A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis

Toll-like receptors (TLRs) and members of their signaling pathway are important in the initiation of the innate immune response to a wide variety of pathogens. The adaptor protein Mal (also known as TIRAP), encoded by TIRAP (MIM 606252), mediates downstream signaling of TLR2 and TLR4 (refs. 4-6). We report a case-control study of 6,106 individuals from the UK, Vietnam and several African countries with invasive pneumococcal disease, bacteremia, malaria and tuberculosis. We genotyped 33 SNPs, including rs8177374, which encodes a leucine substitution at Ser180 of Mal. We found that heterozygous carriage of this variant associated independently with all four infectious diseases in the different study populations. Combining the study groups, we found substantial support for a protective effect of S180L heterozygosity against these infectious diseases (N = 6,106; overall P = 9.6 x 10(-8)). We found that the Mal S180L variant attenuated TLR2 signal transduction.     

Fixed or Probable Ideas?

This commentary on Nescolarde-Selva and Usó-Doménech (Found Sci, 2013) raises questions about the dynamic versus static nature of the model proposed, and in addition asks whether the model might be used to explain ethical flexibility and rigidity.     

Systems and Beliefs

Systems thinking provides insights into how ideas interact and change, and constructivism is an example of this type of systemic approach. In the 1970s constructivism emphasised the development of mathematical and scientific ideas in children. Recently constructivist ideas are applied much more generally. Here I use this approach to consider beliefs and their role in conflicts and the conditions needed for reconciliation. If we look at Reality in terms of how we construct it as a human cognitive process, we recognise two things. First, that we cannot go beyond our senses and thoughts to what exists independently of us, and second, if we construct what we know we have to take responsibility for this. This inevitably focuses our thinking on the relation we have with the physical and social world, we are a part of the universe rather than apart from it. This paper argues that accepting and understanding these limits of human knowing together with our interconnectedness provide opportunities to understand conflicting positions. To resolve conflict, people with opposing viewpoints have to be prepared to understand each other. That is a challenge because our own reality plays a vital role in our lives, for everything from personal survival to social support.     

Science,Respect for Nature,and Human Well-Being: Democratic Values and the Responsibilities of Scientists Today

The central question addressed is: How should scientific research be conducted so as to ensure that nature is respected and the well being of everyone everywhere enhanced? After pointing to the importance of methodological pluralism for an acceptable answer and to obstacles posed by characterizing scientific methodology too narrowly, which are reinforced by the ‘commercial-scientific ethos’, two additional questions are considered: How might research, conducted in this way, have impact on—and depend on—strengthening democratic values and practices? And: What is thereby implied for the responsibilities of scientists today?     

Reproduction of three species of pocket mice ( Perognathus ) in the Bonneville Basin, Utah

Data on reproduction of three species of pocket mice ( Perognathus ) occurring in northern Utah are summarized. Perognathus parvus and P. formosus bred in spring but not the remainder of the year. This occurred despite mild fall and winter temperatures and shallow snowcover. Litter sizes for P. parvus and P. formosus were similar to those reported by previous investigators. A small sample of P. longimembris indicated they may have much larger litters (averaging 5.78 young) than previously reported for laboratory populations. Adult body mass was positively correlated with testis mass in all species, and with litter size in P. parvus .     

Observations of reproduction in mountain lions from Nebraska

Occurrences of mountain lions ( Puma concolor ) in Nebraska have been steadily increasing; however, reproductive activity in mountain lions has not been documented in the state. We present the first evidence of mountain lion reproduction in Nebraska since mountain lions recolonized the state in the early 1990s. On 28 February 2007, a spotted kitten was hit by a vehicle in northwestern Nebraska; and based on body length and weight, we estimate its age at 3.9 months. On 20 December 2008, a female mountain lion and spotted kitten were photographed in the northwestern part of the state. On 9 May 2009, a female mountain lion with a juvenile was also photographed. All records were from the Pine Ridge region of Dawes County, Nebraska. Our records suggest that mountain lions are establishing a permanent population in at least one region of Nebraska.     

Light-dependent phosphorylation of Bardet–Biedl syndrome 5 in photoreceptor cells modulates its interaction with arrestin1

Arrestins are dynamic proteins that move between cell compartments triggered by stimulation of G-protein-coupled receptors. Even more dynamically in vertebrate photoreceptors, arrestin1 (Arr1) moves between the inner and outer segments according to the light conditions. Previous studies have shown that the light-driven translocation of Arr1 in rod photoreceptors is initiated by rhodopsin through a phospholipase C/protein kinase C (PKC) signaling cascade. The purpose of this study is to identify the PKC substrate that regulates the translocation of Arr1. Mass spectrometry was used to identify the primary phosphorylated proteins in extracts prepared from PKC-stimulated mouse eye cups, confirming the finding with in vitro phosphorylation assays. Our results show that Bardet–Biedl syndrome 5 (BBS5) is the principal protein phosphorylated either by phorbol ester stimulation or by light stimulation of PKC. Via immunoprecipitation of BBS5 in rod outer segments, Arr1 was pulled down; phosphorylation of BBS5 reduced this co-precipitation of Arr1. Immunofluorescence and immunoelectron microscopy showed that BBS5 principally localizes along the axonemes of rods and cones, but also in photoreceptor inner segments, and synaptic regions. Our principal findings in this study are threefold. First, we demonstrate that BBS5 is post-translationally regulated by phosphorylation via PKC, an event that is triggered by light in photoreceptor cells. Second, we find a direct interaction between BBS5 and Arr1, an interaction that is modulated by phosphorylation of BBS5. Finally, we show that BBS5 is distributed along the photoreceptor axoneme, co-localizing with Arr1 in the dark. These findings suggest a role for BBS5 in regulating light-dependent translocation of Arr1 and a model describing its role in Arr1 translocation is proposed.