Biology subjects

Ferrer, M.

Publications and source records attributed to Ferrer, M..

24 records · Page 2Linked to original sources

bioRxiv2020

Meta-analysis of epigenome-wide associations between DNA methylation at birth and childhood cognitive skills.

Cognitive skills are a strong predictor of a wide range of later life outcomes. Genetic and epigenetic associations across the genome explain some of the variation in general cognitive abilities in the general population and it is plausible that epigenetic associations might arise from prenatal environmental exposures and/or genetic variation early in life. We investigated the association between cord blood DNA methylation at birth and cognitive skills assessed in children from eight pregnancy cohorts (N=2196-3798) within the Pregnancy And Childhood Epigenetics (PACE) Consortium across overall, verbal and non-verbal cognitive scores. The associations at single CpG sites were weak for all of the cognitive domains investigated. One region near DUSP22 on chromosome 6 was associated with non-verbal cognition in a model adjusted for maternal IQ. We conclude that there is little evidence to support the idea that cord blood DNA methylation at single CpGs can predict cognitive skills and further studies are needed to confirm regional differences.

developmental biology↗

bioRxiv2020

An OpenData portal to share COVID-19 drug repurposing data in real time

The National Center for Advancing Translational Sciences (NCATS) has developed an online open science platform - named the NCATS OpenData Portal (ODP) - for quickly and freely sharing complete NCATS translational datasets via an open-access, user-friendly interface. This paper describes the establishment of the ODP, initially deployed during the COVID-19 crisis, and provides a detailed analysis of COVID-19 drug repurposing screening datasets that served as the first large-scale use case for the platform. Over 10,000 compounds were tested across 17 quantitative high-throughput assays, covering a wide spectrum of the SARS-CoV-2 life cycle. In total, over 87,000 concentration-response curves and 426,000 data points were made publicly available on ODP in near real-time, enabling immediate access to complete datasets. The resource is flexible in accommodating various types and structures of data, and it has already expanded since its launch to host additional datasets for COVID-19, other viruses of pandemic potential, and beyond. The OpenData Portal has been designed as a scalable platform for real-time data sharing across drug discovery campaigns, regardless of disease area, with the overarching goal of accelerating discovery at NCATS, the NIH, and the greater scientific community.

microbiology↗

bioRxiv2020

Promiscuous esterases counterintuitively are less flexible than specific ones

Understanding mechanisms of promiscuity is increasingly important from a fundamental and application point of view. As to enzyme structural dynamics, more promiscuous enzymes generally have been recognized to also be more flexible. However, examples for the opposite received much less attention. Here, we exploit comprehensive experimental information on the substrate promiscuity of 147 esterases tested against 96 esters together with computationally efficient rigidity analyses to understand the molecular origin of the observed promiscuity range. Unexpectedly, our data reveal that promiscuous esterases are significantly less flexible than specific ones, are significantly more thermostable, and have a significantly increased specific activity. These results may be reconciled with a model according to which structural flexibility in the case of specific esterases serves for conformational proofreading. Our results signify that esterase sequence space can be screened by rigidity analyses for promiscuous esterases as starting points for further exploration in biotechnology and synthetic chemistry.

biophysics↗

bioRxiv2020

Deciphering a marine bone degrading microbiome reveals a complex community effort

The marine bone biome is a complex assemblage of macro- and microorganisms, however the enzymatic repertoire to access bone-derived nutrients remains unknown. The bone matrix is a composite material made up mainly of organic collagen and inorganic hydroxyapatite. We conducted field experiments to study microbial assemblages that can use organic bone components as nutrient source. Bovine and turkey bones were deposited at 69 m depth in a Norwegian fjord (Byfjorden, Bergen). Metagenomic sequence analysis was used to assess the functional potential of microbial assemblages from bone surface and the bone eating worm Osedax mucofloris, which is a frequent colonizer of whale falls and known to degrade bone. The bone microbiome displayed a surprising taxonomic diversity revealed by the examination of 59 high-quality metagenome assembled genomes from at least 23 bacterial families. Over 700 genes encoding enzymes from twelve relevant enzymatic families pertaining to collagenases, peptidases, glycosidases putatively involved in bone degradation were identified. Metagenome assembled genomes (MAGs) of the class Bacteroidia contained the most diverse gene repertoires. We postulate that demineralization of inorganic bone components is achieved by a timely succession of a closed sulfur biogeochemical cycle between sulfur-oxidizing and sulfur-reducing bacteria, causing a drop in pH and subsequent enzymatic processing of organic components in the bone surface communities. An unusually large and novel collagen utilization gene cluster was retrieved from one genome belonging to the gammaproteobacterial genus Colwellia. ImportanceBones are an underexploited, yet potentially profitable feedstock for biotechnological advances and value chains, due to the sheer amounts of residues produced by the modern meat and poultry processing industry. In this metagenomic study we decipher the microbial pathways and enzymes that we postulate to be involved in bone degradation marine environment. We herein demonstrate the interplay between different bacterial community members, each supplying different enzymatic functions with the potential to cover an array of reactions relating to the degradation of bone matrix components. We identify and describe a novel gene cluster for collagen utilization, which is a key function in this unique environment. We propose that the interplay between the different microbial taxa is necessary to achieve the complex task of bone degradation in the marine environment.

microbiology↗

bioRxiv2019

The DNA damage response regulates the oocyte pool in mammals

Mammalian oogonia proliferate without completing cytokinesis producing germ cell cysts. Within these cysts, oocytes differentiate and enter meiosis, promote genome-wide double-strand break (DSBs) formation which repair by homologous recombination leads to synapsis of the homologous chromosomes. Errors in homologous recombination or synapsis trigger the activation of surveillance mechanisms, traditionally called pachytene checkpoint, to either repair them or send the cells to programmed death. Contrary to what is found in spermatocytes, most oocytes present a remarkable persistence of unrepaired DSBs at pachynema. Simultaneously, there is a massive oocyte death accompanying the oocyte cyst breakdown. This oocyte elimination is thought to be required to properly form the follicles, which constitute the pool of germ cells females will use during their adult life. Based on all the above mentioned, we hypothesized that the apparently inefficient meiotic recombination occurring in mouse oocytes may be required to eliminate most of the oocytes in order to regulate the oocyte number, promote cyst breakdown and follicle formation in mammalian females. To test this idea, we analyzed perinatal ovaries to evaluate the oocyte population, cyst breakdown and follicle formation in control and mutant mice for the effector kinase of the DNA damage response, CHK2. Our results confirm the involvement of CHK2 in the elimination of oocytes that accumulate unrepaired DSBs and show that CHK2 regulates the number of oocytes in fetal ovaries. We also show that CHK2 is required to eliminate oocytes as a result of LINE-1 activation, which was previously shown to be responsible for fetal oocyte loss. Nonetheless, the number of oocytes found in Chk2 mutant ovaries three days after birth was similar to that of control ovaries, suggesting the existence of CHK2-independent mechanisms capable of eliminating oocytes. In vitro inhibition of CHK1 rescued the oocyte number in Chk2 mutant ovaries suggesting that CHK1 regulates postnatal oocyte death. Moreover, both CHK1 and CHK2 functions are required to timely breakdown cyst and form follicles. Altogether, we propose the DNA damage response controls the number of oocytes present perinatally and is required to properly break down oocyte cysts and form follicles, highlighting the importance of the DNA damage response in setting the reserve of oocytes each female will use during their entire lifespan.

developmental biology↗

bioRxiv2019

Differential polysaccharide utilization is the basis for a nanohaloarchaeon : haloarchaeon symbiosis.

Nanohaloarchaeota, a clade of diminutive archaea, with small genomes and limited metabolic capabilities, are ubiquitous in hypersaline habitats, which they share with the extremely halophilic and phylogenetically distant euryarchaea. Some of these nanohaloarchaeota and euryarchaea appear to interact with each other. In this study, we investigate the genetic and physiological nature of their relationship. We isolated the nanohaloarchaeon Candidatus Nanohalobium constans LC1Nh and the haloarchaeon Halomicrobium sp. LC1Hm from a solar saltern, reproducibly co-cultivated these species, sequenced their genomes, and characterized their metabolic/trophic interactions. The nanohaloarchaeon is a magnesium-dependent aerotolerant heterotrophic anaerobe of the DPANN superphylum; it lacks respiratory complexes and its energy production relies on fermentative metabolism of sugar derivatives, obtained by depolymerizing alpha-glucans or by acquiring the chitin monomer N-acetylglucosamine from the chitinolytic haloarchaeal host. Halomicrobium is a member of the class Halobacteria and a chitinotrophic aerobe. The nanohaloarchaeon lacks key biosynthetic pathways and is likely to be provided with amino acids, lipids, nucleotides and cofactors via physical contact with its host Halomicrobium. In turn, the ability of Ca. Nanohalobium to hydrolyse alpha-glucans boosts the hosts growth in the absence of a chitin substrate. These findings suggest that at least some members of the nanohaloarchaea, previously considered ecologically unimportant given their limited metabolic potential, in fact may play significant roles in the microbial carbon turnover, food chains, and ecosystem function. The behaviour of Halomicrobium, which accommodates the colonization by Ca. Nanohalobium, can be interpreted as a bet-hedging strategy, maximizing its long-term fitness in a habitat where the availability of carbon substrates can vary both spatially and temporarily.

microbiology↗