Hibernation in pygmy lorises (Nycticebus pygmaeus)–what does it mean?

Torpor use in primates appeared to be restricted to African species and was only recently discovered in a species from Asia, the pygmy loris (Nycticebus pygmaeus). This finding has considerable implications for our perception of torpor in this mammal group and demonstrates that torpor is probably more widespread in mammals than commonly thought. This article summarizes the current knowledge on the use of torpor in the pygmy loris and places it into the context of ongoing research on this topic

Existential witness extraction in classical realizability and via a negative translation

We show how to extract existential witnesses from classical proofs using Krivine's classical realizability---where classical proofs are interpreted as lambda-terms with the call/cc control operator. We first recall the basic framework of classical realizability (in classical second-order arithmetic) and show how to extend it with primitive numerals for faster computations. Then we show how to perform witness extraction in this framework, by discussing several techniques depending on the shape of the existential formula. In particular, we show that in the Sigma01-case, Krivine's witness extraction method reduces to Friedman's through a well-suited negative translation to intuitionistic second-order arithmetic. Finally we discuss the advantages of using call/cc rather than a negative translation, especially from the point of view of an implementation.Comment: 52 pages. Accepted in Logical Methods for Computer Science (LMCS), 201

Spinal cord from body donors is suitable for multicolor immunofluorescence

Immunohistochemistry is a powerful tool for studying neuronal tissue from humans at the molecular level. Obtaining fresh neuronal tissue from human organ donors is difficult and sometimes impossible. In anatomical body donations, neuronal tissue is dedicated to research purposes and because of its easier availability, it may be an alternative source for research. In this study, we harvested spinal cord from a single organ donor 2 h (h) postmortem and spinal cord from body donors 24, 48, and 72 h postmortem and tested how long after death, valid multi-color immunofluorescence or horseradish peroxidase (HRP) immunohistochemistry is possible. We used general and specific neuronal markers and glial markers for immunolabeling experiments. Here we showed that it is possible to visualize molecularly different neuronal elements with high precision in the body donor spinal cord 24 h postmortem and the quality of the image data was comparable to those from the fresh organ donor spinal cord. High-contrast multicolor images of the 24-h spinal cords allowed accurate automated quantification of different neuronal elements in the same sample. Although there was antibody-specific signal reduction over postmortem intervals, the signal quality for most antibodies was acceptable at 48 h but no longer at 72 h postmortem. In conclusion, our study has defined a postmortem time window of more than 24 h during which valid immunohistochemical information can be obtained from the body donor spinal cord. Due to the easier availability, neuronal tissue from body donors is an alternative source for basic and clinical research

Remarkable Ancient Divergences Amongst Neglected Lorisiform Primates

Lorisiform primates (Primates: Strepsirrhini: Lorisiformes) represent almost 10% of the living primate species and are widely distributed in sub-Saharan Africa and South/South-East Asia; however, their taxonomy, evolutionary history, and biogeography are still poorly understood. In this study we report the largest molecular phylogeny in terms of the number of represented taxa. We sequenced the complete mitochondrial cytochrome b gene for 86 lorisiform specimens, including ∼80% of all the species currently recognized. Our results support the monophyly of the Galagidae, but a common ancestry of the Lorisinae and Perodicticinae (family Lorisidae) was not recovered. These three lineages have early origins, with the Galagidae and the Lorisinae diverging in the Oligocene at about 30 Mya and the Perodicticinae emerging in the early Miocene. Our mitochondrial phylogeny agrees with recent studies based on nuclear data, and supports Euoticus as the oldest galagid lineage and the polyphyletic status of Galagoides. Moreover, we have elucidated phylogenetic relationships for several species never included before in a molecular phylogeny. The results obtained in this study suggest that lorisiform diversity remains substantially underestimated and that previously unnoticed cryptic diversity might be present within many lineages, thus urgently requiring a comprehensive taxonomic revision of this primate group

Hiding from the Moonlight: Luminosity and Temperature Affect Activity of Asian Nocturnal Primates in a Highly Seasonal Forest

The effect of moonlight and temperature on activity of slow lorises was previously little known and this knowledge might be useful for understanding many aspects of their behavioural ecology, and developing strategies to monitor and protect populations. In this study we aimed to determine if the activity of the pygmy loris (Nycticebus pygmaeus) is affected by ambient temperature and/or moonlight in a mixed deciduous forest. We radio-collared five females and five males in the Seima Protection Forest, Cambodia, in February to May, 2008 and January to March, 2009 and recorded their behaviour at 5 minutes intervals, totalling 2736 observations. We classified each observation as either inactive (sleeping or alert) or active behaviour (travel, feeding, grooming, or others). Moon luminosity (bright/dark) and ambient temperature were recorded for each observation. The response variable, activity, was binary (active or inactive), and a logit link function was used. Ambient temperature alone did not significantly affect mean activity. Although mean activity was significantly affected by moonlight, the interaction between moonlight and temperature was also significant: on bright nights, studied animals were increasingly more active with higher temperature; and on dark nights they were consistently active regardless of temperature. The most plausible explanation is that on bright cold nights the combined risk of being seen and attacked by predators and heat loss outweigh the benefit of active behaviours

The AMANDA Neutrino Telescope

With an effective telescope area of order $10^4$ m$^2$ for TeV neutrinos, a threshold near $\sim$50 GeV and a pointing accuracy of 2.5 degrees per muon track, the AMANDA detector represents the first of a new generation of high energy neutrino telescopes, reaching a scale envisaged over 25 years ago. We describe early results on the calibration of natural deep ice as a particle detector as well as on AMANDA's performance as a neutrino telescope.Comment: 12 pages, Latex2.09, uses espcrc2.sty and epsf.sty, 13 postscript files included. Talk presented at the 18th International Conference on Neutrino Physics and Astrophysics (Neutrino 98), Takayama, Japan, June 199

A Non-Specific Effect Associated with Conditional Transgene Expression Based on Cre-loxP Strategy in Mice

Transgenes flanked by loxP sites have been widely used to generate transgenic mice where the transgene expression can be controlled spatially and temporally by Cre recombinase. Data from this approach has led to important conclusions in cancer, neurodevelopment and neurodegeneration. Using this approach to conditionally express micro RNAs (miRNAs) in mice, we found that Cre-mediated recombination in neural progenitor cells caused microcephaly in five of our ten independent transgenic lines. This effect was not associated with the types or the quantity of miRNAs being expressed, nor was it associated with specific target knockdown. Rather, it was correlated with the presence of multiple tandem transgene copies and inverted (head-to-head or tail-to-tail) transgene repeats. The presence of these inverted repeats caused a high level of cell death in the ventricular zone of the embryonic brain, where Cre was expressed. Therefore, results from this Cre-loxP approach to generate inducible transgenic alleles must be interpreted with caution and conclusions drawn in previous reports may need reexamination

Melanoma: A model for testing new agents in combination therapies

Treatment for both early and advanced melanoma has changed little since the introduction of interferon and IL-2 in the early 1990s. Recent data from trials testing targeted agents or immune modulators suggest the promise of new strategies to treat patients with advanced melanoma. These include a new generation of B-RAF inhibitors with greater selectivity for the mutant protein, c-Kit inhibitors, anti-angiogenesis agents, the immune modulators anti-CTLA4, anti-PD-1, and anti-CD40, and adoptive cellular therapies. The high success rate of mutant B-RAF and c-Kit inhibitors relies on the selection of patients with corresponding mutations. However, although response rates with small molecule inhibitors are high, most are not durable. Moreover, for a large subset of patients, reliable predictive biomarkers especially for immunologic modulators have not yet been identified. Progress may also depend on identifying additional molecular targets, which in turn depends upon a better understanding of the mechanisms leading to response or resistance. More challenging but equally important will be understanding how to optimize the treatment of individual patients using these active agents sequentially or in combination with each other, with other experimental treatment, or with traditional anticancer modalities such as chemotherapy, radiation, or surgery. Compared to the standard approach of developing new single agents for licensing in advanced disease, the identification and validation of patient specific and multi-modality treatments will require increased involvement by several stakeholders in designing trials aimed at identifying, even in early stages of drug development, the most effective way to use molecularly guided approaches to treat tumors as they evolve over time

Genome-wide association study of pancreatic fat: The multiethnic cohort adiposity phenotype study

Several studies have found associations between higher pancreatic fat content and adverse health outcomes, such as diabetes and the metabolic syndrome, but investigations into the genetic contributions to pancreatic fat are limited. This genome-wide association study, comprised of 804 participants with MRI-assessed pancreatic fat measurements, was conducted in the ethnically diverse Multiethnic Cohort-Adiposity Phenotype Study (MEC-APS). Two genetic variants reaching genome-wide significance, rs73449607 on chromosome 13q21.2 (Beta = -0.67, P = 4.50x10-8) and rs7996760 on chromosome 6q14 (Beta = -0.90, P = 4.91x10-8) were associated with percent pancreatic fat on the log scale. Rs73449607 was most common in the African American population (13%) and rs79967607 was most common in the European American population (6%). Rs73449607 was also associated with lower risk of type 2 diabetes (OR = 0.95, 95% CI = 0.89-1.00, P = 0.047) in the Population Architecture Genomics and Epidemiology (PAGE) Study and the DIAbetes Genetics Replication and Meta-analysis (DIAGRAM), which included substantial numbers of non-European ancestry participants (53,102 cases and 193,679 controls). Rs73449607 is located in an intergenic region between GSX1 and PLUTO, and rs79967607 is in intron 1 of EPM2A. PLUTO, a lncRNA, regulates transcription of an adjacent gene, PDX1, that controls beta-cell function in the mature pancreas, and EPM2A encodes the protein laforin, which plays a critical role in regulating glycogen production. If validated, these variants may suggest a genetic component for pancreatic fat and a common etiologic link between pancreatic fat and type 2 diabetes