Metabolite–Enzyme Coevolution: From Single Enzymes to Metabolic Pathways and Networks

2018 ◽  
Vol 87 (1) ◽  
pp. 187-216 ◽  
Author(s):  
Lianet Noda-Garcia ◽  
Wolfram Liebermeister ◽  
Dan S. Tawfik

How individual enzymes evolved is relatively well understood. However, individual enzymes rarely confer a physiological advantage on their own. Judging by its current state, the emergence of metabolism seemingly demanded the simultaneous emergence of many enzymes. Indeed, how multicomponent interlocked systems, like metabolic pathways, evolved is largely an open question. This complexity can be unlocked if we assume that survival of the fittest applies not only to genes and enzymes but also to the metabolites they produce. This review develops our current knowledge of enzyme evolution into a wider hypothesis of pathway and network evolution. We describe the current models for pathway evolution and offer an integrative metabolite–enzyme coevolution hypothesis. Our hypothesis addresses the origins of new metabolites and of new enzymes and the order of their recruitment. We aim to not only survey established knowledge but also present open questions and potential ways of addressing them.

Author(s):  
Gabriel D. Orebi Gann ◽  
Kai Zuber ◽  
Daniel Bemmerer ◽  
Aldo Serenelli

In this article we review the current state of the field of solar neutrinos, including flavor oscillations, nonstandard effects, solar models, cross section measurements, and the broad experimental program thus motivated and enabled. We describe the historical discoveries that contributed to current knowledge, and define critical open questions to be addressed in the next decade. We discuss standard solar models, including uncertainties and problems related to the solar composition, and review experimental and model solar neutrino fluxes, including future prospects. We review the state of the art of the nuclear reaction data relevant for solar fusion in the proton–proton chain and carbon–nitrogen–oxygen cycle. Finally, we review the current and future experimental programs that can address outstanding questions in this field. Expected final online publication date for the Annual Review of Nuclear and Particle Science, Volume 71 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


The Oxford Handbook of the Auditory Brainstem provides an in-depth reference to the organization and function of ascending and descending auditory pathways in the mammalian brainstem. Individual chapters are organized along the auditory pathway, beginning with the cochlea and ending with the auditory midbrain. Each chapter provides an introduction to the respective area and summarizes our current knowledge before discussing the disputes and challenges that the field currently faces.The handbook emphasizes the numerous forms of plasticity that are increasingly observed in many areas of the auditory brainstem. Several chapters focus on neuronal modulation of function and plasticity on the synaptic, neuronal, and circuit level, especially during development, aging, and following peripheral hearing loss. In addition, the book addresses the role of trauma-induced maladaptive plasticity with respect to its contribution in generating central hearing dysfunction, such as hyperacusis and tinnitus.The book is intended for students and postdoctoral fellows starting in the auditory field and for researchers of related fields who wish to get an authoritative and up-to-date summary of the current state of auditory brainstem research. For clinical practitioners in audiology, otolaryngology, and neurology, the book is a valuable resource of information about the neuronal mechanisms that are currently discussed as major candidates for the generation of central hearing dysfunction.


2021 ◽  
Vol 63 (1) ◽  
Author(s):  
Katy Satué ◽  
Juan Carlos Gardon ◽  
Ana Muñoz

AbstractMyeloid disorders are conditions being characterized by abnormal proliferation and development of myeloid lineage including granulocytes (neutrophils, eosinophils and basophils), monocytes, erythroids, and megakaryocytes precursor cells. Myeloid leukemia, based on clinical presentation and proliferative rate of neoplastic cells, is divided into acute (AML) and myeloproliferative neoplasms (MPN). The most commonly myeloid leukemia reported in horses are AML-M4 (myelomonocytic) and AML-M5 (monocytic). Isolated cases of AML-M6B (acute erythroid leukemia), and chronic granulocytic leukemia have also been reported. Additionally, bone marrow disorders with dysplastic alterations and ineffective hematopoiesis affecting single or multiple cell lineages or myelodysplastic diseases (MDS), have also been reported in horses. MDSs have increased myeloblasts numbers in blood or bone marrow, although less than 20%, which is the minimum level required for diagnosis of AML. This review performed a detailed description of the current state of knowlegde of the myeloproliferative disorders in horses following the criteria established by the World Health Organization.


Healthcare ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 578
Author(s):  
Dorota Ozga ◽  
Sabina Krupa ◽  
Paweł Witt ◽  
Wioletta Mędrzycka-Dąbrowska

It has become a standard measure in recent years to utilise evidence-based practice, which is associated with a greater need to implement and use advanced, reliable methods of summarising the achievements of various scientific disciplines, including such highly specialised approaches as personalised medicine. The aim of this paper was to discuss the current state of knowledge related to improvements in “nursing” involving management of delirium in intensive care units during the SARS-CoV-2 pandemic. This narrative review summarises the current knowledge concerning the challenges associated with assessment of delirium in patients with COVID-19 by ICU nurses, and the role and tasks in the personalised approach to patients with COVID-19.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Claus Kordes ◽  
Hans H. Bock ◽  
Doreen Reichert ◽  
Petra May ◽  
Dieter Häussinger

Abstract This review article summarizes 20 years of our research on hepatic stellate cells within the framework of two collaborative research centers CRC575 and CRC974 at the Heinrich Heine University. Over this period, stellate cells were identified for the first time as mesenchymal stem cells of the liver, and important functions of these cells in the context of liver regeneration were discovered. Furthermore, it was determined that the space of Disse – bounded by the sinusoidal endothelium and hepatocytes – functions as a stem cell niche for stellate cells. Essential elements of this niche that control the maintenance of hepatic stellate cells have been identified alongside their impairment with age. This article aims to highlight previous studies on stellate cells and critically examine and identify open questions and future research directions.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Dongge Guo ◽  
Jianan Ding ◽  
Heng Liu ◽  
Lin Zhou ◽  
Jiang Feng ◽  
...  

Abstract Background Why a variety of social animals emit foraging-associated calls during group foraging remains an open question. These vocalizations may be used to recruit conspecifics to food patches (i.e. food advertisement hypothesis) or defend food resources against competitors (food defence hypothesis), presumably depending on food availability. Insectivorous bats rely heavily on vocalizations for navigation, foraging, and social interactions. In this study, we used free-ranging big-footed myotis (Myotis macrodactylus Temminck, 1840) to test whether social calls produced in a foraging context serve to advertise food patches or to ward off food competitors. Using a combination of acoustic recordings, playback experiments with adult females and dietary monitoring (light trapping and DNA metabarcoding techniques), we investigated the relationship between insect availability and social vocalizations in foraging bats. Results The big-footed myotis uttered low-frequency social calls composed of 7 syllable types during foraging interactions. Although the dietary composition of bats varied across different sampling periods, Diptera, Lepidoptera, and Trichoptera were the most common prey consumed. The number of social vocalizations was primarily predicted by insect abundance, insect species composition, and echolocation vocalizations from conspecifics. The number of conspecific echolocation pulses tended to decrease following the emission of most social calls. Feeding bats consistently decreased foraging attempts and food consumption during playbacks of social calls with distinctive structures compared to control trials. The duration of flight decreased 1.29–1.96 fold in the presence of social calls versus controls. Conclusions These results support the food defence hypothesis, suggesting that foraging bats employ social calls to engage in intraspecific food competition. This study provides correlative evidence for the role of insect abundance and diversity in influencing the emission of social calls in insectivorous bats. Our findings add to the current knowledge of the function of social calls in echolocating bats.


Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 299
Author(s):  
Vítor Ennes-Vidal ◽  
Marta Helena Branquinha ◽  
André Luis Souza dos Santos ◽  
Claudia Masini d’Avila-Levy

Calpains are calcium-dependent cysteine peptidases that were originally described in mammals and, thereafter, their homologues were identified in almost all known living organisms. The deregulated activity of these peptidases is associated with several pathologies and, consequently, huge efforts have been made to identify selective inhibitors. Trypanosomatids, responsible for life-threatening human diseases, possess a large and diverse family of calpain sequences in their genomes. Considering that the current therapy to treat trypanosomatid diseases is limited to a handful of drugs that suffer from unacceptable toxicity, tough administration routes, like parenteral, and increasing treatment failures, a repurposed approach with calpain inhibitors could be a shortcut to successful chemotherapy. However, there is a general lack of knowledge about calpain functions in these parasites and, currently, the proteolytic activity of these proteins is still an open question. Here, we highlight the current research and perspectives on trypanosomatid calpains, overview calpain description in these organisms, and explore the potential of targeting the calpain system as a therapeutic strategy. This review gathers the current knowledge about this fascinating family of peptidases as well as insights into the puzzle: are we unable to measure calpain activity in trypanosomatids, or are the functions of these proteins devoid of proteolytic activity in these parasites?


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Philipp Schult ◽  
Katrin Paeschke

AbstractDHX36 is a member of the DExD/H box helicase family, which comprises a large number of proteins involved in various cellular functions. Recently, the function of DHX36 in the regulation of G-quadruplexes (G4s) was demonstrated. G4s are alternative nucleic acid structures, which influence many cellular pathways on a transcriptional and post-transcriptional level. In this review we provide an overview of the current knowledge about DHX36 structure, substrate specificity, and mechanism of action based on the available models and crystal structures. Moreover, we outline its multiple functions in cellular homeostasis, immunity, and disease. Finally, we discuss the open questions and provide potential directions for future research.


Author(s):  
Stefan A. Rensing ◽  
Dolf Weijers

AbstractThe seeds of flowering plants are sexually produced propagules that ensure dispersal and resilience of the next generation. Seeds harbor embryos, three dimensional structures that are often miniatures of the adult plant in terms of general structure and primordial organs. In addition, embryos contain the meristems that give rise to post-embryonically generated structures. However common, flowering plant embryos are an evolutionary derived state. Flowering plants are part of a much larger group of embryo-bearing plants, aptly termed Embryophyta. A key question is what evolutionary trajectory led to the emergence of flowering plant embryos. In this opinion, we deconstruct the flowering plant embryo and describe the current state of knowledge of embryos in other plant lineages. While we are far yet from understanding the ancestral state of plant embryogenesis, we argue what current knowledge may suggest and how the knowledge gaps may be closed.


Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1155
Author(s):  
Eva Garcia-Lopez ◽  
Paula Alcazar ◽  
Cristina Cid

Cold-loving microorganisms of all three domains of life have unique and special abilities that allow them to live in harsh environments. They have acquired structural and molecular mechanisms of adaptation to the cold that include the production of anti-freeze proteins, carbohydrate-based extracellular polymeric substances and lipids which serve as cryo- and osmoprotectants by maintaining the fluidity of their membranes. They also produce a wide diversity of pigmented molecules to obtain energy, carry out photosynthesis, increase their resistance to stress and provide them with ultraviolet light protection. Recently developed analytical techniques have been applied as high-throughoutput technologies for function discovery and for reconstructing functional networks in psychrophiles. Among them, omics deserve special mention, such as genomics, transcriptomics, proteomics, glycomics, lipidomics and metabolomics. These techniques have allowed the identification of microorganisms and the study of their biogeochemical activities. They have also made it possible to infer their metabolic capacities and identify the biomolecules that are parts of their structures or that they secrete into the environment, which can be useful in various fields of biotechnology. This Review summarizes current knowledge on psychrophiles as sources of biomolecules and the metabolic pathways for their production. New strategies and next-generation approaches are needed to increase the chances of discovering new biomolecules.


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