bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of differentially expressed gene categories in microarray studies using nonparametric multivariate analysis
Authors: Nettleton Dan , Recknor Justin , Reecy James M. 
Published: November 2007

AbstractMotivation: The field of microarray data analysis is shifting emphasis from methods for identifying differentially expressed genes to methods for identifying differentially expressed gene categories. The latter approaches utilize a priori information about genes to group genes into categories and enhance the interpretation of experiments aimed at identifying expression differences across treatments. While almost all of the existing approaches for identifying differentially expressed gene categories are practically useful, they suffer from a variety of drawbacks. Perhaps most notably, many popular tools are based exclusively on gene-specific statistics that cannot detect many types of multivariate expression change.Results: We have developed a nonparametric multivariate method for identifying gene categories whose multivariate expression distribution differs across two or more conditions. We illustrate our approach and compare its performance to several existing procedures via the analysis of a real data set and a unique data-based simulation study designed to capture the challenges and complexities of practical data analysis. We show that our method has good power for differentiating between differentially expressed and non-differentially expressed gene categories, and we utilize a resampling based strategy for controling the false discovery rate when testing multiple categories.Availability: R code (www.r-project.org) for implementing our approach is available from the first author by request.Contact: dnett@iastate.eduSupplementary information: Supplementary data are available at Bioinformatics online.
Direct method to construct integrals for
N
th-order autonomous ordinary difference equations
Authors: Sahadevan R , Uma Maheswari C 
Published: November 2007

A direct method to construct integrals for an
N
th-order autonomous ordinary difference equation (
O
Δ
E
):
w

n
+
N

=
F
(
w

n

, …,
w

n
+
N
−1

) is presented. As an illustration we first consider third-order autonomous
O
Δ
E w

n
+3

=
F
(
w

n

,
w

n
+1

,
w

n
+2

) and identify the forms of
F
for which two independent integrals exist. The effectiveness of the method to construct two or more integrals for fourth- and fifth-order
O
Δ
E
s is also demonstrated. The question of integrability of each of the identified difference equations with more than one integral is also discussed.
Ixolaris binding to factor X reveals a precursor state of factor Xa heparin‐binding exosite
Authors: Monteiro Robson Q. , Rezaie Alireza R. , Bae Jong‐Sup , Calvo Eric , Andersen John F. , Francischetti Ivo M.B. 
Published: November 2007

AbstractIxolaris is a two‐Kunitz tick salivary gland tissue factor pathway inhibitor (TFPI). In contrast to human TFPI, Ixolaris specifically binds to factor Xa (FXa) heparin‐binding exosite (HBE). In addition, Ixolaris interacts with zymogen FX. In the present work we characterized the interaction of Ixolaris with human FX quantitatively, and identified a precursor state of the heparin‐binding exosite (proexosite, HBPE) as the Ixolaris‐binding site on the zymogen. Gel‐filtration chromatography demonstrated 1:1 complex formation between fluorescein‐labeled Ixolaris and FX. Isothermal titration calorimetry confirmed that the binding of Ixolaris to FX occurs at stoichiometric concentrations in a reaction which is characteristically exothermic, with a favorable enthalpy (ΔH) of −10.78 kcal/mol. ELISA and plasmon resonance experiments also indicate that Ixolaris binds to plasma FX and FXa, or to recombinant Gla domain‐containing FX/FXa with comparable affinities (∼1 nM). Using a series of mutants on the HBPE, we identified the most important amino acids involved in zymogen/Ixolaris interaction—Arg‐93 >>> Arg‐165 ≥ Lys‐169 > Lys‐236 > Arg‐125—which was identical to that observed for FXa/Ixolaris interaction. Remarkably, Ixolaris strongly inhibited FX activation by factor IXa in the presence but not in the absence of factor VIIIa, suggesting a specific interference in the cofactor activity. Further, solid phase assays demonstrated that Ixolaris inhibits FX interaction with immobilized FVIIIa. Altogether, Ixolaris is the first inhibitor characterized to date that specifically binds to FX HBPE. Ixolaris may be a useful tool to study the physiological role of the FX HBPE and to evaluate this domain as a target for anticoagulant drugs.
Amyloid—a state in many guises: Survival of the fittest fibril fold
Authors: Pedersen Jesper S. , Otzen Daniel E. 
Published: November 2007

AbstractUnder appropriate conditions, essentially all proteins are able to aggregate to form long, well‐ordered and β‐sheet‐rich arrays known as amyloid‐like fibrils. These fibrils consist of varying numbers of intertwined protofibrils and can for any given protein exhibit a wealth of different forms at the ultrastructural level. Traditionally, this structural variability or polymorphism has been attributed to differences in the assembly of a common protofibril structure. However, recent work on glucagon, insulin, and the Aβ peptide suggests that this polymorphism can occur at the level of secondary structure. Simple variations in either solvent conditions such as temperature, protein concentration, and ionic strength or external mechanical influences such as agitation can lead to formation of fibrils with markedly different characteristics. In some cases, these characteristics can be passed on to new fibrils in a strain‐specific manner, similar to what is known for prions. The preferred structure of fibrils formed can be explained in terms of selective pressure and survival of the fittest; the most populated types of fibrils we observe at the end of an experiment are those that had the fastest overall growth rate under the given conditions. Fibrillar polymorphism is probably a consequence of the lack of structural restraints on a nonfunctional conformational state.
Crystal structure of Mycobacterium tuberculosis LrpA, a leucine‐responsive global regulator associated with starvation response
Authors: Reddy Manchi C.M. , Gokulan Kuppan , Jacobs William R. , Ioerger Thomas R. , Sacchettini James C. 
Published: November 2007

AbstractThe bacterial leucine‐responsive regulatory protein (Lrp) is a global transcriptional regulator that controls the expression of many genes during starvation and the transition to stationary phase. The Mycobacterium tuberculosis gene Rv3291c encodes a 150‐amino acid protein (designated here as Mtb LrpA) with homology with Escherichia coli Lrp. The crystal structure of the native form of Mtb LrpA was solved at 2.1 Å. The Mtb LrpA structure shows an N‐terminal DNA‐binding domain with a helix‐turn‐helix (HTH) motif, and a C‐terminal regulatory domain. In comparison to the complex of E. coli AsnC with asparagine, the effector‐binding pocket (including loop 100–106) in LrpA appears to be largely preserved, with hydrophobic substitutions consistent with its specificity for leucine. The effector‐binding pocket is formed at the interface between adjacent dimers, with an opening to the core of the octamer as in AsnC, and an additional substrate‐access channel opening to the outer surface of the octamer. Using electrophoretic mobility shift assays, purified Mtb LrpA protein was shown to form a protein–DNA complex with the lat promoter, demonstrating that the lat operon is a direct target of LrpA. Using computational analysis, a putative motif is identified in this region that is also present upstream of other operons differentially regulated under starvation. This study provides insights into the potential role of LrpA as a global regulator in the transition of M. tuberculosis to a persistent state.
Energetic rationale for an unexpected and abrupt reversal of guanidinium chloride‐induced unfolding of peptide deformylase
Authors: Berg Alexander K. , Manokaran Sumathra , Eiler Daniel , Kooren Joel , Mallik Sanku , Srivastava D.K. 
Published: November 2007

AbstractPeptide deformylase (PDF) catalyzes the removal of formyl group from the N‐terminal methionine residues of nascent proteins in prokaryotes, and this enzyme is a high priority target for antibiotic design. In pursuit of delineating the structural–functional features of Escherichia coli PDF (EcPDF), we investigated the mechanistic pathway for the guanidinium chloride (GdmCl)‐induced unfolding of the enzyme by monitoring the secondary structural changes via CD spectroscopy. The experimental data revealed that EcPDF is a highly stable enzyme, and it undergoes slow denaturation in the presence of varying concentrations of GdmCl. The most interesting aspect of these studies has been the abrupt reversal of the unfolding pathway at low to moderate concentrations of the denaturant, but not at high concentration. An energetic rationale for such an unprecedented feature in protein chemistry is offered.
Some physicochemical and antinutritional properties of raw flours and protein isolates from Mucuna pruriens (velvet bean) and Canavalia ensiformis (jack bean)
Authors: Betancur‐Ancona David , Gallegos‐Tintoré Santiago , Delgado‐Herrera América , Pérez‐Flores Virginia , Castellanos Ruelas Arturo , Chel‐Guerrero Luis 
Published: November 2007

SummaryThe legumes Canavalia ensiformis and Mucuna pruriens are underexploited in tropical Mexico. Their seeds have good nutritional potential, but contain antinutritional factors. Physicochemical and antinutritional properties were determined for raw flours (RF) and protein isolates (PI) produced from these legumes. Protein content in the PI was 737 g kg–1 for C. ensiformis and 666 g kg–1 for M. pruriens. Protein isolation improved in vitro digestibility, while maintaining high lysine levels and adequate sulphur amino acids content. Antinutritional factors such as cyanogenic glucosides, cyanide precursors from hydrolysis, tannins and trypsin inhibitors were lower in the PIs than in the RFs. The reduction in canavanine levels, a structural analogue of arginine, in the C. ensiformis PI was noteworthy. These PIs thus have potential applications in the development of new food ingredients in tropical regions using processes that improve nutritional value.
Broad-line Balmer decrements in blue active galactic nuclei
Authors: Dong Xiaobo , Wang Tinggui , Wang Jianguo , Yuan Weimin , Zhou Hongyan , Dai Haifeng , Zhang Kai 
Published: November 2007

Abstract
We have investigated the broad-line Balmer decrements (Hα/Hβ) for a large, homogeneous sample of Seyfert 1 galaxies and quasi-stellar objects (QSOs) using spectroscopic data obtained in the Sloan Digital Sky Survey. The sample, drawn from the Fourth Data Release, comprises 446 low-redshift (z≲ 0.35) active galactic nuclei (AGN) that have blue optical continua as indicated by the spectral slopes in order to minimize the effect of dust extinction. We find that (i) the distribution of the intrinsic broad-line Hα/Hβ ratio can be well described by log-Gaussian, with a peak at Hα/Hβ= 3.06 and a standard deviation of about 0.03 dex only; (ii) the Balmer decrement does not correlate with AGN properties such as luminosity, accretion rate and continuum slope, etc.; (iii) on average, the Balmer decrements are found to be only slightly larger in radio-loud sources (3.37) and sources having double-peaked emission-line profiles (3.27) compared to the rest of the sample. We therefore suggest that the broad-line Hα/Hβ ratio can be used as a good indicator for dust extinction in the AGN broad-line region; this is especially true for radio-quiet AGN with regular emission-line profiles, which constitute the vast majority of the AGN population.
Is the modulation of retinoid and retinoid‐associated signaling a future therapeutic strategy in neurological trauma and neurodegeneration?
Authors: Malaspina Andrea , Michael‐Titus Adina T. 
Published: November 2007

AbstractThe complex molecular pathways that mediate the effects of vitamin A and its derivatives, are increasingly recognized as a component of the repair capacity that could be activated to induce protection and regeneration in the mature nervous tissue. Retinoid and retinoid‐associated signaling plays an essential role in normal neurodevelopment and appears to remain active in the adult CNS. In this paper, we review evidence which supports the hypothesis of an activation of retinoid‐associated signaling molecular pathways in the mature nervous tissue and its significance in the context of neurodegenerative, trauma‐induced and psychiatric disorders, at spinal and supra‐spinal levels. Finally, we summarize the potential therapeutic avenues based on the modulation of retinoid targets undergoing reactivation under conditions of acute injury and chronic degeneration in the central nervous system, and discuss some of the unresolved issues linked to this treatment strategy.
Nitrated alpha‐synuclein‐activated microglial profiling for Parkinson’s disease
Authors: Reynolds Ashley D. , Glanzer Jason G. , Kadiu Irena , Ricardo‐Dukelow Mary , Chaudhuri Anathbandhu , Ciborowski Pawel , Cerny Ronald , Gelman Benjamin , Thomas Mark P. , Mosley R. Lee , Gendelman Howard E. 
Published: November 2007

J. Neurochem. (2008) 104, 1504–1525.AbstractMicroglial neuroinflammatory processes play a primary role in dopaminergic neurodegeneration for Parkinson’s disease (PD). This can occur, in part, by modulation of glial function following activation by soluble or insoluble modified alpha‐synuclein (α‐syn), a chief component of Lewy bodies that is released from affected dopaminergic neurons. α‐Syn is nitrated during oxidative stress responses and in its aggregated form, induces inflammatory microglial functions. Elucidation of these microglial function changes in PD could lead to new insights into disease mechanisms. To this end, PD‐associated inflammation was modeled by stimulation of microglia with aggregated and nitrated α‐syn. These activated microglia were ameboid in morphology and elicited dopaminergic neurotoxicity. A profile of nitrated, aggregated α‐syn‐stimulated microglia was generated using combinations of genomic (microarrays) and proteomic (liquid chromatography‐tandem mass spectrometry, differential gel electrophoresis, and protein array) assays. Genomic studies revealed a substantive role for nuclear factor‐kappa B transcriptional activation. Qualitative changes in the microglial proteome showed robust increases in inflammatory, redox, enzyme, and cytoskeletal proteins supporting the genomic tests. Autopsy brain tissue acquired from substantia nigra and basal ganglia of PD patients demonstrated that parallel nuclear factor‐kappa B‐related inflammatory processes were, in part, active during human disease. Taken together, the transcriptome and proteome of nitrated α‐syn activated microglia, shown herein, provide new potential insights into disease mechanisms.
Differential expression of duplicated VAL‐opsin genes in the developing zebrafish
Authors: Kojima Daisuke , Torii Masaki , Fukada Yoshitaka , Dowling John E. 
Published: November 2007

AbstractNon‐visual opsins mediate various light‐dependent physiological events. Our previous search for non‐visual opsin genes in zebrafish led to the discovery of VAL‐opsin (VAL‐opsinA) in deep brain cells and retinal horizontal cells of the adult fish. In this study, we report the identification and characterization of its duplicated gene, VAL‐opsinB, in zebrafish. A molecular phylogenetic analysis indicates that VAL‐opsinB is orthologous to a previously reported salmon gene and that the duplication of the VAL‐opsin gene occurred in the teleost lineage. The recombinant protein of zebrafish VAL‐opsinB forms a green‐sensitive photopigment when reconstituted with 11‐cis‐retinal. VAL‐opsinB expression was detected in a limited number of cells of the brain and the eye, and the expression pattern is distinct from that of the VAL‐opsinA gene. Such a differential expression pattern suggests that VAL‐opsinA and VAL‐opsinB are involved in different physiological events in zebrafish.
The use of GIS in estimating spatial variation in habitat quality: a case study of lay‐date in the Great TitParus major
Authors: WILKIN TEDDY A. , PERRINS CHRISTOPHER M. , SHELDON BEN C. 
Published: November 2007

Finding the most biologically meaningful scale at which to describe environmental variation is a persistent problem in ecology. Most studies of forest passerines are conducted at the scale of the habitat or woodland and do not account for environmental variation between individual breeding sites. Here we employ two GIS models, and four spatial scales, to describe environmental variation among 4683 Great TitParus majorbreeding sites occupied over a 32‐year period in Wytham Wood, Oxford, UK, and use these data to help explain variation in an environmentally sensitive trait, first egg date. Model 1 used Thiessen polygons to generate individual spatial scales for each breeding pair, while Model 2 used a range of predetermined radial scales around each breeding site. Environmental variables included local altitude and aspect estimated from a Digital Terrain Model, and the number of OakQuercus roburtrees around each nest‐site, used here as a surrogate for local food (caterpillar) availability. In a Linear Mixed Model, Model 2 explained the most variation in lay‐date at a scale of 25 m from each nestbox. However, the model that returned the lowest Akaike Information Criterion (AIC) contained environmental variables from Model 2, but measured at different fixed spatial scales of between 25 and 75 m. Results from this final model showed that birds breeding in low‐altitude, north‐facing and Oak‐rich areas bred earlier than those in high‐altitude, south‐facing and Oak‐poor areas, at radial scales of 25, 75 and 75 m from each nestbox, respectively. In addition, birds in interior sites bred earlier than those nearer the woodland edge, although this edge effect was only apparent on north‐facing slopes. Thus, the current study demonstrates that a range of GIS models can be effectively used to scale and describe environmental variation between individual breeding sites, and that fine‐scale topographic variation, food availability and edge proximity can affect the breeding date of Great Tits.
Grenville Arthur James Cole (1859–1924): the cycling geologist
Authors: Jackson P. N. Wyse 
Published: November 2007

Abstract
Grenville Arthur James Cole (1859–1924), Professor of Geology at the Royal College of Science for Ireland, was an avid cyclist and shared this passion with his wife Blanche. Born in London, Cole studied at the Royal School of Mines and lectured for a number of years at Bedford College for Ladies. Largely concurrent with his professorship he served as Director of the Geological Survey of Ireland at a time when it was in moderate decline.

He undertook many cycling tours around continental Europe and Ireland. These trips were recounted in two early travel books.
The Gypsy Road: a Journey from Krakow to Coblentz
, published in 1894, provides a delightful account of a tour undertaken by him on a tricycle and his companion on a penny farthing, across what is now Poland, the Czech Republic, and eastern Germany. In a later slim volume entitled
As We Ride
, co-authored with his wife, a number of expeditions to France and the Balkans are eloquently described. Between 1902 and 1908 he organized a week-long geological excursion to various parts of Ireland for his students, and transport was by train and bicycle.

His cycling trips provided him with the opportunity to collect research materials, make geological observations, and to photograph features of interest. Subsequently much of this material was used in his publications and in teaching. Cole's main academic studies were in igneous and metamorphic petrology. He valued and promoted fieldwork as an essential component of geological training. He was heavily involved with professional and amateur scientific societies, and was a prolific author of both academic and popular geological papers and books.
Clarence Edward Dutton (1841–1912): soldier, polymath and aesthete
Authors: Orme Antony R. 
Published: November 2007

Abstract

Clarence Edward Dutton (1841–1912) was one of several scientists who laid the foundations for modern geology from their work in North America during the late nineteenth century. Dutton was a career soldier who fought in the American Civil War and remained with the US Army Ordnance Corps to his retirement in 1901. Despite military obligations, Dutton developed a profound interest in geology and, on secondment first to the Powell Survey and later to the fledgling US Geological Survey, made important contributions to volcanic geology, seismology and physical geology. His lifelong fascination with volcanism led to improved understanding of the volcanic geology of the American West, Hawaii, and Central America. This work linked naturally with the emerging science of seismology, as reflected in his study of the 1886 earthquake in Charleston, South Carolina, and he is often credited with introducing the ‘new seismology’ to American scientific audiences. Awareness of volcanic and seismic hazards in turn led him to caution against a proposed sea-level canal across the Nicaraguan isthmus. His contributions to physical geology are most evident in several reports on the American West, notably the
Report on the Geology of the High Plateaus of Utah
(1880), the
Tertiary History of the Grand Cañon District
(1882), and
Mount Taylor and the Zuni Plateau
(1885). These reports, presented in colourful prose, reveal both the author's scientific acumen and his aesthetic appreciation of nature.

Whereas most of Dutton's work must now be placed in its historical context, in his recognition of isostasy, a term he coined in 1882 to reflect the debate then raging concerning Earth's crustal behaviour, his ideas were remarkably prescient. Dutton's interest in isostasy derived in part from his studies of volcanic geology, seismology, and crustal behaviour, and in part from his fieldwork in the American West. Initially, however, it was Dutton's description of the great denudation of the Colorado Plateau, rather than any isostatic implications, that influenced geomorphology during the earlier twentienth century, dominated as it was by Davis' cycle of erosion. The subsequent demise of Davisian geomorphology, and the ensuing quest for alternative models, led to a reawakening of interest in isostasy as a concept basic to the explanation of Earth's surface features. Somewhat belatedly, Dutton's concept of isostasy is once again at the centre of debate regarding denudation and crustal behaviour. Wherever these debates focus, they confront a problem fundamental to geology, geodesy and geophysics, namely the extent to which the Earth's present relief reflects a quest for balance between the subsurface forces generating uplift, subsidence and mass transfers at depth, and the climate-induced processes responsible for denudation and mass transfers of rock waste across the surface. Dutton's probing of isostasy predated modern debate in geomorphology by more than a century.