5,279 research outputs found
Stochastic dynamics of macromolecular-assembly networks
The formation and regulation of macromolecular complexes provides the
backbone of most cellular processes, including gene regulation and signal
transduction. The inherent complexity of assembling macromolecular structures
makes current computational methods strongly limited for understanding how the
physical interactions between cellular components give rise to systemic
properties of cells. Here we present a stochastic approach to study the
dynamics of networks formed by macromolecular complexes in terms of the
molecular interactions of their components. Exploiting key thermodynamic
concepts, this approach makes it possible to both estimate reaction rates and
incorporate the resulting assembly dynamics into the stochastic kinetics of
cellular networks. As prototype systems, we consider the lac operon and phage
lambda induction switches, which rely on the formation of DNA loops by proteins
and on the integration of these protein-DNA complexes into intracellular
networks. This cross-scale approach offers an effective starting point to move
forward from network diagrams, such as those of protein-protein and DNA-protein
interaction networks, to the actual dynamics of cellular processes.Comment: Open Access article available at
http://www.nature.com/msb/journal/v2/n1/full/msb4100061.htm
mPUMA: a computational approach to microbiota analysis by de novo assembly of operational taxonomic units based on protein-coding barcode sequences.
BACKGROUND: Formation of operational taxonomic units (OTU) is a common approach to data aggregation in microbial ecology studies based on amplification and sequencing of individual gene targets. The de novo assembly of OTU sequences has been recently demonstrated as an alternative to widely used clustering methods, providing robust information from experimental data alone, without any reliance on an external reference database. RESULTS: Here we introduce mPUMA (microbial Profiling Using Metagenomic Assembly, http://mpuma.sourceforge.net), a software package for identification and analysis of protein-coding barcode sequence data. It was developed originally for Cpn60 universal target sequences (also known as GroEL or Hsp60). Using an unattended process that is independent of external reference sequences, mPUMA forms OTUs by DNA sequence assembly and is capable of tracking OTU abundance. mPUMA processes microbial profiles both in terms of the direct DNA sequence as well as in the translated amino acid sequence for protein coding barcodes. By forming OTUs and calculating abundance through an assembly approach, mPUMA is capable of generating inputs for several popular microbiota analysis tools. Using SFF data from sequencing of a synthetic community of Cpn60 sequences derived from the human vaginal microbiome, we demonstrate that mPUMA can faithfully reconstruct all expected OTU sequences and produce compositional profiles consistent with actual community structure. CONCLUSIONS: mPUMA enables analysis of microbial communities while empowering the discovery of novel organisms through OTU assembly
Characterization of the upper respiratory tract microbiomes of patients with pandemic H1N1 influenza.
The upper respiratory tract microbiome has an important role in respiratory health. Influenza A is a common viral infection that challenges that health, and a well-recognized sequela is bacterial pneumonia. Given this connection, we sought to characterize the upper respiratory tract microbiota of individuals suffering from the pandemic H1N1 influenza A outbreak of 2009 and determine if microbiome profiles could be correlated with patient characteristics. We determined the microbial profiles of 65 samples from H1N1 patients by cpn60 universal target amplification and sequencing. Profiles were examined at the phylum and nearest neighbor species levels using the characteristics of patient gender, age, originating health authority, sample type and designation (STAT/non-STAT). At the phylum level, Actinobacteria-, Firmicutes- and Proteobacteria-dominated microbiomes were observed, with none of the patient characteristics showing significant profile composition differences. At the nearest neighbor species level, the upper respiratory tract microbiomes were composed of 13-20 species and showed a trend towards increasing diversity with patient age. Interestingly, at an individual level, most patients had one to three organisms dominant in their microbiota. A limited number of discrete microbiome profiles were observed, shared among influenza patients regardless of patient status variables. To assess the validity of analyses derived from sequence read abundance, several bacterial species were quantified by quantitative PCR and compared to the abundance of cpn60 sequence read counts obtained in the study. A strong positive correlation between read abundance and absolute bacterial quantification was observed. This study represents the first examination of the upper respiratory tract microbiome using a target other than the 16S rRNA gene and to our knowledge, the first thorough examination of this microbiome during a viral infection
DNA looping: the consequences and its control
The formation of DNA loops by proteins and protein complexes is ubiquitous to
many fundamental cellular processes, including transcription, recombination,
and replication. Here we review recent advances in understanding the properties
of DNA looping in its natural context and how they propagate to the cellular
behavior through gene regulation. The results of connecting the molecular
properties with cellular physiology indicate that looping of DNA in vivo is
much more complex and easier than predicted from current models and reveals a
wealth of previously unappreciated details
Effect of aging on H-reflex response to fatigue
Injury as a result of tripping is relatively common among older people. The risk of falling increases with fatigue and of importance is the ability to dorsiflex the foot through timely activation of the tibialis anterior (TA) muscle to ensure the foot clears the ground, or an obstacle, during the swing phase of walking. We, therefore, questioned whether the muscle spindle input to the motoneurons alters with ongoing fatigue in older people. We electrically stimulated the common peroneal nerve to assess the TA primary afferent efficacy using H-reflex before, immediately following and after a fatiguing maximal isometric contraction. M-response was kept unchanged throughout the experiment to ensure a similar stimulus intensity was delivered across time points. H-reflex increased significantly while the TA muscle was in a state of fatigue for the younger participants but tended to decrease with increasing age. The main contributor to the tonicity of TA muscle, i.e., excitatory synapses of spindle primary endings of motoneurons that innervate TA muscle, tend to lose their efficacy during fatigue in the older individuals but increased efficiency in the majority of the younger people. Since TA muscle is the main dorsiflexor of the foot and it needs to be active during the swing phase of stepping to prevent tripping, older individuals become more susceptible to falling when their muscles are fatigued. This finding may help improve devices/treatments to overcome the problem of tripping among older individuals
The 1979 outburst of U Scorpii
Optical and ultraviolet observations are presented of the 1979 outburst of the recurrent nova U Sco. For the first time the evolution through outburst is documented photometrically and spectroscopically. Lines of the following ions are identified: H I, He II, C IV, N III, N IV, N V, O IV, O VI and Si IV. No forbidden lines were observed. Mg I was seen in absorption at a late stage in the decline. The Balmer lines have broad and narrow components which change with time. There is evidence that nitrogen is overabundant with respect to carbon and the helium to hydrogen number ratio is about 2
What Can We Conclude from Death Registration? Improved Methods for Evaluating Completeness
Julie Rajaratnam and colleagues evaluate the performance of a suite of demographic methods that estimate the fraction of deaths registered and counted by civil registration systems, and identify three variants that generally perform the best
The phases of deuterium at extreme densities
We consider deuterium compressed to higher than atomic, but lower than
nuclear densities. At such densities deuterium is a superconducting quantum
liquid. Generically, two superconducting phases compete, a "ferromagnetic" and
a "nematic" one. We provide a power counting argument suggesting that the
dominant interactions in the deuteron liquid are perturbative (but screened)
Coulomb interactions. At very high densities the ground state is determined by
very small nuclear interaction effects that probably favor the ferromagnetic
phase. At lower densities the symmetry of the theory is effectively enhanced to
SU(3), and the quantum liquid enters a novel phase, neither ferromagnetic nor
nematic. Our results can serve as a starting point for investigations of the
phase dynamics of deuteron liquids, as well as exploration of the stability and
dynamics of the rich variety of topological objects that may occur in phases of
the deuteron quantum liquid, which range from Alice strings to spin skyrmions
to Z_2 vortices.Comment: 9 pages, 6 figures; v2: fixed typo
Recommended from our members
“When the felid’s away, the mesocarnivores play”: seasonal temporal segregation in a neotropical carnivore guild
Interspecific competition within a carnivore guild can result in segregation along dietary, spatial, and temporal scales. Species interactions and resulting avoidance behavior can change seasonally as landscape features and resource abundance may fluctuate. In this study, we examined a carnivore guild in the Pantanal wetland of Brazil to determine whether temporal niche partitioning was a mechanism for coexistence, and if this differed between the wet and dry season. We used camera trapping data to fit kernel density functions of time observations for five species of carnivores to determine activity patterns. We calculated the coefficient of overlap between all species-pair’s activity patterns. Our results found support for temporal segregation among this carnivore guild, with stronger segregation evident during the dry season. Jaguars and pumas showed large overlap in activity in both seasons, while all three mesocarnivores (ocelot, tayra, and crab-eating fox) showed temporal avoidance toward pumas. Mesocarnivores displayed segregating temporal patterns between pairs in both seasons. Temporal segregation is a mechanism for coexistence within this carnivore guild, suggesting increased competition between species especially during the dry season. To maintain carnivore populations, a broader knowledge of interspecific interactions and how this may affect species, utilization or avoidance of habitats is needed. Given the complexities of interspecific interactions among carnivores, conservation efforts should address the needs of the entire guild rather than focus on a single species
Anomalies and the chiral magnetic effect in the Sakai-Sugimoto model
In the chiral magnetic effect an imbalance in the number of left- and
right-handed quarks gives rise to an electromagnetic current parallel to the
magnetic field produced in noncentral heavy-ion collisions. The chiral
imbalance may be induced by topologically nontrivial gluon configurations via
the QCD axial anomaly, while the resulting electromagnetic current itself is a
consequence of the QED anomaly. In the Sakai-Sugimoto model, which in a certain
limit is dual to large-N_c QCD, we discuss the proper implementation of the QED
axial anomaly, the (ambiguous) definition of chiral currents, and the
calculation of the chiral magnetic effect. We show that this model correctly
contains the so-called consistent anomaly, but requires the introduction of a
(holographic) finite counterterm to yield the correct covariant anomaly.
Introducing net chirality through an axial chemical potential, we find a
nonvanishing vector current only before including this counterterm. This seems
to imply the absence of the chiral magnetic effect in this model. On the other
hand, for a conventional quark chemical potential and large magnetic field,
which is of interest in the physics of compact stars, we obtain a nontrivial
result for the axial current that is in agreement with previous calculations
and known exact results for QCD.Comment: 35 pages, 4 figures, v2: added comments about frequency-dependent
conductivity at the end of section 4; references added; version to appear in
JHE
- …