333 research outputs found
Min-oscillations in Escherichia coli induced by interactions of membrane-bound proteins
During division it is of primary importance for a cell to correctly determine
the site of cleavage. The bacterium Escherichia coli divides in the center,
producing two daughter cells of equal size. Selection of the center as the
correct division site is in part achieved by the Min-proteins. They oscillate
between the two cell poles and thereby prevent division at these locations.
Here, a phenomenological description for these oscillations is presented, where
lateral interactions between proteins on the cell membrane play a key role.
Solutions to the dynamic equations are compared to experimental findings. In
particular, the temporal period of the oscillations is measured as a function
of the cell length and found to be compatible with the theoretical prediction.Comment: 17 pages, 5 figures. Submitted to Physical Biolog
SARS-CoV-2 infection: A role for S1P/S1P receptor signaling in the nervous system?
The recent coronavirus disease (COVID-19) is still spreading worldwide. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus responsible for COVID-19, binds to its receptor angiotensin-converting enzyme 2 (ACE2), and replicates within the cells of the nasal cavity, then spreads along the airway tracts, causing mild clinical manifestations, and, in a majority of patients, a persisting loss of smell. In some individuals, SARS-CoV-2 reaches and infects several organs, including the lung, leading to severe pulmonary disease. SARS-CoV-2 induces neurological symptoms, likely contributing to morbidity and mortality through unknown mechanisms. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid with pleiotropic properties and functions in many tissues, including the nervous system. S1P regulates neurogenesis and inflammation and it is implicated in multiple sclerosis (MS). Notably, Fingolimod (FTY720), a modulator of S1P receptors, has been approved for the treatment of MS and is being tested for COVID-19. Here, we discuss the putative role of S1P on viral infection and in the modulation of inflammation and survival in the stem cell niche of the olfactory epithelium. This could help to design therapeutic strategies based on S1P-mediated signaling to limit or overcome the host–virus interaction, virus propagation and the pathogenesis and complications involving the nervous system
Stuttering Min oscillations within E. coli bacteria: A stochastic polymerization model
We have developed a 3D off-lattice stochastic polymerization model to study
subcellular oscillation of Min proteins in the bacteria Escherichia coli, and
used it to investigate the experimental phenomenon of Min oscillation
stuttering. Stuttering was affected by the rate of immediate rebinding of MinE
released from depolymerizing filament tips (processivity), protection of
depolymerizing filament tips from MinD binding, and fragmentation of MinD
filaments due to MinE. Each of processivity, protection, and fragmentation
reduces stuttering, speeds oscillations, and reduces MinD filament lengths.
Neither processivity or tip-protection were, on their own, sufficient to
produce fast stutter-free oscillations. While filament fragmentation could, on
its own, lead to fast oscillations with infrequent stuttering; high levels of
fragmentation degraded oscillations. The infrequent stuttering observed in
standard Min oscillations are consistent with short filaments of MinD, while we
expect that mutants that exhibit higher stuttering frequencies will exhibit
longer MinD filaments. Increased stuttering rate may be a useful diagnostic to
find observable MinD polymerization in experimental conditions.Comment: 21 pages, 7 figures, missing unit for k_f inserte
A stochastic model of Min oscillations in Escherichia coli and Min protein segregation during cell division
The Min system in Escherichia coli directs division to the centre of the cell
through pole-to-pole oscillations of the MinCDE proteins. We present a one
dimensional stochastic model of these oscillations which incorporates membrane
polymerisation of MinD into linear chains. This model reproduces much of the
observed phenomenology of the Min system, including pole-to-pole oscillations
of the Min proteins. We then apply this model to investigate the Min system
during cell division. Oscillations continue initially unaffected by the closing
septum, before cutting off rapidly. The fractions of Min proteins in the
daughter cells vary widely, from 50%-50% up to 85%-15% of the total from the
parent cell, suggesting that there may be another mechanism for regulating
these levels in vivo.Comment: 19 pages, 12 figures (25 figure files); published at
http://www.iop.org/EJ/journal/physbi
Dual HDAC/BRD4 Inhibitors Relieves Neuropathic Pain by Attenuating Inflammatory Response in Microglia After Spared Nerve Injury
Characteristics of drug-resistant tuberculosis in Abkhazia (Georgia), a high-prevalence area in Eastern Europe
Although multidrug-resistant (MDR) tuberculosis (TB) is a major public health problem in Eastern Europe, the factors contributing to emergence, spread and containment of MDR-TB are not well defined. Here, we analysed the characteristics of drug-resistant TB in a cross-sectional study in Abkhazia (Georgia) between 2003 and 2005, where standard short-course chemotherapy is supplemented with individualized drug-resistance therapy. Drug susceptibility testing (DST) and molecular typing were carried out for Mycobacterium tuberculosis complex strains from consecutive smear-positive TB patients. Out of 366 patients, 60.4% were resistant to any first-line drugs and 21% had MDR-TB. Overall, 25% of all strains belong to the Beijing genotype, which was found to be strongly associated with the risk of MDR-TB (OR 25.9, 95% CI 10.2-66.0) and transmission (OR 2.8, 95% CI 1.6-5.0). One dominant MDR Beijing clone represents 23% of all MDR-TB cases. The level of MDR-TB did not decline during the study period, coinciding with increasing levels of MDR Beijing strains among previously treated cases. Standard chemotherapy plus individualized drug-resistance therapy, guided by conventional DST, might be not sufficient to control MDR-TB in Eastern Europe in light of the spread of "highly transmissible" MDR Beijing strains circulating in the community
Fracture precursors in disordered systems
A two-dimensional lattice model with bond disorder is used to investigate the
fracture behaviour under stress-controlled conditions. Although the cumulative
energy of precursors does not diverge at the critical point, its derivative
with respect to the control parameter (reduced stress) exhibits a singular
behaviour. Our results are nevertheless compatible with previous experimental
findings, if one restricts the comparison to the (limited) range accessible in
the experiment. A power-law avalanche distribution is also found with an
exponent close to the experimental values.Comment: 4 pages, 5 figures. Submitted to Europhysics Letter
- …