Investigating the structural compaction of biomolecules upon transition to the gas-phase using ESI-TWIMS-MS

Collision cross-section (CCS) measurements obtained from ion mobility spectrometry-mass spectrometry (IMS-MS) analyses often provide useful information concerning a protein’s size and shape and can be complemented by modeling procedures. However, there have been some concerns about the extent to which certain proteins maintain a native-like conformation during the gas-phase analysis, especially proteins with dynamic or extended regions. Here we have measured the CCSs of a range of biomolecules including non-globular proteins and RNAs of different sequence, size, and stability. Using traveling wave IMS-MS, we show that for the proteins studied, the measured CCS deviates significantly from predicted CCS values based upon currently available structures. The results presented indicate that these proteins collapse to different extents varying on their elongated structures upon transition into the gas-phase. Comparing two RNAs of similar mass but different solution structures, we show that these biomolecules may also be susceptible to gas-phase compaction. Together, the results suggest that caution is needed when predicting structural models based on CCS data for RNAs as well as proteins with non-globular folds

A method for the objective selection of landscape-scale study regions and sites at the national level

1. Ecological processes operating on large spatio-temporal scales are difficult to disentangle with traditional empirical approaches. Alternatively, researchers can take advantage of ‘natural’ experiments, where experimental control is exercised by careful site selection. Recent advances in developing protocols for designing these ‘pseudo-experiments’ commonly do not consider the selection of the focal region and predictor variables are usually restricted to two. Here, we advance this type of site selection protocol to study the impact of multiple landscape scale factors on pollinator abundance and diversity across multiple regions. 2. Using datasets of geographic and ecological variables with national coverage, we applied a novel hierarchical computation approach to select study sites that contrast as much as possible in four key variables, while attempting to maintain regional comparability and national representativeness. There were three main steps to the protocol: (i) selection of six 100 9 100 km2 regions that collectively provided land cover representative of the national land average, (ii) mapping of potential sites into a multivariate space with axes representing four key factors potentially influencing insect pollinator abundance, and (iii) applying a selection algorithm which maximized differences between the four key variables, while controlling for a set of external constraints. 3. Validation data for the site selection metrics were recorded alongside the collection of data on pollinator populations during two field campaigns. While the accuracy of the metric estimates varied, the site selection succeeded in objectively identifying field sites that differed significantly in values for each of the four key variables. Between-variable correlations were also reduced or eliminated, thus facilitating analysis of their separate effects. 4. This study has shown that national datasets can be used to select randomized and replicated field sites objectively within multiple regions and along multiple interacting gradients. Similar protocols could be used for studying a range of alternative research questions related to land use or other spatially explicit environmental variables, and to identify networks of field sites for other countries, regions, drivers and response taxa in a wide range of scenarios

Multiregional Emergence of Mobile Pastoralism and Nonuniform Institutional Complexity across Eurasia

In this article I present a new archaeological synthesis concerning the earliest formation of mobile pastoralist economies across central Eurasia. I argue that Eurasian steppe pastoralism developed along distinct local trajectories in the western, central, and (south)eastern steppe, sparking the development of regional networks of interaction in the late fourth and third millennia BC. The “Inner Asian Mountain Corridor” exemplifies the relationship between such incipient regional networks and the process of economic change in the eastern steppe territory. The diverse regional innovations, technologies, and ideologies evident across Eurasia in the mid-third millennium BC are cast as the building blocks of a unique political economy shaped by “nonuniform” institutional alignments among steppe populations throughout the second millennium BC. This theoretical model illustrates how regional channels of interaction between distinct societies positioned Eurasian mobile pastoralists as key players in wide-scale institutional developments among traditionally conceived “core” civilizations while also enabling them to remain strategically independent and small-scale in terms of their own sociopolitical organization. The development of nonuniform institutional complexity among Eurasian pastoralists demonstrates a unique political and economic structure applicable to societies whose variable political and territorial scales are inconsistent with commonly understood evolutionary or corporate sociopolitical typologies such as chiefdoms, states, or empires

Complexation of lanthanides, actinides and transition metal cations with a 6-(1,2,4-triazin-3-yl)-2,2’:6’,2’’-terpyridine ligand: implications for actinide(III) /lanthanide(III) partitioning

The quadridentate N-heterocyclic ligand 6-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-1,2,4-benzotriazin-3-yl)-2,2’:6’,2’’-terpyridine (CyMe4-hemi-BTBP) has been synthesized and its interactions with Am(III), U(VI), Ln(III) and some transition metal cations have been evaluated by X-ray crystallographic analysis, Am(III)/Eu(III) solvent extraction experiments, UV absorption spectrophotometry, NMR studies and ESI-MS. Structures of the 1:1 complexes with Eu(III), Ce(III) and the linear uranyl (UO22+) ion were obtained by X-ray crystallographic analysis, and showed similar coordination behavior to related BTBP complexes. In methanol, the stability constants of the Ln(III) complexes are slightly lower than those of the analogous quadridentate bis-triazine BTBP ligands, while the stability constant for the Yb(III) complex is higher. 1H NMR titrations and ESI-MS with lanthanide nitrates showed that the ligand forms only 1:1 complexes with Eu(III), Ce(III) and Yb(III), while both 1:1 and 1:2 complexes were formed with La(III) and Y(III) in acetonitrile. A mixture of isomeric chiral 2:2 helical complexes was formed with Cu(I), with a slight preference (1.4:1) for a single directional isomer. In contrast, a 1:1 complex was observed with the larger Ag(I) ion. The ligand was unable to extract Am(III) or Eu(III) from nitric acid solutions into 1-octanol, except in the presence of a synergist at low acidity. The results show that the presence of two outer 1,2,4-triazine rings is required for the efficient extraction and separation of An(III) from Ln(III) by quadridentate N-donor ligand

Prediction of Dengue Disease Severity among Pediatric Thai Patients Using Early Clinical Laboratory Indicators

Patients with severe dengue illness typically develop complications in the later stages of illness, making early clinical management of all patients with suspected dengue infection difficult. An early prediction tool to identify which patients will have a severe dengue illness will improve the utilization of limited hospital resources in dengue endemic regions. We performed classification and regression tree (CART) analysis to establish predictive algorithms of severe dengue illness. Using a Thai hospital pediatric cohort of patients presenting within the first 72 hours of a suspected dengue illness, we developed diagnostic decision algorithms using simple clinical laboratory data obtained on the day of presentation. These algorithms correctly classified near 100% of patients who developed a severe dengue illness while excluding upwards of 50% of patients with mild dengue or other febrile illnesses. Our algorithms utilized white blood cell counts, percent white blood cell differentials, platelet counts, elevated aspartate aminotransferase, hematocrit, and age. If these algorithms can be validated in other regions and age groups, they will help in the clinical management of patients with suspected dengue illness who present within the first three days of fever onset

In search of the authentic nation: landscape and national identity in Canada and Switzerland

While the study of nationalism and national identity has flourished in the last decade, little attention has been devoted to the conditions under which natural environments acquire significance in definitions of nationhood. This article examines the identity-forming role of landscape depictions in two polyethnic nation-states: Canada and Switzerland. Two types of geographical national identity are identified. The first – what we call the ‘nationalisation of nature’– portrays zarticular landscapes as expressions of national authenticity. The second pattern – what we refer to as the ‘naturalisation of the nation’– rests upon a notion of geographical determinism that depicts specific landscapes as forces capable of determining national identity. The authors offer two reasons why the second pattern came to prevail in the cases under consideration: (1) the affinity between wild landscape and the Romantic ideal of pure, rugged nature, and (2) a divergence between the nationalist ideal of ethnic homogeneity and the polyethnic composition of the two societies under consideration

Zebrafish dou yan mutation causes patterning defects and extensive cell death in the retina

The size of an organ is largely determined by the number of cells it contains, which in turn is regulated by two opposing processes, cell proliferation and cell death, however, it is generally not clear how cell proliferation and cell death are coordinated during development. Here, we characterize the zebrafish dou yan mi234 mutation that results in a dramatic reduction of retinal size and a disruption of retinal differentiation and lamination. The retinal size reduction is caused by increased retinal cell death in a non–cell-autonomous manner during early development. The phenotypic defect in dou yan mi234 arises coincident with the onset of retinal neurogenesis and differentiation. Interestingly, unlike many other small eye mutations, the mutation does not increase the level of cell death in the brain, suggesting that the brain and retina use different mechanisms to maintain cell survival. Identification and further study of the dou yan gene will enhance our understanding of the molecular mechanisms regulating retinal cellular homeostasis, i.e., the balance between cell proliferation and cell death. Developmental Dynamics 236:1295–1306, 2007. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56024/1/21148_ftp.pd

Condensin I Recruitment to Base Damage-Enriched DNA Lesions Is Modulated by PARP1

Condensin I is important for chromosome organization and segregation in mitosis. We previously showed that condensin I also interacts with PARP1 in response to DNA damage and plays a role in single-strand break repair. However, whether condensin I physically associates with DNA damage sites and how PARP1 may contribute to this process were unclear. We found that condensin I is preferentially recruited to DNA damage sites enriched for base damage. This process is dictated by PARP1 through its interaction with the chromosome-targeting domain of the hCAP-D2 subunit of condensin I