scholarly journals Generalizing game-changing species across microbial communities

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Jie Deng ◽  
Marco Tulio Angulo ◽  
Serguei Saavedra

AbstractMicrobes form multispecies communities that play essential roles in our environment and health. Not surprisingly, there is an increasing need for understanding if certain invader species will modify a given microbial community, producing either a desired or undesired change in the observed collection of resident species. However, the complex interactions that species can establish between each other and the diverse external factors underlying their dynamics have made constructing such understanding context-specific. Here we integrate tractable theoretical systems with tractable experimental systems to find general conditions under which non-resident species can change the collection of resident communities—game-changing species. We show that non-resident colonizers are more likely to be game-changers than transients, whereas game-changers are more likely to suppress than to promote resident species. Importantly, we find general heuristic rules for game-changers under controlled environments by integrating mutual invasibility theory with in vitro experimental systems, and general heuristic rules under changing environments by integrating structuralist theory with in vivo experimental systems. Despite the strong context-dependency of microbial communities, our work shows that under an appropriate integration of tractable theoretical and experimental systems, it is possible to unveil regularities that can then be potentially extended to understand the behavior of complex natural communities.

Blood ◽  
2008 ◽  
Vol 112 (4) ◽  
pp. 1056-1067 ◽  
Author(s):  
Mira T. Kassouf ◽  
Hedia Chagraoui ◽  
Paresh Vyas ◽  
Catherine Porcher

Abstract Dissecting the molecular mechanisms used by developmental regulators is essential to understand tissue specification/differentiation. SCL/TAL-1 is a basic helix-loop-helix transcription factor absolutely critical for hematopoietic stem/progenitor cell specification and lineage maturation. Using in vitro and forced expression experimental systems, we previously suggested that SCL might have DNA-binding–independent functions. Here, to assess the requirements for SCL DNA-binding activity in vivo, we examined hematopoietic development in mice carrying a germline DNA-binding mutation. Remarkably, in contrast to complete absence of hematopoiesis and early lethality in scl-null embryos, specification of hematopoietic cells occurred in homozygous mutant embryos, indicating that direct DNA binding is dispensable for this process. Lethality was forestalled to later in development, although some mice survived to adulthood. Anemia was documented throughout development and in adulthood. Cellular and molecular studies showed requirements for SCL direct DNA binding in red cell maturation and indicated that scl expression is positively autoregulated in terminally differentiating erythroid cells. Thus, different mechanisms of SCL's action predominate depending on the developmental/cellular context: indirect DNA binding activities and/or sequestration of other nuclear regulators are sufficient in specification processes, whereas direct DNA binding functions with transcriptional autoregulation are critically required in terminal maturation processes.


Metals ◽  
2016 ◽  
Vol 6 (3) ◽  
pp. 71 ◽  
Author(s):  
Johanna Ollig ◽  
Veronika Kloubert ◽  
Inga Weßels ◽  
Hajo Haase ◽  
Lothar Rink
Keyword(s):  

Author(s):  
Sabiha Imran ◽  
Twinkle Gupta ◽  
Aarti Arora ◽  
Nilanjan Das

  Bacteriocins are ribosomally synthesized antimicrobial peptides produced by microbes owned by different eubacterial taxonomic branches. Most of them are small cationic membrane-active compounds that form pores in the targeted cells, disrupting membrane possibilities, and triggering cell fatality. The availability of small cationic peptides with antimicrobial activity is a protection strategy found not only in bacteria but also in plants and animals. The antibiotics which have extensive applications in the treatment of various bacterial diseases have developed alarming resistance against them in many pathogens due to improper use besides this antibiotics have adverse side effects also. There are an extensive variety of bacteriocins made by different bacterial genera have promising alternative to antibiotics that needs to be further studied to show the no existence of undesirable effects, which must be performed both in vitro and in vivo experimental systems. Most of the bacteriocin have narrow spectrum of their activity and effective only on the related species. There is an urgent need for the identification of broad-spectrum bacteriocins isolated from the species from different habitats that can be effective against both Gram-positive and Gram-negative pathogens. In this review, we focus on the main physical and chemical characteristics of broad-spectrum bacteriocin and discuss their application as an alternative option to antibiotics.


2020 ◽  
Vol 21 (8) ◽  
pp. 2970 ◽  
Author(s):  
Vance G. Nielsen

The demonstration that carbon monoxide releasing molecules (CORMs) affect experimental systems by the release of carbon monoxide, and not via the interaction of the inactivated CORM, has been an accepted paradigm for decades. However, it has recently been documented that a radical intermediate formed during carbon monoxide release from ruthenium (Ru)-based CORM (CORM-2) interacts with histidine and can inactivate bee phospholipase A2 activity. Using a thrombelastographic based paradigm to assess procoagulant activity in human plasma, this study tested the hypothesis that a Ru-based radical and not carbon monoxide was responsible for CORM-2 mediated inhibition of Atheris, Echis, and Pseudonaja species snake venoms. Assessment of the inhibitory effects of ruthenium chloride (RuCl3) on snake venom activity was also determined. CORM-2 mediated inhibition of the three venoms was found to be independent of carbon monoxide release, as the presence of histidine-rich albumin abrogated CORM-2 inhibition. Exposure to RuCl3 had little effect on Atheris venom activity, but Echis and Pseudonaja venom had procoagulant activity significantly reduced. In conclusion, a Ru-based radical and ion inhibited procoagulant snake venoms, not carbon monoxide. These data continue to add to our mechanistic understanding of how Ru-based molecules can modulate hemotoxic venoms, and these results can serve as a rationale to focus on perhaps other, complementary compounds containing Ru as antivenom agents in vitro and, ultimately, in vivo.


2020 ◽  
Vol 12 (1) ◽  
pp. 19-35 ◽  
Author(s):  
Dimitrios Trafalis ◽  
Panagiotis Dalezis ◽  
Elena Geromichalou ◽  
Sofia Sagredou ◽  
Eleni Sflakidou ◽  
...  

Aim: Steroidal prodrugs of nitrogen mustards such as estramustine and prednimustine have proven effective anticancer agents in clinical use since the 1970s. In this work, we aimed to develop steroidal prodrugs of the novel nitrogen mustard POPAM-NH2. POPAM-NH2 is a melphalan analogue that was coupled with three different steroidal lactams. Methodology: The new conjugates were preclinically tested for anticancer activity against nine human and one rodent cancer experimental models, in vitro and in vivo. Results & conclusion: All the steroidal alkylators showed high antitumor activity, in vitro and in vivo, in the experimental systems tested. Moreover, these hybrid compounds showed by far superior anticancer activity compared with the alkylating agents, melphalan and POPAM-NH2.


Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1116
Author(s):  
Emna Benzarti ◽  
Mutien Garigliany

Usutu virus (USUV), a mosquito-borne zoonotic flavivirus discovered in South Africa in 1959, has spread to many European countries over the last 20 years. The virus is currently a major concern for animal health due to its expanding host range and the growing number of avian mass mortality events. Although human infections with USUV are often asymptomatic, they are occasionally accompanied by neurological complications reminiscent of those due to West Nile virus (another flavivirus closely related to USUV). Whilst USUV actually appears less threatening than some other emergent arboviruses, the lessons learned from Chikungunya, Dengue, and Zika viruses during the past few years should not be ignored. Further, it would not be surprising if, with time, USUV disperses further eastwards towards Asia and possibly westwards to the Americas, which may result in more pathogenic USUV strains to humans and/or animals. These observations, inviting the scientific community to be more vigilant about the spread and genetic evolution of USUV, have prompted the use of experimental systems to understand USUV pathogenesis and to boost the development of vaccines and antivirals. This review is the first to provide comprehensive coverage of existing in vitro and in vivo models for USUV infection and to discuss their contribution in advancing data concerning this neurotropic virus. We believe that this paper is a helpful tool for scientists to identify gaps in the knowledge about USUV and to design their future experiments to study the virus.


2018 ◽  
Author(s):  
Egle Cekanaviciute ◽  
Anne-Katrin Pröbstel ◽  
Anna Thomann ◽  
Tessel F. Runia ◽  
Patrizia Casaccia ◽  
...  

AbstractMultiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by adaptive and innate immune system dysregulation. Recent work has revealed moderate alteration of gut microbial communities in subjects with MS and in experimental, induced models. However, a mechanistic understanding linking the observed changes in the microbiota and the presence of the disease is still missing. Chloroform-resistant, spore-forming bacteria have been shown to exhibit immunomodulatory properties in vitro and in vivo, but they have not yet been characterized in the context of human disease. This study addresses the community composition and immune function of this bacterial fraction in MS. We identify MS-associated spore-forming taxa and show that their presence correlates with impaired differentiation of IL-10 secreting, regulatory T lymphocytes in-vitro. Colonization of antibiotic-treated mice with spore-forming bacteria allowed us to identify some bacterial taxa favoring IL-10+ lymphocyte differentiation and others inducing differentiation of pro-inflammatory, IFNγ+ T lymphocytes. However, when fed into antibiotic-treated mice, both MS and control derived spore-forming bacteria were able to induce immunoregulatory responses.Our analysis also identified Akkermansia muciniphila as a key organism that may interact either directly or indirectly with spore-forming bacteria to exacerbate the inflammatory effects of MS-associated gut microbiota. Thus, changes in the spore-forming fraction may influence T lymphocyte-mediated inflammation in MS. This experimental approach of isolating a subset of microbiota based on its functional characteristics may be useful to investigate other microbial fractions at greater depth.ImportanceDespite the rapid emergence of microbiome related studies in human diseases, few go beyond a simple description of relative taxa levels in a select group of patients. Our study integrates computational analysis with in vitro and in vivo exploration of inflammatory properties of both complete microbial communities and individual taxa, revealing novel functional associations. We specifically show that while small differences exist between the microbiomes of MS patients and healthy subjects, these differences are exacerbated in the chloroform resistant fraction. We further demonstrate that, when purified from MS patients, this fraction is associated with impaired immunomodulatory responses in vitro.


2020 ◽  
Author(s):  
Zhen Gu ◽  
Jia Guo ◽  
Jinglei Zhai ◽  
Guihai Feng ◽  
Xianning Wang ◽  
...  

Abstract The mammalian embryo must undergo dramatic morphogenetic changes to invade the uterine endometrium and achieve implantation. Thus, recapitulation of implantation using in vitro systems is crucial for revealing the mechanisms controlling early development and the main problems compromising human fertility. Experimental systems based on two-dimensional (2D) platforms cannot fully recapitulate the in vivo 3D microenvironments of the embryo. Therefore, here we use collagen grafted onto polydimethylsiloxane (PDMS) based on the uterine mechanics and microstructure to establish a uterus-inspired 3D niche (U3N). Our U3N enables mouse embryos to form egg cylinders at high rate and reach the developmental stages of heartbeat. Moreover, a unique interface forms between the embryo and collagen, showing the invasion of trophoblasts into collagen fires, which simulate the developmental process of implantation. Our findings highlight embryo-substrate interaction as a key characteristic of post-implantation development in vitro and as an important design parameter of 3D conditions for embryo culture.


2020 ◽  
Author(s):  
Motomasa Tanaka ◽  
Yoshiko Nakagawa ◽  
Howard C.-H. Shen ◽  
Shinju Sugiyama ◽  
Yuri Tomabechi ◽  
...  

Abstract Disaggregation of amyloid fibrils is a fundamental biological process required for amyloid propagation. However, due to the lack of experimental systems, the molecular mechanism of how amyloid is disaggregated by cellular factors remains poorly understood. Here, we established a robust, in vitro reconstituted system of yeast prion propagation and found that Hsp104, Ssa1, and Sis1 chaperones are essential for efficient disaggregation of Sup35 amyloid. Real-time imaging of single-molecule fluorescence coupled with the reconstitution system revealed that amyloid disaggregation is achieved by ordered, timely binding of the chaperones to the amyloid. Remarkably, we uncovered two distinct, prion strain conformation-dependent modes of disaggregation, fragmentation and dissolution. We characterized distinct chaperon dynamics in each mode and found that transient, repeated binding of Hsp104 to the same site of amyloid results in fragmentation. These findings provide a physical foundation for otherwise puzzling in vivo observations and for therapeutic development for amyloid-associated neurodegenerative diseases.


1993 ◽  
Vol 180 (1) ◽  
pp. 27-37
Author(s):  
S F Perry ◽  
S Thomas

Respiratory variables of rainbow trout (Oncorhynchus mykiss) blood were monitored continuously in vivo using an extracorporeal circulation or in vitro using blood flowing in a semi- closed loop. The experiments were designed to assess the rapid effects of endogenous catecholamines on red blood cell (RBC) O2 and CO2 transport. The addition of catecholamines (nominal final blood concentrations were 250 nmol l-1 adrenaline and 20 nmol l-1 noradrenaline) caused activation of RBC Na+/H+ exchange both in vivo and in vitro as indicated by the reductions in whole-blood pH. In both experimental systems, the activation of Na+/H+ exchange was associated with a rapid reduction of blood PCO2, indicating a sudden net movement of plasma CO2 into the RBC. In vitro the initial reduction of blood PCO2 was followed by a pronounced elevation as a result of the titration of plasma HCO3- by H+ extruded from the RBC. Blood PO2 fell markedly in a transitory manner after the addition of catecholamines. The decreases in PO2 were probably caused by rapid increases in the affinity/capacity of haemoglobin for O2 which, in turn, caused O2 molecules to enter the RBC from the plasma. The results are discussed with reference to the role of circulating catecholamines in rapidly modifying blood O2 and CO2 transport in rainbow trout.


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