Collective properties of evolving molecular quasispecies

<p>Abstract</p> <p>Background</p> <p>RNA molecules, through their dual appearance as sequence and structure, represent a suitable model to study evolutionary properties of quasispecies. The essential ingredient in this model is the differentiation between genotype (molecular sequences which are affected by mutation) and phenotype (molecular structure, affected by selection). This framework allows a quantitative analysis of organizational properties of quasispecies as they adapt to different environments, such as their robustness, the effect of the degeneration of the sequence space, or the adaptation under different mutation rates and the error threshold associated.</p> <p>Results</p> <p>We describe and analyze the structural properties of molecular quasispecies adapting to different environments both during the transient time before adaptation takes place and in the asymptotic state, once optimization has occurred. We observe a minimum in the adaptation time at values of the mutation rate relatively far from the phenotypic error threshold. Through the definition of a consensus structure, it is shown that the quasispecies retains relevant structural information in a distributed fashion even above the error threshold. This structural robustness depends on the precise shape of the secondary structure used as target of selection. Experimental results available for natural RNA populations are in qualitative agreement with our observations.</p> <p>Conclusion</p> <p>Adaptation time of molecular quasispecies to a given environment is optimized at values of the mutation rate well below the phenotypic error threshold. The optimal value results from a trade-off between diversity generation and fixation of advantageous mutants. The critical value of the mutation rate is a function not only of the sequence length, but also of the specific properties of the environment, in this case the selection pressure and the shape of the secondary structure used as target phenotype. Certain functional motifs of RNA secondary structure that withstand high mutation rates (as the ubiquitous hairpin motif) might appear early in evolution and be actually frozen evolutionary accidents.</p

On the structural repertoire of pools of short, random RNA sequences

A detailed knowledge of the mapping between sequence and structure spaces in populations of RNA molecules is essential to better understand their present-day functional properties, to envisage a plausible early evolution of RNA in a prebiotic chemical environment and to improve the design of in vitro evolution experiments, among others. Analysis of natural RNAs, as well as in vitro and computational studies, show that certain RNA structural motifs are much more abundant than others, pointing out a complex relation between sequence and structure. Within this framework, we have investigated computationally the structural properties of a large pool (10 molecules) of single-stranded, 35 nt-long, random RNA sequences. The secondary structures obtained are ranked and classified into structure families. The number of structures in main families is analytically calculated and compared with the numerical results. This permits a quantification of the fraction of structure space covered by a large pool of sequences. We further show that the number of structural motifs and their frequency is highly unbalanced with respect to the nucleotide composition: simple structures such as stem-loops and hairpins arise from sequences depleted in G, while more complex structures require an enrichment of G. In general, we observe a strong correlation between subfamilies-characterized by a fixed number of paired nucleotides-and nucleotide composition. Our results are compared to the structural repertoire obtained in a second pool where isolated base pairs are prohibited

Orbital and spin magnetic moments of transforming 1D iron inside metallic and semiconducting carbon nanotubes

The orbital and spin magnetic properties of iron inside transforming metallic and semiconducting 1D carbon nanotube hybrids are studied by means of local x-ray magnetic circular dichroism (XMCD) and bulk superconducting quantum interference device (SQUID) measurements. Nanotube hybrids are initially ferrocene filled single-walled carbon nanotubes (SWCNT) of different metallicities. After a high temperature nanochemical reaction ferrocene molecules react with each other to form iron nano clusters. We show that the ferrocenes molecular orbitals interact differently with the SWCNT of different metallicities without significant XMCD response. This XMCD at various temperatures and magnetic fields reveals that the orbital and/or spin magnetic moments of the encapsulated iron are altered drastically as the transformation to 1D Fe nanoclusters takes place. The orbital and spin magnetic moments are both found to be larger in filled semiconducting nanotubes than in the metallic sample. This could mean that the magnetic polarizations of the encapsulated material is dependent on the metallicity of the tubes. From a comparison between the iron 3d magnetic moments and the bulk magnetism measured by SQUID, we conclude that the delocalized magnetisms dictate the magnetic properties of these 1D hybrid nanostructures

Lsh Mediated RNA Polymerase II Stalling at HoxC6 and HoxC8 Involves DNA Methylation

DNA cytosine methylation is an important epigenetic mechanism that is involved in transcriptional silencing of developmental genes. Several molecular pathways have been described that interfere with Pol II initiation, but at individual genes the molecular mechanism of repression remains uncertain. Here, we study the molecular mechanism of transcriptional regulation at Hox genes in dependence of the epigenetic regulator Lsh that controls CpG methylation at selected Hox genes. Wild type cells show a nucleosomal deprived region around the transcriptional start site at methylated Hox genes and mediate gene silencing via Pol II stalling. Hypomethylation in Lsh−/− cells is associated with efficient transcriptional elongation and splicing, in part mediated by the chromodomain protein Chd1. Dynamic modulation of DNA methylation in Lsh−/− and wild type cells demonstrates that catalytically active DNA methyltransferase activity is required for Pol II stalling. Taken together, the data suggests that DNA methylation can be compatible with Pol II binding at selected genes and Pol II stalling can act as alternate mechanism to explain transcriptional silencing associated with DNA methylation

Genome-wide profiling of human cap-independent translation-enhancing elements.

We report an in vitro selection strategy to identify RNA sequences that mediate cap-independent initiation of translation. This method entails mRNA display of trillions of genomic fragments, selection for initiation of translation and high-throughput deep sequencing. We identified &gt;12,000 translation-enhancing elements (TEEs) in the human genome, generated a high-resolution map of human TEE-bearing regions (TBRs), and validated the function of a subset of sequences in vitro and in cultured cells

Efficient HIV-1 inhibition by a 16 nt-long RNA aptamer designed by combining in vitro selection and in silico optimisation strategies

The human immunodeficiency virus type-1 (HIV-1) genome contains multiple, highly conserved structural RNA domains that play key roles in essential viral processes. Interference with the function of these RNA domains either by disrupting their structures or by blocking their interaction with viral or cellular factors may seriously compromise HIV-1 viability. RNA aptamers are amongst the most promising synthetic molecules able to interact with structural domains of viral genomes. However, aptamer shortening up to their minimal active domain is usually necessary for scaling up production, what requires very time-consuming, trial-and-error approaches. Here we report on the in vitro selection of 64 nt-long specific aptamers against the complete 5' -untranslated region of HIV-1 genome, which inhibit more than 75% of HIV-1 production in a human cell line. The analysis of the selected sequences and structures allowed for the identification of a highly conserved 16 nt-long stem-loop motif containing a common 8 nt-long apical loop. Based on this result, an in silico designed 16 nt-long RNA aptamer, termed RNApt16, was synthesized, with sequence 5'-CCCCGGCAAGGAGGGG-3-'. The HIV-1 inhibition efficiency of such an aptamer was close to 85%, thus constituting the shortest RNA molecule so far described that efficiently interferes with HIV-1 replication

Report on the number of births during the COVID-19 pandemic in the Philippines, January 2020 to May 2021

One of the effects of the COVID-19 pandemic in the decrease in the number of births in the country. In 2020, there were 1.53 million registered births, down 8.3% from 2019. There were 117 thousand registered births in December 2020, 18% lower than the same month the previous year. From January to May 2021, there were 461 thousand registered births in the country, down 24% from 2020 and 31% from 2019. Home births increased during the pandemic. On the other hand, births from women aged 20 and below decreased from December 2020 to February 2021. Assuming that current trends continue, projections show that births in 2021 will go down by 521 thousand births. This is equivalent to 1.16 million registered births in 2021, down 24% from 2020

Report on excess deaths associated with the COVID-19 pandemic in the Philippines, January 2020 to May 2021

One of the effects of the COVID-19 pandemic is the increase in the number of excess deaths experienced by the country. From January 2020 to May 2021, the estimated number of excess deaths was 91,024 – around 11% higher than the expected number of deaths under pre-pandemic or "normal" conditions. These excess deaths came from Covid-19 Related Deaths and deaths from all other causes that suddenly increased during the pandemic, such as cardiovascular-related diseases. In particular, a large share of the excess deaths came from the age group 50 years and over and from Luzon, including the National Capital Region. Assuming that the current trends continue, projections show that the excess deaths for the full year 2021 will reach approximately 228,000

Internal migration and the COVID-19 pandemic in the Philippines

The COVID-19 pandemic has created economic disruption in the Philippines, resulting in loss of income for many workers. Because of this, many internal migrants, particularly those who continued to have close ties to their place of origin, returned home. This report investigates internal migrants in the country using preliminary data from the 2020 Census of Population and Housing (CPH) by the Philippine Statistics Authority. While not completely exhaustive, the 2020 CPH may help identify arease where the population has increased or decreased compared to expectations or population projections. Higher-than-expected population is due to relocation of families from danger zones to resettlement areas. Lower-than expected population, on the other hand, is seen areas where natural calamities frequently strike and in urbanized areas usually populated by students and worker residents before the pandemic

Adaptive Coding and Modulation Experiment With NASA's Space Communication and Navigation Testbed

National Aeronautics and Space Administration (NASA)'s Space Communication and Navigation Testbed is an advanced integrated communication payload on the International Space Station. This paper presents results from an adaptive coding and modulation (ACM) experiment over S-band using a direct-to-earth link between the SCaN Testbed and the Glenn Research Center. The testing leverages the established Digital Video Broadcasting Second Generation (DVB-S2) standard to provide various modulation and coding options, and uses the Space Data Link Protocol (Consultative Committee for Space Data Systems (CCSDS) standard) for the uplink and downlink data framing. The experiment was con- ducted in a challenging environment due to the multipath and shadowing caused by the International Space Station structure. Several approaches for improving the ACM system are presented, including predictive and learning techniques to accommodate signal fades. Performance of the system is evaluated as a function of end-to-end system latency (round- trip delay), and compared to the capacity of the link. Finally, improvements over standard NASA waveforms are presented