Reaction-induced molecular dancing and boosted diffusion of enzymes

A novel mechanism of reaction-induced active molecular motion, not involving any kind of self-propulsion, is proposed and analyzed. Because of the momentum exchange with the surrounding solvent, conformational transitions in mechano-chemical enzymes are accompanied by motions of their centers of mass. As we show, in combination with rotational diffusion, such repeated reciprocal motions generate an additional random walk - or molecular dancing - and hence boost translational diffusion of an enzyme. A systematic theory of this phenomenon is developed, using as an example a simple enzyme model of a rigid two-state dumbbell. To support the analysis, numerical simulations are performed. Our conclusion is that the phenomenon of molecular dancing could underlie the observations of reaction-induced diffusion enhancement in enzymes. Major experimental findings, such as the occurrence of leaps, the anti-chemotaxis, the linear dependence on the reaction turnover rate and on the rate of energy supply, become thus explained. Moreover, the dancing behavior is possible in other systems, natural and synthetic, too. In the future, interesting biotechnology applications may be developed using such effects

Diffusion in crowded colloids of particles cyclically changing their shapes

A simple model of an active colloid consisting of dumbbell-shaped particles that cyclically change their length without propelling themselves is proposed and analyzed. At nanoscales, it represents an idealization for bacterial cytoplasm or for a biomembrane with active protein inclusions. Our numerical simulations demonstrate that non-equilibrium conformational activity of particles can strongly affect diffusion and structural relaxation: while a passive colloid behaves as a glass, it gets progressively fluidized when the activity is turned on. Qualitatively, this agrees with experimental results on optical tracking of probe particles in bacterial and yeast cells where metabolism-induced fluidization of cytoplasm was observed

Drift instability in the motion of a fluid droplet with a chemically reactive surface driven by Marangoni flow

We theoretically derive the amplitude equations for a self-propelled droplet driven by Marangoni flow. As advective flow driven by surface tension gradient is enhanced, the stationary state becomes unstable and the droplet starts to move. The velocity of the droplet is determined from a cubic nonlinear term in the amplitude equations. The obtained critical point and the characteristic velocity are well supported by numerical simulations.Comment: 9 pages, 4 figure

Association Between Chronic Hepatitis C Virus Infection and Myocardial Infarction Among People Living With HIV in the United States.

Hepatitis C virus (HCV) infection is common among people living with human immunodeficiency virus (PLWH). Extrahepatic manifestations of HCV, including myocardial infarction (MI), are a topic of active research. MI is classified into types, predominantly atheroembolic type 1 MI (T1MI) and supply-demand mismatch type 2 MI (T2MI). We examined the association between HCV and MI among patients in the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems, a US multicenter clinical cohort of PLWH. MIs were centrally adjudicated and categorized by type using the Third Universal Definition of Myocardial Infarction. We estimated the association between chronic HCV (RNA+) and time to MI while adjusting for demographic characteristics, cardiovascular risk factors, clinical characteristics, and history of injecting drug use. Among 23,407 PLWH aged ≥18 years, there were 336 T1MIs and 330 T2MIs during a median of 4.7 years of follow-up between 1998 and 2016. HCV was associated with a 46% greater risk of T2MI (adjusted hazard ratio (aHR) = 1.46, 95% confidence interval (CI): 1.09, 1.97) but not T1MI (aHR = 0.87, 95% CI: 0.58, 1.29). In an exploratory cause-specific analysis of T2MI, HCV was associated with a 2-fold greater risk of T2MI attributed to sepsis (aHR = 2.01, 95% CI: 1.25, 3.24). Extrahepatic manifestations of HCV in this high-risk population are an important area for continued research

Transmitted Drug Resistance in the CFAR Network of Integrated Clinical Systems Cohort: Prevalence and Effects on Pre-Therapy CD4 and Viral Load

Human immunodeficiency virus type 1 (HIV-1) genomes often carry one or more mutations associated with drug resistance upon transmission into a therapy-naïve individual. We assessed the prevalence and clinical significance of transmitted drug resistance (TDR) in chronically-infected therapy-naïve patients enrolled in a multi-center cohort in North America. Pre-therapy clinical significance was quantified by plasma viral load (pVL) and CD4+ cell count (CD4) at baseline. Naïve bulk sequences of HIV-1 protease and reverse transcriptase (RT) were screened for resistance mutations as defined by the World Health Organization surveillance list. The overall prevalence of TDR was 14.2%. We used a Bayesian network to identify co-transmission of TDR mutations in clusters associated with specific drugs or drug classes. Aggregate effects of mutations by drug class were estimated by fitting linear models of pVL and CD4 on weighted sums over TDR mutations according to the Stanford HIV Database algorithm. Transmitted resistance to both classes of reverse transcriptase inhibitors was significantly associated with lower CD4, but had opposing effects on pVL. In contrast, position-specific analyses of TDR mutations revealed substantial effects on CD4 and pVL at several residue positions that were being masked in the aggregate analyses, and significant interaction effects as well. Residue positions in RT with predominant effects on CD4 or pVL (D67 and M184) were re-evaluated in causal models using an inverse probability-weighting scheme to address the problem of confounding by other mutations and demographic or risk factors. We found that causal effect estimates of mutations M184V/I ( pVL) and D67N/G ( and pVL) were compensated by K103N/S and K219Q/E/N/R. As TDR becomes an increasing dilemma in this modern era of highly-active antiretroviral therapy, these results have immediate significance for the clinical management of HIV-1 infections and our understanding of the ongoing adaptation of HIV-1 to human populations

Poorly Controlled HIV Infection: An Independent Risk Factor for Liver Fibrosis

Liver disease is a major cause of mortality among HIV-infected persons. There is limited information about the extent to which HIV disease severity impacts liver disease progression

Does abscisic acid affect strigolactone biosynthesis?

Strigolactones are considered a novel class of plant hormones that, in addition to their endogenous signalling function, are exuded into the rhizosphere acting as a signal to stimulate hyphal branching of arbuscular mycorrhizal (AM) fungi and germination of root parasitic plant seeds. Considering the importance of the strigolactones and their biosynthetic origin (from carotenoids), we investigated the relationship with the plant hormone abscisic acid (ABA). Strigolactone production and ABA content in the presence of specific inhibitors of oxidative carotenoid cleavage enzymes and in several tomato ABA-deficient mutants were analysed by LC-MS/MS. In addition, the expression of two genes involved in strigolactone biosynthesis was studied. * • The carotenoid cleavage dioxygenase (CCD) inhibitor D2 reduced strigolactone but not ABA content of roots. However, in abamineSG-treated plants, an inhibitor of 9-cis-epoxycarotenoid dioxygenase (NCED), and the ABA mutants notabilis, sitiens and flacca, ABA and strigolactones were greatly reduced. The reduction in strigolactone production correlated with the downregulation of LeCCD7 and LeCCD8 genes in all three mutants. * • The results show a correlation between ABA levels and strigolactone production, and suggest a role for ABA in the regulation of strigolactone biosynthesis

Mortality after cancer diagnosis in HIV-infected individuals treated with antiretroviral therapy

To evaluate survival and predictors of mortality after cancer diagnosis among HIV-infected persons receiving combination antiretroviral therapy (cART)

Lancet Glob Health

BackgroundAs mobile phone access continues to expand globally, opportunities exist to leverage these technologies to support demand for immunisation services and improve vaccine coverage. We aimed to assess whether short message service (SMS) reminders and monetary incentives can improve immunisation uptake in Kenya.MethodsIn this cluster-randomised controlled trial, villages were randomly and evenly allocated to four groups: control, SMS only, SMS plus a 75 Kenya Shilling (KES) incentive, and SMS plus 200 KES (85 KES\u2008=\u2008USD$1). Caregivers were eligible if they had a child younger than 5 weeks who had not yet received a first dose of pentavalent vaccine. Participants in the intervention groups received SMS reminders before scheduled pentavalent and measles immunisation visits. Participants in incentive groups, additionally, received money if their child was timely immunised (immunisation within 2 weeks of the due date). Caregivers and interviewers were not masked. The proportion of fully immunised children (receiving BCG, three doses of polio vaccine, three doses of pentavalent vaccine, and measles vaccine) by 12 months of age constituted the primary outcome and was analysed with log-binomial regression and General Estimating Equations to account for correlation within clusters. This trial is registered with ClinicalTrials.gov, number NCT01878435.FindingsBetween Oct 14, 2013, and Oct 17, 2014, we enrolled 2018 caregivers and their infants from 152 villages into the following four groups: control (n=489), SMS only (n=476), SMS plus 75 KES (n=562), and SMS plus 200 KES (n=491). Overall, 1375 (86%) of 1600 children who were successfully followed up achieved the primary outcome, full immunisation by 12 months of age (296 [82%] of 360 control participants, 332 [86%] of 388 SMS only participants, 383 [86%] of 446 SMS plus 75 KES participants, and 364 [90%] of 406 SMS plus 200 KES participants). Children in the SMS plus 200 KES group were significantly more likely to achieve full immunisation at 12 months of age (relative risk 1\ub709, 95% CI 1\ub702\u20131\ub716, p=0\ub7014) than children in the control group.InterpretationIn a setting with high baseline immunisation coverage levels, SMS reminders coupled with incentives significantly improved immunisation coverage and timeliness. Given that global immunisation coverage levels have stagnated around 85%, the use of incentives might be one option to reach the remaining 15%.FundingBill & Melinda Gates Foundation.2017-03-11T00:00:00Z28288747PMC5348605789