1,376 research outputs found
The temporal response of the Mycobacterium tuberculosis gene regulatory network during growth arrest
The virulence of Mycobacterium tuberculosis depends on the ability of the bacilli to switch between replicative (growth) and non-replicative (dormancy) states in response to host immunity. However, the gene regulatory events associated with transition to dormancy are largely unknown. To address this question, we have assembled the largest M. tuberculosis transcriptional-regulatory network to date, and characterized the temporal response of this network during adaptation to stationary phase and hypoxia, using published microarray data. Distinct sets of transcriptional subnetworks (origons) were responsive at various stages of adaptation, showing a gradual progression of network response under both conditions. Most of the responsive origons were in common between the two conditions and may help define a general transcriptional signature of M. tuberculosis growth arrest. These results open the door for a systems-level understanding of transition to non-replicative persistence, a phenotypic state that prevents sterilization of infection by the host immune response and promotes the establishment of latent M. tuberculosis infection, a condition found in two billion people worldwide
Minimal Brownian Ratchet: An Exactly Solvable Model
We develop an exactly-solvable three-state discrete-time minimal Brownian
ratchet (MBR), where the transition probabilities between states are
asymmetric. By solving the master equations we obtain the steady-state
probabilities. Generally the steady-state solution does not display detailed
balance, giving rise to an induced directional motion in the MBR. For a reduced
two-dimensional parameter space we find the null-curve on which the net current
vanishes and detailed balance holds. A system on this curve is said to be
balanced. On the null-curve, an additional source of external random noise is
introduced to show that a directional motion can be induced under the zero
overall driving force. We also indicate the off-balance behavior with biased
random noise.Comment: 4 pages, 4 figures, RevTex source, General solution added. To be
appeared in Phys. Rev. Let
Recommended from our members
International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.
The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations
Bridging Alone: Religious Conservatism, Marital Homogamy, and Voluntary Association Membership
This study characterizes social insularity of religiously conservative American married couples by examining patterns of voluntary associationmembership. Constructing a dataset of 3938 marital dyads from the second wave of the National Survey of Families and Households, the author investigates whether conservative religious homogamy encourages membership in religious voluntary groups and discourages membership in secular voluntary groups. Results indicate that couples’ shared affiliation with conservative denominations, paired with beliefs in biblical authority and inerrancy, increases the likelihood of religious group membership for husbands and wives and reduces the likelihood of secular group membership for wives, but not for husbands. The social insularity of conservative religious groups appears to be reinforced by homogamy—particularly by wives who share faith with husbands
Liposomal Co-Entrapment of CD40mAb Induces Enhanced IgG Responses against Bacterial Polysaccharide and Protein
Background
Antibody against CD40 is effective in enhancing immune responses to vaccines when chemically conjugated to the vaccine antigen. Unfortunately the requirement for chemical conjugation presents some difficulties in vaccine production and quality control which are compounded when multivalent vaccines are required. We explore here an alternative to chemical conjugation, involving the co-encapsulation of CD40 antibody and antigens in liposomal vehicles.
Methodology/Principal Findings
Anti-mouse CD40 mAb or isotype control mAb were co-entrapped individually in cationic liposomal vehicles with pneumococcal polysaccharides or diphtheria and tetanus toxoids. Retention of CD40 binding activity upon liposomal entrapment was assessed by ELISA and flow cytometry. After subcutaneous immunization of BALB/c female mice, anti-polysaccharide and DT/TT responses were measured by ELISA. Simple co-encapsulation of CD40 antibody allowed for the retention of CD40 binding on the liposome surface, and also produced vaccines with enhanced imunogenicity. Antibody responses against both co-entrapped protein in the form of tetanus toxoid, and Streptococcus pneumoniae capsular polysaccharide, were enhanced by co-encapsulation with CD40 antibody. Surprisingly, liposomal encapsulation also appeared to decrease the toxicity of high doses of CD40 antibody as assessed by the degree of splenomegaly induced.
Conclusions/Significance
Liposomal co-encapsulation with CD40 antibody may represent a practical means of producing more immunogenic multivalent vaccines and inducing IgG responses against polysaccharides without the need for conjugation
Adsorption of mono- and multivalent cat- and anions on DNA molecules
Adsorption of monovalent and multivalent cat- and anions on a deoxyribose
nucleic acid (DNA) molecule from a salt solution is investigated by computer
simulation. The ions are modelled as charged hard spheres, the DNA molecule as
a point charge pattern following the double-helical phosphate strands. The
geometrical shape of the DNA molecules is modelled on different levels ranging
from a simple cylindrical shape to structured models which include the major
and minor grooves between the phosphate strands. The densities of the ions
adsorbed on the phosphate strands, in the major and in the minor grooves are
calculated. First, we find that the adsorption pattern on the DNA surface
depends strongly on its geometrical shape: counterions adsorb preferentially
along the phosphate strands for a cylindrical model shape, but in the minor
groove for a geometrically structured model. Second, we find that an addition
of monovalent salt ions results in an increase of the charge density in the
minor groove while the total charge density of ions adsorbed in the major
groove stays unchanged. The adsorbed ion densities are highly structured along
the minor groove while they are almost smeared along the major groove.
Furthermore, for a fixed amount of added salt, the major groove cationic charge
is independent on the counterion valency. For increasing salt concentration the
major groove is neutralized while the total charge adsorbed in the minor groove
is constant. DNA overcharging is detected for multivalent salt. Simulations for
a larger ion radii, which mimic the effect of the ion hydration, indicate an
increased adsorbtion of cations in the major groove.Comment: 34 pages with 14 figure
Search for anomalous t t-bar production in the highly-boosted all-hadronic final state
A search is presented for a massive particle, generically referred to as a
Z', decaying into a t t-bar pair. The search focuses on Z' resonances that are
sufficiently massive to produce highly Lorentz-boosted top quarks, which yield
collimated decay products that are partially or fully merged into single jets.
The analysis uses new methods to analyze jet substructure, providing
suppression of the non-top multijet backgrounds. The analysis is based on a
data sample of proton-proton collisions at a center-of-mass energy of 7 TeV,
corresponding to an integrated luminosity of 5 inverse femtobarns. Upper limits
in the range of 1 pb are set on the product of the production cross section and
branching fraction for a topcolor Z' modeled for several widths, as well as for
a Randall--Sundrum Kaluza--Klein gluon. In addition, the results constrain any
enhancement in t t-bar production beyond expectations of the standard model for
t t-bar invariant masses larger than 1 TeV.Comment: Submitted to the Journal of High Energy Physics; this version
includes a minor typo correction that will be submitted as an erratu
Measurement of the t t-bar production cross section in the dilepton channel in pp collisions at sqrt(s) = 7 TeV
The t t-bar production cross section (sigma[t t-bar]) is measured in
proton-proton collisions at sqrt(s) = 7 TeV in data collected by the CMS
experiment, corresponding to an integrated luminosity of 2.3 inverse
femtobarns. The measurement is performed in events with two leptons (electrons
or muons) in the final state, at least two jets identified as jets originating
from b quarks, and the presence of an imbalance in transverse momentum. The
measured value of sigma[t t-bar] for a top-quark mass of 172.5 GeV is 161.9 +/-
2.5 (stat.) +5.1/-5.0 (syst.) +/- 3.6(lumi.) pb, consistent with the prediction
of the standard model.Comment: Replaced with published version. Included journal reference and DO
- …