The heterocyst regulatory protein HetP and its homologs modulate heterocyst commitment in Anabaena sp. strain PCC 7120

The commitment of differentiating cells to a specialized fate is fundamental to the correct assembly of tissues within a multicellular organism. Because commitment is often irreversible, entry into and progression through this phase of development must be tightly regulated. Under nitrogen-limiting conditions, the multicellular cyanobacterium Anabaena sp. strain PCC 7120 terminally commits ∼10% of its cells to become specialized nitrogen-fixing heterocysts. Although commitment is known to occur 9–14 h after the induction of differentiation, the factors that regulate the initiation and duration of this phase have yet to be elucidated. Here, we report the identification of four genes that share a functional domain and modulate heterocyst commitment: hetP (alr2818), asl1930, alr2902, and alr3234. Epistatic relationships between all four genes relating to commitment were revealed by deleting them individually and in combination; asl1930 and alr3234 acted most upstream to delay commitment, alr2902 acted next in the pathway to inhibit development, and hetP acted most downstream to drive commitment forward. Possible protein–protein interactions between HetP, its homologs, and the heterocyst master regulator, HetR, were assessed, and interaction partners were defined. Finally, patterns of gene expression for each homolog, as determined by promoter fusions to gfp and reverse transcription–quantitative PCR, were distinct from that of hetP in both spatiotemporal organization and regulation. We posit that a dynamic succession of protein–protein interactions modulates the timing and efficiency of the commitment phase of development and note that this work highlights the utility of a multicellular cyanobacterium as a model for the study of developmental processes

Functional polymorphisms of macrophage migration inhibitory factor as predictors of morbidity and mortality of pneumococcal meningitis.

Pneumococcal meningitis is the most frequent and critical type of bacterial meningitis. Because cytokines play an important role in the pathogenesis of bacterial meningitis, we examined whether functional polymorphisms of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) were associated with morbidity and mortality of pneumococcal meningitis. Two functional MIF promoter polymorphisms, a microsatellite (-794 CATT5-8; rs5844572) and a single-nucleotide polymorphism (-173 G/C; rs755622) were genotyped in a prospective, nationwide cohort of 405 patients with pneumococcal meningitis and in 329 controls matched for age, gender, and ethnicity. Carriages of the CATT7 and -173 C high-expression MIF alleles were associated with unfavorable outcome (P= 0.005 and 0.003) and death (P= 0.03 and 0.01). In a multivariate logistic regression model, shock [odds ratio (OR) 26.0, P= 0.02] and carriage of the CATT7 allele (OR 5.12,P= 0.04) were the main predictors of mortality. MIF levels in the cerebrospinal fluid were associated with systemic complications and death (P= 0.0002). Streptococcus pneumoniae strongly up-regulated MIF production in whole blood and transcription activity of high-expression MIF promoter Luciferase reporter constructs in THP-1 monocytes. Consistent with these findings, treatment with anti-MIF immunoglogulin G (IgG) antibodies reduced bacterial loads and improved survival in a mouse model of pneumococcal pneumonia and sepsis. The present study provides strong evidence that carriage of high-expression MIF alleles is a genetic marker of morbidity and mortality of pneumococcal meningitis and also suggests a potential role for MIF as a target of immune-modulating adjunctive therapy

An acceptor-substrate binding site determining glycosyl transfer emerges from mutant analysis of a plant vacuolar invertase and a fructosyltransferase

Glycoside hydrolase family 32 (GH32) harbors hydrolyzing and transglycosylating enzymes that are highly homologous in their primary structure. Eight amino acids dispersed along the sequence correlated with either hydrolase or glycosyltransferase activity. These were mutated in onion vacuolar invertase (acINV) according to the residue in festuca sucrose:sucrose 1-fructosyltransferase (saSST) and vice versa. acINV(W440Y) doubles transferase capacity. Reciprocally, saSST(C223N) and saSST(F362Y) double hydrolysis. SaSST(N425S) shows a hydrolyzing activity three to four times its transferase activity. Interestingly, modeling acINV and saSST according to the 3D structure of crystallized GH32 enzymes indicates that mutations saSST(N425S), acINV(W440Y), and the previously reported acINV(W161Y) reside very close together at the surface in the entrance of the active-site pocket. Residues in- and outside the sucrose-binding box determine hydrolase and transferase capabilities of GH32 enzymes. Modeling suggests that residues dispersed along the sequence identify a location for acceptor-substrate binding in the 3D structure of fructosyltransferases

Knowledge Distance, Cognitive-Search Processes, and Creativity: The Making of Winning Solutions in Science Contests

Prior research has provided conflicting arguments and evidence about whether people who are outsiders or insiders relative to a knowledge domain are more likely to demonstrate scientific creativity in that particular domain. We propose that the nature of the relationship between creativity and the distance of an individual’s expertise from a knowledge domain depends on his or her cognitive processes of problem solving (i.e., cognitive-search effort and cognitive-search variation). In an analysis of 230 solutions generated in a science contest platform, we found that distance was positively associated with creativity when problem solvers engaged in a focused search (i.e., low cognitive-search variation) and exerted a high level of cognitive effort. People whose expertise was close to a knowledge domain, however, were more likely to demonstrate creativity in that domain when they drew on a wide variety of different knowledge elements for recombination (i.e., high cognitive-search variation) and exerted substantial cognitive effort

From past to present: biodiversity in a changing delta

A large-scale coastal engineering project (the ‘Delta works’) changed large-scale, dynamic estuarine nature in the southwest of the Netherlands into a diverse mosaic of ecosystems with different characteristics. This led to a suite of ecological problems, which is why plans are made to restore estuarine dynamics. Until today the effect of the Delta works on biodiversity in the subsystems is still poorly understood. We combined long-term datasets on macrobenthos, fish, birds and key species and present reliable and factual information on changes in biodiversity in the Southwest Delta in the past decennia in relation to the Delta works and other developments. Effects of the Delta works on biodiversity are highly diverse and depend on many different factors and histories specific for the different water bodies. If connections are restored, effects on species richness and biodiversity will depend on the specific characteristics of the separate basins. Because restoration of estuarine dynamics likely occurs on a reduced scale, effects on biodiversity may only be modest. However, effects on the occurrence of rare species of the brackish and intertidal transition zones may be more significant. It is recommended to study this further

Biodiversity in a changing Oosterschelde: from past to present

De biodiversiteit onder vogels in de Oosterschelde neemt significant toe van 84 soorten in 1987 tot 105 soorten in 2008. Metname de herbivore en piscivore vogels zijn verantwoordelijk voor deze toename. Broedvogels nemen toe in aantal vanaf1994. Vissen vertonen echter weinig verandering in de gemeten periode (1970-2008) en vertonen een lichte significantetoename in het aantal soorten in de periode 1996-2001. De macrofauna-gemeenschap vertoont een constant hoge ShannonWiener-index tussen de 2,5 en 3,5, maar de aantallen tussen soorten zijn erg ongelijk verdeeld doordat er veel soorten metrelatief lage aantallen zijn en een paar soorten voorkomen in relatief hoge aantallen. De aantallen individuen voor suspensie- enfilter feeders en oppervlakte deposit- en facultatieve suspensie feeders nemen significant af over de gehele gemeten periode(1993-2008). Zeehonden (twee soorten) nemen in aantallen toe. Met name Gewone zeehond (Phoca vitulina) vertoont eenforse stijging in aantallen en ook de Grijze zeehond (Halichoerus grypus), hoewel minder abundant, vertoont een stijging inaantal waargenomen individuen. Bruinvissen (Phocoena phocoena) zijn niet beschouwd in de analyse. Het areaal aan zeegrasvertoont een sterke daling in 1984-1993 van 657 tot 63, een afname van 90%. Ook het schorareaal neemt af

Are entrepreneurs' forecasts of economic indicators biased?

Insight into the investment behaviour of firms is central in understanding economic dynamics. A critical question, however, is whether firms provide sufficiently reliable data to enable them to make plausible forecasts at the meso (regional or sectoral) level. This paper analyses Dutch investment forecasts at different levels of aggregation. The central research question is whether entrepreneurs, individually or as a group, make systematic errors in their investment forecasts. A statistical test reveals that investment forecasts are not biased at the aggregated (regional and sectoral) level. At the micro level, however, there is a significant bias. Hence, using aggregated (regional and sectoral) data to test the lack of bias (unbiasedness) of forecasts may lead to the wrong conclusions. Moreover, aggregated investment forecasts may then be an inappropriate source for policy recommendations, despite their seemingly high reliability. This finding may in principle be valid for many European countries, since data collection on investment is organized in similar ways throughout Europe