Un esquema conceptual para identificar localidades con poblaciones en riesgo de anemia y desnutrición crónica

Datos nacionales e incluso departamentales de anemia y desnutrición crónica se recolectan con periodicidad. Es raro encontrar datos a nivel municipal del estado nutricional de una población, información necesaria para focalizar intervenciones. Un esquema conceptual se desarrolló, aplicó y válido. Datos bioquímicos (prevalencia departamental de hemoglobina infantil < 11 g/dL), antropométricos (prevalencia departamental de talla/edad infantil < -2 Desviación Estándar) y socioeconómicos (a nivel municipal, índice de intensidad de pobreza ó población bajo la línea de pobreza extrema) se usaron para identificar localidades con riesgo de presentar anemia y desnutrición crónica, en 11 países latinoamericanos. En un sistema de información geográfica, se unificaron datos nutricionales y socioeconómicos a un mismo formato espacial, que representaba una localidad en un determinado departamento de un país. Se ubicaron aquellas localidades donde coincidían alta desnutrición (anemia o crónica) y pobreza. Para la desnutrición crónica, hubo una alta relación de localidades identificadas con el esquema, al compararlas con datos recolectados a nivel municipal (= 66%), mas no cuando se comparó con un método estadístico (0%). Este esquema articulado a un software de mapeo facilitó la identificación de localidades con poblaciones en riesgo a anemia y desnutrición crónica. Es importante validar el esquema con estudios de campo

Behavior of a Model Dynamical System with Applications to Weak Turbulence

We experimentally explore solutions to a model Hamiltonian dynamical system derived in Colliander et al., 2012, to study frequency cascades in the cubic defocusing nonlinear Schr\"odinger equation on the torus. Our results include a statistical analysis of the evolution of data with localized amplitudes and random phases, which supports the conjecture that energy cascades are a generic phenomenon. We also identify stationary solutions, periodic solutions in an associated problem and find experimental evidence of hyperbolic behavior. Many of our results rely upon reframing the dynamical system using a hydrodynamic formulation.Comment: 22 pages, 14 figure

Dynamics of multi-stage infections on networks

This paper investigates the dynamics of infectious diseases with a nonexponentially distributed infectious period. This is achieved by considering a multistage infection model on networks. Using pairwise approximation with a standard closure, a number of important characteristics of disease dynamics are derived analytically, including the final size of an epidemic and a threshold for epidemic outbreaks, and it is shown how these quantities depend on disease characteristics, as well as the number of disease stages. Stochastic simulations of dynamics on networks are performed and compared to output of pairwise models for several realistic examples of infectious diseases to illustrate the role played by the number of stages in the disease dynamics. These results show that a higher number of disease stages results in faster epidemic outbreaks with a higher peak prevalence and a larger final size of the epidemic. The agreement between the pairwise and simulation models is excellent in the cases we consider

Integrating the promotion of physical activity within a smoking cessation programme: Findings from collaborative action research in UK Stop Smoking Services

Background: Within the framework of collaborative action research, the aim was to explore the feasibility of developing and embedding physical activity promotion as a smoking cessation aid within UK 6/7-week National Health Service (NHS) Stop Smoking Services. Methods: In Phase 1 three initial cycles of collaborative action research (observation, reflection, planning, implementation and re-evaluation), in an urban Stop Smoking Service, led to the development of an integrated intervention in which physical activity was promoted as a cessation aid, with the support of a theoretically based self-help guide, and self monitoring using pedometers. In Phase 2 advisors underwent training and offered the intervention, and changes in physical activity promoting behaviour and beliefs were monitored. Also, changes in clients’ stage of readiness to use physical activity as a cessation aid, physical activity beliefs and behaviour and physical activity levels were assessed, among those who attended the clinic at 4-week post-quit. Qualitative data were collected, in the form of clinic observation, informal interviews with advisors and field notes. Results: The integrated intervention emerged through cycles of collaboration as something quite different to previous practice. Based on field notes, there were many positive elements associated with the integrated intervention in Phase 2. Self-reported advisors’ physical activity promoting behaviour increased as a result of training and adapting to the intervention. There was a significant advancement in clients’ stage of readiness to use physical activity as a smoking cessation aid. Conclusions: Collaboration with advisors was key in ensuring that a feasible intervention was developed as an aid to smoking cessation. There is scope to further develop tailored support to increasing physical activity and smoking cessation, mediated through changes in perceptions about the benefits of, and confidence to do physical activity

MAPping out distribution routes for kinesin couriers

In the crowded environment of eukaryotic cells, diffusion is an inefficient distribution mechanism for cellular components. Long-distance active transport is required and is performed by molecular motors including kinesins. Furthermore, in highly polarized, compartmentalized and plastic cells such as neurons, regulatory mechanisms are required to ensure appropriate spatio-temporal delivery of neuronal components. The kinesin machinery has diversified into a large number of kinesin motor proteins as well as adaptor proteins that are associated with subsets of cargo. However, many mechanisms contribute to the correct delivery of these cargos to their target domains. One mechanism is through motor recognition of subdomain-specific microtubule (MT) tracks, sign-posted by different tubulin isoforms, tubulin post-translational modifications (PTMs), tubulin GTPase activity and MT associated proteins (MAPs). With neurons as a model system, a critical review of these regulatory mechanisms is presented here, with particular focus on the emerging contribution of compartmentalised MAPs. Overall, we conclude that – especially for axonal cargo – alterations to the MT track can influence transport, although in vivo, it is likely that multiple track-based effects act synergistically to ensure accurate cargo distribution

PIP5KIβ Selectively Modulates Apical Endocytosis in Polarized Renal Epithelial Cells

Localized synthesis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] at clathrin coated pits (CCPs) is crucial for the recruitment of adaptors and other components of the internalization machinery, as well as for regulating actin dynamics during endocytosis. PtdIns(4,5)P2 is synthesized from phosphatidylinositol 4-phosphate by any of three phosphatidylinositol 5-kinase type I (PIP5KI) isoforms (α, β or γ). PIP5KIβ localizes almost exclusively to the apical surface in polarized mouse cortical collecting duct cells, whereas the other isoforms have a less polarized membrane distribution. We therefore investigated the role of PIP5KI isoforms in endocytosis at the apical and basolateral domains. Endocytosis at the apical surface is known to occur more slowly than at the basolateral surface. Apical endocytosis was selectively stimulated by overexpression of PIP5KIβ whereas the other isoforms had no effect on either apical or basolateral internalization. We found no difference in the affinity for PtdIns(4,5)P2-containing liposomes of the PtdIns(4,5)P2 binding domains of epsin and Dab2, consistent with a generic effect of elevated PtdIns(4,5)P2 on apical endocytosis. Additionally, using apical total internal reflection fluorescence imaging and electron microscopy we found that cells overexpressing PIP5KIβ have fewer apical CCPs but more internalized coated structures than control cells, consistent with enhanced maturation of apical CCPs. Together, our results suggest that synthesis of PtdIns(4,5)P2 mediated by PIP5KIβ is rate limiting for apical but not basolateral endocytosis in polarized kidney cells. PtdIns(4,5)P2 may be required to overcome specific structural constraints that limit the efficiency of apical endocytosis. © 2013 Szalinski et al

Spontaneous Preterm Birth Is Associated with Differential Expression of Vaginal Metabolites by Lactobacilli-Dominated Microflora

A major challenge in preventing preterm birth (PTB) is identifying women at greatest risk. This pilot study prospectively examined the differences in vaginal microbiota and metabolite profiles of women who delivered prematurely compared to their term counterparts in a cohort of asymptomatic (studied at 20–22, n = 80; and 26–28 weeks, n = 41) and symptomatic women (studied at 24–36 weeks, n = 37). Using 16S rRNA sequencing, the vaginal microbiota from cervicovaginal fluid samples was characterized into five Community State Types (CST) dominated by Lactobacillus spp.: CSTI (Lactobacillus crispatus), CSTII (Lactobacillus gasseri), CSTIII (Lactobacillus iners), CSTV (Lactobacillus jensenii); and mixed anaerobes—CSTIV. This was then related to the vaginal metabolite profile and pH determined by 1H-Nuclear Magnetic Resonance spectroscopy and pH indicator paper, respectively. At 20–22 weeks, the term-delivered women (TDW) indicated a proportion of CSTI-dominated microbiota &gt;2-fold higher compared to the preterm-delivered women (PTDW) (40.3 vs. 16.7%, P = 0.0002), and a slightly higher proportion at 26–28 weeks (20.7 vs. 16.7%, P = 0.03). CSTV was &gt;2-fold higher in the PTDW compared to TDW at 20–22 (22.2 vs. 9.7%, P = 0.0002) and 26–28 weeks (25.0 vs. 10.3%, P = 0.03). Furthermore, at 26–28 weeks no PTDW had a CSTII-dominated microbiome, in contrast to 28% of TDW (P &lt; 0.0001). CSTI-dominated samples showed higher lactate levels than CSTV at 20–22 weeks (P &lt; 0.01), and 26–28 weeks (P &lt; 0.05), while CSTII-dominated samples indicated raised succinate levels over CSTV at 26–28 weeks (P &lt; 0.05). These were supported by Principal coordinates analysis, which revealed strong clustering of metabolites according to CST. In addition, the CSTI-dominated samples had an average pH of 3.8, which was lower than those of CSTII—4.4, and CSTV—4.2 (P &lt; 0.05). Elevated vaginal lactate and succinate were associated with predominance of CSTI and II over CSTV in women who delivered at term compared with their preterm counterparts. This suggests that L. jensenii-dominance and decreased lactate and/or succinate could increase the risk of PTB, while L. crispatus/gasseri may confer some protection against inflammation-associated PTB and highlight the need for further study in this area

Stu2p binds tubulin and undergoes an open-to-closed conformational change

Stu2p from budding yeast belongs to the conserved Dis1/XMAP215 family of microtubule-associated proteins (MAPs). The common feature of proteins in this family is the presence of HEAT repeat–containing TOG domains near the NH2 terminus. We have investigated the functions of the two TOG domains of Stu2p in vivo and in vitro. Our data suggest that Stu2p regulates microtubule dynamics through two separate activities. First, Stu2p binds to a single free tubulin heterodimer through its first TOG domain. A large conformational transition in homodimeric Stu2p from an open structure to a closed one accompanies the capture of a single free tubulin heterodimer. Second, Stu2p has the capacity to associate directly with microtubule ends, at least in part, through its second TOG domain. These two properties lead to the stabilization of microtubules in vivo, perhaps by the loading of tubulin dimers at microtubule ends. We suggest that this mechanism of microtubule regulation is a conserved feature of the Dis1/XMAP215 family of MAPs

Disrupting astrocyte-neuron lactate transfer persistently reduces conditioned responses to cocaine.

A central problem in the treatment of drug addiction is the high risk of relapse often precipitated by drug-associated cues. The transfer of glycogen-derived lactate from astrocytes to neurons is required for long-term memory. Whereas blockade of drug memory reconsolidation represents a potential therapeutic strategy, the role of astrocyte-neuron lactate transport in long-term conditioning has received little attention. By infusing an inhibitor of glycogen phosphorylase into the basolateral amygdala of rats, we report that disruption of astrocyte-derived lactate not only transiently impaired the acquisition of a cocaine-induced conditioned place preference but also persistently disrupted an established conditioning. The drug memory was rescued by L-Lactate co-administration through a mechanism requiring the synaptic plasticity-related transcription factor Zif268 and extracellular signal-regulated kinase (ERK) signalling pathway but not the brain-derived neurotrophic factor (Bdnf). The long-term amnesia induced by glycogenolysis inhibition and the concomitant decreased expression of phospho-ERK were both restored with L-Lactate co-administration. These findings reveal a critical role for astrocyte-derived lactate in positive memory formation and highlight a novel amygdala-dependent reconsolidation process, whose disruption may offer a novel therapeutic target to reduce the long-lasting conditioned responses to cocaine

A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome

Down syndrome, caused by an extra copy of chromosome 21, is associated with a greatly increased risk of early onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP), an Alzheimer risk factor, although the possession of extra copies of other chromosome 21 genes may also play a role. Further study of the mechanisms underlying the development of Alzheimer disease in Down syndrome could provide insights into the mechanisms that cause dementia in the general population