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The bio-synthesis of pyoverdine (PVD) in Pseudomonas aeruginosa involves multiple enzymatic steps including the action of non-ribosomal peptide synthetases (NRPSs). One hallmark of NRPS is their ability to make usage of non-proteinogenic amino-acids synthesized by co-expressed accessory enzymes. It is generally proposed that different enzymes of a secondary metabolic pathway assemble into large supra-molecular complexes. However, evidence for the assembly of sequential enzymes in the cellular context is sparse. Here, we used in cellulo single-molecule tracking and Förster resonance energy transfer measured by fluorescence lifetime microscopy (FRET-FLIM) to explore the spatial partitioning of the ornithine hydroxylase PvdA and its interactions with NRPS. We found PvdA was mostly diffusing bound to large complexes in the cytoplasm with a small exchangeable trapped fraction. FRET-FLIM clearly showed that PvdA is physically interacting with PvdJ, PvdI, PvdL, and PvdD, the four NRPS involved in the PVD pathway in Pseudomonas aeruginosa PAO1. The binding modes of PvdA were strikingly different according to the NRPS it is interacting with, suggesting that PvdA binding sites have co-evolved with the enzymatic active sites of NRPS. Our data provide evidence for strongly organized multi-enzymatic complexes responsible for the bio-synthesis of PVD and illustrate how binding sites have evolved to finely control the co-localization of sequential enzymes and promote metabolic pathway efficiency.
Native language (L1) processing draws on implicit expectations. An open question is whether non-native learners of a second language (L2) similarly draw on expectations, and whether these expectations are based on learners’ L1 or L2 knowledge. We approach this question by studying inverse preference effects on lexical encoding. L1 and L2 speakers of Spanish described motion events, while they were either primed to express path, manner, or neither. In line with other work, we find that L1 speakers adapted more strongly after primes that are unexpected in their L1. For L2 speakers, adaptation depended on their L2 proficiency: The least proficient speakers exhibited the inverse preference effect on adaptation based on what was unexpected in their L1; but the more proficient speakers were, the more they exhibited inverse preference effects based on what was unexpected in the L2. We discuss implications for L1 transfer and L2 acquisition.
Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS) are two imprinting disorders associated with opposite molecular alterations in the 11p15.5 imprinting centres. Their clinical diagnosis is confirmed by molecular testing in 50–70% of patients. The authors from different reference centres for BWS and SRS have identified single patients with unexpected and even contradictory molecular findings in respect to the clinical diagnosis. These patients clinically do not fit the characteristic phenotypes of SRS or BWS, but illustrate their clinical heterogeneity. Thus, comprehensive molecular testing is essential for accurate diagnosis and appropriate management, to avoid premature clinical diagnosis and anxiety for the families.
The nucleocapsid protein NC is a crucial component in the human immunodeficiency virus type 1 life cycle. It functions both in its processed mature form and as part of the polyprotein Gag that plays a key role in the formation of new viruses. NC can protect nucleic acids (NAs) from degradation by compacting them to a dense coil. Moreover, through its NA chaperone activity, NC can also promote the most stable conformation of NAs. Here, we explore the balance between these activities for NC and Gag by confining DNA–protein complexes in nanochannels. The chaperone activity is visualized as concatemerization and circularization of long DNA via annealing of short single-stranded DNA overhangs. The first ten amino acids of NC are important for the chaperone activity that is almost completely absent for Gag. Gag condenses DNA more efficiently than mature NC, suggesting that additional residues of Gag are involved. Importantly, this is the first single DNA molecule study of full-length Gag and we reveal important differences to the truncated Δ-p6 Gag that has been used before. In addition, the study also highlights how nanochannels can be used to study reactions on ends of long single DNA molecules, which is not trivial with competing single DNA molecule techniques.
A comparative study was undertaken to adopt and evaluate a radiocarbon (14C) preparation procedure for accelerator mass spectrometry (AMS) measurements of cremated bones at our laboratory, including different types of archaeological samples (cremated bone, bone, charcoal, charred grain). All 14C analyses were performed using the EnvironMICADAS AMS instrument at the Hertelendi Laboratory of Environmental Studies (HEKAL) and the ancillary analyses were also performed at the Institute for Nuclear Research (ATOMKI). After the physical and chemical cleaning of cremated bones, CO2 was extracted by acid hydrolysis followed by sealed-tube graphitization and 14C measurement. The supplementary δ13C measurements were also performed on CO2 gas while FTIR was measured on the powder fraction. Based on the FTIR and 14C analyses, our chemical pretreatment protocol was successful in removing contamination from the samples. Good reproducibility was obtained for the 0.2–0.3 mm fraction of blind-tested cremated samples and a maximum age difference of only 150 yr was found for the remaining case studies. This confirms the reliability of our procedure for 14C dating of cremated bones. However, in one case study, the age difference of 300 yr between two cremated fragments originating from the same urn shows that other processes affecting the cremated samples in the post-burial environment can substantially influence the 14C age, so caution must be exercised.
Common bean (Phaseolus vulgaris L.) is amongst the most important grain legume crops in Africa in general, and Ethiopia in particular. The Mexican been weevil (Zabrotes subfasciatus Boheman) heavily attacks the grain of common bean. A total of 300 common bean entries were subjected to a ‘no-choice’ test at Melkassa Agricultural Research Centre, Ethiopia, using a randomized complete block design with three replications, to evaluate for resistance to the Mexican bean weevil. Data on insect and seed traits were collected and a significant level (P<0.01) of variation in all parameters measured was observed amongst genotypes. Relative resistance was recorded in landraces, improved genotypes and breeding lines, but the resistant genotypes, RAZ-11, RAZ-36, RAZ-2, RAZ-44, RAZ-120, RAZ-40 and MAZ-203, showed consistently complete resistance, with zero index of susceptibility value. Two other promising entries were also identified from the breeding lines (SCR-11) and landrace collections (NC-16) of Ethiopia. Stratified ranking diagrams showed that accessions from different eco-geographical origins in Ethiopia and those with different colours showed different patterns of response to infestation. The Ethiopian bean breeding programme should take up the resistant genotypes for a comprehensive yield trial at the national level and direct release them as commercial varieties. The incorporation of bean weevil resistance genes into adapted varieties through backcross breeding techniques, supported with marker assisted selection, seems to be the best strategy not only in terms of time saving but also in terms of effectiveness and efficiency.
The dwarf galaxies in the Local Group (LG) reveal a surprising amount of spatial structuring. In particular, almost all non-satellite dwarfs belong to one of two planes that show a very pronounced symmetry. In order to determine if these structures in the LG are dynamically stable or, alternatively, if they only represent transient alignments, proper motion measurements of these galaxies are required. A viable method to derive proper motions is offered by VLBI studies of 22-GHz water (and 6.7-GHz methanol) maser lines in star-forming regions.
In 2016, in the framework of the Early Science Program of the Sardinia Radio Telescope (SRT), we have conducted an extensive observational campaign to map the entire optical body of all the LG dwarf galaxies that belong to the two planes, at C and K band, in a search for methanol and water maser emission.
Here, we outline the project and present its first results on 3 targets, NGC 6822, IC 1613, and WLM. While no luminous maser emission has been detected in these galaxies, a number of interesting weaker detections has been obtained, associated with particularly active star forming regions. In addition, we have produced deep radio continuum maps for these galaxies, aimed at investigating their star forming activity and providing an improved assessment of star formation rates in these galaxies.
The Sardinia Radio Telescope (SRT) is a modern, fully-steerable 64-m dish located in San Basilio, Sardinia (Italy). It is characterized by an active surface that allows it to cover a wide range of radio frequencies (300 MHz to 100 GHz). During SRT’s commissioning phase, we installed the hardware and software needed for pulsar observations. Since then, SRT has taken part in Large European Array for Pulsars and European Pulsar Timing Array observations for the purpose of gravitational wave detection. We have installed a new S-band receiver that will allow us to search for pulsars in the Galactic Center. We also plan to combine our efforts to search for Extraterrestrial Intelligence (SETI) with the search for pulsars and Fast Radio Bursts.
Dementia is a neurodegenerative syndrome that interferes with multiple aspects of life, including cognition, daily functioning, and behavior. Despite the large heterogeneity in symptom development, these three domains are seldom studied simultaneously. This study investigates how trajectories of these domains are interrelated within individuals over time, and how they in turn are related to dementia severity and quality of life (QoL).
We used data from a longitudinal clinical cohort study, including 331 dementia patients. Cognitive status was measured using the Mini-Mental State Examination, daily functioning was measured with the disability assessment for dementia and neuropsychiatric symptoms (NPS) were scored using the neuropsychiatric inventory. We investigated the relationships in the time course of the various dementia domains using random effects multilevel models and parallel-process growth models.
Changes in cognition and daily functioning were highly correlated over time (r = 0.85, p < 0.01), as were changes in NPS and functioning (r = −0.60, p < 0.01), while changes in cognition and NPS were not (r = −0.20, p = 0.06). All three domains were strongly associated with dementia severity over time (p < 0.01). Decreased functioning and increased NPS were both associated with decreased QoL (β = 2.97, p < 0.01 and β = −2.41, p < 0.01, respectively), while cognition was not (β = 0.01, p = 0.93).
This study demonstrates the heterogeneity of dementia progression between individuals and between different dementia domains within individuals. To improve our understanding of dementia progression, future research should embrace a broader perspective encompassing multiple outcome measures along with the patient's profile, including neurological factors as well as physical, social, and psychiatric health.
In the framework of the Astronomical Validation and Early Science activities of the Sardinia Radio Telescope (SRT, www.srt.inaf.it), we performed 22 GHz imaging observations of SNR W44 and IC443. Thanks to the single-dish imaging performances of SRT and innovative ad hoc imaging techniques, we obtained maps that provide a detailed view of the structure of the remnants. We are planning to exploit the high-frequency radio data of SNRs to better characterize the spatially-resolved spectra and search for possible spectral steepening or breaks in selected SNR regions, assessing the high-energy tail of the region-dependent electron distribution.
Su Fossu de Cannas (SFC) cave is one of several known cavities in the Sadali plateau in Sardinia, Italy. The evolution of the cave is the result of complex erosional and deposital processes that occurred during the Neogene and Quaternary. A fossiliferous cemented conglomerate, containing various deer remains, now forms the ceiling of a cavity (tunnel). The faunal remains belong to a large cervid, which show some morphological affinity with large deer that have an endemic Sardinian lineage (Praemegaceros sardous — Praemegaceros cazioti). Palaeoecological data based on some peculiar features and the large size of the SFC deer suggest that it is the most primitive Megacerine found in Sardinia to date, and the first representative of the endemic lineage. The 450 ka U—Th age for the flowstone capping the fossiliferous layer defines: the end of sedimentation in which Sadali deer remains are preserved; and the dispersal from the mainland of the ancestor of the endemic Sardinian Megacerini. Stratigraphic and micromorphological analyses of the cave deposits allow the reconstruction of the timing of the cave’s development throughout the Pliocene to the Holocene.
We study the interaction of relativistic jets with their environment, using 3-dimen- sional relativistic particle-in-cell simulations for two cases of jet composition: (i) electron-proton (e− − p+) and (ii) electron-positron (e±) plasmas containing helical magnetic fields. We have performed simulations of “global” jets containing helical magnetic fields in order to examine how helical magnetic fields affect kinetic instabilities such as the Weibel instability, the kinetic Kelvin-Helmholtz instability and the Mushroom instability. We have found that these kinetic instabilities are suppressed and new types of instabilities can grow. For the e− − p+ jet, a recollimation-like instability occurs and jet electrons are strongly perturbed, whereas for the e± jet, a recollimation-like instability occurs at early times followed by kinetic instability and the general structure is similar to a simulation without a helical magnetic field. We plan to perform further simulations using much larger systems to confirm these new findings.
Does the way we talk about events correspond to how we conceptualize them? Three experiments (N = 135) examined how Spanish and Swedish native speakers judge event similarity in the domain of caused motion (‘He rolled the tyre into the barn’). Spanish and Swedish motion descriptions regularly encode path (‘into’), but differ in how systematically they include manner information (‘roll’). We designed a similarity arrangement task which allowed participants to give varying weights to different dimensions when gauging event similarity. The three experiments progressively reduced the likelihood that speakers were using language to solve the task. We found that, as long as the use of language was possible (Experiments 1 and 2), Swedish speakers were more likely than Spanish speakers to base their similarity arrangements on object manner (rolling/sliding). However, when recruitment of language was hindered through verbal interference, cross-linguistic differences disappeared (Experiment 3). A compound analysis of all experiments further showed that (i) cross-linguistic differences were played out against a backdrop of commonly represented event components, and (ii) describing vs. not describing the events did not augment cross-linguistic differences, but instead had similar effects across languages. We interpret these findings as suggesting a dynamic role of language in event conceptualization.
In accordance with strict requirements of portability, cheapness, and modularity, an innovative assistive device for hand disabilities has been developed and validated. This robotic orthosis is designed to be a low-cost, portable hand exoskeleton to assist people with physical disabilities in their everyday lives. Referring to hand opening disabilities, the authors have developed a methodology which, by starting from the geometrical characteristics of the patient's hand, defines the novel kinematic mechanism that better fits to the finger trajectories. The authors have validated the proposed novel mechanism by carrying out a Hand Exoskeleton System (HES) prototype, based on a single-phalanx mechanism, cable driven. The testing phase of the real prototype with a patient is currently on going.
Main sequence stars hosting extreme quantities of inner planetary system debris are likely experiencing transient dust production events. The nature of these events, if they can be unambiguously attributed to a single process, can potentially inform us on the formation and/or early evolution of rocky Earth-like planets. In this contribution I examine some of the dustiest main sequence stars known and three processes that may be capable of reproducing their observed properties. Through this activity I also make an estimate for the likelihood of an A-type star to have an asteroid belt-like planetesimal population.
CONTROVERSY OVER MYANMAR AND CAMBODIA's MEMBERSHIP
ASEAN was mired in controversy over the admission of new members. Just as ASEAN was preparing for the ASEAN Ministerial Summit in July 1997 and its thirtieth anniversary celebrations, Cambodia was caught in a power struggle. Cambodia's second prime minister, Hun Sen, staged a coup to oust Prince Ranariddh as first prime minister. As a consequence, ASEAN decided to delay Cambodia's admission into ASEAN. ASEAN's decision was to drive home the point that no leadership or form of government by violent means was ever to be encouraged.
The deferment of Cambodia's membership juxtaposed against the admission of Myanmar earned ASEAN a lot of flak for its inconsistency and double standard. ASEAN's position was that while Myanmar's political conditions were regarded as internal matters of the state, Cambodia's case was viewed differently. The latter was regarded as one that had serious implications for ASEAN since Cambodia broke the regional norm of the non-use of force. As a consequence, ASEAN insisted that Cambodia met certain conditions before its admission, which included among others, the holding of free and fair elections and the establishment of the Cambodian Senate. ASEAN also formed the ASEAN Troika to deal with efforts at restoring political stability in Cambodia. However, ASEAN's drawing of a distinction between the cases of Myanmar and Cambodia based on the norms of non-interference and non-use of force was not lost on its critics.
Controversy notwithstanding, the Cam-bodian episode eventually led to the formal establishment of the ASEAN Troika in 1999. As defined by its experience in Cambodia, the ASEAN Troika was to be an ad hoc body comprising the ASEAN Foreign Ministers of the present, past, and future chairs of the ASEAN Standing Committee (ASC). The positions would rotate in accordance with the ASC's chairmanship. The purpose of the Troika was to enable ASEAN to address urgent and important political and security issues in a timely manner. However, the mandate of the Troika as stipulated in the Troika paper had to be compatible with the principles enshrined in the TAC, particularly the core principles of consensus and non-interference in domestic affairs of states.
THE REGIONAL HAZE PROBLEM
The regional challenges brought on by the financial crisis were exacerbated by the onset of the haze problem that enveloped most of Southeast Asia between 1997 and 1998.
This paper addresses the financing of public pensions in a stochastic environment. Traditionally, funded and unfunded pension schemes have been viewed as opposite solutions for the first pillar of public pensions. However, more recently countries as Sweden and Poland have explored mixed solutions that combine pay-as-you-go (PAYG) with funding mechanisms. The aims of this paper are to examine the rationality of such a combination using portfolio theory arguments and to find the optimal split of the contributions between the two systems. We first introduce the classical deterministic model leading to the well-known Samuelson–Aaron rule according to which diversification is never optimal. We then introduce different stochastic models in which the main processes (wage growth, population growth, financial rate of return) are random. In particular, we obtain conditions on parameters to justify diversification and explicit optimal sharing between PAYG and funding. We also introduce the possibility of investing in several financial assets and explore the impact of introducing systematic longevity risk.