Mechanisms that shape microbial pangenomes

Analyses of multiple whole-genome sequences from the same species have revealed that differences in gene content can be substantial, particularly in prokaryotes. Such variation has led to the recognition of pangenomes, the complete set of genes present in a species – consisting of core genes present in all individuals, and accessory genes whose presence is variable. Questions now arise about how pangenomes originate and evolve. We describe how gene content variation can arise as a result of the combination of several processes including random drift, selection, gain-loss balance, and the influence of ecological and epistatic interactions. We believe that identifying the contributions of these processes to pangenomes will need novel theoretical approaches and empirical data

Del silencio al empoderamiento comunicacional: Una propuesta de gestión digital para el Foro Nacional de Mujeres de Partidos Políticos de Panamá

El Fonamupp és una organització del Tercer Sector conformada per militants de diferents partits amb l'objectiu de defensar els drets polítics de les dones. La investigació proposa, a partir de l'autonomia en l'ús de la tecnologia, una gestió organitzada del seu ecosistema digital per augmentar la visibilitat de les dones polítiques. Es pretén amplificar el seu ja existent, però poc actiu, perfil a les xarxes socials per tal de connectar i generar aliances amb altres veus interessades en la transformació de les formes hegemòniques de participació política.El Fonamupp es una organización del Tercer Sector, conformado por militantes de distintos partidos cuyo objetivo es defender los derechos políticos de las mujeres. La investigación propone, a partir de la autonomía en el uso de la tecnología, una gestión organizada de su ecosistema digital para aumentar la visibilidad de las mujeres políticas. Se pretende amplificar su ya existente, pero poco activa, perfil en las redes sociales a fin de conectar y generar alianzas con otras voces interesadas en la transformación de las formas hegemónicas de participación política.Fonamupp is an organization of the Third Sector, made up of members of different parties whose objective is to defend the political rights of women. The research proposes, based on the autonomy in the use of technology, an organized management of its digital ecosystem to increase the visibility of women politicians. The aim is to amplify their already existing, but not very active, profile in social media in order to connect and generate alliances with other voices interested in the transformation of hegemonic forms of political participation

Horizontal gene transfer as a source of conflict and cooperation in prokaryotes

Horizontal gene transfer (HGT) is one of the most important processes in prokaryote evolution. The sharing of DNA can spread neutral or beneficial genes, as well as genetic parasites across populations and communities, creating a large proportion of the variability acted on by natural selection. Here, we highlight the role of HGT in enhancing the opportunities for conflict and cooperation within and between prokaryote genomes. We discuss how horizontally acquired genes can cooperate or conflict both with each other and with a recipient genome, resulting in signature patterns of gene co-occurrence, avoidance, and dependence. We then describe how interactions involving horizontally transferred genes may influence cooperation and conflict at higher levels (populations, communities, and symbioses). Finally, we consider the benefits and drawbacks of HGT for prokaryotes and its fundamental role in understanding conflict and cooperation from the gene-gene to the microbiome level

Basement membrane proteins as a substrate for efficient Trypanosoma brucei differentiation in vitro

The ability to reproduce the developmental events of trypanosomes that occur in their mammalian host in vitro offers significant potential to assist in understanding of the underlying biology of the process. For example, the transition from bloodstream slender to bloodstream stumpy forms is a quorum-sensing response to the parasite-derived peptidase digestion products of environmental proteins. As an abundant physiological substrate in vivo, we studied the ability of a basement membrane matrix enriched gel (BME) in the culture medium to support differentiation of pleomorphic Trypanosoma brucei to stumpy forms. BME comprises extracellular matrix proteins, which are among the most abundant proteins found in connective tissues in mammals and known substrates of parasite-released peptidases. We previously showed that two of these released peptidases are involved in generating a signal that promotes slender-to-stumpy differentiation. Here, we tested the ability of basement membrane extract to enhance parasite differentiation through its provision of suitable substrates to generate the quorum sensing signal, namely oligopeptides. Our results show that when grown in the presence of BME, T. brucei pleomorphic cells arrest at the G0/1 phase of the cell cycle and express the differentiation marker PAD1, the response being restricted to differentiation-competent parasites. Further, the stumpy forms generated in BME medium are able to efficiently proceed onto the next life cycle stage in vitro, procyclic forms, when incubated with cis-aconitate, further validating the in vitro BME differentiation system. Hence, BME provides a suitable in vitro substrate able to accurately recapitulate physiological parasite differentiation without the use of experimental animals

PP2A/B55 and Fcp1 regulate Greatwall and Ensa desphorylation during mitotic exit

Entry into mitosis is triggered by activation of Cdk1 and inactivation of its counteracting phosphatase PP2A/B55. Greatwall kinase inactivates PP2A/B55 via its substrates Ensa and ARPP19. Both Greatwall and Ensa/ARPP19 are regulated by phosphorylation, but the dynamic regulation of Greatwall activity and the phosphatases that control Greatwall kinase and its substrates are poorly understood. To address these questions we applied a combination of mathematical modelling and experiments using phospho-specific antibodies to monitor Greatwall, Ensa/ARPP19 and Cdk substrate phosphorylation during mitotic entry and exit. We demonstrate that PP2A/B55 is required for Gwl dephosphorylation at the essential Cdk site Thr194. Ensa/ARPP19 dephosphorylation is mediated by the RNA Polymerase II carboxy terminal domain phosphatase Fcp1. Surprisingly, neither Fcp1 nor PP2A appear to essential to dephosphorylate the bulk of mitotic Cdk1 substrates following Cdk1 inhibition. Taken together our results suggest a hierarchy of phosphatases coordinating Greatwall, Ensa/ARPP19 and Cdk substrate dephosphorylation during mitotic exit

Transcriptional Regulation Is a Major Controller of Cell Cycle Transition Dynamics

DNA replication, mitosis and mitotic exit are critical transitions of the cell cycle which normally occur only once per cycle. A universal control mechanism was proposed for the regulation of mitotic entry in which Cdk helps its own activation through two positive feedback loops. Recent discoveries in various organisms showed the importance of positive feedbacks in other transitions as well. Here we investigate if a universal control system with transcriptional regulation(s) and post-translational positive feedback(s) can be proposed for the regulation of all cell cycle transitions. Through computational modeling, we analyze the transition dynamics in all possible combinations of transcriptional and post-translational regulations. We find that some combinations lead to ‘sloppy’ transitions, while others give very precise control. The periodic transcriptional regulation through the activator or the inhibitor leads to radically different dynamics. Experimental evidence shows that in cell cycle transitions of organisms investigated for cell cycle dependent periodic transcription, only the inhibitor OR the activator is under cyclic control and never both of them. Based on these observations, we propose two transcriptional control modes of cell cycle regulation that either STOP or let the cycle GO in case of a transcriptional failure. We discuss the biological relevance of such differences

Different effects of redundant feedback loops on a bistable switch.

Bistable switches have important roles in cellular decision-making processes. Bistability can be the consequence of positive or double-negative feedback loops. Although necessary, such feedback is not sufficient for bistability, which also requires nonlinearity. Nonlinearity can be provided by synergy of multiple feedback loops or by an ultrasensitive response within a single feedback loop. However, these two possibilities are not mutually exclusive; a combination of them is also possible. Here we analyze a biochemical regulatory network that controls a crucial cell cycle transition in all eukaryotic cells and contains multiple redundant feedback loops and nonlinearity. We show in this realistic biological example that two redundant feedback loops have different effects on the position of one of the saddle-node bifurcations of the system, which determines where the system switches. This illustrates that even though the roles of positive and double-negative feedbacks have been regarded as equivalent, the difference in their architectures can lead to differences in their effects on the system. We speculate that this conclusion could be general for other bistable systems with redundant feedback loops

Switches and latches: a biochemical tug-of-war between the kinases and phosphatases that control mitosis.

Activation of the cyclin-dependent kinase (Cdk1) cyclin B (CycB) complex (Cdk1:CycB) in mitosis brings about a remarkable extent of protein phosphorylation. Cdk1:CycB activation is switch-like, controlled by two auto-amplification loops--Cdk1:CycB activates its activating phosphatase, Cdc25, and inhibits its inhibiting kinase, Wee1. Recent experimental evidence suggests that parallel to Cdk1:CycB activation during mitosis, there is inhibition of its counteracting phosphatase activity. We argue that the downregulation of the phosphatase is not just a simple latch that suppresses futile cycles of phosphorylation/dephosphorylation during mitosis. Instead, we propose that phosphatase regulation creates coherent feed-forward loops and adds extra amplification loops to the Cdk1:CycB regulatory network, thus forming an integral part of the mitotic switch. These network motifs further strengthen the bistable characteristic of the mitotic switch, which is based on the antagonistic interaction of two groups of proteins: M-phase promoting factors (Cdk1:CycB, Cdc25, Greatwall and Endosulfine/Arpp19) and interphase promoting factors (Wee1, PP2A-B55 and a Greatwall counteracting phosphatase, probably PP1). The bistable character of the switch implies the existence of a CycB threshold for entry into mitosis. The end of G2 phase is determined by the point where CycB level crosses the CycB threshold for Cdk1 activation