Wilder/Dargent Collection about Peruvian Author Ricardo Palma (1833-1919)

Ricardo Palma (1833-1919) was a literary figure in Peru as well as a leader in culture and politics. He played a role in the War of the Pacific (1879-1883), in the rebuilding of the National Library of Peru destroyed in that war, and in the founding of the Peruvian Academy of Language. His principal work, the Tradiciones Peruanas, was read widely throughout Iberian America and influenced writing styles. The Wilder/Dargent Collection assembles all of the published writings of Palma, either as facsimiles of first editions or as later republications. Added to this is a gathering of scholarly and journalistic writing on the Palma legacy during the century after his death

Nutrition and colony investment in Solenopsis invicta workers

Dissertação de Mestrado em Biologia Celular e Molecular, apresentada ao Departamento de Ciências da Vida Da Faculdade de Ciências e Tecnologia da Universidade de Coimbra.A proteína Tau é responsável pela ligação e estabilização dos microtúbulos (MT) no citoesqueleto, sendo fundamental na função neuronal. A atividade desta proteína pode ser regulada por modificações pós-translacionais, como a fosforilação, que promovem a separação dos microtúbulos. A alteração na conformação da Tau provocada por uma deficiente regulação, como a híper-fosforilação, causa destabilização dos MT e agregação da mesma em filamentos helicoidais emparelhados e tranças neurofibrilares. Estas estruturas são uma das principais características na doença de Alzheimer (AD), e o seu processo de formação pode representar um dos principais motivos que leva a morte celular nas Tauopatias, inclusivamente AD e outras patologias neurodegenerativas. Nos últimos anos, recursos têm sido empregues na descoberta de novas estratégias que permitam diminuir a formação ou diminuam a quantidade de agregados da Tau dentro das células. Estudos recentes identificaram a indução da autofagia através da rapamicina como um dos potenciais alvos no aumento da remoção de agregados proteicos associados a doenças neurodegenerativas, melhorando também a esperança de vida em ratos e outros modelos. Recentemente, o nosso laboratório desenvolveu um modelo celular baseado no trabalho de Guo e Lee (2011) que mimetiza a agregação intracelular da Tau depois de induzida a expressão de uma forma mutada desta proteína seguido do seeding com fibrilas K18:P301L pré-agregadas. Neste estudo, foi possível demonstrar como a utilização destes modelos permite identificar novos compostos com atividade nas vias de redução da Tau. Curiosamente estas moléculas foram responsáveis pelo desenvolvimento de um fenótipo vesicular que identificámos como sendo lisossomas, derivados de um possível estímulo na via endócitica. As alterações na morfologia sub-celular foram acompanhadas por modificações em marcadores de autofagia, sem aumento no fluxo autofágico. Estes dados sugerem que o aumento na degradação de proteínas e estruturas por autofagia poderão ter origem em efeitos colaterais de outras vias em detrimento do estímulo direto. Para além disso, testamos uma série de moléculas com atividade reconhecida e validadas para induzir autofagia ou bloquear a degradação no lisossoma. Foi demonstrado que no nosso modelo, a ativação da autofagia não é responsável pela remoção de agregados. Por outro lado, provámos que os lisossomas são extremamente importantes da degradação de agregados da Tau. Por fim, usámos o fator de transcrição EB (TFEB) para aumentar a biogénese de lisossomas e a autofagia. Células transfectadas com este fator apresentaram menos agregados de Tau e um aumento na viabilidade celular. Quando considerados em conjunto, estes resultados demonstram que a biogénese de lisossomas seguida por estímulos na autofagia podem ser mais importantes do que a ativação da autofagia por si só. Concluindo, com este projeto foi não só possível identificar os mecanismos dos compostos responsáveis pela degradação dos agregados de Tau, como também foi possível validar o TFEB como um potencial novo alvo na descoberta de novos fármacos.Tau protein is responsible for binding and stabilizing microtubules (MT) in the cytoskeleton, thus supporting neuronal function. This protein activity can be regulated by post-translation modifications, such as phosphorylation, which promotes MT detachment. Tau misfolding provoked by abnormal regulation, like hyperphosphorilation, causes MT destabilization and Tau aggregation into paired helical filaments (PHF) and neurofibrillary tangles (NFTs). These structures are one of the main hallmarks in Alzheimer’s disease (AD), and its formation process may represent the principal motive for cell death in many Tauopathies, including AD and other neurodegenerative disorders. Over the last years, great efforts have been placed to find new strategies to either diminish the build-up or decrease the amount of aggregated Tau inside cells. Recent studies have identified induction of autophagy through rapamycin as a potential target in increasing the clearance of aggregated proteins associated with neurodegenerative diseases, as well as ameliorating life expectancy in rats and other animal models. Recently, our lab developed a cellular model based on the work by Guo and Lee (2011) that mimics the intracellular aggregation of Tau after overexpression of a mutated form of this protein and seeding with pre-aggregated K18:P301L fibrils. In this study, we have taken advantage of the developed model to discover new compounds active in Tau reduction pathways. Interestingly these molecules were responsible for the development of a vesicular phenotype that we identified as lysosomes due to a possible stimulation of the endocytic pathway. The change of the sub cellular morphology was followed by changes in autophagy markers, with no increase in the autophagic flux. This suggests an increment in the degradation of proteins and structures by autophagy as a collateral result from the activation of other pathways rather than a direct stimulus. Furthermore, we have tested a series of molecules with known and validated activity to induce autophagy or disable degradation via the lysosome. We showed that at least in our model, autophagy activation is not responsible for the clearance of aggregates. On the other hand, we have proven that lysosomes play a critical role in Tau aggregates degradation. Finally, we have used the transcription factor EB (TFEB) to intensify lysosomal biogenesis and autophagy. Cells transfected with this transcription factor had less Tau aggregates and cell viability was slightly increased. When considered together, these results show that lysosomal biogenesis followed by autophagy stimulation may be more important for clearance of Tau aggregates than autophagy by itself. In conclusion, we have not only determined the mechanisms targeted by the compounds responsible for the degradation of Tau aggregates, but also validated TFEB as a potential new target for drug discovery

Heart rate changes during partial seizures: A study amongst Singaporean patients

INTRODUCTION: Studies in Europe and America showed that tachycardia, less often bradycardia, frequently accompanied partial seizures in Caucasian patients. We determine frequency, magnitude and type of ictal heart rate changes during partial seizures in non-Caucasian patients in Singapore. METHODS: Partial seizures recorded during routine EEGs performed in a tertiary hospital between 1995 and 1999 were retrospectively reviewed. All routine EEGs had simultaneous ECG recording. Heart rate before and during seizures was determined and correlated with epileptogenic focus. Differences in heart rate before and during seizures were grouped into 4 types: (1) >10% decrease; (2) -10 to +20% change; (3) 20–50% increase; (3) >50% increase. RESULTS: Of the total of 37 partial seizures, 18 were left hemisphere (LH), 13 were right hemisphere (RH) and 6 were bilateral (BL) in onset. 51% of all seizures showed no significant change in heart rate (type 2), 22% had moderate sinus tachycardia (type 3), 11% showed severe sinus tachycardia (type 4), while 16% had sinus bradycardia (type 1). Asystole was recorded in one seizure. Apart from having more tachycardia in bilateral onset seizures, there was no correlation between side of ictal discharge and heart rate response. Compared to Caucasian patients, sinus tachycardia was considerably less frequent. Frequency of bradycardia was similar to those recorded in the literature. CONCLUSIONS: Significant heart rate changes during partial seizures were seen in half of Singaporean patients. Although sinus tachycardia was the most common heart rate change, the frequency was considerably lower compared to Caucasian patients. This might be due to methodological and ethnic differences. Rates of bradycardia are similar to those recorded in the literature

Computing the zeros of the partial sums of the Riemann zeta function

In this paper, we introduce a formula for the exact number of zeros of every partial sum of the Riemann zeta function inside infinitely many rectangles of the critical strips where they are situated

Disruption of Ant-Aphid Mutualism in Canopy Enhances the Abundance of Beetles on the Forest Floor

Ant-aphid mutualism is known to play a key role in the structure of the arthropod community in the tree canopy, but its possible ecological effects for the forest floor are unknown. We hypothesized that aphids in the canopy can increase the abundance of ants on the forest floor, thus intensifying the impacts of ants on other arthropods on the forest floor. We tested this hypothesis in a deciduous temperate forest in Beijing, China. We excluded the aphid-tending ants Lasius fuliginosus from the canopy using plots of varying sizes, and monitored the change in the abundance of ants and other arthropods on the forest floor in the treated and control plots. We also surveyed the abundance of ants and other arthropods on the forest floor to explore the relationships between ants and other arthropods in the field. Through a three-year experimental study, we found that the exclusion of ants from the canopy significantly decreased the abundance of ants on the forest floor, but increased the abundance of beetles, although the effect was only significant in the large ant-exclusion plot (80*60 m). The field survey showed that the abundance of both beetles and spiders was negatively related to the abundance of ants. These results suggest that aphids located in the tree canopy have indirect negative effects on beetles by enhancing the ant abundance on the forest floor. Considering that most of the beetles in our study are important predators, the ant-aphid mutualism can have further trophic cascading effects on the forest floor food web

The Pheromone of the Cave Cricket, Hadenoecus cumberlandicus, Causes Cricket Aggregation but Does Not Attract the Co-Distributed Predatory Spider, Meta ovalis

Food input by the cave cricket, Hadenoecus cumberlandicus Hubble & Norton (Orthoptera: Rhaphidophoridae), is vital to the cave community, making this cricket a true keystone species. Bioassays conducted on cave walls and in the laboratory show that clustering in H. cumberlandicus is guided by a pheromone, presumably excreta. This aggregation pheromone was demonstrated by using filter paper discs that had previous adult H. cumberlandicus exposure, resulting in > 70% response by either nymphs or adults, prompting attraction (thus, active component is a volatile), followed by reduced mobility (arrestment) on treated surfaces. Adults were similarly responsive to pheromone from nymphs, agreeing with mixed stage composition of clusters in the cave. Effects of [0.001M – 0.1M] uric acid (insect excreta's principle component) on H. cumberlandicus behavior were inconsistent. This pheromone is not a host cue (kairomone) and is not used as a repellent (allomone) as noted through lack of responses to natural H. cumberlandicus pheromone and uric acid concentrations by a co-occurring predatory cave orb weaver spider, Meta ovalis Gertsch (Araneae: Tetragnathidae). This pheromone is not serving as a sex pheromone because nymphs were affected by it and because this population of H. cumberlandicus is parthenogenic. The conclusion of this study is that the biological value of the aggregation pheromone is to concentrate H. cumberlandicus in sheltered sites in the cave conducive for minimizing water stress. Rather than signaling H. cumberlandicus presence and quality, the reduced mobility expressed as a result of contacting this pheromone conceivably may act as a defense tactic (antipredator behavior) against M. ovalis, which shares this favored habitat site

Linkage mapping bovine EST-based SNP

BACKGROUND: Existing linkage maps of the bovine genome primarily contain anonymous microsatellite markers. These maps have proved valuable for mapping quantitative trait loci (QTL) to broad regions of the genome, but more closely spaced markers are needed to fine-map QTL, and markers associated with genes and annotated sequence are needed to identify genes and sequence variation that may explain QTL. RESULTS: Bovine expressed sequence tag (EST) and bacterial artificial chromosome (BAC)sequence data were used to develop 918 single nucleotide polymorphism (SNP) markers to map genes on the bovine linkage map. DNA of sires from the MARC reference population was used to detect SNPs, and progeny and mates of heterozygous sires were genotyped. Chromosome assignments for 861 SNPs were determined by twopoint analysis, and positions for 735 SNPs were established by multipoint analyses. Linkage maps of bovine autosomes with these SNPs represent 4585 markers in 2475 positions spanning 3058 cM . Markers include 3612 microsatellites, 913 SNPs and 60 other markers. Mean separation between marker positions is 1.2 cM. New SNP markers appear in 511 positions, with mean separation of 4.7 cM. Multi-allelic markers, mostly microsatellites, had a mean (maximum) of 216 (366) informative meioses, and a mean 3-lod confidence interval of 3.6 cM Bi-allelic markers, including SNP and other marker types, had a mean (maximum) of 55 (191) informative meioses, and were placed within a mean 8.5 cM 3-lod confidence interval. Homologous human sequences were identified for 1159 markers, including 582 newly developed and mapped SNP. CONCLUSION: Addition of these EST- and BAC-based SNPs to the bovine linkage map not only increases marker density, but provides connections to gene-rich physical maps, including annotated human sequence. The map provides a resource for fine-mapping quantitative trait loci and identification of positional candidate genes, and can be integrated with other data to guide and refine assembly of bovine genome sequence. Even after the bovine genome is completely sequenced, the map will continue to be a useful tool to link observable phenotypes and animal genotypes to underlying genes and molecular mechanisms influencing economically important beef and dairy traits