Transmembrane helix dynamics of bacterial chemoreceptors supports a piston model of signalling.

Transmembrane α-helices play a key role in many receptors, transmitting a signal from one side to the other of the lipid bilayer membrane. Bacterial chemoreceptors are one of the best studied such systems, with a wealth of biophysical and mutational data indicating a key role for the TM2 helix in signalling. In particular, aromatic (Trp and Tyr) and basic (Arg) residues help to lock α-helices into a membrane. Mutants in TM2 of E. coli Tar and related chemoreceptors involving these residues implicate changes in helix location and/or orientation in signalling. We have investigated the detailed structural basis of this via high throughput coarse-grained molecular dynamics (CG-MD) of Tar TM2 and its mutants in lipid bilayers. We focus on the position (shift) and orientation (tilt, rotation) of TM2 relative to the bilayer and how these are perturbed in mutants relative to the wildtype. The simulations reveal a clear correlation between small (ca. 1.5 Å) shift in position of TM2 along the bilayer normal and downstream changes in signalling activity. Weaker correlations are seen with helix tilt, and little/none between signalling and helix twist. This analysis of relatively subtle changes was only possible because the high throughput simulation method allowed us to run large (n = 100) ensembles for substantial numbers of different helix sequences, amounting to ca. 2000 simulations in total. Overall, this analysis supports a swinging-piston model of transmembrane signalling by Tar and related chemoreceptors

Frequent burning promotes invasions of alien plants into a mesic African savanna

Fire is both inevitable and necessary for maintaining the structure and functioning of mesic savannas. Without disturbances such as fire and herbivory, tree cover can increase at the expense of grass cover and over time dominate mesic savannas. Consequently, repeated burning is widely used to suppress tree recruitment and control bush encroachment. However, the effect of regular burning on invasion by alien plant species is little understood. Here, vegetation data from a long-term fire experiment, which began in 1953 in a mesic Zimbabwean savanna, were used to test whether the frequency of burning promoted alien plant invasion. The fire treatments consisted of late season fires, lit at 1-, 2-, 3-, and 4-year intervals, and these regularly burnt plots were compared with unburnt plots. Results show that over half a century of frequent burning promoted the invasion by alien plants relative to areas where fire was excluded. More alien plant species became established in plots that had a higher frequency of burning. The proportion of alien species in the species assemblage was highest in the annually burnt plots followed by plots burnt biennially. Alien plant invasion was lowest in plots protected from fire but did not differ significantly between plots burnt triennially and quadrennially. Further, the abundance of five alien forbs increased significantly as the interval (in years) between fires became shorter. On average, the density of these alien forbs in annually burnt plots was at least ten times as high as the density of unburnt plots. Plant diversity was also altered by long-term burning. Total plant species richness was significantly lower in the unburnt plots compared to regularly burnt plots. These findings suggest that frequent burning of mesic savannas enhances invasion by alien plants, with short intervals between fires favouring alien forbs. Therefore, reducing the frequency of burning may be a key to minimising the risk of alien plant spread into mesic savannas, which is important because invasive plants pose a threat to native biodiversity and may alter savanna functioning

Vitamin D levels in children and adolescents with chronic tic disorders: a multicentre study.

This study investigated whether vitamin D is associated with the presence or severity of chronic tic disorders and their psychiatric comorbidities. This cross-sectional study compared serum 25-hydroxyvitamin D [25(OH)D] (ng/ml) levels among three groups: children and adolescents (3-16 years) with CTD (n = 327); first-degree relatives (3-10 years) of individuals with CTD who were assessed for a period of up to 7 years for possible onset of tics and developed tics within this period (n = 31); and first-degree relatives who did not develop tics and were ≥ 10 years old at their last assessment (n = 93). The relationship between 25(OH)D and the presence and severity of tics, as well as comorbid obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD), were analysed controlling for age, sex, season, centre, latitude, family relatedness, and comorbidities. When comparing the CTD cohort to the unaffected cohort, the observed result was contrary to the one expected: a 10 ng/ml increase in 25(OH)D was associated with higher odds of having CTD (OR 2.08, 95% CI 1.27-3.42, p < 0.01). There was no association between 25(OH)D and tic severity. However, a 10 ng/ml increase in 25(OH)D was associated with lower odds of having comorbid ADHD within the CTD cohort (OR 0.55, 95% CI 0.36-0.84, p = 0.01) and was inversely associated with ADHD symptom severity (β = - 2.52, 95% CI - 4.16-0.88, p < 0.01). In conclusion, lower vitamin D levels were not associated with a higher presence or severity of tics but were associated with the presence and severity of comorbid ADHD in children and adolescents with CTD

Comparing ecosystem and soil respiration : Review and key challenges of tower-based and soil measurements

The net ecosystem exchange (NEE) is the difference between ecosystem CO2 assimilation and CO2 losses to the atmosphere. Ecosystem respiration (R-eco), the efflux of CO2 from the ecosystem to the atmosphere, includes the soil-to-atmosphere carbon flux (i.e., soil respiration; R-soil) and aboveground plant respiration. Therefore, R-soil is a fraction of R-eco and theoretically has to be smaller than R-eco at daily, seasonal, and annual scales. However, several studies estimating R-eco with the eddy covariance technique and measuring R-soll within the footprint of the tower have reported higher R-soil than R-eco, at different time scales. Here, we compare four different and contrasting ecosystems (from forest to grasslands, and from boreal to semiarid) to test if measurements of R-eco are consistently higher than R-soil. In general, both fluxes showed similar temporal patterns, but R-eco, was not consistently higher than R-soil from daily to annual scales across sites. We identified several issues that apply for measuring NEE and measuring/upscaling R-soil that could result in an underestimation of R-eco and/or an overestimation of R-soil. These issues are discussed based on (a) nighttime measurements of NEE, (b) R-soil measurements, and (c) the interpretation of the functional relationships of these fluxes with temperature (i.e., Q(10)). We highlight that there is still a need for better integration of R-soil with eddy covariance measurements to address challenges related to the spatial and temporal variability of R-eco, and R-soil.Peer reviewe

Measuring hospital-wide activity volume for patient safety and infection control: a multi-centre study in Japan

<p>Abstract</p> <p>Background</p> <p>In Japan, as in many other countries, several quality and safety assurance measures have been implemented since the 1990's. This has occurred in spite of cost containment efforts. Although government and hospital decision-makers demand comprehensive analysis of these activities at the hospital-wide level, there have been few studies that actually quantify them. Therefore, the aims of this study were to measure hospital-wide activities for patient safety and infection control through a systematic framework, and to identify the incremental volume of these activities implemented over the last five years.</p> <p>Methods</p> <p>Using the conceptual framework of incremental activity corresponding to incremental cost, we defined the scope of patient safety and infection control activities. We then drafted a questionnaire to analyze these realms. After implementing the questionnaire, we conducted several in-person interviews with managers and other staff in charge of patient safety and infection control in seven acute care teaching hospitals in Japan.</p> <p>Results</p> <p>At most hospitals, nurses and clerical employees acted as the main figures in patient safety practices. The annual amount of activity ranged from 14,557 to 72,996 person-hours (per 100 beds: 6,240; per 100 staff: 3,323) across participant hospitals. Pharmacists performed more incremental activities than their proportional share. With respect to infection control activities, the annual volume ranged from 3,015 to 12,196 person-hours (per 100 beds: 1,141; per 100 staff: 613). For infection control, medical doctors and nurses tended to perform somewhat more of the duties relative to their share.</p> <p>Conclusion</p> <p>We developed a systematic framework to quantify hospital-wide activities for patient safety and infection control. We also assessed the incremental volume of these activities in Japanese hospitals under the reimbursement containment policy. Government and hospital decision makers can benefit from this type of analytic framework and its empirical findings.</p

Internalisation Theory and outward direct investment by emerging market multinationals

The rise of multinational enterprises from emerging countries (EMNEs) poses an important test for theories of the multinational enterprise such as internalisation theory. It has been contended that new phenomena need new theory. This paper proposes that internalisation theory is appropriate to analyse EMNEs. This paper examines four approaches to EMNEs—international investment strategies, domestic market imperfections, international corporate networks and domestic institutions—and three case studies—Chinese outward FDI, Indian foreign acquisitions and investment in tax havens—to show the enduring relevance and predictive power of internalisation theory. This analysis encompasses many other approaches as special cases of internalisation theory. The use of internalisation theory to analyse EMNEs is to be commended, not only because of its theoretical inclusivity, but also because it has the ability to connect and to explain seemingly desperate phenomena

Hydrocarbons Are Essential for Optimal Cell Size, Division, and Growth of Cyanobacteria.

Cyanobacteria are intricately organized, incorporating an array of internal thylakoid membranes, the site of photosynthesis, into cells no larger than other bacteria. They also synthesize C15-C19 alkanes and alkenes, which results in substantial production of hydrocarbons in the environment. All sequenced cyanobacteria encode hydrocarbon biosynthesis pathways, suggesting an important, undefined physiological role for these compounds. Here, we demonstrate that hydrocarbon-deficient mutants of $\textit{Synechocystis }$ sp. PCC 7002 and $\textit{Synechocystis }$ sp. PCC 6803 exhibit significant phenotypic differences from wild type, including enlarged cell size, reduced growth, and increased division defects. Photosynthetic rates were similar between strains, although a minor reduction in energy transfer between the soluble light harvesting phycobilisome complex and membrane-bound photosystems was observed. Hydrocarbons were shown to accumulate in thylakoid and cytoplasmic membranes. Modeling of membranes suggests these compounds aggregate in the center of the lipid bilayer, potentially promoting membrane flexibility and facilitating curvature. In vivo measurements confirmed that $\textit{Synechocystis }$ sp. PCC 7002 mutants lacking hydrocarbons exhibit reduced thylakoid membrane curvature compared to wild type. We propose that hydrocarbons may have a role in inducing the flexibility in membranes required for optimal cell division, size, and growth, and efficient association of soluble and membrane bound proteins. The recent identification of C15-C17 alkanes and alkenes in microalgal species suggests hydrocarbons may serve a similar function in a broad range of photosynthetic organisms.T.L. was supported by BBSRC Research Grant BB/J016985/1 to C.W.M. D.J.L-S. was supported by the Environmental Services Association Education Trust. L.L.B was supported by a BBSRC Doctoral Training Grant (BB/F017464/1)

Hydrocarbons Are Essential for Optimal Cell Size, Division, and Growth of Cyanobacteria.

Cyanobacteria are intricately organized, incorporating an array of internal thylakoid membranes, the site of photosynthesis, into cells no larger than other bacteria. They also synthesize C15-C19 alkanes and alkenes, which results in substantial production of hydrocarbons in the environment. All sequenced cyanobacteria encode hydrocarbon biosynthesis pathways, suggesting an important, undefined physiological role for these compounds. Here, we demonstrate that hydrocarbon-deficient mutants of $\textit{Synechocystis }$ sp. PCC 7002 and $\textit{Synechocystis }$ sp. PCC 6803 exhibit significant phenotypic differences from wild type, including enlarged cell size, reduced growth, and increased division defects. Photosynthetic rates were similar between strains, although a minor reduction in energy transfer between the soluble light harvesting phycobilisome complex and membrane-bound photosystems was observed. Hydrocarbons were shown to accumulate in thylakoid and cytoplasmic membranes. Modeling of membranes suggests these compounds aggregate in the center of the lipid bilayer, potentially promoting membrane flexibility and facilitating curvature. In vivo measurements confirmed that $\textit{Synechocystis }$ sp. PCC 7002 mutants lacking hydrocarbons exhibit reduced thylakoid membrane curvature compared to wild type. We propose that hydrocarbons may have a role in inducing the flexibility in membranes required for optimal cell division, size, and growth, and efficient association of soluble and membrane bound proteins. The recent identification of C15-C17 alkanes and alkenes in microalgal species suggests hydrocarbons may serve a similar function in a broad range of photosynthetic organisms.T.L. was supported by BBSRC Research Grant BB/J016985/1 to C.W.M. D.J.L-S. was supported by the Environmental Services Association Education Trust. L.L.B was supported by a BBSRC Doctoral Training Grant (BB/F017464/1)

A Comparative Study of National Infrastructures for Digital (Open) Educational Resources in Higher Education

This paper reports on the first stage of an international comparative study for the project “Digital educational architectures: Open learning resources in distributed learning infrastructures–EduArc”, funded by the German Federal Ministry of Education and Research. This study reviews the situation of digital educational resources (or (O)ER) framed within the digital transformation of ten different Higher Education (HE) systems (Australia, Canada, China, Germany, Japan, South Africa, South Korea, Spain, Turkey and the United States). Following a comparative case study approach, we investigated issues related to the existence of policies, quality assurance mechanisms and measures for the promotion of change in supporting infrastructure development for (O)ER at the national level in HE in the different countries. The results of this mainly documentary research highlight differences and similarities, which are largely due to variations in these countries’ political structure organisation. The discussion and conclusion point at the importance of understanding each country’s context and culture, in order to understand the differences between them, as well as the challenges they face

A two-domain elevator mechanism for sodium/proton antiport

Sodium/proton (Na+/H+) antiporters, located at the plasma membrane in every cell, are vital for cell homeostasis1. In humans, their dysfunction has been linked to diseases, such as hypertension, heart failure and epilepsy, and they are well-established drug targets2. The best understood model system for Na+/H+ antiport is NhaA from Escherichia coli1, 3, for which both electron microscopy and crystal structures are available4, 5, 6. NhaA is made up of two distinct domains: a core domain and a dimerization domain. In the NhaA crystal structure a cavity is located between the two domains, providing access to the ion-binding site from the inward-facing surface of the protein1, 4. Like many Na+/H+ antiporters, the activity of NhaA is regulated by pH, only becoming active above pH 6.5, at which point a conformational change is thought to occur7. The only reported NhaA crystal structure so far is of the low pH inactivated form4. Here we describe the active-state structure of a Na+/H+ antiporter, NapA from Thermus thermophilus, at 3 Å resolution, solved from crystals grown at pH 7.8. In the NapA structure, the core and dimerization domains are in different positions to those seen in NhaA, and a negatively charged cavity has now opened to the outside. The extracellular cavity allows access to a strictly conserved aspartate residue thought to coordinate ion binding1, 8, 9 directly, a role supported here by molecular dynamics simulations. To alternate access to this ion-binding site, however, requires a surprisingly large rotation of the core domain, some 20° against the dimerization interface. We conclude that despite their fast transport rates of up to 1,500 ions per second3, Na+/H+ antiporters operate by a two-domain rocking bundle model, revealing themes relevant to secondary-active transporters in general