures of a P. chartarum isolate (GAIO) obtained from Tribulus terrestris plants collected during an outbreak of geeldikkop in the Karoo. Thus for the first time a mechanism whereby T. terrestris plants can contribute to the causation of ovine hepatogenous photosensitivity was demonstrated. When cultures of GA10 equivalent to approximately 0, 75-4,0 mg/kg sporidesmin were dosed at Onderstepoort Veterinary Research Institute to Highveld and Karoo sheep on a diet of lucerne, facial eczema was produced. Dosing the same cultures at levels equivalent to c. 1,0 mg/kg of sporidesmin in the Karoo resulted in lesions characteristic of both facial eczema and geeldikkop. Typical hepatic lesions of geeldikkop could be elicited by dosing GAIO at levels equivalent to c. 0,25- 0,7 mg/kg of sporidesmin to Karoo sheep grazing on predominantly T. terrestris pastures in the Karoo. In the latter experiment geeldikkop was induced in the sheep on T. terrestris pastures, while those receiving identical doses on veld with little T. terrestris developed facial aczema. Geeldikkop, therefore, can be brought about by the ingestion of T. terrestris plants together with toxic cultures of P. chartarum. The plant appears not only to act as a vehicle for ingestion of spores, but also to interact with sporidesmin to induce lesions typical of geeldikkop, whereas sporidesmin alone results in facial eczema. Indications are that it can enhance the ability of sporidesmin to cause photosensitivity or, possibly, vice versa. The histopathological findings of these experiments are described in detail.The articles have been scanned in colour with a HP Scanjet 5590; 300dpi. Adobe Acrobat XI Pro was used to OCR the text and also for the merging and conversion to the final presentation PDF-format

Multi-isotopic and morphometric evidence for the migration of farmers leading up to the Inka conquest of the southern Andes

We present isotopic and morphometric evidence suggesting the migration of farmers in the southern Andes in the period AD 1270–1420, leading up to the Inka conquest occurring ~ AD 1400. This is based on the interdisciplinary study of human remains from archaeological cemeteries in the Andean Uspallata Valley (Argentina), located in the southern frontier of the Inka Empire. The studied samples span AD 800–1500, encompassing the highly dynamic Late Intermediate Period and culminating with the imperial expansion. Our research combines a macro-regional study of human paleomobility and migration based on a new strontium isoscape across the Andes that allows identifying locals and migrants, a geometric morphometric analysis of cranio-facial morphology suggesting separate ancestral lineages, and a paleodietary reconstruction based on stable isotopes showing that the migrants had diets exceptionally high in C4 plants and largely based on maize agriculture. Significantly, this migration influx occurred during a period of regional demographic increase and would have been part of a widespread period of change in settlement patterns and population movements that preceded the Inka expansion. These processes increased local social diversity and may have been subsequently utilized by the Inka to channel interaction with the local societies.Fil: Barberena, Ramiro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Interdisciplinario de Ciencias Básicas. - Universidad Nacional de Cuyo. Instituto Interdisciplinario de Ciencias Básicas; Argentina. Universidad Nacional de Cuyo. Facultad de Filosofía y Letras; ArgentinaFil: Menéndez, Lumila. Universitat Bonn; AlemaniaFil: le Roux, Petrus J.. University of Cape Town; SudáfricaFil: Marsh, Erik Johnson. Universidad Nacional de Cuyo. Facultad de Filosofía y Letras; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Interdisciplinario de Ciencias Básicas. - Universidad Nacional de Cuyo. Instituto Interdisciplinario de Ciencias Básicas; ArgentinaFil: Tessone, Augusto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geocronología y Geología Isotópica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geocronología y Geología Isotópica; ArgentinaFil: Novellino, Paula Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Museo de Ciencias Naturales y Antropológicas J. Cornelio Moyano; ArgentinaFil: Lucero, Gustavo. Universidad Católica de Temuco; ChileFil: Luyt, Julie. University of Cape Town; SudáfricaFil: Sealy, Judith. University of Cape Town; SudáfricaFil: Cardillo, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Multidisciplinario de Historia y Ciencias Humanas; ArgentinaFil: Gasco, Alejandra Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Interdisciplinario de Ciencias Básicas. - Universidad Nacional de Cuyo. Instituto Interdisciplinario de Ciencias Básicas; Argentina. Universidad Nacional de Cuyo. Facultad de Filosofía y Letras; ArgentinaFil: Llano, Carina Lourdes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Interdisciplinario de Ciencias Básicas. - Universidad Nacional de Cuyo. Instituto Interdisciplinario de Ciencias Básicas; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Aplicadas a la Industria; ArgentinaFil: Frigolé, Cecilia Andrea. Universidad Nacional de Cuyo. Facultad de Filosofía y Letras; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Interdisciplinario de Ciencias Básicas. - Universidad Nacional de Cuyo. Instituto Interdisciplinario de Ciencias Básicas; ArgentinaFil: Guevara, Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Museo de Ciencias Naturales y Antropológicas J. Cornelio Moyano; ArgentinaFil: Da Peña, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Museo de Ciencias Naturales y Antropológicas J. Cornelio Moyano; ArgentinaFil: Winocur, Diego Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; ArgentinaFil: Benítez, Anahí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; ArgentinaFil: Cornejo, Luis. Universidad Alberto Hurtado; ChileFil: Falabella, Fernanda. Universidad de Chile; ChileFil: Méndez, César. Centro de Investigación en Ecosistemas de la Patagonia; ChileFil: Nuevo Delaunay, Amalia. Centro de Investigación en Ecosistemas de la Patagonia; ChileFil: Sanhueza, Lorena. Universidad de Chile; ChileFil: Santana Sagredo, Francisca. Pontificia Universidad Católica de Chile; ChileFil: Troncoso, Andrés. Universidad de Chile; ChileFil: Zárate, Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Interdisciplinario de Ciencias Básicas. - Universidad Nacional de Cuyo. Instituto Interdisciplinario de Ciencias Básicas; ArgentinaFil: Duran, Victor Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Interdisciplinario de Ciencias Básicas. - Universidad Nacional de Cuyo. Instituto Interdisciplinario de Ciencias Básicas; Argentina. Universidad Nacional de Cuyo. Facultad de Filosofía y Letras; ArgentinaFil: Cortegoso, Valeria. Universidad Nacional de Cuyo. Facultad de Filosofía y Letras; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Interdisciplinario de Ciencias Básicas. - Universidad Nacional de Cuyo. Instituto Interdisciplinario de Ciencias Básicas; Argentin

AP4 deficiency: A novel form of neurodegeneration with brain iron accumulation?

OBJECTIVE: To describe the clinico-radiological phenotype of 3 patients harboring a homozygous novel AP4M1 pathogenic mutation. METHODS: The 3 patients from an inbred family who exhibited early-onset developmental delay, tetraparesis, juvenile motor function deterioration, and intellectual deficiency were investigated by magnetic brain imaging using T1-weighted, T2-weighted, T2*-weighted, fluid-attenuated inversion recovery, susceptibility weighted imaging (SWI) sequences. Whole-exome sequencing was performed on the 3 patients. RESULTS: In the 3 patients, brain imaging identified the same pattern of bilateral SWI hyposignal of the globus pallidus, concordant with iron accumulation. A novel homozygous nonsense mutation was identified in AP4M1, segregating with the disease and leading to truncation of half of the adap domain of the protein. CONCLUSIONS: Our results suggest that AP4M1 represents a new candidate gene that should be considered in the neurodegeneration with brain iron accumulation (NBIA) spectrum of disorders and highlight the intersections between hereditary spastic paraplegia and NBIA clinical presentations