Mapping of neuropeptide Y expression in Octopus brains

Neuropeptide Y (NPY) is an evolutionarily conserved neurosecretory molecule implicated in a diverse complement of functions across taxa and in regulating feeding behavior and reproductive maturation in Octopus. However, little is known about the precise molecular circuitry of NPY-mediated behaviors and physiological processes, which likely involve a complex interaction of multiple signal molecules in specific brain regions. Here, we examined the expression of NPY throughout the Octopus central nervous system. The sequence analysis of Octopus NPY precursor confirmed the presence of both, signal peptide and putative active peptides, which are highly conserved across bilaterians. In situ hybridization revealed distinct expression of NPY in specialized compartments, including potential “integration centers,” where visual, tactile, and other behavioral circuitries converge. These centers integrating separate circuits may maintain and modulate learning and memory or other behaviors not yet attributed to NPY-dependent modulation in Octopus. Extrasomatic localization of NPY mRNA in the neurites of specific neuron populations in the brain suggests a potential demand for immediate translation at synapses and a crucial temporal role for NPY in these cell populations. We also documented the presence of NPY mRNA in a small cell population in the olfactory lobe, which is a component of the Octopus feeding and reproductive control centers. However, the molecular mapping of NPY expression only partially overlapped with that produced by immunohistochemistry in previous studies. Our study provides a precise molecular map of NPY mRNA expression that can be used to design and test future hypotheses about molecular signaling in various Octopus behaviors.     

Assessing conservation attitudes and behaviors of Congolese children neighboring the world's first bonobo (Pan paniscus) release site

Poaching and habitat destruction in the Congo Basin threaten African great apes including the bonobo (Pan paniscus), chimpanzees (Pan troglodytes), and gorillas (Gorilla spp.) with extinction. One way to combat extinction is to reintroduce rescued and rehabilitated apes and repopulate native habitats. Reintroduction programs are only successful if they are supported by local populations. Ekolo ya Bonobo, located in Equateur province of the Democratic Republic of Congo (DRC), is the world's only reintroduction site for rehabilitated bonobos. Here we assess whether children, of the Ilonga‐Pôo, living adjacent to Ekolo ya Bonobo demonstrate more pro‐ape conservation attitudes than children living in, Kinshasa, the capital city. We examined children's attitudes toward great apes because children are typically the focus of conservation education programs. We used the Great Ape Attitude Questionnaire to test the Contact Hypothesis, which posits that proximity to great ape habitat influences pro‐conservation attitudes toward great apes. Ilonga‐Pôo children who live in closer contact with wild bonobos felt greater responsibility to protect great apes compared to those in Kinshasa who live outside the natural habitat of great apes. These results suggest that among participants in the DRC, spatial proximity to a species fosters a greater sense of responsibility to protect and conserve. These results have implications for the successful implementation of great ape reintroduction programs in the Congo Basin. The data analyzed in this study were collected in 2010 and therefore provide a baseline for longitudinal study of this reintroduction site.     

Molecular chaperones in biology and medicine at Obernai

No Abstract Available     

Cutting edge: precursor frequency affects the helper dependence of cytotoxic T cells.

Generation of CTL immunity often depends on the availability of CD4 T cell help. In this report, we show that CTL responses induced by cross-priming can be converted from CD4-dependent to CD4-independent by increasing the frequency of CTL precursors. In the absence of CD4 T cells, high numbers of CTL precursors were able to expand in number and become effector CTL. The ability of high frequencies of CD8 T cells to override help was not due to their ability to signal CD40 via expression of CD154. These findings suggest that when precursor frequencies are high, priming of CD8 T cell responses may not require CD4 T cell help.     

Intracellular Calcium Deficits in Drosophila Cholinergic Neurons Expressing Wild Type or FAD-Mutant Presenilin

Much of our current understanding about neurodegenerative diseases can be attributed to the study of inherited forms of these disorders. For example, mutations in the presenilin 1 and 2 genes have been linked to early onset familial forms of Alzheimer''s disease (FAD). Using the Drosophila central nervous system as a model we have investigated the role of presenilin in one of the earliest cellular defects associated with Alzheimer''s disease, intracellular calcium deregulation. We show that expression of either wild type or FAD-mutant presenilin in Drosophila CNS neurons has no impact on resting calcium levels but does give rise to deficits in intracellular calcium stores. Furthermore, we show that a loss-of-function mutation in calmodulin, a key regulator of intracellular calcium, can suppress presenilin-induced deficits in calcium stores. Our data support a model whereby presenilin plays a role in regulating intracellular calcium stores and demonstrate that Drosophila can be used to study the link between presenilin and calcium deregulation.     

Clinical effectiveness of biologics in clinical practice

TNF inhibitors are currently considered both effective and cost-effective in patients with active rheumatoid arthritis (RA), particularly in patients who have not responded fully to methotrexate. There is substantial doubt about the cost-effectiveness of TNF inhibitors as initial treatment for active RA. New data from the National Data Bank for Rheumatic Diseases now question the current consensus in methotrexate failures. The data suggest that in routine clinical practice TNF inhibitors provide only modest incremental benefits over best conventional therapy. If confirmed, these observational studies suggest that the economic argument underpinning the widespread use of TNF inhibitors in established RA is unsustainable.     

The intD mobile genetic element from Dichelobacter nodosus, the causative agent of ovine footrot, is associated with the benign phenotype

The Gram-negative anaerobic pathogen Dichelobacter nodosus is the principal causative agent of footrot in sheep. The intA, intB and intC elements are mobile genetic elements which integrate into two tRNA genes downstream from csrA (formerly glpA) and pnpA in the D. nodosus chromosome. CsrA homologues act as global repressors of virulence in several bacterial pathogens, as does polynucleotide phosphorylase, the product of pnpA. We have proposed a model in which virulence in D. nodosus is controlled in part by the integration of genetic elements downstream from csrA and pnpA, altering the expression of these putative global regulators of virulence. We describe here a novel integrated genetic element, the intD element, which is 32 kb in size and contains an integrase gene, intD, several genes related to genes on other integrated elements of D. nodosus, a type IV secretion system and a putative mobilisation region, suggesting that the intD element has a role in the transfer of other genetic elements. Most of the D. nodosus strains examined which contained the intD gene were benign, with intD integrated next to pnpA, supporting our previous observation that virulent strains of D. nodosus have the intA element next to pnpA.     

In Vivo Neutralization of α-Cobratoxin with High-Affinity Llama Single-Domain Antibodies (VHHs) and a VHH-Fc Antibody

Small recombinant antibody fragments (e.g. scFvs and V_HHs), which are highly tissue permeable, are being investigated for antivenom production as conventional antivenoms consisting of IgG or F(ab’)₂ antibody fragments do not effectively neutralize venom toxins located in deep tissues. However, antivenoms composed entirely of small antibody fragments may have poor therapeutic efficacy due to their short serum half-lives. To increase serum persistence and maintain tissue penetration, we prepared low and high molecular mass antivenom antibodies. Four llama V_HHs were isolated from an immune V_HH-displayed phage library and were shown to have high affinity, in the low nM range, for α-cobratoxin (α–Cbtx), the most lethal component of Naja kaouthia venom. Subsequently, our highest affinity V_HH (C2) was fused to a human Fc fragment to create a V_HH2-Fc antibody that would offer prolonged serum persistence. After in planta (Nicotiana benthamiana) expression and purification, we show that our V_HH2-Fc antibody retained high affinity binding to α–Cbtx. Mouse α–Cbtx challenge studies showed that our highest affinity V_HHs (C2 and C20) and the V_HH2-Fc antibody effectively neutralized lethality induced by α–Cbtx at an antibody:toxin molar ratio as low as ca. 0.75×:1. Further research towards the development of an antivenom therapeutic involving these anti-α-Cbtx V_HHs and V_HH2-Fc antibody molecules should involve testing them as a combination, to determine whether they maintain tissue penetration capability and low immunogenicity, and whether they exhibit improved serum persistence and therapeutic efficacy.