Transient viral replication during analytical treatment interruptions in SIV infected macaques can alter the rebound-competent viral reservoir

Analytical treatment interruptions (ATIs) of antiretroviral therapy (ART) play a central role in evaluating the efficacy of HIV-1 treatment strategies targeting virus that persists despite ART. However, it remains unclear if ATIs alter the rebound-competent viral reservoir (RCVR), the virus population that persists during ART and from which viral recrudescence originates after ART discontinuation. To assess the impact of ATIs on the RCVR, we used a barcode sequence tagged SIV to track individual viral lineages through a series of ATIs in Rhesus macaques. We demonstrate that transient replication of individual rebounding lineages during an ATI can lead to their enrichment in the RCVR, increasing their probability of reactivating again after treatment discontinuation. These data establish that the RCVR can be altered by uncontrolled replication during ATI.     

Acute Phase IL-10 Plasma Concentration Associates with the High Risk Sources of Cardiogenic Stroke

Background

Etiological assessment of stroke is essential for accurate treatment decisions and for secondary prevention of recurrence. There is evidence that interleukin-10 (IL-10) associates with ischemic stroke. The aim of this prospective study was to assess the levels of IL-10 in ischemic stroke with unknown or suspected cardiogenic etiology, and evaluate the correlation between IL-10 plasma concentration and the number of diagnosed high risk sources for cardioembolism.

Methods

A total of 141 patients (97 males; mean age 61±11 years) with acute ischemic stroke with unknown etiology or suspected cardiogenic etiology other than known atrial fibrillation (AF) underwent imaging investigations to assess high risk sources for cardioembolic stroke established by the European Association of Echocardiography (EAE). IL-10 was measured on admission to the hospital and on a three month follow-up visit.

Results

Acute phase IL-10 concentration was higher in patients with EAE high risk sources, and correlated with their number (p<0.01). In patients with no risk sources (n = 104), the mean IL-10 concentration was 2.7±3.1 ng/L (range 0.3–16.3 ng/L), with one risk source (n = 26) 3.7±5.5 ng/L (0.3–23.6 ng/L), with two risk sources (n = 10) 7.0±10.0 ng/L (1.29–34.8 ng/L) and with three risk sources (n = 1) 37.2 ng/L. IL-10 level was not significantly associated with cerebral infarct volume, presence of previous or recent myocardial infarction, carotid/vertebral artery atherosclerosis, paroxysmal AF registered on 24-hour ECG Holter monitoring or given intravenous thrombolytic treatment.

Conclusion

IL-10 plasma concentration correlates independently with the number of EAE cardioembolic risk sources in patients with acute stroke. IL-10 may have potential to improve differential diagnostics of stroke with unknown etiology.     

Tricholoma matsutake dominates diverse microbial communities in different forest soils

Fungal and actinobacterial communities were analyzed together with soil chemistry and enzyme activities in order to profile the microbial diversity associated with the economically important mushroom Tricholoma matsutake. Samples of mycelium-soil aggregation (shiro) were collected from three experimental sites where sporocarps naturally formed. PCR was used to confirm the presence and absence of matsutake in soil samples. PCR-denaturing gradient gel electrophoresis (DGGE) fingerprinting and direct sequencing were used to identify fungi and actinobacteria in the mineral and organic soil layers separately. Soil enzyme activities and hemicellulotic carbohydrates were analyzed in a productive experimental site. Soil chemistry was investigated in both organic and mineral soil layers at all three experimental sites. Matsutake dominated in the shiro but also coexisted with a high diversity of fungi and actinobacteria. Tomentollopsis sp. in the organic layer above the shiro and Piloderma sp. in the shiro correlated positively with the presence of T. matsutake in all experimental sites. A Thermomonosporaceae bacterium and Nocardia sp. correlated positively with the presence of T. matsutake, and Streptomyces sp. was a common cohabitant in the shiro, although these operational taxonomic units (OTUs) did not occur at all sites. Significantly higher enzyme activity levels were detected in shiro soil. These enzymes are involved in the mobilization of carbon from organic matter decomposition. Matsutake was not associated with a particular soil chemistry compared to that of nearby sites where the fungus does not occur. The presence of a significant hemicellulose pool and the enzymes to degrade it indicates the potential for obtaining carbon from the soil rather than tree roots.     

Evidence for the role of the oxygen-evolving manganese complex in photoinhibition of Photosystem II

Photoinhibition of PSII occurs at the same quantum efficiency from very low to very high light, which raises a question about how important is the rate of photosynthetic electron transfer in photoinhibition. We modulated electron transfer rate and light intensity independently of each other in lincomycin-treated pea leaves and in isolated thylakoids, in order to elucidate the specific effects of light and PSII electron transport on photoinhibition. Major changes in the rate of electron transport caused only small changes in the rate of photoinhibition, suggesting the existence of a significant photoinhibitory pathway that contains an electron-transfer-independent phase. We compared the action spectrum of photoinhibition with absorption spectra of PSII components that could function as photoreceptors of the electron-transfer-independent phase of photoinhibition and found that the absorption spectra of Mn(III) and Mn(IV) compounds resemble the action spectrum of photoinhibition, showing a steep decrease from UV-C to blue light and a low visible-light tail. Our results show that the release of a Mn ion to the thylakoid lumen is the earliest detectable step of both UV- and visible-light-induced photoinhibition. After Mn release from the oxygen-evolving complex, oxidative damage to the PSII reaction center occurs because the Mn-depleted oxygen-evolving complex cannot reduce P680+ normally.     

Morphological and Volumetric Analysis of Left Atrial Appendage and Left Atrium: Cardiac Computed Tomography-Based Reproducibility Assessment

Objectives

Left atrial appendage (LAA) dilatation and morphology may influence an individual''s risk for intracardiac thrombi and ischemic stroke. LAA size and morphology can be evaluated using cardiac computed tomography (cCT). The present study evaluated the reproducibility of LAA volume and morphology assessments.

Methods

A total of 149 patients (47 females; mean age 60.9±10.6 years) with suspected cardioembolic stroke/transient ischemic attack underwent cCT. Image quality was rated based on four categories. Ten patients were selected from each image quality category (N = 40) for volumetric reproducibility analysis by two individual readers. LAA and left atrium (LA) volume were measured in both two-chamber (2CV) and transversal view (TV) orientation. Intertechnique reproducibility was assessed between 2CV and TV (200 measurement pairs). LAA morphology (A = Cactus, B = ChickenWing, C = WindSock, D = CauliFlower), LAA opening height, number of LAA lobes, trabeculation, and orientation of the LAA tip was analysed in all study subjects by three individual readers (447 interobserver measurement pairs). The reproducibility of volume measurements was assessed by intra-class correlation (ICC) and the reproducibility of LAA morphology assessments by Cohen''s kappa.

Results

The intra-observer and interobserver reproducibility of LAA and LA volume measurements was excellent (ICCs>0.9). The LAA (ICC = 0.954) and LA (ICC = 0.945) volume measurements were comparable between 2CV and TV. Morphological classification (ĸ = 0.24) and assessments of LAA opening height (ĸ = 0.1), number of LAA lobes (ĸ = 0.16), trabeculation (ĸ = 0.15), and orientation of the LAA tip (ĸ = 0.37) was only slightly to fairly reproducible.

Conclusions

LA and LAA volume measurements on cCT provide excellent reproducibility, whereas visual assessment of LAA morphological features is challenging and results in unsatisfactory agreement between readers.     

Recombination Enhances HIV-1 Envelope Diversity by Facilitating the Survival of Latent Genomic Fragments in the Plasma Virus Population

HIV-1 is subject to immune pressure exerted by the host, giving variants that escape the immune response an advantage. Virus released from activated latent cells competes against variants that have continually evolved and adapted to host immune pressure. Nevertheless, there is increasing evidence that virus displaying a signal of latency survives in patient plasma despite having reduced fitness due to long-term immune memory. We investigated the survival of virus with latent envelope genomic fragments by simulating within-host HIV-1 sequence evolution and the cycling of viral lineages in and out of the latent reservoir. Our model incorporates a detailed mutation process including nucleotide substitution, recombination, latent reservoir dynamics, diversifying selection pressure driven by the immune response, and purifying selection pressure asserted by deleterious mutations. We evaluated the ability of our model to capture sequence evolution in vivo by comparing our simulated sequences to HIV-1 envelope sequence data from 16 HIV-infected untreated patients. Empirical sequence divergence and diversity measures were qualitatively and quantitatively similar to those of our simulated HIV-1 populations, suggesting that our model invokes realistic trends of HIV-1 genetic evolution. Moreover, reconstructed phylogenies of simulated and patient HIV-1 populations showed similar topological structures. Our simulation results suggest that recombination is a key mechanism facilitating the persistence of virus with latent envelope genomic fragments in the productively infected cell population. Recombination increased the survival probability of latent virus forms approximately 13-fold. Prevalence of virus with latent fragments in productively infected cells was observed in only 2% of simulations when we ignored recombination, while the proportion increased to 27% of simulations when we allowed recombination. We also found that the selection pressures exerted by different fitness landscapes influenced the shape of phylogenies, diversity trends, and survival of virus with latent genomic fragments. Our model predicts that the persistence of latent genomic fragments from multiple different ancestral origins increases sequence diversity in plasma for reasonable fitness landscapes.     

Moving through Life-Space Areas and Objectively Measured Physical Activity of Older People

Objectives

Physical activity–an important determinant of health and function in old age–may vary according to the life-space area reached. Our aim was to study how moving through greater life-space areas is associated with greater physical activity of community-dwelling older people. The association between objectively measured physical activity and life-space area reached on different days by the same individual was studied using one-week longitudinal data, to provide insight in causal relationships.

Methods

One-week surveillance of objectively assessed physical activity of community-dwelling 70–90-year-old people in central Finland from the “Life-space mobility in old age” cohort substudy (N = 174). In spring 2012, participants wore an accelerometer for 7 days and completed a daily diary including the largest life-space area reached (inside home, outside home, neighborhood, town, and beyond town). The daily step count, and the time in moderate (incl. walking) and low activity and sedentary behavior were assessed. Differences in physical activity between days on which different life-space areas were reached were tested using Generalized Estimation Equation models (within-group comparison).

Results

Participants’ mean age was 80.4±4.2 years and 63.5% were female. Participants had higher average step counts (p < .001) and greater moderate and low activity time (p < .001) on days when greater life-space areas were reached, from the home to the town area. Only low activity time continued to increase when moving beyond the town.

Conclusion

Community-dwelling older people were more physically active on days when they moved through greater life-space areas. While it is unknown whether physical activity was a motivator to leave the home, intervention studies are needed to determine whether facilitation of daily outdoor mobility, regardless of the purpose, may be beneficial in terms of promoting physical activity.     

New and classic families of secreted fungal heme peroxidases

Heme-containing peroxidases secreted by fungi are a fascinating group of biocatalysts with various ecological and biotechnological implications. For example, they are involved in the biodegradation of lignocelluloses and lignins and participate in the bioconversion of other diverse recalcitrant compounds as well as in the natural turnover of humic substances and organohalogens. The current review focuses on the most recently discovered and novel types of heme-dependent peroxidases, aromatic peroxygenases (APOs), and dye-decolorizing peroxidases (DyPs), which catalyze remarkable reactions such as peroxide-driven oxygen transfer and cleavage of anthraquinone derivatives, respectively, and represent own separate peroxidase superfamilies. Furthermore, several aspects of the “classic” fungal heme-containing peroxidases, i.e., lignin, manganese, and versatile peroxidases (LiP, MnP, and VP), phenol-oxidizing peroxidases as well as chloroperoxidase (CPO), are discussed against the background of recent scientific developments.