A conserved protein interaction network involving the yeast MAP kinases Fus3 and Kss1

The Saccharomyces cerevisiae mitogen-activated protein kinases (MAPKs) Fus3 and Kss1 bind to multiple regulators and substrates. We show that mutations in a conserved docking site in these MAPKs (the CD/7m region) disrupt binding to an important subset of their binding partners, including the Ste7 MAPK kinase, the Ste5 adaptor/scaffold protein, and the Dig1 and Dig2 transcriptional repressors. Supporting the possibility that Ste5 and Ste7 bind to the same region of the MAPKs, they partially competed for Fus3 binding. In vivo, some of the MAPK mutants displayed reduced Ste7-dependent phosphorylation, and all of them exhibited multiple defects in mating and pheromone response. The Kss1 mutants were also defective in Kss1-imposed repression of Ste12. We conclude that MAPKs contain a structurally and functionally conserved docking site that mediates an overall positively acting network of interactions with cognate docking sites on their regulators and substrates. Key features of this interaction network appear to have been conserved from yeast to humans

The role of ecosystem transpiration in creating alternate moisture regimes by influencing atmospheric moisture convergence

The terrestrial water cycle links the soil and atmosphere moisture reservoirs through four fluxes: precipitation, evaporation, runoff, and atmospheric moisture convergence (net import of water vapor to balance runoff). Each of these processes is essential for human and ecosystem well-being. Predicting how the water cycle responds to changes in vegetation cover remains a challenge. Recently, changes in plant transpiration across the Amazon basin were shown to be associated disproportionately with changes in rainfall, suggesting that even small declines in transpiration (e.g., from deforestation) would lead to much larger declines in rainfall. Here, constraining these results by the law of mass conservation, we show that in a sufficiently wet atmosphere, forest transpiration can control atmospheric moisture convergence such that increased transpiration enhances atmospheric moisture import and resulting water yield. Conversely, in a sufficiently dry atmosphere increased transpiration reduces atmospheric moisture convergence and water yield. This previously unrecognized dichotomy can explain the otherwise mixed observations of how water yield responds to re-greening, as we illustrate with examples from China's Loess Plateau. Our analysis indicates that any additional precipitation recycling by additional vegetation increases precipitation but decreases local water yield and steady-state runoff. Therefore, in the drier regions and early stages of ecological restoration, the role of vegetation can be confined to precipitation recycling, while once a wetter stage is achieved, additional vegetation enhances atmospheric moisture convergence and water yield. Evaluating the transition between regimes, and recognizing the potential of vegetation for enhancing moisture convergence, are crucial for characterizing the consequences of deforestation and for motivating and guiding ecological restoration.Comment: Revised version; response to the reviewers can be found in Appendix A, 39 pages, 11 figures, 2 table

Genome-wide diversity and gene expression profiling of Babesia microti isolates identify polymorphic genes that mediate host-pathogen interactions

Babesia microti, a tick-transmitted, intraerythrocytic protozoan parasite circulating mainly among small mammals, is the primary cause of human babesiosis. While most cases are transmitted by Ixodes ticks, the disease may also be transmitted through blood transfusion and perinatally. A comprehensive analysis of genome composition, genetic diversity, and gene expression profiling of seven B. microti isolates revealed that genetic variation in isolates from the Northeast United States is almost exclusively associated with genes encoding the surface proteome and secretome of the parasite. Furthermore, we found that polymorphism is restricted to a small number of genes, which are highly expressed during infection. In order to identify pathogen-encoded factors involved in host-parasite interactions, we screened a proteome array comprised of 174 B. microti proteins, including several predicted members of the parasite secretome. Using this immuno-proteomic approach we identified several novel antigens that trigger strong host immune responses during the onset of infection. The genomic and immunological data presented herein provide the first insights into the determinants of B. microti interaction with its mammalian hosts and their relevance for understanding the selective pressures acting on parasite evolution

Holographic Geometry of Entanglement Renormalization in Quantum Field Theories

We study a conjectured connection between the AdS/CFT and a real-space quantum renormalization group scheme, the multi-scale entanglement renormalization ansatz (MERA). By making a close contact with the holographic formula of the entanglement entropy, we propose a general definition of the metric in the MERA in the extra holographic direction, which is formulated purely in terms of quantum field theoretical data. Using the continuum version of the MERA (cMERA), we calculate this emergent holographic metric explicitly for free scalar boson and free fermions theories, and check that the metric so computed has the properties expected from AdS/CFT. We also discuss the cMERA in a time-dependent background induced by quantum quench and estimate its corresponding metric.Comment: 42pages, 9figures, reference added, minor chang

Bose-Einstein correlations of same-sign charged pions in the forward region in pp collisions at √s=7 TeV

Bose-Einstein correlations of same-sign charged pions, produced in protonproton collisions at a 7 TeV centre-of-mass energy, are studied using a data sample collected by the LHCb experiment. The signature for Bose-Einstein correlations is observed in the form of an enhancement of pairs of like-sign charged pions with small four-momentum difference squared. The charged-particle multiplicity dependence of the Bose-Einstein correlation parameters describing the correlation strength and the size of the emitting source is investigated, determining both the correlation radius and the chaoticity parameter. The measured correlation radius is found to increase as a function of increasing charged-particle multiplicity, while the chaoticity parameter is seen to decreas

Measurement of the inelastic pp cross-section at a centre-of-mass energy of 13TeV

The cross-section for inelastic proton-proton collisions at a centre-of-mass energy of 13TeV is measured with the LHCb detector. The fiducial cross-section for inelastic interactions producing at least one prompt long-lived charged particle with momentum p > 2 GeV/c in the pseudorapidity range 2 < η < 5 is determined to be ϭ acc = 62:2 ± 0:2 ± 2:5mb. The first uncertainty is the intrinsic systematic uncertainty of the measurement, the second is due to the uncertainty on the integrated luminosity. The statistical uncertainty is negligible. Extrapolation to full phase space yields the total inelastic proton-proton cross-section ϭ inel = 75:4 ± 3:0 ± 4:5mb, where the first uncertainty is experimental and the second due to the extrapolation. An updated value of the inelastic cross-section at a centre-of-mass energy of 7TeV is also reported

S100b in acute ischemic stroke clots is a biomarker for post-thrombectomy intracranial hemorrhages

Background and purposePost-thrombectomy intracranial hemorrhages (PTIH) are dangerous complications of acute ischemic stroke (AIS) following mechanical thrombectomy. We aimed to investigate if S100b levels in AIS clots removed by mechanical thrombectomy correlated to increased risk of PTIH.MethodsWe analyzed 122 thrombi from 80 AIS patients in the RESTORE Registry of AIS clots, selecting an equal number of patients having been pre-treated or not with rtPA (40 each group). Within each subgroup, 20 patients had developed PTIH and 20 patients showed no signs of hemorrhage. Gross photos of each clot were taken and extracted clot area (ECA) was measured using ImageJ. Immunohistochemistry for S100b was performed and Orbit Image Analysis was used for quantification. Immunofluorescence was performed to investigate co-localization between S100b and T-lymphocytes, neutrophils and macrophages. Chi-square or Kruskal-Wallis test were used for statistical analysis.ResultsPTIH was associated with higher S100b levels in clots (0.33 [0.08–0.85] vs. 0.07 [0.02–0.27] mm2, H1 = 6.021, P = 0.014*), but S100b levels were not significantly affected by acute thrombolytic treatment (P = 0.386). PTIH was also associated with patients having higher NIHSS at admission (20.0 [17.0–23.0] vs. 14.0 [10.5–19.0], H1 = 8.006, P = 0.005) and higher number of passes during thrombectomy (2 [1–4] vs. 1 [1–2.5], H1 = 5.995, P = 0.014*). S100b co-localized with neutrophils, macrophages and with T-lymphocytes in the clots.ConclusionsHigher S100b expression in AIS clots, higher NIHSS at admission and higher number of passes during thrombectomy are all associated with PTIH. Further investigation of S100b expression in AIS clots by neutrophils, macrophages and T-lymphocytes could provide insight into the role of S100b in thromboinflammation

Analysis of Different Views and Conceptualizations of the Literacy Practices of Pupils, Families, and Teachers in Costa Rican Primary Education

This article is based on a socio-cultural discourse model of literacy, whereby literacy events are regarded as being situated within social practices, creating various formal, informal, and non-formal literacy events that are part of 10multiliteracies. The aim of the research was to analyze primary pupils ’ literacy practices (8–12 years) from the perspectives of 1,354 primary pupils, 1,020 family members, and 96 teachers in Costa Rica, using an ex-post facto design and a survey method. The findings indicate that the three groups of participants (pupils, family members, and teachers) have different views on 15and conceptualizations of literacy practices in school and in the community. The results show that young learners develop their literacy practices according to their different communicative needs inside and outside school. A multimodal literacy is promoted outside school to meet students’ daily communicative needs. However, the school promotes a monomodal lit20eracy, which allows pupils to respond essentially to school needs

Cellular injury and neuroinflammation in children with chronic intractable epilepsy

<p>Abstract</p> <p>Objective</p> <p>To elucidate the presence and potential involvement of brain inflammation and cell death in neurological morbidity and intractable seizures in childhood epilepsy, we quantified cell death, astrocyte proliferation, microglial activation and cytokine release in brain tissue from patients who underwent epilepsy surgery.</p> <p>Methods</p> <p>Cortical tissue was collected from thirteen patients with intractable epilepsy due to focal cortical dysplasia (6), encephalomalacia (5), Rasmussen's encephalitis (1) or mesial temporal lobe epilepsy (1). Sections were processed for immunohistochemistry using markers for neuron, astrocyte, microglia or cellular injury. Cytokine assay was performed on frozen cortices. Controls were autopsy brains from eight patients without history of neurological diseases.</p> <p>Results</p> <p>Marked activation of microglia and astrocytes and diffuse cell death were observed in epileptogenic tissue. Numerous fibrillary astrocytes and their processes covered the entire cortex and converged on to blood vessels, neurons and microglia. An overwhelming number of neurons and astrocytes showed DNA fragmentation and its magnitude significantly correlated with seizure frequency. Majority of our patients with abundant cell death in the cortex have mental retardation. IL-1beta, IL-8, IL-12p70 and MIP-1beta were significantly increased in the epileptogenic cortex; IL-6 and MCP-1 were significantly higher in patients with family history of epilepsy.</p> <p>Conclusions</p> <p>Our results suggest that active neuroinflammation and marked cellular injury occur in pediatric epilepsy and may play a common pathogenic role or consequences in childhood epilepsy of diverse etiologies. Our findings support the concept that immunomodulation targeting activated microglia and astrocytes may be a novel therapeutic strategy to reduce neurological morbidity and prevent intractable epilepsy.</p

Health for sale: the medicinal plant markets in Trujillo and Chiclayo, Northern Peru

Traditional methods of healing have been beneficial in many countries with or without access to conventional allopathic medicine. In the United States, these traditional practices are increasingly being sought after for illnesses that cannot be easily treated by allopathic medicine. More and more people are becoming interested in the knowledge maintained by traditional healers and in the diversity of medicinal plants that flourish in areas like Northern Peru. While scientific studies of medicinal plants are underway, concern has arisen over the preservation of both the large diversity of medicinal plants and the traditional knowledge of healing methods that accompanies them. To promote further conservation work, this study attempted to document the sources of the most popular and rarest medicinal plants sold in the markets of Trujillo (Mayorista and Hermelinda) and Chiclayo (Modelo and Moshoqueque), as well as to create an inventory of the plants sold in these markets, which will serve as a basis for comparison with future inventories. Individual markets and market stalls were subjected to cluster analysis based on the diversity of the medicinal plants they carry. The results show that markets were grouped based on the presence of: (1) common exotic medicinal plants; (2) plants used by laypeople for self-medication related to common ailments ("everyday remedies"); (3) specialized medicinal plants used by curanderos or traditional healers; and (4) highly "specialized" plants used for magical purposes. The plant trade in the study areas seems to correspond well with the specific health care demands from clientele in those areas. The specific market patterns of plant diversity observed in the present study represent a foundation for comparative market research in Peru and elsewhere