Multiple origins of a frameshift insertion in a mitochondrial gene in birds and turtles

BACKGROUND: During evolutionary history, molecular mechanisms have emerged to cope with deleterious mutations. Frameshift insertions in protein-coding sequences are extremely rare because they disrupt the reading frame. There are a few known examples of their correction through translational frameshifting, a process that enables ribosomes to skip nucleotides during translation to regain proper reading frame. Corrective frameshifting has been proposed to act on the single base pair insertion at position 174 of the mitochondrial NADH dehydrogenase subunit 3 gene (ND3) that has been observed in several turtles and birds. However, the relatively sparse taxonomic representation has hampered our understanding of the evolution of this insertion in vertebrates. RESULTS: Here, we analyzed 87,707 ND3 sequences from 10,309 vertebrate taxa to reveal the evolutionary history of this insertion and its common genomic characteristics. We confirmed that the insertion only appears in turtles and birds and reconstructed that it evolved independently in both groups with complex patterns of gains and losses. The insertion was observed in almost all bird orders but was absent in all members of the diverse Passeriformes. We found strong conservation in the nucleotides surrounding the insertion in both turtles and birds, which implies that the insertion enforces structural constraints that could be involved in its correction. CONCLUSIONS: Our study demonstrates that frameshifts can be widespread and can be retained for millions of years if they are embedded in a conserved sequence theme

Gut microbiome and bile acids in obesity-related diseases

Dysbiosis has been implemented in the etiologies of obesity-related chronic diseases such as type 2 diabetes, NAFLD and cardiovascular diseases. Bile acids, a class of amphipathic steroids produced in the liver and extensively modified by the microbiome, are increasingly recognized as actors in onset and progression of these diseases. Indeed, human obesity is associated with altered bile acid metabolism. Bile acids facilitate intestinal fat absorption but also exert hormone-like functions through activation of nuclear and membrane-bound receptors and thereby modulate glucose, lipid and energy metabolism, intestinal integrity and immunity. Bile acid signaling pathways have thus been identified as potential pharmacological targets for obesity-related diseases. Interfering with micro biome composition may also be considered, as liver-and microbiomederived bile acid species have different signaling functions. This review summarizes recent developments in this rapidly expanding field of research and addresses potential clinical prospects of interference with bile acid signaling pathways in human diseases. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/)

A Benchmark of Genetic Variant Calling Pipelines Using Metagenomic Short-Read Sequencing

Microbes live in complex communities that are of major importance for environmental ecology, public health, and animal physiology and pathology. Short-read metagenomic shotgun sequencing is currently the state-of-the-art technique for exploring these communities. With the aid of metagenomics, our understanding of the microbiome is moving from composition toward functionality, even down to the genetic variant level. While the exploration of single-nucleotide variation in a genome is a standard procedure in genomics, and many sophisticated tools exist to perform this task, identification of genetic variation in metagenomes remains challenging. Major factors that hamper the widespread application of variant-calling analysis include low-depth sequencing of individual genomes (which is especially significant for the microorganisms present in low abundance), the existence of large genomic variation even within the same species, the absence of comprehensive reference genomes, and the noise introduced by next-generation sequencing errors. Some bioinformatics tools, such as metaSNV or InStrain, have been created to identify genetic variants in metagenomes, but the performance of these tools has not been systematically assessed or compared with the variant callers commonly used on single or pooled genomes. In this study, we benchmark seven bioinformatic tools for genetic variant calling in metagenomics data and assess their performance. To do so, we simulated metagenomic reads to mimic human microbial composition, sequencing errors, and genetic variability. We also simulated different conditions, including low and high depth of coverage and unique or multiple strains per species. Our analysis of the simulated data shows that probabilistic method-based tools such as HaplotypeCaller and Mutect2 from the GATK toolset show the best performance. By applying these tools to longitudinal gut microbiome data from the Human Microbiome Project, we show that the genetic similarity between longitudinal samples from the same individuals is significantly greater than the similarity between samples from different individuals. Our benchmark shows that probabilistic tools can be used to call metagenomes, and we recommend the use of GATK's tools as reliable variant callers for metagenomic samples

Oral Microbiome in Relation to Periodontitis Severity and Systemic Inflammation

Systemic inflammation induced by periodontitis is suggested to be the link between periodontitis and cardiovascular disease. The aim of this work was to explore the oral microbiome in periodontitis in relation to disease severity and systemic inflammation. The saliva and subgingival microbiome from periodontal pocket samples of patients with severe (n = 12) and mild periodontitis (n = 13) were analyzed using metagenomic shotgun sequencing. The taxa and pathways abundances were quantified. The diversity was assessed and the abundances to phenotype associations were performed using ANCOM and linear regression. A panel of inflammatory markers was measured in blood and was associated with taxa abundance. The microbial diversity and species richness did not differ between severe and mild periodontitis in either saliva or periodontal pockets. However, there were significant differences in the microbial composition between severe and mild periodontitis in the subgingival microbiome (i.e., pocket samples) and, in a lower grade, in saliva, and this is positively associated with systemic inflammatory markers. The “red complex” and “cluster B” abundances in periodontal pockets were strongly associated with inflammatory markers interleukin-6 and the white blood cell count. Our data suggest that systemic inflammation in severe periodontitis may be driven by the oral microbiome and may support the indirect (inflammatory) mechanism for the association between periodontitis and cardiovascular disease

Selective enrichment of founding reproductive microbiomes allows extensive vertical transmission in a fungus-farming termite

Mutualistic coevolution can be mediated by vertical transmission of symbionts between host generations. Termites host complex gut bacterial communities with evolutionary histories indicative of mixed-mode transmission. Here, we document that vertical transmission of gut bacterial strains is congruent across parent to offspring colonies in four pedigrees of the fungus-farming termite Macrotermes natalensis. We show that 44% of the offspring colony microbiome, including more than 80 bacterial genera and pedigree-specific strains, are consistently inherited. We go on to demonstrate that this is achieved because colony-founding reproductives are selectively enriched with a set of non-random, environmentally sensitive and termite-specific gut microbes from their colonies of origin. These symbionts transfer to offspring colony workers with high fidelity, after which priority effects appear to influence the composition of the establishing microbiome. Termite reproductives thus secure transmission of complex communities of specific, co-evolved microbes that are critical to their offspring colonies. Extensive yet imperfect inheritance implies that the maturing colony benefits from acquiring environmental microbes to complement combinations of termite, fungus and vertically transmitted microbes; a mode of transmission that is emerging as a prevailing strategy for hosts to assemble complex adaptive microbiomes. </p

Genetic, parental and lifestyle factors influence telomere length

The average length of telomere repeats (TL) declines with age and is considered to be a marker of biological ageing. Here, we measured TL in six blood cell types from 1046 individuals using the clinically validated Flow-FISH method. We identified remarkable cell-type-specific variations in TL. Host genetics, environmental, parental and intrinsic factors such as sex, parental age, and smoking are associated to variations in TL. By analysing the genome-wide methylation patterns, we identified that the association of maternal, but not paternal, age to TL is mediated by epigenetics. Single-cell RNA-sequencing data for 62 participants revealed differential gene expression in T-cells. Genes negatively associated with TL were enriched for pathways related to translation and nonsense-mediated decay. Altogether, this study addresses cell-type-specific differences in telomere biology and its relation to cell-type-specific gene expression and highlights how perinatal factors play a role in determining TL, on top of genetics and lifestyle.We thank J. Dekens for management, A. Maatman and M. Platteel for technical support and K. Mc Intyre for English editing. This project was funded by the BBMRI grant for measuring telomere length and by a Rosalind Franklin Fellowship to A.Z. The researchers participated in this project are supported by Netherlands Heart Foundation (IN-CONTROL CVON grants 2012-03 and 2018-27); the Netherlands Organization for Scientific Research (NWO) Gravitation Netherlands Organ-on-Chip Initiative to J.F. and C.W.; NWO Gravitation Exposome-NL (024.004.017) to J.F., A.K. and A.Z.; NWO-VIDI (864.13.013) and NWO-VICI (VI.C.202.022) to J.F.; NWO-VIDI (016.178.056) to A.Z.; NWO-VIDI (917.14.374) to L.F.; NWO-VENI (194.006) to D.V.Z.; NWO-VENI (192.029) to M.W.; NWO Spinoza Prize SPI 92–266 to C.W.; the European Research Council (ERC) (FP7/2007–2013/ERC Advanced Grant 2012-322698) to C.W.; ERC Starting grant 637640 to L.F.; ERC Starting Grant 715772 to A.Z.; ERC Consolidator Grant (grant agreement No. 101001678) to J.F.; and RuG Investment Agenda Grant Personalized Health to C.W. MM work is supported by RYC- 2017-22249 and PID2019-107937GA-I00 grants. T.S. holds scholarships from the Junior Scientific Masterclass, University of Groningen[grant no. 17–34]. AR is funded by a Formación Personal Investigador (FPI) grant [grant no. PRE2019-090193]. The Lifelines Biobank initiative has been made possible by a subsidy from the Dutch Ministry of Health, Welfare and Sport; the Dutch Ministry of Economic Affairs; the University Medical Centre Groningen (UMCG, the Netherlands); the University of Groningen and the Northern Provinces of the Netherlands. The authors wish to acknowledge the services of the Lifelines Cohort Study, the contributing research centres delivering data to Lifelines and all the study participants. Finally, we would like to acknowledge the Genomics Coordination Centre (GCC) at the University Medical College Groningen for the HPC support and the MOLGENIS team for the cloud storage of the data associated with this work.Peer Reviewed"Article signat per 16 autors/es: Sergio Andreu-Sánchez, Geraldine Aubert, Aida Ripoll-Cladellas, Sandra Henkelman, Daria V. Zhernakova, Trishla Sinha, Alexander Kurilshikov, Maria Carmen Cenit, Marc Jan Bonder, Lude Franke, Cisca Wijmenga, Jingyuan Fu, Monique G. P. van der Wijst, Marta Melé, Peter Lansdorp & Alexandra Zhernakova"Postprint (published version

Western and carnivorous dietary patterns are associated with greater likelihood of IBD-development in a large prospective population-based cohort

OBJECTIVE: Nutrition plays a role in the development of Crohn's disease (CD) and ulcerative colitis (UC). However, prospective data on nutrition and disease-onset is limited. Here, we analysed dietary patterns and scores to IBD-development in a prospective population-based cohort. DESIGN: We analysed 125,445 participants of whom 224 individuals developed de novo UC and 97 CD over a maximum 14-year follow-up period. Participants answered health-related (also prospectively) and dietary questionnaires (FFQ) at baseline. Principal Component Analysis (PCA) was conducted deriving a-posteriori dietary patterns. Hypotheses-based a-priori dietary scores were also calculated, including the protein score, Healthy Eating Index, LifeLines Diet Score (LLDS) and alternate Mediterranean Diet Score. Logistic regression models were performed between dietary patterns, scores, and IBD-development. RESULTS: PCA identified five dietary patterns. A pattern characterized by high intake of snacks, prepared meals, non-alcoholic beverages, sauces along with low vegetables and fruit consumption was associated with higher likelihood of CD-development (OR: 1.16, 95% CI: 1.03-1.30, p=0.013). A pattern comprising red meat, poultry, and processed meat, was associated with increased likelihood of UC-development (OR: 1.11, 95% CI: 1.01-1.20, p=0.023). A high diet quality score (LLDS) was associated with decreased risk of CD (OR: 0.95, 95% CI: 0.92-0.99, p=0.009). CONCLUSIONS: A Western dietary pattern was associated with a greater likelihood of CD-development and a carnivorous pattern with UC-development, while a relatively high diet quality (LLDS) was protective for CD-development. Our study strengthens the importance of evaluating dietary patterns to aid prevention of IBD in the general population

HRFlexToT: A High Dynamic Range ASIC for Time-of-Flight Positron Emission Tomography

Time-of-Flight positron emission tomography scanners demand fast and efficient photo sensors and scintillators coupled to fast readout electronics. This article presents the high resolution flexible Time-over-Threshold (HRFlexToT), a 16-channel application-specific-integrated circuit for silicon photomultipliers (SiPM) anode readout manufactured using XFAB 0.18- \mu \text{m} CMOS technology. The main features of the HRFlexToT are a linear Time-over-Threshold with an extended dynamic range (10 bits) for energy measurement, low power consumption (≈ 3.5 mW/ch), and an excellent timing response. The experimental measurements show an energy linearity error of ≈ 3% and an energy resolution of about 12% at 511 keV. Single-photon time resolution measurements performed using an Fondazione Bruno Kessler (FBK) SiPM NUV-HD ( 4 \times 4 mm2 pixel, 40- \mu \text{m} cell) and a Hamamatsu SiPM S13360-3050CS are around 142 and 167 ps full width at half maximum (FWHM), respectively. Coincidence time resolution (CTR) measurements with small cross-section pixelated crystals (LSO:Ce,Ca 0.4%, 2 \times 2 \times 5 mm3) coupled to the same Hamamatsu S13360-3050CS and FBK NUV-HD sensors yield a CTR of 117 ps and 119 ps, respectively. Measurements performed with a large cross-section monolithic crystal (LFS crystal measuring 25 \times 25 \times 20 mm3) and a Hamamatsu SiPM array S13361-6050NE-04 show a CTR of 324 ps FWHM after time-walk and time-skew correction

Karst: a very diverse concept

La gran diversidad intrínseca del karst y la variedad de campos científicos desde los que ha sido estudiado este medio ha generado un espectacular aumento de su conocimiento. Ese avance ha venido acompañado también de nuevas incógnitas y nuevos planteamientos. El presente trabajo trata de recoger una pequeña muestra de esa amplia diversidad, asociada a un elevado grado de especialización, que de forma integrada permite completar el puzzle del karst. Inicialmente, se presenta una revisión sintética del concepto de karst, del proceso de karstificación y de las morfologías asociadas al mismo. Seguidamente, y planteado a partir de una serie de interrogantes, se muestran algunos aspectos y curiosidades relacionadas con el karst. Las características microclimáticas subterráneas, el karst no tradicional o los depósitos y mineralizaciones asociados al karst, son algunos de los temas que se incluyen en este trabajo y que puede interesar a los docentes que imparten docencia sobre el karst.The great intrinsic diversity of karst and the variety of scientific fields in which it has been studied has generated a dramatic increase in our knowledge about it. This advance has also been accompanied by new questions and issues that open the door to new approaches. Our work intends to show a small sample of the wide diversity, often associated with a high degree of specialization, which allows completing the karst puzzle. In the first place, this paper provides a synthetic review of the concept of karst, the karstification process and the morphologies associated with it. Next, starting with a few questions, it shows some aspects and curiosities related to karst. The features of the underground microclimate, the non-traditional karst or deposits and mineralization associated with karst, are some of the topics included in this work, which can be interesting for the teachers dealing with the topic of karst in their classes