Modeling chemotaxis reveals the role of reversed phosphotransfer and a bi-functional kinase-phosphatase

Understanding how multiple signals are integrated in living cells to produce a balanced response is a major challenge in biology. Two-component signal transduction pathways, such as bacterial chemotaxis, comprise histidine protein kinases (HPKs) and response regulators (RRs). These are used to sense and respond to changes in the environment. Rhodobacter sphaeroides has a complex chemosensory network with two signaling clusters, each containing a HPK, CheA. Here we demonstrate, using a mathematical model, how the outputs of the two signaling clusters may be integrated. We use our mathematical model supported by experimental data to predict that: (1) the main RR controlling flagellar rotation, CheY6, aided by its specific phosphatase, the bifunctional kinase CheA3, acts as a phosphate sink for the other RRs; and (2) a phosphorelay pathway involving CheB2 connects the cytoplasmic cluster kinase CheA3 with the polar localised kinase CheA2, and allows CheA3-P to phosphorylate non-cognate chemotaxis RRs. These two mechanisms enable the bifunctional kinase/phosphatase activity of CheA3 to integrate and tune the sensory output of each signaling cluster to produce a balanced response. The signal integration mechanisms identified here may be widely used by other bacteria, since like R. sphaeroides, over 50% of chemotactic bacteria have multiple cheA homologues and need to integrate signals from different sources

Cross-culturally adapted psychological interventions for the treatment of depression and/or anxiety among young people: A scoping review

BACKGROUND: Mental health problems among young people are a major global public health challenge. Psychological interventions may improve mental health, yet most are developed in western cultures, and it is unclear whether they are applicable to other geographical settings and can be delivered successfully to diverse populations. We identified empirical studies focusing upon cross-culturally adapted psychological interventions and examined the cultural adaptation process used and the effectiveness of the interventions in the treatment of depression and/or anxiety disorders among young people (defined here as children and adolescents aged between 8-18 years). METHOD: We conducted a scoping review aligning to the guidelines reported in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR) Statement. Stakeholder engagement enabled us to discuss the findings of the review and obtain feedback. RESULTS: We identified 17 studies of cross-culturally adapted psychological interventions that considered the appropriate language, metaphors, culturally appropriate terms, and cultural values of young people. Most studies (n = 11) adopted a randomised control trial (RCT) methodology. Six studies used the ecological validity and cultural sensitivity framework. Planned adaptation, cultural adaptation of content, and surface and deep structure level adaptations were used in other studies. Apart from one pilot study, all studies reported that culturally adapted interventions resulted in improvements in depression and/or anxiety symptoms in young people. The results suggest the potential effectiveness of cross-culturally adapted interventions within this context. Our stakeholder consultations demonstrated that engaging different community-level stakeholders in the adaptation process was highly recommended. CONCLUSIONS: Whilst most included studies indicated improvements in depression and/or anxiety symptoms in young people following a cross-culturally adapted intervention, more work is needed in this area. In particular, focus should be placed upon identifying the dimensions of interventions that should be culturally adapted to make them acceptable, engaging and effective

The effects of phonics in reading and writing programs for young children

Phonics is being taught in many kindergartens and .most first grades in the nation to introduce children to reading and writing. A large number of educators believe that phonics instruction is necessary for children to learn to read and to spell, but many psycholinguists question the value of this instruction (M. Manning, G. Manning, & C. Kamii, 1988). The teaching of phonics has been a source of controversy since Rudolf Flesch\u27s (1955) book, Why Johnny Can\u27t Read. Chall (1967) addressed the debate in her book, Learning to Read: The Great Debate, concluding that a code-emphasis approach produced better reading achievement than a meaning-emphasis one. Since the publication of Chall\u27s book, there has been a movement towards greater code-emphasis approaches in beginning reading until the popularity of whole language approach that has been building over the last ten years and continues today

Geographical Differences in the Forefoot Morphology – A Comparative Radiological Study of Feet in Malawi and UK

Background: Many skeletal morphological differences between populations have been reported with possible but unproven clinical importance. This study was aimed at identifying the normal radiographic findings and measurements seen in patients from Southern Africa and compares them to a European population’s values.Methods: AP foot radiographs of 40 adults from Blantyre, Malawi were compared with those of 40 adults from London, UK. For each patient, measurements were taken of: 1st and 2nd metatarsal lengths, the 1st/2nd intermetatarsal angle, the 1st metatarso- phalangeal angle (the ‘bunion’ angle), and the 2nd metatarsal mortice joint medial and lateral depths.Results: Our results show an increased 1st/2nd metatarsal angle in Malawian feet, but a reduced ‘bunion’ angle. We also found the second metatarsal length to be longer relative to the first in the Malawian foot, and the 2nd metatarsal base to be significantly more covered by its mortice than in UK feet.Conclusion: This racial anatomical variation may convey more stability and less risk of a Lisfranc dislocation. It is also important to be aware of the normal range of these values when considering the need for forefoot arthroplasty procedures

Theory of commensurable magnetic structures in holmium

The tendency for the period of the helically ordered moments in holmium to lock into values which are commensurable with the lattice is studied theoretically as a function of temperature and magnetic field. The commensurable effects are derived in the mean-field approximation from numerical calculations of the free energy of various commensurable structures, and the results are compared with the extensive experimental evidence collected during the last ten years on the magnetic structures in holmium. In general the stability of the different commensurable structures is found to be in accord with the experiments, except for the tau=5/18 structure observed a few degrees below T_N in a b-axis field. The trigonal coupling recently detected in holmium is found to be the interaction required to explain the increased stability of the tau=1/5 structure around 42 K, and of the tau=1/4 structure around 96 K, when a field is applied along the c-axis.Comment: REVTEX, 31 pages, 7 postscript figure

The effect of community interventions on alcohol-related assault in Geelong, Australia

Alcohol has consistently been demonstrated to increase levels of aggression and violence, particularly in late night licensed venues. Since 2005, the City of Geelong in Australia has implemented a substantial number of interventions to reduce alcohol related violence, including a liquor accord, increased police surveillance, ID scanners, CCTV, a radio network and an alcohol industry sponsored social marketing campaign. The aim of the current study is to assess the individual and collective impact of community interventions on indicators of alcohol-related assaults in the Geelong region. This paper reports stage one findings from the Dealing with Alcohol-related problems in the Night-time Economy project (DANTE) and specifically examines assault rate data from both emergency department presentations, ICD-10 classification codes, and police records of assaults. None of the interventions were associated with reductions in alcohol-related as-sault or intoxication in Geelong, either individually or when combined. However, the alcohol industry sponsored social marketing campaign ‘Just Think’ was associated with an increase in assault rates. Community level interventions appeared to have had little effect on assault rates during high alcohol times. It is also possible that social marketing campaigns without practical strategies are associated with increased assault rates. The findings also raise questions about whether interventions should be targeted at reducing whole-of-community alcohol consumption

A high-density immunoblotting methodology for quantification of total protein levels and phosphorylation modifications

The components of many signaling pathways have been identified and there is now a need to conduct quantitative data-rich temporal experiments for systems biology and modeling approaches to better understand pathway dynamics and regulation. Here we present a modified Western blotting method that allows the rapid and reproducible quantification and analysis of hundreds of data points per day on proteins and their phosphorylation state at individual sites. The approach is of particular use where samples show a high degree of sample-to-sample variability such as primary cells from multiple donors. We present a case study on the analysis of >800 phosphorylation data points from three phosphorylation sites in three signaling proteins over multiple time points from platelets isolated from ten donors, demonstrating the technique's potential to determine kinetic and regulatory information from limited cell numbers and to investigate signaling variation within a population. We envisage the approach being of use in the analysis of many cellular processes such as signaling pathway dynamics to identify regulatory feedback loops and the investigation of potential drug/inhibitor responses, using primary cells and tissues, to generate information about how a cell's physiological state changes over time

The role of atmospheric CO2 in controlling sea surface temperature change during the Pliocene,

We present the role of CO2 forcing in controlling Late Pliocene sea surface temperature (SST) change using six models from Phase 2 of the Pliocene Model Intercomparison Project (PlioMIP2) and palaeoclimate proxy data from the PlioVAR working group. At a global scale, SST change in the Late Pliocene relative to the pre-industrial is predominantly driven by CO2 forcing in the low and mid-latitudes and non-CO2 forcing in the high latitudes. We find that CO2 is the dominant driver of SST change at the vast majority of proxy data sites assessed (17 out of 19), but the relative dominance of this forcing varies between all proxy sites, with CO2 forcing accounting for between 27 % and 82 % of the total change seen. The dearth of proxy data sites in the high latitudes means that only two sites assessed here are predominantly forced by non-CO2 forcing (such as changes to ice sheets and orography), both of which are in the North Atlantic Ocean.We extend the analysis to show the seasonal patterns of SST change and its drivers at a global scale and at a site-specific level for three chosen proxy data sites. We also present a new estimate of Late Pliocene climate sensitivity using site-specific proxy data values. This is the first assessment of site-specific drivers of SST change in the Late Pliocene and highlights the strengths of using palaeoclimate proxy data alongside model outputs to further develop our understanding of the Late Pliocene. We use the best available proxy and model data, but the sample sizes remain limited, and the confidence in our results would be improved with greater data availability