25 research outputs found
Suppression of ovarian hormones in adolescent rats has no effect on anxiety-like behaviour or c-fos activation in the amygdala
Support was provided the British Society for Neuroendocrinology, Carnegie Trust for the Universities of Scotland and School of Psychology & Neuroscience, University of St Andrews.In humans, sex differences in mood disorders emerge during adolescence, with prevalence rates being consistently higher in females than males. It has been hypothesised that exposure to endogenous ovarian hormones during adolescence enhances the susceptibility of females to mood disorders from this stage of life onwards. However, experimental evidence in favour of this hypothesis is lacking. In the present study, we examined the longâterm effects of suppressing adolescent gonadal hormone levels in a group of female Listerâhooded rats via administration of a gonadotrophinâreleasing hormone antagonist (Antide; administered on postnatal day [PND] 28 and 42) compared to control females and males (n = 14 per group). We predicted that, in adulthood, Antideâtreated female rats would exhibit more maleâlike behaviour than control females in novel environments (elevatedâplus maze, open field and lightâdark box), in response to novel objects and novel social partners, and in an acoustic startle task. Progesterone and luteinising hormone assays (which were conducted on blood samples collected on PND 55/56 and 69/70) confirmed that the hypothalamicâpituitaryâgonadal axis was temporarily suppressed by Antide treatment. In addition, Antideâtreated females were found to exhibit a modest pubertal delay, as measured by vaginal opening, which was comparable in length to the pubertal delay that has been induced by adolescent exposure to alcohol or stress in previous studies of female rats. However, Antideâtreated females did not substantially differ from control females on any of the behavioural tests, despite the evidence for predicted sex differences in some measures. Following the acoustic startle response task, all subjects were culled and perfused, and câFos staining was conducted in the medial and basolateral amygdala, with the results showing no significant differences in cell counts between the groups. These findings suggest that ovarian hormone exposure during adolescence does not have longâterm effects on anxietyârelated responses in female rats.Publisher PDFPeer reviewe
Genetic Manipulation of Schistosoma haematobium, the Neglected Schistosome
More people are infected with Schistosoma haematobium than other major human schistosomes yet it has been less studied because of difficulty in maintaining the life cycle in the laboratory. S. haematobium might be considered the âneglected schistosomeâ since minimal information on the genome and proteome of S. haematobium is available, in marked contrast to the other major schistosomes. In this report we describe tools and protocols to investigate the genome and genetics of this neglected schistosome. We cultured developmental stages of S. haematobium, and investigated the utility of introducing gene probes into the parasites to silence two model genes. One of these, firefly luciferase, was a reporter gene whereas the second was a schistosome gene encoding a surface protein, termed Sh-tsp-2. We observed that both genes could be silenced â a phenomenon known as experimental RNA interference (RNAi). These findings indicated that the genome of S. haematobium will be amenable to genetic manipulation investigations designed to determine the function and importance of genes of this schistosome and to investigate for novel anti-parasite treatments
TGFÎČ pathway limits dedifferentiation following WNT and MAPK pathway activation to suppress intestinal tumourigenesis
Recent studies have suggested increased plasticity of differentiated cells within the intestine to act both as intestinal stem cells (ISCs) and tumour-initiating cells. However, little is known of the processes that regulate this plasticity. Our previous work has shown that activating mutations of Kras or the NF-ÎșB pathway can drive dedifferentiation of intestinal cells lacking Apc. To investigate this process further, we profiled both cells undergoing dedifferentiation in vitro and tumours generated from these cells in vivo by gene expression analysis. Remarkably, no clear differences were observed in the tumours; however, during dedifferentiation in vitro we found a marked upregulation of TGFÎČ signalling, a pathway commonly mutated in colorectal cancer (CRC). Genetic inactivation of TGFÎČ type 1 receptor (Tgfbr1/Alk5) enhanced the ability of KrasG12D/+ mutation to drive dedifferentiation and markedly accelerated tumourigenesis. Mechanistically this is associated with a marked activation of MAPK signalling. Tumourigenesis from differentiated compartments is potently inhibited by MEK inhibition. Taken together, we show that tumours arising in differentiated compartments will be exposed to different suppressive signals, for example, TGFÎČ and blockade of these makes tumourigenesis more efficient from this compartment
Back to the Grindstone? The Archaeological Potential of Grinding-Stone Studies in Africa with Reference to Contemporary Grinding Practices in Marakwet, Northwest Kenya
This article presents observations on grinding-stone implements and their uses in Elgeyo-Marakwet County, northwest Kenya. Tool use in Marakwet is contextualized with a select overview of literature on grinding-stones in Africa. Grinding-stones in Marakwet are incorporated not only into quotidian but also into more performative and ritual aspects of life. These tools have distinct local traditions laden with social as well as functional importance. It is argued that regionally and temporally specific studies of grinding-stone tool assemblages can be informative on the processing of various substances. Despite being common occurrences, grinding-stone tools are an under-discussed component of many African archaeological assemblages. Yet the significance of grinding-stones must be reevaluated, as they hold the potential to inform on landscapes of past food and material processing
Meat and Nicotinamide:A Causal Role in Human Evolution, History, and Demographics
Hunting for meat was a critical step in all animal and human evolution. A key brain-trophic element in meat is vitamin B 3 /nicotinamide. The supply of meat and nicotinamide steadily increased from the Cambrian origin of animal predators ratcheting ever larger brains. This culminated in the 3-million-year evolution of Homo sapiens and our overall demographic success. We view human evolution, recent history, and agricultural and demographic transitions in the light of meat and nicotinamide intake. A biochemical and immunological switch is highlighted that affects fertility in the âde novoâ tryptophan-to-kynurenine-nicotinamide âimmune toleranceâ pathway. Longevity relates to nicotinamide adenine dinucleotide consumer pathways. High meat intake correlates with moderate fertility, high intelligence, good health, and longevity with consequent population stability, whereas low meat/high cereal intake (short of starvation) correlates with high fertility, disease, and population booms and busts. Too high a meat intake and fertility falls below replacement levels. Reducing variances in meat consumption might help stabilise population growth and improve human capital