Regulation of Th-1 T cell-dominated immunity to Neisseria meningitidis within the human mucosa

Neisseria meningitidis is commonly carried asymptomatically in the upper respiratory tract and only occasionally invades the bloodstream and meninges to cause disease. Naturally acquired immunity appears protective but the nature of the cellular immune response within the mucosa is uncertain. We show that following in vitro stimulation with N. meningitidis serogroup B (MenB) antigens, approximately 66% of the dividing mucosal CD4(+)CD45RO(+) memory population express the Th1-associated IL18-R while the remainder express CRTH2, a Th2-associated marker. The pro-inflammatory bias of this anti-MenB response is not evident in blood, demonstrating compartmentalization at the induction site; and occurs in the presence or absence of lipopolysacharide indicating that these responses are already fully committed. Depletion of CD25(+) cells reveals suppression of the effector CD4(+) T cell response restricted to the mucosa and most marked in children (i.e. those at greatest risk of disease). Mucosal T-regulatory cell (Treg) activity is partially overcome by blocking the human glucocorticoid-induced TNF receptor (GITR) and is not seen following stimulation with antigens from another mucosal pathogen, influenza virus. Pro-inflammatory, antimeningococcal T cell responses may limit invasive disease at the mucosa but Treg induction while reducing immunopathological damage, may also restrict the effectiveness of the protective response, particularly in children.     

Contemplating the future: Acting now on long‐term monitoring to answer 2050's questions

In 2050, which aspects of ecosystem change will we regret not having measured? Long‐term monitoring plays a crucial part in managing Australia's natural environment because time is a key factor underpinning changes in ecosystems. It is critical to start measuring key attributes of ecosystems – and the human and natural process affecting them – now, so that we can track the trajectory of change over time. This will facilitate informed choices about how to manage ecological changes (including interventions where they are required) and promote better understanding by 2050 of how particular ecosystems have been shaped over time. There will be considerable value in building on existing long‐term monitoring programmes because this can add significantly to the temporal depth of information. The economic and social processes driving change in ecosystems are not identical in all ecosystems, so much of what is monitored (and the means by which it is monitored) will most likely target specific ecosystems or groups of ecosystems. To best understand the effects of ecosystem‐specific threats and drivers, monitoring also will need to address the economic and social factors underpinning ecosystem‐specific change. Therefore, robust assessments of the state of Australia's environment will be best achieved by reporting on the ecological performance of a representative sample of ecosystems over time. Political, policy and financial support to implement appropriate ecosystem‐specific monitoring is a perennial problem. We suggest that the value of ecological monitoring will be demonstrable, when plot‐based monitoring data make a unique and crucial contribution to Australia's ability to produce environmental accounts, environmental reports (e.g. the State of the Environment, State of the Forests) and to fulfilling reporting obligations under international agreements, such as the Convention on Biological Diversity. This paper suggests what must be done to meet Australia's ecological information needs by 2050.     

Edge effects across boundaries between natural and restored jarrah (Eucalyptus marginata) forests in south‐western Australia

Edge effects are a widespread and ubiquitous ecological phenomenon, yet they remain poorly studied across edges between restored and natural forests. To address this lack of knowledge, we studied vertebrate communities across edges between 3‐year old restored mine‐pits and adjacent unmined forest in the jarrah (Eucalyptus marginata) forest of south‐western Australia. We found that mammal communities showed no edge response but reptile communities did. Overall reptile abundance and Morethia obscura abundance were higher in unmined forest along edges, Egernia napoleonis abundance was lower in unmined forest along edges, while Pogona minor abundance was lower in restored mine‐pits along edges. Predictive models were unable to predict species edge responses, due to the lack of knowledge of the ecology of jarrah forest reptiles, but proved useful in identifying potential ecological mechanisms behind observed edge responses and suggested that potential mechanisms were likely different for each species. Our study is the first to show edge responses in both habitats forming the edge between restored and natural forests, emphasizing the importance of studying both habitats forming the edge. Our results also suggest that, despite being poorly studied, edge responses are common across edges between restored and natural forest and result from a variety of ecological mechanisms. An increased understanding of the ecological mechanisms driving edge responses across edges between restored and natural forests will improve our ability to integrate restored areas into cross‐landscape management and, ultimately, improve our ability to manage landscapes for biodiversity conservation.     

Dietary protein content affects the response of meadow voles, <Emphasis Type="Italic">Microtus pennsylvanicus</Emphasis>, to over-marks

The response to signals, including scent marks, from opposite-sex conspecifics can be affected by the nutritional state of both the sender and receiver of these signals. Protein content of the diet affects how meadow voles (Microtus pennsylvanicus) respond to single scent marks, but it is unknown how it affects an individual’s response to the overlapping scent marks of two donors (an over-mark). In experiment 1, we tested the hypothesis that protein content of the diet affects the amount of time voles spend investigating the marks of the top- and bottom-scent donors of an over-mark. Males and females fed a 22% protein diet spent more time investigating the scent mark of the top-scent donor than that of the bottom-scent donor; voles fed 9% and 13% protein diets spent similar amounts of time investigating the top- and bottom-scent donors. In experiment 2, we tested the hypothesis that protein content of the diet of the top- and bottom-scent donors affects the amount of time conspecifics spend investigating their scent marks. Female voles spent more time investigating the mark of the top-scent male than that of the bottom-scent male, independent of the differences in protein content of the diets of the top- and bottom-scent donors. Male voles, however, spent more time investigating the top-scent female when she was fed a diet higher in protein content than that of the bottom-scent female. Our results are discussed within the context of the natural history of voles.     

An expanding universe of small proteins

Historically, small proteins (sproteins) of less than 50 amino acids, in their final processed forms or genetically encoded as such, have been understudied. However, both serendipity and more recent focused efforts have led to the identification of a number of new sproteins in both Gram-negative and Gram-positive bacteria. Increasing evidence demonstrates that sproteins participate in a wide array of cellular processes and exhibit great diversity in their mechanisms of action, yet general principles of sprotein function are emerging. This review highlights examples of sproteins that participate in cell signaling, act as antibiotics and toxins, and serve as structural proteins. We also describe roles for sproteins in detecting and altering membrane features, acting as chaperones, and regulating the functions of larger proteins.     

Distinct contributions of T1R2 and T1R3 taste receptor subunits to the detection of sweet stimuli

Animals utilize hundreds of distinct G protein-coupled receptor (GPCR)-type chemosensory receptors to detect a diverse array of chemical signals in their environment, including odors, pheromones, and tastants. However, the molecular mechanisms by which these receptors selectively interact with their cognate ligands remain poorly understood. There is growing evidence that many chemosensory receptors exist in multimeric complexes, though little is known about the relative contributions of individual subunits to receptor functions. Here, we report that each of the two subunits in the heteromeric T1R2:T1R3 sweet taste receptor binds sweet stimuli though with distinct affinities and conformational changes. Furthermore, ligand affinities for T1R3 are drastically reduced by the introduction of a single amino acid change associated with decreased sweet taste sensitivity in behaving mice. Thus, individual T1R subunits increase the receptive range of the sweet taste receptor, offering a functional mechanism for phenotypic variations in sweet taste.     

Unusual olefin formation by PhSe-F trans-elimination

A new approach to the synthesis of 2',3'-didehydro-2',3-dideoxynucleosides was described in excellent yield through unusual olefin formation by PhSe-F trans-elimination.     

ABCG5 and ABCG8 require MDR2 for secretion of cholesterol into bile

The major pathway for the removal of cholesterol from the body is via secretion into the bile. Three members of the ATP binding cassette (ABC) family, ABCG5 (G5), ABCG8 (G8), and ABCB4 (MDR2), are required for the efficient biliary export of sterols. Here, we examined the interdependence of these three ABC transporters for biliary sterol secretion. Biliary lipid levels in mice expressing no MDR2 (Mdr2-/- mice) were compared with those of Mdr2-/- mice expressing 14 copies of a human G5 (hG5) and hG8 transgene (Mdr2-/-;hG5G8Tg mice). Mdr2-/- mice had only trace amounts of biliary cholesterol and phospholipids. The Mdr2-/-;hG5G8Tg mice had biliary cholesterol levels as low as those of Mdr2-/- mice. Thus, MDR2 expression is required for G5G8-mediated biliary sterol secretion. To determine whether the reduction in fractional absorption of dietary sterols associated with G5G8 overexpression is secondary to the associated increase in biliary cholesterol, we compared the fractional absorption of sterols in Mdr2-/-;hG5G8Tg and hG5G8Tg animals. Inactivation of MDR2 markedly attenuated the reduction in fractional sterol absorption associated with G5G8 overexpression. These results are consistent with the notion that increased biliary cholesterol secretion contributes to the reduction in fractional sterol absorption associated with G5G8 overexpression.