466 research outputs found
New light on old fingermarks: The detection of historic latent fingermarks on old paper documents using 1,2-indanedione/zinc
This study explores trends in the effectiveness of 1,2-indandione/zinc chloride (IND/Zn) for visualizing latent fingermarks on paper substrates of various ages. Preliminary investigation of contemporaneous documents showed that high quality fingermarks could be deposited through incidental handling, although smudging and overlapping were evident. IND/Zn was then applied to incidentally handled documents up to 80 years old and successfully developed potentially identifiable fingermarks, significantly increasing the established timescale for fingermark detection with amino acid sensitive reagents. The results indicate that IND/Zn remains effective over longer periods than has been previously demonstrated, although a comparison between documents of different ages suggest that progressive diffusion of the target amino acids occurs over time, affecting the proportion of potentially identifiable marks. The findings of this study reinforce the applicability of IND/Zn for the detection of historic latent fingermarks on old paper documents
Probing key DNA contacts in AraR-mediated transcriptional repression of the Bacillus subtilis arabinose regulon
In the absence of arabinose, the AraR transcription factor represses the expression of genes involved in the utilization of arabinose, xylose and galactose in Bacillus subtilis. AraR exhibits a chimeric organization: the N-terminal DNA-binding region belongs to the GntR family and the C-terminal effector-binding domain is homologous to the GalR/LacI family. Here, the AraR–DNA-binding interactions were characterized in vivo and in vitro. The effect of residue substitutions in the AraR N-terminal domain and of base-pair exchanges into an AraR–DNA-binding operator site were examined by assaying for AraR-mediated regulatory activity in vivo and DNA-binding activity in vitro. The results showed that residues K4, R45 and Q61, located in or near the winged-helix DNA-binding motif, were the most critical amino acids required for AraR function. In addition, the analysis of the various mutations in an AraR palindromic operator sequence indicated that bases G9, A11 and T16 are crucial for AraR binding. Moreover, an AraR mutant M34T was isolated that partially suppressed the effect of mutations in the regulatory cis-elements. Together, these findings extend the knowledge on the nature of AraR nucleoprotein complexes and provide insight into the mechanism that underlies the mode of action of AraR and its orthologues
Validating module network learning algorithms using simulated data
In recent years, several authors have used probabilistic graphical models to
learn expression modules and their regulatory programs from gene expression
data. Here, we demonstrate the use of the synthetic data generator SynTReN for
the purpose of testing and comparing module network learning algorithms. We
introduce a software package for learning module networks, called LeMoNe, which
incorporates a novel strategy for learning regulatory programs. Novelties
include the use of a bottom-up Bayesian hierarchical clustering to construct
the regulatory programs, and the use of a conditional entropy measure to assign
regulators to the regulation program nodes. Using SynTReN data, we test the
performance of LeMoNe in a completely controlled situation and assess the
effect of the methodological changes we made with respect to an existing
software package, namely Genomica. Additionally, we assess the effect of
various parameters, such as the size of the data set and the amount of noise,
on the inference performance. Overall, application of Genomica and LeMoNe to
simulated data sets gave comparable results. However, LeMoNe offers some
advantages, one of them being that the learning process is considerably faster
for larger data sets. Additionally, we show that the location of the regulators
in the LeMoNe regulation programs and their conditional entropy may be used to
prioritize regulators for functional validation, and that the combination of
the bottom-up clustering strategy with the conditional entropy-based assignment
of regulators improves the handling of missing or hidden regulators.Comment: 13 pages, 6 figures + 2 pages, 2 figures supplementary informatio
Factors underpinning caregiver burden in frontotemporal dementia differ in spouses and their children
The objectives of this observational study were to (1) compare spousal and child caregiver burden; (2) compare co-resident and live-out child caregiver burden; and (3) investigate factors influencing spousal and child caregiver burden. Data was collected from 90 caregivers of people with frontotemporal degeneration (FTD) recruited from the Frontotemporal Dementia Research Group (Frontier) at Neuroscience Research, Australia. Of this caregiver group, 43 were spousal caregivers and 47 were child caregivers. Caregiver burden and emotional state were evaluated using the short Zarit Burden Interview and the short version of the Depression, Anxiety and Stress Scale-21. The Social Network Index was applied to ascertain the social network of the caregiver, while the Intimate Bond Measure was used to evaluate the current quality of the relationship between the caregiver and the person with dementia. The Frontotemporal Dementia Rating Scale was used to assess severity of dementia. Spousal and child caregivers experienced similar levels of burden, depression, anxiety, and stress, regardless of disease severity. Co-resident child caregivers had smaller social networks and greater burden than live-out caregivers. Dementia severity was key in spousal caregiver burden, whereas caregiver depression was most important in child caregiver burden. Child and spousal caregivers of individuals with FTD share similar levels of burden, influenced by different factors. Future interventions need to account for these differences
On the basic computational structure of gene regulatory networks
Gene regulatory networks constitute the first layer of the cellular
computation for cell adaptation and surveillance. In these webs, a set of
causal relations is built up from thousands of interactions between
transcription factors and their target genes. The large size of these webs and
their entangled nature make difficult to achieve a global view of their
internal organisation. Here, this problem has been addressed through a
comparative study for {\em Escherichia coli}, {\em Bacillus subtilis} and {\em
Saccharomyces cerevisiae} gene regulatory networks. We extract the minimal core
of causal relations, uncovering the hierarchical and modular organisation from
a novel dynamical/causal perspective. Our results reveal a marked top-down
hierarchy containing several small dynamical modules for \textit{E. coli} and
\textit{B. subtilis}. Conversely, the yeast network displays a single but large
dynamical module in the middle of a bow-tie structure. We found that these
dynamical modules capture the relevant wiring among both common and
organism-specific biological functions such as transcription initiation,
metabolic control, signal transduction, response to stress, sporulation and
cell cycle. Functional and topological results suggest that two fundamentally
different forms of logic organisation may have evolved in bacteria and yeast.Comment: This article is published at Molecular Biosystems, Please cite as:
Carlos Rodriguez-Caso, Bernat Corominas-Murtra and Ricard V. Sole. Mol.
BioSyst., 2009, 5 pp 1617--171
Structural determinants of specific DNA-recognition by the THAP zinc finger
Human THAP1 is the prototype of a large family of cellular factors sharing an original THAP zinc-finger motif responsible for DNA binding. Human THAP1 regulates endothelial cell proliferation and G1/S cell-cycle progression, through modulation of pRb/E2F cell-cycle target genes including rrm1. Recently, mutations in THAP1 have been found to cause DYT6 primary torsion dystonia, a human neurological disease. We report here the first 3D structure of the complex formed by the DNA-binding domain of THAP1 and its specific DNA target (THABS) found within the rrm1 target gene. The THAP zinc finger uses its double-stranded β-sheet to fill the DNA major groove and provides a unique combination of contacts from the β-sheet, the N-terminal tail and surrounding loops toward the five invariant base pairs of the THABS sequence. Our studies reveal unprecedented insights into the specific DNA recognition mechanisms within this large family of proteins controlling cell proliferation, cell cycle and pluripotency
A self-organized model for cell-differentiation based on variations of molecular decay rates
Systemic properties of living cells are the result of molecular dynamics
governed by so-called genetic regulatory networks (GRN). These networks capture
all possible features of cells and are responsible for the immense levels of
adaptation characteristic to living systems. At any point in time only small
subsets of these networks are active. Any active subset of the GRN leads to the
expression of particular sets of molecules (expression modes). The subsets of
active networks change over time, leading to the observed complex dynamics of
expression patterns. Understanding of this dynamics becomes increasingly
important in systems biology and medicine. While the importance of
transcription rates and catalytic interactions has been widely recognized in
modeling genetic regulatory systems, the understanding of the role of
degradation of biochemical agents (mRNA, protein) in regulatory dynamics
remains limited. Recent experimental data suggests that there exists a
functional relation between mRNA and protein decay rates and expression modes.
In this paper we propose a model for the dynamics of successions of sequences
of active subnetworks of the GRN. The model is able to reproduce key
characteristics of molecular dynamics, including homeostasis, multi-stability,
periodic dynamics, alternating activity, differentiability, and self-organized
critical dynamics. Moreover the model allows to naturally understand the
mechanism behind the relation between decay rates and expression modes. The
model explains recent experimental observations that decay-rates (or turnovers)
vary between differentiated tissue-classes at a general systemic level and
highlights the role of intracellular decay rate control mechanisms in cell
differentiation.Comment: 16 pages, 5 figure
Protein status elicits compensatory changes in food intake and food preferences123
Background: Protein is an indispensable component within the human diet. It is unclear, however, whether behavioral strategies exist to avoid shortages
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