Physiological role of the GlnK signal transduction protein of Escherichia coli : survival of nitrogen starvation

Escherichia coli contains two PII-like signal trans-duction proteins, PII and GlnK, involved in nitrogen assimilation. We examined the roles of PII and GlnK in controlling expression of glnALG , glnK and nac during the transition from growth on ammonia to nitrogen starvation and vice versa. The PII protein exclusively controlled glnALG expression in cells adapted to growth on ammonia, but was unable to limit nac and glnK expression under conditions of nitrogen starvation. Conversely, GlnK was unable to limit glnALG expression in cells adapted to growth on ammonia, but was required to limit expression of the glnK and nac promoters during nitrogen starvation. In the absence of GlnK, very high expression of the glnK and nac promoters occurred in nitrogen-starved cells, and the cells did not reduce glnK and nac expression when given ammonia. Thus, one specific role of GlnK is to regulate the expression of Ntr genes during nitrogen starvation. GlnK also had a dramatic effect on the ability of cells to survive nitrogen starvation and resume rapid growth when fed ammonia. After being nitrogen starved for as little as 10 h, cells lacking GlnK were unable to resume rapid growth when given ammonia. In contrast, wild-type cells that were starved immediately resumed rapid growth when fed ammonia. Cells lacking GlnK also showed faster loss of viability during extended nitrogen starvation relative to wild-type cells. This complex phenotype resulted partly from the requirement for GlnK to regulate nac expression; deletion of nac restored wild-type growth rates after ammonia starvation and refeeding to cells lacking GlnK, but did not improve viability during nitrogen starvation. The specific roles of GlnK during nitrogen starvation were not the result of a distinct function of the protein, as expression of PII from the glnK promoter in cells lacking GlnK restored the wild-type phenotypes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72950/1/j.1365-2958.2002.03153.x.pd

How the high-income class uses a public space: The neighbourhood square in Goiánia/Brazil

The public space has an important role in fostering urban life, since it absorbs and mediatesconflicts between public and private dimensions (CALDEIRA, 2007; VAZ, 2010; OLIVEIRA, 2013). Its appropriation and maintenance in Brazil havebeen considered ineffective, discontinued or privileged; the special differentiation and pressure is run by the higher income classes, which have territory control (LOJKINE, 1981; CASTELLS, 1983; VILLAÇA, 2001). This elite is composed by landowners who command the production process and is politically and ideologically dominant (OLIVEIRA, 1975). Its residencecommonly occurs: (I) in the central areas in vertical condominiums (with easy accessibility to commerce, retail, and other services); and (II) horizontal condominiumsin the urban fringes (because of safety, distinction, and availability of space). Basedon these premises, this study aims at understanding in which way the higher income classes take possession of public spaces in the context of “neighbourhood squares”. With a descriptive and exploratory approach, it considers as a case study T-23 square inGoiânia, an expensive regionthat ownsa complete infrastructure. The analysis is structured in two parts: (1) identification of existing elements, activities, and ways of occupation; and (2), through interviews, recordsof motivating criteria of use and residential rental. The results point to a consistent appropriation, by users of different ages and profiles, in distinct activities in different periods; they reveal use and socialization of the residents. Vitality promoting elements, associated with the proximity of quality equipment and its good conservation, seems to justify the occupation and appropriatio

Can MONDian vector theories explain the cosmic speed up ?

Generalized Einstein - Aether vector field models have been shown to provide, in the weak field regime, modifications to gravity which can be reconciled with the successfull MOND proposal. Very little is known, however, on the function F(K) defining the vector field Lagrangian so that an analysis of the viability of such theories at the cosmological scales has never been performed. As a first step along this route, we rely on the relation between F(K) and the MOND interpolating function $\mu(a/a_0)$ to assign the vector field Lagrangian thus obtaining what we refer to as "MONDian vector models". Since they are able by construction to recover the MOND successes on galaxy scales, we investigate whether they can also drive the observed accelerated expansion by fitting the models to the Type Ia Supernovae data. Should be this the case, we have a unified framework where both dark energy and dark matter can be seen as different manifestations of a single vector field. It turns out that both MONDian vector models are able to well fit the low redshift data on Type Ia Supernovae, while some tension could be present in the high z regime.Comment: 15 pages, 5 tables, 4 figures, accepted for publication on Physical Review

Non-equilibrium phase transitions in biomolecular signal transduction

We study a mechanism for reliable switching in biomolecular signal-transduction cascades. Steady bistable states are created by system-size cooperative effects in populations of proteins, in spite of the fact that the phosphorylation-state transitions of any molecule, by means of which the switch is implemented, are highly stochastic. The emergence of switching is a nonequilibrium phase transition in an energetically driven, dissipative system described by a master equation. We use operator and functional integral methods from reaction-diffusion theory to solve for the phase structure, noise spectrum, and escape trajectories and first-passage times of a class of minimal models of switches, showing how all critical properties for switch behavior can be computed within a unified framework

Indigenous Knowledge System of Fishers on Siganids in Lagonoy

Anchored on the social learning theory, this study aims to infuse indigenous knowledge system in the management of fishery resources that are peculiar to a fishing ground. The study determined the indigenous knowledge of the fishers for the purpose of valuing, preserving and infusing them in managing fishery resources that are peculiar to a locality, which in this phase of the research is focused on siganids (Siganidae) in Lagonoy Gulf, Bicol Region, Philippines where a fishery management initiative exists. Formal knowledge on the species was consolidated and catalogued to serve as references in explicating the indigenous knowledge. The study adopted the qualitative method of research, and made use of key informant interview, focus group discussion and documentary analysis to gather and analyze data.  Fishers were the key informants and formed part of focus group discussions. The researchers who have studied siganids in the area and whose findings formed the basis of resource management strategies in the Lagonoy Gulf were interviewed to explicate the IKs to formal knowledge. The electronic and print media, books, information and communication materials, laws and ordinances were the sources of documents that were analyzed. Indigenous knowledge of fishers on siganids covers diversity, biology and events that indicate the species’ abundance during its spawning season.  Literature on siganids that were reviewed cover the areas of morphology, distribution and stock assessment, habitat, feeding fecundity and maturation, spawning behavior and season, fisheries and socio-economic aspects.  Notable were the locally-generated knowledge from studies that were conducted by a local academic institution, Bicol University Tabaco Campus, which formed the bases of local-government resource management initiatives.  The scientific bases of majority of the indigenous knowledge on siganids were found in the results of studies on siganids in the locality and elsewhere. However, some astronomical and natural events which fishers use to predict production like the date of new moon and production are either spuriously correlated, or limited to certain levels of exploitation.  The results of studies on siganid by the Bicol University Tabaco Campus were published in technical journals but dissemination of the results through printed materials was not sustained. Although siganids are important to fisheries in villages in Lagonoy Gulf, topics on the fish are not included in the text books and are not among the collection of information, communication and educational (IEC) materials of local government units and educational institutions. Siganids in the gulf continue to be overfished, despite several initiatives to manage the resource, which point to the need for effective knowledge management for siganids resource management. Keywords: Indigenous knowledge system, siganids, Lagonoy Gulf, fisheries managemen

Nac-mediated repression of the serA promoter of Escherichia coli

Escherichia coli and related bacteria contain two paralogous PII-like proteins involved in nitrogen regulation, the glnB product, PII, and the glnK product, GlnK. Previous studies have shown that cells lacking both PII and GlnK have a severe growth defect on minimal media, resulting from elevated expression of the Ntr regulon. Here, we show that this growth defect is caused by activity of the nac product, Nac, a LysR-type transcription factor that is part of the Ntr regulon. Cells with elevated Ntr expression that also contain a null mutation in nac displayed growth rates on minimal medium similar to the wild type. When expressed from high-copy plasmids, Nac imparts a growth defect to wild-type cells in an expression level-dependent manner. Neither expression of Nac nor lack thereof significantly affected Ntr gene expression, suggesting that the activity of Nac at one or more promoters outside the Ntr regulon was responsible for its effects. The growth defect of cells lacking both PII and GlnK was also eliminated upon supplementation of minimal medium with serine or glycine for solid medium or with serine or glycine and glutamine for liquid medium. These observations suggest that high Nac expression results in a reduction in serine biosynthesis. β -Galactosidase activity expressed from a Mu d1 insertion in serA was reduced approximately 10-fold in cells with high Nac expression. We hypothesize that one role of Nac is to limit serine biosynthesis as part of a cellular mechanism to reduce metabolism in a co-ordinated manner when cells become starved for nitrogen.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72401/1/j.1365-2958.2002.02994.x.pd

Identification of direct residue contacts in protein-protein interaction by message passing

Understanding the molecular determinants of specificity in protein-protein interaction is an outstanding challenge of postgenome biology. The availability of large protein databases generated from sequences of hundreds of bacterial genomes enables various statistical approaches to this problem. In this context covariance-based methods have been used to identify correlation between amino acid positions in interacting proteins. However, these methods have an important shortcoming, in that they cannot distinguish between directly and indirectly correlated residues. We developed a method that combines covariance analysis with global inference analysis, adopted from use in statistical physics. Applied to a set of >2,500 representatives of the bacterial two-component signal transduction system, the combination of covariance with global inference successfully and robustly identified residue pairs that are proximal in space without resorting to ad hoc tuning parameters, both for heterointeractions between sensor kinase (SK) and response regulator (RR) proteins and for homointeractions between RR proteins. The spectacular success of this approach illustrates the effectiveness of the global inference approach in identifying direct interaction based on sequence information alone. We expect this method to be applicable soon to interaction surfaces between proteins present in only 1 copy per genome as the number of sequenced genomes continues to expand. Use of this method could significantly increase the potential targets for therapeutic intervention, shed light on the mechanism of protein-protein interaction, and establish the foundation for the accurate prediction of interacting protein partners.Comment: Supplementary information available on http://www.pnas.org/content/106/1/67.abstrac

Uso de inhibidores de la bomba de protones y antagonistas de los receptores H2 de histamina como profilaxis en úlceras por estrés: ¿una práctica justificada?

La introducción de los moduladores de acidez gástrica como profilaxis contra las úlceras por estrés en pacientes críticos se ha ido convirtiendo en una práctica de rutina tanto en la unidad de cuidados intensivos como fuera de esta; sin embargo, el desconocimiento de la fisiopatología de la enfermedad, las indicaciones de uso de moduladores de pH como profilácticos, los riesgos asociados a la prescripción indiscriminada y de las guías disponibles sobre esta práctica han llevado a un uso descontrolado de medicamentos como omeprazol y ranitidina, lo cual aumenta los costos para los hospitales y predispone a los pacientes a presentar enfermedades como neumonía. Con el objetivo de revisar los factores de riesgo asociados a esta patología, la eficacia de esta medida, sus indicaciones y posibles complicaciones tanto dentro como fuera de las unidades de cuidados intensivos, se realizó una revisión de la literatura. Esta incluyó artículos disponibles en diferentes bases de datos que hicieran referencia al manejo profiláctico de úlceras por estrés desde 1980 hasta 2014. Se encontró que, según la literatura actual, el uso de la profilaxis contra úlceras por estrés es una práctica muy debatida en el caso de los pacientes críticos y, lo que es más importante, en los no críticos aún no existen recomendaciones de uso o factores de riesgo establecidos. Por esta razón, la extrapolación de esta conducta a pacientes fuera de la unidad de cuidados intensivos es injustificada hasta el moment

Microalbuminuria en pacientes con diabetes tipo 2

La diabetes constituye una afección común en el Paraguay, donde unas 300.000 personas la padecen y aproximadamente otras 500.000 personas presentan un estado previo a la enfermedad. La nefropatía es una de las complicaciones mas graves, que sobreviene por la faltade control de la enfermedad. En la actualidad, el acceso al tratamiento sustitutivo, hemodiálisis y transplante renal ha desplazado a la insuficiencia renal al tercer puesto como causa de muerte del paciente diabético, después de la cardiopatía isquémica y del accidente cerebro vascular. La presencia de microalbuminuria en orina es un claro marcador de riesgo hacia la progresión de las complicaciones de la enfermedad, especialmente las nefropatías. En este estudio la prevalencia demicroalbuminuria hallada en los pacientes diabéticos tipo 2, fue de 34.7%, porcentaje elevado con respeto a la referencia que oscila alrededor del 20 al 40% en la Diabetes tipo 2.Existen factores deriesgo que predisponen al desarrollo de la microalbuminuria y su progresión, como son la duración de la diabetes, la falta de control de la glicemia, la hipertensión arterial, una mala alimentación y eltabaquismo. Con el control de dichos factores se vería reducido el riesgo de avance de la enfermedad. Se observó que a medida que aumenta el tiempo de evolución de la enfermedad aumenta la proporción de pacientes diabéticos con microalbuminuria, acompañados por unprogresivo aumento de la presión arterial