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2022 ◽  
Claire M&eacuterot ◽  
Kristina S R Stenl&oslashkk ◽  
Clare Venney ◽  
Martin Laporte ◽  
Michel Moser ◽  

The parallel evolution of nascent pairs of ecologically differentiated species offers an opportunity to get a better glimpse at the genetic architecture of speciation. Of particular interest is our recent ability to consider a wider range of genomic variants, not only single-nucleotide polymorphisms (SNPs), thanks to long-read sequencing technology. We can now identify structural variants (SVs) like insertions, deletions, and other structural rearrangements, allowing further insights into the genetic architecture of speciation and how different variants are involved in species differentiation. Here, we investigated genomic patterns of differentiation between sympatric species pairs (Dwarf and Normal) belonging to the Lake Whitefish (Coregonus clupeaformis) species complex. We assembled the first reference genomes for both Dwarf and Normal Lake Whitefish, annotated the transposable elements, and analysed the genome in the light of related coregonid species. Next, we used a combination of long-read and short-read sequencing to characterize SVs and genotype them at population-scale using genome-graph approaches, showing that SVs cover five times more of the genome than SNPs. We then integrated both SNPs and SVs to investigate the genetic architecture of species differentiation in two different lakes and highlighted an excess of shared outliers of differentiation. In particular, a large fraction of SVs differentiating the two species was driven by transposable elements (TEs), suggesting that TE accumulation during a period of allopatry predating secondary contact may have been a key process in the speciation of the Dwarf and Normal Whitefish. Altogether, our results suggest that SVs play an important role in speciation and that by combining second and third generation sequencing we now have the ability to integrate SVs into speciation genomics.

2022 ◽  
Soumyanetra Chandra ◽  
Kritika Gupta ◽  
Shruti Khare ◽  
Pehu Kohli ◽  
Aparna Asok ◽  

Deep mutational scanning studies suggest that single synonymous mutations are typically silent and that most exposed, non active-site residues are tolerant to mutations. Here we show that the ccdA antitoxin component of the E.coli ccdAB toxin-antitoxin operonic system is unusually sensitive to mutations when studied in the operonic context. A large fraction (~80%) of single codon mutations, including many synonymous mutations in the ccdA gene show inactive phenotypes that are correlated with the E.coli codon usage frequency but retain native-like binding affinity towards cognate toxin, CcdB. Therefore, the observed phenotypic effects are largely not due to alterations in protein structure or stability, consistent with the fact that a large region of CcdA is intrinsically disordered. In select cases, proteomics studies reveal altered ratios of CcdA:CcdB protein levels in vivo, suggesting that these mutations likely alter relative translation efficiencies of the two genes in the operon. We extend these results by predicting and validating single synonymous mutations that lead to loss of function phenotypes in the relBE operon upon introduction of rarer codons. Thus, in their native context, genes are likely to be more sensitive to both synonymous and non-synonymous point mutations than inferred from previous saturation mutagenesis studies.

2022 ◽  
Vol 2022 ◽  
pp. 1-9
Sara Assadpour ◽  
Mohammad Reza Shiran ◽  
Peyman Asadi ◽  
Javad Akhtari ◽  
Amirhossein Sahebkar

Sumatriptan (ST) is a commonly prescribed drug for treating migraine. The efficiency of several routes of ST administration has been investigated. Recently, the intranasal route with different delivery systems has gained interest owing to its fast-acting and effectiveness. The present study is aimed at reviewing the available studies on novel delivery systems for intranasal ST administration. The oral route of ST administration is common but complicated with some problems. Gastroparesis in patients with migraine may reduce the absorption and effectiveness of ST upon oral use. Furthermore, the gastrointestinal (GI) system and hepatic metabolism can alter the pharmacokinetics and clinical effects of ST. The bioavailability of conventional nasal liquids is low due to the deposition of a large fraction of the delivered dose of a drug in the nasal cavity. Several delivery systems have been utilized in a wide range of preclinical and clinical studies to enhance the bioavailability of ST. The beneficial effects of the dry nasal powder of ST (AVP-825) have been proven in clinical studies. Moreover, other delivery systems based on microemulsions, microspheres, and nanoparticles have been introduced, and their higher bioavailability and efficacy were demonstrated in preclinical studies. Based on the extant findings, harnessing novel delivery systems can improve the bioavailability of ST and enhance its effectiveness against migraine attacks. However, further clinical studies are needed to approve the safety and efficacy of employing such systems in humans.

2022 ◽  
Zhen Wu ◽  
Dikla Aharonovich ◽  
Dalit Roth-Rosenberg ◽  
Osnat Weissberg ◽  
Tal Luzzatto-Knaan ◽  

Marine phytoplankton are responsible for about half of the photosynthesis on Earth. Many are mixotrophs, combining photosynthesis with heterotrophic assimilation of organic carbon but the relative contribution of these two carbon sources is not well quantified. Here, single-cell measurements reveal that Prochlorococcus at the base of the photic zone in the Eastern Mediterranean Sea are obtaining only ~20% of carbon required for growth by photosynthesis. Consistently, laboratory-calibrated evaluations of Prochlorococcus photosynthesis indicate that carbon fixation is systematically too low to support published in situ growth rates in the deep photic layer of the Pacific Ocean. Furthermore, agent-based model simulations show that mixotrophic cells maintain realistic growth rates and populations 10s of meters deeper than obligate photo-autotrophs, deepening the nutricline and Deep Chlorophyll Maximum by ~20 m. Time-series of Prochlorococcus ecotype-abundance from the subtropical North Atlantic and North Pacific suggest that up to 30% of the Prochlorococcus cells live where light intensity is not enough to sustain obligate photo-autotrophic populations during warm, stratified periods. Together, these data and models suggest that mixotrophy underpins the ecological success of a large fraction of the global Prochlorococcus population and its collective genetic diversity.

2022 ◽  
Elise Parey ◽  
Alexandra Louis ◽  
Jerome Monfort ◽  
Yann Guiguen ◽  
Hugues Roest Crollius ◽  

Teleost fish are one of the most species-rich and diverse clades amongst vertebrates, which makes them an outstanding model group for evolutionary, ecological and functional genomics. Yet, despite a growing number of sequence reference genomes, large-scale comparative analysis remains challenging in teleosts due to the specifics of their genomic organization. As legacy of a whole genome duplication dated 320 million years ago, a large fraction of teleost genomes remain in duplicate paralogous copies. This ancestral polyploidy confounds the detailed identification of orthologous genomic regions across teleost species. Here, we combine tailored gene phylogeny methodology together with the state-of-the art ancestral karyotype reconstruction to establish the first high resolution comparative atlas of paleopolyploid regions across 74 teleost fish genomes. We show that this atlas represents a unique, robust and reliable resource for fish genomics. We then use the comparative atlas to study the tetraploidization and rediploidization mechanisms that affected the ancestor of teleosts. Although the polyploid history of teleost genomes appears complex, we uncover that meiotic recombination persisted between duplicated chromosomes for over 60 million years after polyploidization, suggesting that the teleost ancestor was an autotetraploid.

2022 ◽  
Robin Halamicek ◽  
Dirk W Schubert ◽  
Fritjof Nilsson

Abstract The ongoing Covid-19 pandemic has already caused more than 5 million casualties despite hard restrictions and relatively high vaccine coverage in many countries. The crucial question is therefore, how large vaccination rate and how severe restrictions are required to terminate the spread of the decease, assuming that the vaccine efficiency and the basic reproduction ratio (R0) are known? To answer this question, a mathematical equation was applied to visualize the required vaccination level as function of vaccine efficiency, restriction efficiency and basic reproduction ratio (R0). In addition to the modelling study, Covid-19 data from Europe was collected during 19/11-26/11 (2021) to assess the relation between vaccination rate and incidence. The analysis indicates that a vaccination rate of ~92% (2 doses) is required to stop Delta (B.1.617.2) without severe restrictions, under conditions like those in Europe late November 2021. A third vaccine dose, improved vaccines, higher vaccination rates and/or stronger restrictions will be required to force Omicron (B.1.1.529) to expire without infecting a large fraction of the population.

2022 ◽  
Vol 5 (1) ◽  
Ole Bunjes ◽  
Lucas A. Paul ◽  
Xinyue Dai ◽  
Hongyan Jiang ◽  
Tobias Claus ◽  

AbstractAtomic scale studies of the anchoring of catalytically active complexes to surfaces may provide valuable insights for the design of new catalytically active hybrid systems. In this work, the self-assembly of 1D, 2D and 3D structures of the complex fac-Re(bpy)(CO)3Cl (bpy = 2,2′-bipyridine), a CO2 reduction catalyst, on the Ag(001) surface are studied by a combination of low-temperature scanning tunneling microscopy and density functional theory calculations. Infrared and sum frequency generation spectroscopy confirm that the complex remains chemically intact under sublimation. Deposition of the complexes onto the silver surface at 300 K leads to strong local variations in the resulting surface coverage on the nanometer scale, indicating that in the initial phase of deposition a large fraction of the molecules is desorbing from the surface. Low coverage regions show a decoration of step edges aligned along the crystal’s symmetry axes <110>. These crystallographic directions are found to be of major importance to the binding of the complexes to the surface. Moreover, the interaction between the molecules and the substrate promotes the restructuring of surface steps along these directions. Well-aligned and decorated steps are found to act as nucleation point for monolayer growth (2D) before 3D growth starts.

2022 ◽  
Hongxing Jiang ◽  
Jun Li ◽  
Jiao Tang ◽  
Min Cui ◽  
Shizhen Zhao ◽  

Abstract. Organosulfur compounds (OrgSs), especially organosulfates, have been widely reported at large quantities in particulate organic matter found in various atmospheric environments. Despite various kinds of organosulfates and their formation mechanisms being previously identified, a large fraction of OrgSs remain unexplained at the molecular level, impeding further knowledge on additional formation pathways and critical environmental parameters that help to explain their concentrations. In this work, the abundance and molecular composition of OrgSs in fine particulate samples collected in Guangzhou was reported. Our results revealed that organic sulfur can averagely contribute to 30 % of total particulate sulfur, and showed positively correlations with the SO2 (r = 0.37, p < 0.05) and oxidants (NOx+O3, r = 0.40, p < 0.01). Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) results presented that more than 80 % by number of the detected OrgSs in our samples have the elemental composition of O/(4S+3N)  ≥ 1, indicating that they were largely in the form of oxidized organosulfates and/or nitrooxy organosulfates. Many OrgSs, which are tentatively attributed to previously identified biogenic and anthropogenic origins, were also present in aerosols derived from freshly-emitted combustion sources. Results show that the formation of OrgSs through an epoxide intermediate pathway could be as much as 46 %, and the oxidants levels could explain 20 % variation of organic sulfur mass. The analysis from our large FT-ICR MS dataset suggests that relative humidity, oxidation of biogenic volatile organic compounds via ozonolysis, and NOx-related nitrooxy organosulfate formations were the major reasons for the molecular variation of OrgSs, possibly highlighting the importance of heterogeneous reactions involving either the uptake of SO2 or the heterogeneous oxidations of particulate organosulfates into additional unrecognized OrgSs.

2022 ◽  
Fulvio Adorni ◽  
Nithiya Jesuthasan ◽  
Elena Perdixi ◽  
Aleksandra Sojic ◽  
Andrea Giacomelli ◽  

Digital technologies have been extensively employed in response to the SARS-CoV-2 pandemic worldwide. This study describes the methodology of the two-phase internet-based EPICOVID19 survey, and the characteristics of the adult volunteers respondents who lived in Italy during the first (April - May 2020) and the second wave (January - February 2021) of the epidemic. Validated scales and ad-hoc questionnaires were used to collect socio-demographic, medical and behavioural characteristics, as well as information on COVID-19. Among those who provided email addresses during phase I (105,355), 41,473 participated in phase II (mean age 50.7 years +/- 13.5 SD, 60.6% females). After a median follow-up of ten months, 52.8% had undergone naso-pharyngeal swab (NPS) testing and 13.2% had positive result. More than 40% had undergone serological test (ST) and 11.9% were positive. Out of the 2,073 participants with at least one positive ST, 72.8% had only negative results from NPS or never performed it. These results indicate that a large fraction of individuals remained undiagnosed, possibly contributing to the spread of the virus in the community. Participatory online surveys offer a unique opportunity to collect relevant data at individual level from large samples during confinement.

2022 ◽  
Athena Lin ◽  
Paul Piehowski ◽  
Chia-Feng Tsai ◽  
Tatyana Makushok ◽  
Lian Yi ◽  

Many individual proteins have been identified as having defined positions relative to cell polarity axes, raising the question of what fraction of all proteins may have polarized localizations. We took advantage of the giant ciliate Stentor coeruleus to quantify the extent of polarized localization proteome-wide. This trumpet-shaped unicellular organism shows a clear morphological anterior-posterior axis defined by a circular array of cilia known as a membranellar band at one end, and a holdfast at the other end. Because individual Stentor cells are over a millimeter in length, we were able to cut the cells into three pieces along the anterior-posterior axis, followed by proteomic analysis of proteins enriched in each piece. We find that approximately 30% of all detected proteins show a polarized location relative to the anterior-posterior cell axis. Proteins with polarized enrichment include centrin-like proteins, calcium-regulated kinases, orthologs of SFI1 and GAS2, and proteases. At the organelle level, nuclear and mitochondrial proteins are enriched in the anterior half of the cell body, but not in the membranellar band itself, while ribosome related proteins are apparently uniformly distributed. RNAi of signaling proteins enriched in the membranellar band, which is the anterior-most structure in the cell, revealed a protein phosphatase 2 subunit b ortholog required for closure of the membranellar band into the ring shape characteristic of Stentor. These results suggest that a large fraction of the Stentor proteome has a polarized localization, and provide a protein-level framework for future analysis of pattern formation and regeneration in Stentor as well as defining a general strategy for subcellular spatial proteomics based on physical dissection of cells.

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