Hydrodynamic collective effects of active proteins in biological membranes

Lipid bilayers forming biological membranes are known to behave as viscous 2D fluids on submicrometer scales; usually they contain a large number of active protein inclusions. Recently, it has been shown [Proc. Nat. Acad. Sci. USA 112, E3639 (2015)] that such active proteins should in- duce non-thermal fluctuating lipid flows leading to diffusion enhancement and chemotaxis-like drift for passive inclusions in biomembranes. Here, a detailed analytical and numerical investigation of such effects is performed. The attention is focused on the situations when proteins are concentrated within lipid rafts. We demonstrate that passive particles tend to become attracted by active rafts and are accumulated inside them.Comment: 12 pages, 7 figure

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

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.Comment: 19 pages, 6 figure

Chemo-Sensitive Running Droplet

Chemical control of the spontaneous motion of a reactive oil droplet moving on a glass substrate under an aqueous phase is reported. Experimental results show that the self-motion of an oil droplet is confined on an acid-treated glass surface. The transient behavior of oil-droplet motion is also observed with a high-speed video camera. A mathematical model that incorporates the effect of the glass surface charge is built based on the experimental observation of oil-droplet motion. A numerical simulation of this mathematical model reproduced the essential features concerning confinement within a certain chemical territory of oil-droplet motion, and also its transient behavior. Our results may shed light on physical aspects of reactive spreading and a chemotaxis in living things.Comment: 17 pages, 10 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

A New Lead Chemical for Strigolactone Biosynthesis Inhibitors

Several triazole-containing chemicals have previously been shown to act as efficient inhibitors of cytochrome P450 monooxygenases. To discover a strigolactone biosynthesis inhibitor, we screened a chemical library of triazole derivatives to find chemicals that induce tiller bud outgrowth of rice seedlings. We discovered a triazole-type chemical, TIS13 [2,2-dimethyl-7-phenoxy-4-(1H-1,2,4-triazol-1-yl)heptan-3-ol], which induced outgrowth of second tiller buds of wild-type seedlings, as observed for non-treated strigolactone-deficient d10 mutant seedlings. TIS13 treatment reduced strigolactone levels in both roots and root exudates in a concentration-dependent manner. Co-application of GR24, a synthetic strigolactone, with TIS13 canceled the TIS13-induced tiller bud outgrowth. Taken together, these results indicate that TIS13 inhibits strigolactone biosynthesis in rice seedlings. We propose that TIS13 is a new lead compound for the development of specific strigolactone biosynthesis inhibitors

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

Swarming in shallow waters

A swarm is a collection of separate objects that move autonomously in the same direction in a concerted fashion. This type of behavior is observed in ensembles of various organisms but has proven inherently difficult to realize in artificial chemical systems, where the components have to self-assemble dynamically and, at the same time, propel themselves. This paper describes a class of systems in which millimeter-sized components interact hydrodynamically and organize into dissipative structures that swarm in thin fluid layers. Depending on the geometry of the particles, various types of swarms can be engineered, including ensembles that rotate, follow a "leader", or are pushed in front of a larger particle

Predictors of linkage to care following community-based HIV counseling and testing in rural Kenya

Despite innovations in HIV counseling and testing (HCT), important gaps remain in understanding linkage to care. We followed a cohort diagnosed with HIV through a community-based HCT campaign that trained persons living with HIV/AIDS (PLHA) as navigators. Individual, interpersonal, and institutional predictors of linkage were assessed using survival analysis of self-reported time to enrollment. Of 483 persons consenting to follow-up, 305 (63.2%) enrolled in HIV care within 3 months. Proportions linking to care were similar across sexes, barring a sub-sample of men aged 18–25 years who were highly unlikely to enroll. Men were more likely to enroll if they had disclosed to their spouse, and women if they had disclosed to family. Women who anticipated violence or relationship breakup were less likely to link to care. Enrolment rates were significantly higher among participants receiving a PLHA visit, suggesting that a navigator approach may improve linkage from community-based HCT campaigns.Vestergaard Frandse