Deep Molecular Characterization of HIV-1 Dynamics under Suppressive HAART

In order to design strategies for eradication of HIV-1 from infected individuals, detailed insight into the HIV-1 reservoirs that persist in patients on suppressive antiretroviral therapy (ART) is required. In this regard, most studies have focused on integrated (proviral) HIV-1 DNA forms in cells circulating in blood. However, the majority of proviral DNA is replication-defective and archival, and as such, has limited ability to reveal the dynamics of the viral population that persists in patients on suppressive ART. In contrast, extrachromosomal (episomal) viral DNA is labile and as a consequence is a better surrogate for recent infection events and is able to inform on the extent to which residual replication contributes to viral reservoir maintenance. To gain insight into the diversity and compartmentalization of HIV-1 under suppressive ART, we extensively analyzed longitudinal peripheral blood mononuclear cells (PBMC) samples by deep sequencing of episomal and integrated HIV-1 DNA from patients undergoing raltegravir intensification. Reverse-transcriptase genes selectively amplified from episomal and proviral HIV-1 DNA were analyzed by deep sequencing 0, 2, 4, 12, 24 and 48 weeks after raltegravir intensification. We used maximum likelihood phylogenies and statistical tests (AMOVA and Slatkin-Maddison (SM)) in order to determine molecular compartmentalization. We observed low molecular variance (mean variability ≤0.042). Although phylogenies showed that both DNA forms were intermingled within the phylogenetic tree, we found a statistically significant compartmentalization between episomal and proviral DNA samples (P<10−6 AMOVA test; P = 0.001 SM test), suggesting that they belong to different viral populations. In addition, longitudinal analysis of episomal and proviral DNA by phylogeny and AMOVA showed signs of non-chronological temporal compartmentalization (all comparisons P<10−6) suggesting that episomal and proviral DNA forms originated from different anatomical compartments. Collectively, this suggests the presence of a chronic viral reservoir in which there is stochastic release of infectious virus and in which there are limited rounds of de novo infection. This could be explained by the existence of different reservoirs with unique pharmacological accessibility properties, which will require strategies that improve drug penetration/retention within these reservoirs in order to minimise maintenance of the viral reservoir by de novo infection

Life-Cycle Switching and Coexistence of Species with No Niche Differentiation

The increasing evidence of coexistence of cryptic species with no recognized niche differentiation has called attention to mechanisms reducing competition that are not based on niche-differentiation. Only sex-based mechanisms have been shown to create the negative feedback needed for stable coexistence of competitors with completely overlapping niches. Here we show that density-dependent sexual and diapause investment can mediate coexistence of facultative sexual species having identical niches. We modelled the dynamics of two competing cyclical parthenogens with species-specific density-dependent sexual and diapause investment and either equal or different competitive abilities. We show that investment in sexual reproduction creates an opportunity for other species to invade and become established. This may happen even if the invading species is an inferior competitor. Our results suggests a previously unnoticed mechanism for species coexistence and can be extended to other facultative sexual species and species investing in diapause where similar density-dependent life-history switches could act to promote coexistence

Diapause as escape strategy to exposure to toxicants: response of Brachionus calyciforus to arsenic

Invertebrate organisms commonly respond to environmental fluctuation by entering diapause. Production of diapause in monogonont rotifers involves a previous switch from asexual to partial sexual reproduction. Although zooplankton have been used in ecotoxicological assays, often their true vulnerability to toxicants is underestimated by not incorporating the sexual phase. We experimentally analyzed traits involved in sexual reproduction and diapause in the cyclically parthenogenetic freshwater rotifer, Brachionus calyciflorus, exposed to arsenic, a metalloid naturally found in high concentrations in desert zones, focusing on the effectiveness of diapause as an escape response in the face of an adverse condition. Addition of sublethal concentrations of arsenic modified the pattern of diapause observed in the rotifer: investment in diapause with arsenic addition peaked earlier and higher than in non-toxicant conditions, which suggests that sexual investment could be enhanced in highly stressed environmental conditions by increased responsiveness to stimulation. Nevertheless, eggs produced in large amount with arsenic, were mostly low quality, and healthy-looking eggs had lower hatching success, therefore it is unclear whether this pattern is optimum in an environment with arsenic, or if rather arsenic presence in water bodies disturbs the optimal allocation of offspring entering diapause. We observed high accumulation of arsenic in organisms exposed to constant concentration after several generations, which suggests that arsenic may be accumulated transgenerationally. The sexual phase in rotifers may be more sensitive to environmental conditions than the asexual one, therefore diapause attributes should be considered in ecotoxicological assessment because of its ecological and evolutionary implications on lakes biodiversity

DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology

Confluence and Convergence in Probabilistically Terminating Reduction Systems

Convergence of an abstract reduction system (ARS) is the property that any derivation from an initial state will end in the same final state, a.k.a. normal form. We generalize this for probabilistic ARS as almost-sure convergence, meaning that the normal form is reached with probability one, even if diverging derivations may exist. We show and exemplify properties that can be used for proving almost-sure convergence of probabilistic ARS, generalizing known results from ARS.Comment: Pre-proceedings paper presented at the 27th International Symposium on Logic-Based Program Synthesis and Transformation (LOPSTR 2017), Namur, Belgium, 10-12 October 2017 (arXiv:1708.07854

Modes, mechanisms and evidence of bet hedging in rotifer diapause traits

In this contribution, we review our knowledge on bet-hedging strategies associated with rotifer diapause. First, we describe the ecological scenario under which bet hedging is likely to have evolved in three diapause-related traits in monogonont rotifer populations: (1) the timing of sex (because diapausing eggs are produced via sexual reproduction), (2) the sexual reproduction ratio (i.e. the fraction of sexually reproducing females) and (3) the timing of diapausing egg hatching. Then, we describe how to discriminate among bet-hedging modes and discuss which modes and mechanisms better fit the variability observed in these traits in rotifers. Finally, we evaluate the strength of the empirical evidence for bet hedging in the scarce studies available, and we call for the need of research at different levels of biological complexity to fully understand bet hedging in rotifer diapause

Modelling India’s coal production with a negatively skewed curve-fitting model

India’s coal demand is forecast to increase at a rapid pace in the future due to the country’s economic and population growth. Analyzing the scope for future production of India’s domestic coal resources, therefore, plays a vital role in the country’s development of sound energy policies. This paper presents a quantitative scenario analysis of India’s potential future coal production by using a negatively skewed curve-fitting model and a range of estimates of the country’s ultimately recoverable resources (URR) of coal. The results show that the resource base is sufficient for India’s coal production to keep increasing over the next few decades, to reach between 2400 and 3200 Mt/y at 2050, depending on the assumed value of URR. A further analysis shows that the high end of this range, which corresponds to our ‘GSI’ scenario, can be considered as the probable upper-bound to India’s domestic coal production. Comparison of production based on the ‘GSI’ scenario with India’s predicted demand shows that the domestic production of coal will be insufficient to meet the country’s rising coal demand, with the gap between demand and production increasing from its current value of about 268 Mt/y to reach 300 Mt/y in 2035, and 700 Mt/y by 2050. This increasing gap will be challenging for the energy security of India

Reconstructing charge-carrier dynamics in porous silicon membranes from time-resolved interferometric measurements

We performed interferometric time-resolved simultaneous reflectance and transmittance measurements to investigate the carrier dynamics in pump-probe experiments on thin porous silicon membranes. The experimental data was analysed by using a method built on the Wentzel-Kramers-Brillouin approximation and the Drude model, allowing us to reconstruct the excited carriers’ non-uniform distribution in space and its evolution in time. The analysis revealed that the carrier dynamics in porous silicon, with ~50% porosity and native oxide chemistry, is governed by the Shockley-Read-Hall recombination process with a characteristic time constant of 375 picoseconds, whereas diffusion makes an insignificant contribution as it is suppressed by the high rate of scattering

Can Geographical Factors Determine the Choices of Farmers in the Ethiopian Highlands to Trade in Livestock Markets?

Proximity and affiliation to the local market appear to be two of the most relevant factors to explain farmer's choices to select a particular trading point. Physical barriers may limit the options , especially in developing countries. A network of villages linked by traders/farmer-traders sharing livestock markets was built with field data collected in 75 villages from 8 kebelles in the Wassona Werna wereda of the Ethiopian Highlands. Two exponential random graph models were fitted with various geographical and demographic attributes of the nodes (dyadic independent model) and three internal network structures (dyadic dependent model). Several diagnostic methods were applied to assess the goodness of fit of the models. The odds of an edge where the distance to the main market Debre Behran and the difference in altitude between two connected villages are both large increases significantly so that villages far away from the main market and at different altitude are more likely to be linked in the network than randomly. The odds of forming an edge between two villages in Abamote or Gudoberet kebelles are approximately 75% lower than an edge between villages in any other kebelles (p<0.05). The conditional log-odds of two villages forming a tie that is not included in a triangle, a 2-star or a 3-star is extremely low, increasing the odds significantly (p<0.05) each time a node is in a 2-star structure and decreasing it when a node is in a 3-star (p<0.05) or in a triangle formation (p<0.05)), conditional on the rest of the network. Two major constraining factors, namely distance and altitude, are not deterrent for the potential contact of susceptible small ruminant populations in the Highlands of Ethiopia

Effect of female aging on the morphology and hatchability of resting eggs in the rotifer Brachionus plicatilis Müller

This study examined the morphology and hatchability of Brachionus plicatilis resting eggs as a function of the aging of maternal fertilized mictic females. One-hundred twenty fertilized B. plicatilis (Australian strain) were individually cultured and monitored daily until death. All cultures were maintained at 25°C, 11 ppt, and fed the micro-algae Tetraselmis tetrathele. Resting eggs produced by the females were investigated using two parameters: egg morphology, and hatching rate. Under these culture conditions, females normally produce 1-6 (mean ± SD = 2.7 ± 1.2) resting eggs during their lifetime. However, the number of resting eggs with abnormal morphology increased as a function of maternal age. Among resting eggs with normal morphology (n = 225), 82.2% were produced during the first and second spawning, and had hatching rates of more than 60%, while the hatching rates were below 30% in resting eggs with a spawning order of >2. Thus, the quality of B. plicatilis resting eggs was negatively correlated with maternal age