851 research outputs found
Quantum capacitor with discrete charge-anticharge: spectrum and forces
The quantum capacitor with discrete charge is modeled by a Hamiltonian
containing an inductive intrinsic term (tunnel effect between plates). The
spectrum is obtained using a double Hilbert space. Fluctuations in the
charge-anticharge pairs (zero total charge) give rise to an elementary
attraction which is compared to the Casimir force. In this case, the
field-fluctuations force could be also interpreted as charge-fluctuations
force
Heuristic derivation of continuum kinetic equations from microscopic dynamics
We present an approximate and heuristic scheme for the derivation of
continuum kinetic equations from microscopic dynamics for stochastic,
interacting systems. The method consists of a mean-field type, decoupled
approximation of the master equation followed by the `naive' continuum limit.
The Ising model and driven diffusive systems are used as illustrations. The
equations derived are in agreement with other approaches, and consequences of
the microscopic dependences of coarse-grained parameters compare favorably with
exact or high-temperature expansions. The method is valuable when more
systematic and rigorous approaches fail, and when microscopic inputs in the
continuum theory are desirable.Comment: 7 pages, RevTeX, two-column, 4 PS figures include
Viability of competing field theories for the driven lattice gas
It has recently been suggested that the driven lattice gas should be
described by a novel field theory in the limit of infinite drive. We review the
original and the new field theory, invoking several well-documented key
features of the microscopics. Since the new field theory fails to reproduce
these characteristics, we argue that it cannot serve as a viable description of
the driven lattice gas. Recent results, for the critical exponents associated
with this theory, are re-analyzed and shown to be incorrect.Comment: 4 pages, revtex, no figure
Non-equilibrium Phase Transitions with Long-Range Interactions
This review article gives an overview of recent progress in the field of
non-equilibrium phase transitions into absorbing states with long-range
interactions. It focuses on two possible types of long-range interactions. The
first one is to replace nearest-neighbor couplings by unrestricted Levy flights
with a power-law distribution P(r) ~ r^(-d-sigma) controlled by an exponent
sigma. Similarly, the temporal evolution can be modified by introducing waiting
times Dt between subsequent moves which are distributed algebraically as P(Dt)~
(Dt)^(-1-kappa). It turns out that such systems with Levy-distributed
long-range interactions still exhibit a continuous phase transition with
critical exponents varying continuously with sigma and/or kappa in certain
ranges of the parameter space. In a field-theoretical framework such
algebraically distributed long-range interactions can be accounted for by
replacing the differential operators nabla^2 and d/dt with fractional
derivatives nabla^sigma and (d/dt)^kappa. As another possibility, one may
introduce algebraically decaying long-range interactions which cannot exceed
the actual distance to the nearest particle. Such interactions are motivated by
studies of non-equilibrium growth processes and may be interpreted as Levy
flights cut off at the actual distance to the nearest particle. In the
continuum limit such truncated Levy flights can be described to leading order
by terms involving fractional powers of the density field while the
differential operators remain short-ranged.Comment: LaTeX, 39 pages, 13 figures, minor revision
Nonequilibrium wetting
When a nonequilibrium growing interface in the presence of a wall is
considered a nonequilibrium wetting transition may take place. This transition
can be studied trough Langevin equations or discrete growth models. In the
first case, the Kardar-Parisi-Zhang equation, which defines a very robust
universality class for nonequilibrium moving interfaces, with a soft-wall
potential is considered. While in the second, microscopic models, in the
corresponding universality class, with evaporation and deposition of particles
in the presence of hard-wall are studied. Equilibrium wetting is related to a
particular case of the problem, it corresponds to the Edwards-Wilkinson
equation with a potential in the continuum approach or to the fulfillment of
detailed balance in the microscopic models. In this review we present the
analytical and numerical methods used to investigate the problem and the very
rich behavior that is observed with them.Comment: Review, 36 pages, 16 figure
In vitro elucidation of the crucial but complex oxidative tailoring steps in rufomycin biosynthesis enables one pot conversion of rufomycin B to rufomycin C
The antimycobacterial peptides, rufomycins, have their antibiotic activity conferred by oxidative tailoring of the cyclic peptide. Here we elucidate the roles of cytochrome P450s RufS and RufM in regioselective epoxidation and alkyl oxidation respectively and demonstrate how RufM and RufS create a complex product profile dependent on redox partner availability. Finally, we report the in vitro one pot conversion of rufomycin B to rufomycin C
Pentamycin biosynthesis in Philippine Streptomyces sp. S816 : cytochrome P450-catalyzed installation of the C-14 hydroxyl group
Pentamycin is a polyene antibiotic, registered in Switzerland for the treatment of vaginal candidiasis, trichomoniasis, and mixed infections. Chemical instability has hindered its widespread application and development as a drug. Here, we report the identification of Streptomyces sp. S816, isolated from Philippine mangrove soil, as a pentamycin producer. Genome sequence analysis identified the putative pentamycin biosynthetic gene cluster, which shows a high degree of similarity to the gene cluster responsible for filipin III biosynthesis. The ptnJ gene, which is absent from the filipin III biosynthetic gene cluster, was shown to encode a cytochrome P450 capable of converting filipin III to pentamycin. This confirms that the cluster directs pentamycin biosynthesis, paving the way for biosynthetic engineering approaches to the production of pentamycin analogues. Several other Streptomyces genomes were found to contain ptnJ orthologues clustered with genes encoding polyketide synthases that appear to have similar architectures to those responsible for the assembly of filipin III and pentamycin, suggesting pentamycin production may be common in Streptomyces species
Bulk dynamics for interfacial growth models
We study the influence of the bulk dynamics of a growing cluster of particles
on the properties of its interface. First, we define a {\it general bulk growth
model} by means of a continuum Master equation for the evolution of the bulk
density field. This general model just considers arbitrary addition of
particles (though it can be easily generalized to consider substraction) with
no other physical restriction. The corresponding Langevin equation for this
bulk density field is derived where the influence of the bulk dynamics is
explicitly shown. Finally, when it is assumed a well-defined interface for the
growing cluster, the Langevin equation for the height field of this interface
for some particular bulk dynamics is written. In particular, we obtain the
celebrated Kardar-Parisi-Zhang (KPZ) equation. A Monte Carlo simulation
illustrates the theoretical results.Comment: 6 pages, 2 figure
MicroRNA signature from extracellular vesicles of HCV/HIV co-infected individuals differs from HCV mono-infected
Hepatitis C virus (HCV) coinfection with human immunodeficiency virus (HIV) has a detrimental impact on disease progression. Increasing evidence points to extracellular vesicles (EVs) as important players of the host-viral cross-talk. The microRNAs (miRNAs), as essential components of EVs cargo, are key regulators of normal cellular processes and also promote viral replication, viral pathogenesis, and disease progression. We aimed to characterize the plasma-derived EVs miRNA signature of chronic HCV infected and HIV coinfected patients to unravel the molecular mechanisms of coinfection. EVs were purified and characterized from 50 plasma samples (21 HCV mono- and 29 HCV/HIV co-infected). EV-derived small RNAs were isolated and analyzed by massive sequencing. Known and de novo miRNAs were identified with miRDeep2. Significant differentially expressed (SDE) miRNA identification was performed with generalized linear models and their putative dysregulated biological pathways were evaluated. Study groups were similar for most clinical and epidemiological characteristics. No differences were observed in EVs size or concentration between groups. Therefore, HCV/HIV co-infection condition did not affect the concentration or size of EVs but produced a disturbance in plasma-derived EVs miRNA cargo. Thus, a total of 149 miRNAs were identified (143 known and 6 de novo) leading to 37 SDE miRNAs of which 15 were upregulated and 22 downregulated in HCV/HIV co-infected patients. SDE miRNAs regulate genes involved in inflammation, fibrosis, and cancer, modulating different biological pathways related to HCV and HIV pathogenesis. These findings may help to develop new generation biomarkers and treatment strategies, in addition to elucidate the mechanisms underlying virus-host interaction. KEY MESSAGES: HCV and HCV/HIV displayed similar plasma-EV size and concentration. EVs- derived miRNA profile was characterized by NGS. 37 SDE miRNAs between HCV and HCV/HIV were observed. SDE miRNAs regulate genes involved in inflammation, fibrosis and cancer.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work has been supported by grants from (1) Institute of Health Carlos III, Spain [PI18CIII/00020/ to AFR], (2) PID2021–126781OB-I00 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”, (3) The SPANISH AIDS Research Network RD16CIII/0002/0002 - ISCIII – FEDER, (4) Centro de Investigación en Red en Enfermedades Infecciosas (CIBERINFEC) CB21/13/00044, (5) the National Agency for Scientific and Technology Promotion (ANPCyT) (PICT 2017 Nº713), and (6) the National Research Council (CONICET, PIP 2021-2023). V.C. received funding form the Asociación Universitaria Iberoamericana de Postgrado (AUIP) for the Academic Mobility Scholarship Program. P.V., E.D.M., and M.V.P. are members of the CONICET-Research Career Program. V.C. is a fellow from ANPCyT. The funder’s had no role in the study design, data collection and analysis, decision to publish, or the preparation of the manuscript.S
A CRISPR-Cas9-engineered mouse model for GPI anchor deficiency mirrors human phenotype and shows hippocampal synaptic dysfunctions
Pathogenic germline mutations in PIGV lead to glycosylphosphatidylinositol biosynthesis deficiency. Individuals with pathogenic biallelic mutations in genes of the glycosylphosphatidylinositol anchor pathway show cognitive impairments, a motor delay and in many cases epilepsy. Thus far, the pathophysiology underlying the disease remains unclear and suitable rodent models that mirror human pathophysiology have not been available. We therefore generated a mouse model using CRISPR-Cas9 to introduce the most prevalent hypomorphic missense mutation in European patients, at a site that is also conserved in mice, Pigv:c.1022C>A (p.A341E). Reflecting the human pathology mutant Pigv(341E) mice showed deficits in motor coordination and cognitive impairment with poorer long-term spatial memory than wild-type mice, as well as alterations in sociability and sleep patterns. Furthermore, immunohistochemistry showed decreased synaptophysin-immunoreactivity and electrophysiology recordings demonstrated reduced hippocampal synaptic transmission in Pigv(341E) mice that may underlie impaired memory formation. To gain a deeper and broader molecular understanding of the consequences of glycosylphosphatidylinositol anchor deficiency, we performed single-cell RNA sequencing on acutely isolated hippocampal cells of Pigv(341E) and wild-type mice. We found that hippocampal cells from adult Pigv(341E) mice exhibited changes in gene expression, most prominently in a subtype of microglia and subicular neurons. A significant reduction of Abl1 transcripts in several cell clusters suggests a link to the signaling pathway of glycosylphosphatidylinositol-anchored ephrins. We also observed increased levels of Hdc that might affect histamine metabolism with consequences in circadian rhythm. In summary, we present here the first mouse model with a patient-specific hypomorphic mutation that mirrors the human phenotype and shows a hippocampal synaptic defect. This new mouse model will not only open the doors for further investigation into the pathophysiology of glycosylphosphatidylinositol biosynthesis deficiency in future studies, but will also deepen our understanding in the role of glycosylphosphatidylinositol-anchor related pathways in brain development
- …