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Tuberculosis (TB) is an infectious and contagious disease that poses a challenge in pediatric practice, since children can present rare manifestations, which makes their diagnosis difficult. Five cases of uncommon manifestations of TB are Residência Pediátrica; 2023: Ahead of Print. DOI: 10.25060/residpediatr-2023-598 presented in children vaccinated with BCG at birth and with no history of previous contact with bacilliferous adults. The difficulty and importance of the diagnostic suspicion of TB in rare cases of the disease in children is emphasized.

Cruise CAGE18-5 was the first research expedition under the helm of UiT The Arctic University of Norway in Tromsø with the new ice-going research vessel R/V Kronprins Håkon. This new vessel provides new opportunities to collect cross-disciplinary data for addressing the objectives of the Norwegian Centre of Excellence for Arctic Gas Hydrate, Environment and Climate, CAGE. CAGE investigates Arctic gas hydrate and methane seepage systems in order to better understand the effects they may have on our oceans, ecosystems and global climate. The new research vessel and its facilities allows CAGE access to a state-of-art remotely-operated vehicle, the ROV Ægir 6000, opening a new domain for experimental work and acquisition of sample material from the seafloor. The overall goal of cruise CAGE18-5 therefore was to utilize the ROV in order to provide guided video imagery and to study active gas seepage systems at the gas-hydrate pingo (GHP) site located in the outer Storfjord Trough, and at Storbanken in the northeastern part of the Barents Sea. The cruise may be known as: CAGE18_5

Background Understanding the specificity and flexibility of the algal symbiosis-host association is fundamental for predicting how species occupy a diverse range of habitats. Here we assessed the algal symbiosis diversity of three species of larger benthic foraminifera from the genus Amphistegina and investigated the role of habitat and species identity in shaping the associated algal community. Results We used next-generation sequencing to identify the associated algal community, and DNA barcoding to identify the diatom endosymbionts associated with species of A. lobifera, A. lessonii, and A. radiata, collected from shallow habitats (A. lobifera and A. lessonii, while A. radiata specimens host predominately diatoms of the order Triceratiales. Conclusions We show that local habitat is the main factor influencing the overall composition of the algal symbiont community. However, host identity and the phylogenetic relationship among hosts is relevant in shaping the specific endosymbiont diatom community, suggesting that the relationship between diatom endosymbiont and hosts plays a crucial role in the evolutionary history of the genus Amphistegina. The capacity of Amphistegina species to associate with a diverse array of diatoms, and possibly other algal groups, likely underpins the ecological success of these crucial calcifying organisms across their extensive geographic range.

Large benthic foraminifera are major carbonate components in tropical carbonate platforms, important carbonate producers, stratigraphic tools and powerful bioindicators (proxies) of environmental change. The application of large benthic foraminifera in tropical coral reef environments has gained considerable momentum in recent years. These modern ecological assessments are often carried out by micropalaeontologists or ecologists with expertise in the identification of foraminifera. However, large benthic foraminifera have been under‐represented in favour of macro reef‐builders, for example, corals and calcareous algae. Large benthic foraminifera contribute about 5% to modern reef‐scale carbonate sediment production. Their substantial size and abundance are reflected by their symbiotic association with the living algae inside their tests. When the foraminiferal holobiont (the combination between the large benthic foraminifera host and the microalgal photosymbiont) dies, the remaining calcareous test renourishes sediment supply, which maintains and stabilizes shorelines and low‐lying islands. Geological records reveal episodes (i.e. late Palaeocene and early Eocene epochs) of prolific carbonate production in warmer oceans than today, and in the absence of corals. This begs for deeper consideration of how large benthic foraminifera will respond under future climatic scenarios of higher atmospheric carbon dioxide (pCO2) and to warmer oceans. In addition, studies highlighting the complex evolutionary associations between large benthic foraminifera hosts and their algal photosymbionts, as well as to associated habitats, suggest the potential for increased tolerance to a wide range of conditions. However, the full range of environments where large benthic foraminifera currently dwell is not well‐understood in terms of present and future carbonate production, and impact of stressors. The evidence for acclimatization, at least by a few species of well‐studied large benthic foraminifera, under intensifying climate change and within degrading reef ecosystems, is a prelude to future host–symbiont resilience under different climatic regimes and habitats than today. This review also highlights knowledge gaps in current understanding of large benthic foraminifera as prolific calcium carbonate producers across shallow carbonate shelf and slope environments under changing ocean conditions., Minerva Foundation http://dx.doi.org/10.13039/501100001658, Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659

We present an algorithm to insert a train path in an existing railway timetable close to operation, when we want to affect the existing (passenger) traffic as little as possible. Thus, we consider all other trains as fixed, and aim for a resulting train path that maximizes the bottleneck robustness, that is, a train path that maximizes the temporal distance to neighboring trains in the timetable. Our algorithm is based on a graph formulation of the problem and uses a variant of Dijkstra’s algorithm. We present an extensive experimental evaluation of our algorithm for the Swedish railway stretch from Malmö to Hallsberg. Moreover, we analyze the size of our constructed graph. Funding agency: Linköping University Shift2Rail

Understanding the role of dispersal and adaptation in the evolutionary history of marine species is essential for predicting their response to changing conditions. We analyzed patterns of genetic differentiation in the key tropical calcifying species of large benthic foraminifera Amphistegina lobifera to reveal the evolutionary processes responsible for its biogeographic distribution. We collected specimens from 16 sites encompassing the entire range of the species and analyzed hypervariable fragments of the 18S SSU rDNA marker. We identified six hierarchically organized genotypes with mutually exclusive distribution organized along a longitudinal gradient. The distribution is consistent with diversification occurring in the Indo‐West Pacific (IWP) followed by dispersal toward the periphery. This pattern can be explained by: (a) high dispersal capacity of the species, (b) habitat heterogeneity driving more recent differentiation in the IWP, and (c) ecological‐scale processes such as niche incumbency reinforcing patterns of genotype mutual exclusion. The dispersal potential of this species drives the ongoing range expansion into the Mediterranean Sea, indicating that A. lobifera is able to expand its distribution by tracking increases in temperature. The genetic structure reveals recent diversification and high rate of extinction in the evolutionary history of the clade suggesting a high turnover rate of the diversity at the cryptic level. This diversification dynamic combined with high dispersal potential, allowed the species to maintain a widespread distribution over periods of geological and climatic upheaval. These characteristics are likely to allow the species to modify its geographic range in response to ongoing global warming without requiring genetic differentiation., Genetic differentiation and distribution of populations can provide clues about processes shaping species evolutionary histories. We examined the genetic signature of globally distributed species of large benthic foraminifera in order to identify mechanisms acting at geological and ecological time scales. We found that while dispersal capacity allows populations to extend their range, geographic distribution was strongly shaped by biogeographic breaks and niche incumbency.

Several foraminifera are deposit feeders that consume organic detritus (dead particulate organic material along with entrained bacteria). However, the role of such foraminifera in the benthic food-web remains understudied. As foraminifera may associate with methanotrophic bacteria, which are 13C-depleted, feeding on them has been suggested to cause negative δ13C values in the foraminiferal cytoplasm and/or calcite. To test whether the foraminiferal diet includes methanotrophs, we performed a short-term (1 d) feeding experiment with Nonionellina labradorica from an active Arctic methane-emission site (Storfjordrenna, Barents Sea) using the marine methanotroph Methyloprofundus sedimenti, and analyzed N. labradorica cytology via Transmission Electron microscopy (TEM). We hypothesized that M. sedimenti would be visible, as evidenced by their ultrastructure, in degradation vacuoles after this feeding experiment. Sediment grains (mostly clay) occurred inside one or several degradation vacuoles in all foraminifers. In 24 % of the specimens from the feeding experiment degradation vacuoles also contained bacteria, although none could be confirmed to be the offered M. sedimenti. Observations of the area adjacent to the aperture after 20 h incubation revealed three putative methanotrophs, close to clay particles. These methanotrophs were identified based on internal characteristics such as a type I stacked intracytoplasmic membranes (ICM), storage granules (SG) and gram-negative cell walls (GNCW). Furthermore, N. labradorica specimens were examined for specific adaptations to this active Arctic methane-emission site; we noted the absence of bacterial endobionts in all specimens examined but confirmed the presence of kleptoplasts, which were often partially degraded. Based on these observations, we suggest that M. sedimenti can be consumed by N. labradorica via untargeted grazing in seeps and that N. labradorica can be generally classified as a deposit feeder at this Arctic site. These results suggest that if methanothrophs are available to the foraminifera in their habitat, their non-selective uptake could make a substantial contribution to altering δ13Ctest values. This in turn may impact metazoans grazing on benthic foraminifera by altering their δ13C signature.

In this paper, we present a novel methodology to manage arrival traffic in terminal airspace. We define two areas around the airport, aiming to efficiently schedule incoming traffic. A four-dimensional (4D) trajectory negotiation/synchronization process between the air traffic control officer (ATCO) and the aircraft is performed in the pre-sequencing area, while the aircraft are still in the en-route phase of flight. On the other hand, in the dynamic-trajectories area, the ATCO, with the help of a ground support tool, generates dynamic arrival routes that automatically adapt to the current traffic demand. These arrival routes allow the aircraft to fly neutral continuous descent operations (CDOs, descents with idle thrust and no speed-brakes usage) and to ensure a separation throughout the arrival procedure. We choose a mixed-integer-programming approach to generate the arrival routes, while we formulate and solve an optimal control problem to generate a set of candidate CDOs per aircraft. Results show that, with a sufficient look-ahead time, it is possible to assign a required time of arrival (RTA) within each aircraft-arrival time window that would allow to efficiently schedule traffic even in the most challenging and dense scenarios. Besides improving efficiency of current operations in terminal airspace, the methodology presented in this paper could become a technical enabler towards an extended arrival manager (E-AMAN) with extended capabilities and, ultimately, to a fully deployed trajectory based operations (TBO) environment.

Spiral Galaxies is a pencil-and-paper puzzle played on a grid of unit squares: given a set of points called centers, the goal is to partition the grid into polyominoes such that each polyomino contains exactly one center and is 180{\deg} rotationally symmetric about its center. We show that this puzzle is NP-complete, ASP-complete, and #P-complete even if (a) all solutions to the puzzle have rectangles for polyominoes; or (b) the polyominoes are required to be rectangles and all solutions to the puzzle have just 1$\times$1, 1$\times$3, and 3$\times$1 rectangles. The proof for the latter variant also implies NP/ASP/#P-completeness of finding a noncrossing perfect matching in distance-2 grid graphs where edges connect vertices of Euclidean distance 2. Moreover, we prove NP-completeness of the design problem of minimizing the number of centers such that there exists a set of galaxies that exactly cover a given shape, Comment: 24 pages, 24 figures. Thorough revision including new Section 2 proof which handles the promise problem

Intimate cell contact and subsequent type three secretion system-dependent cell invasion are key steps in host colonization ofSalmonella. Adhesion to complex glycostructures at the apical membrane of polarized cells is mediated by the giant adhesin SiiE. This protein is secreted by a type 1 secretion system (T1SS) and needs to be retained at the bacterial surface to exert its adhesive function. Here, we show that SiiE surface expression was linked to the presence of L-aspartate sensed by theSalmonella-specific methyl-accepting chemotaxis protein CheM. Bacteria lacking CheM were attenuated for invasion of polarized cells, whereas increased invasion was seen withSalmonellaexposed to the non-metabolizable aspartate analog α-methyl-D, L-aspartate (MeAsp). While components of the chemotaxis phosphorelay or functional flagella were dispensable for the increased invasion, CheM directly interacted with proteins associated with the SiiE T1SS arguing for a novel non-canonical signaling mechanism. As a result, CheM attractant signaling caused a shift from secreted to surface-retained and adhesion-competent SiiE. Thus, CheM controls the virulence function of SiiE in a precise spatio-temporal fashion depending on the host micro-milieu.

Salmonellainvasion is mediated by a concerted action of theSalmonellapathogenicity island 4 (SPI4)-encoded type one secretion system (T1SS) and the SPIl-encoded type three secretion system (T3SS-1). The SPI4-encoded T1SS establishes the first contact to the host membrane. It consists of five proteins (SiiABCDF) that secrete the giant adhesin SiiE. The exact mechanism by which the T1SS enables host cell recognition remains unclear. Here, we investigated structure-function relationships in SiiA, a non-canonical T1SS subunit located at the inner membrane (IM). We observe that SiiA consists of a membrane domain, an intrinsically disordered periplasmic linker region and a folded globular periplasmic domain (SiiA-PD). The crystal structure of SiiA-PD shows homology to that of MotB-PD and other peptidoglycan (PG)-binding domains. Indeed, SiiA-PD binds PGin vitroalbeit at an acidic pH, only, whereas MotB-PD binds PG from pH 5.8 to 8. Mutation of Arg162 in SiiA impedes PG binding and reducesSalmonellainvasion efficacy of polarized epithelial cells. SiiA forms a complex with SiiB at the IM, and the SiiA-MotB homology is likely paralleled by a SiiB-MotA homology. We show that, in addition to PG binding, the SiiAB complex translocates protons across the IM. Substituting Asp13 in SiiA impairs proton translocation. Overall, SiiA displays many properties previously observed in MotB. However, whereas the MotAB complex uses the proton motif force (PMF) to energize the bacterial flagellum, it remains to be shown how the use of the PMF by SiiAB assists T1SS function and ultimatelySalmonellainvasion.

Route planning and airspace sectorisation are two central tasks in air traffic management. Traditionally, the routing and sectorisation problems were considered separately, with aircraft trajectories serving as input to the sectorisation problem and, reciprocally, sectors being part of the input to the path finding algorithms.In this paper we propose a simultaneous design of routes and sectors for a transition airspace. We compare two approaches for this integrated design: one based on mixed integer programming, and one Voronoi-based model that separates potential “hotspots” of controller activity resulting from the terminal routes.We apply our two approaches to the design of Stockholm Terminal Maneuvering Area.

Diurnal vertical migration (DVM) is a widespread phenomenon in the upper ocean, but it remains unclear to what degree it also involves passively transported micro- and meso-zooplankton. These organisms are difficult to monitor by in situ sensing and observations from discrete samples are often inconclusive. Prime examples of such ambiguity are planktonic foraminifera, where contradictory evidence for DVM continues to cast doubt on the stability of species vertical habitats, which introduces uncertainties in geochemical proxy interpretation. To provide a robust answer, we carried out highly replicated randomized sampling with 41 vertically resolved plankton net hauls taken within 26 hours in a confined area of 400 km2 in the tropical North Atlantic, where DVM in larger plankton occurs. Manual enumeration of planktonic foraminifera cell density consistently reveals the highest total cell concentrations in the surface mixed layer (top 50 m) and analysis of cell density in seven individual species representing different shell sizes, life strategies and presumed depth habitats reveals consistent vertical habitats not changing over the 26 hours sampling period. These observations robustly reject the existence of DVM in planktonic foraminifera in a setting where DVM occurs in other organisms.

Background : While primary health care-based prevention and management of heavy drinking is clinically effective and cost-effective, it remains poorly implemented in routine practice. Systematic reviews and multi-country studies have demonstrated the ability of training and support programmes for healthcare professionals to increase primary health care-based measurement and brief advice activity to reduce heavy drinking. However, gains have been only modest and short term at best. WHO studies have concluded that a more effective uptake could be achieved by embedding primary health care activity within broader municipal-based support. Methods : A quasi-experimental study will compare primary health care-based prevention and management of heavy drinking in three intervention municipal areas from Colombia, Mexico and Peru with three comparator municipal areas from the same countries. In the implementation municipal areas, primary health care units will receive training embedded within ongoing supportive municipal action over an 18-month implementation test period. In the comparator municipal areas, half the units will receive training, and the other half will continue with practice as usual. The primary outcome is the proportion of the adult population (aged 18+ years) registered with the unit that has their alcohol consumption measured. Return-on-investment analyses and full process evaluation will be undertaken, coupled with an analysis of potential contextual, financial and political-economy influencing factors. Discussion : This multi-country study will test the extent to which embedding primary health care-based prevention and management of heavy drinking within supportive municipal action leads to improved scale-up of more patients having their alcohol consumption measured, and subsequently receiving appropriate advice and treatment.

Background Revealing the specificity and flexibility of the algal symbiont-host association is fundamental for understanding how species can occupy a diverse range of habitats. Here we assessed the global distribution of the algal symbiont diversity for three shallow-water species of large benthic foraminifera (LBF) of the genus Amphistegina . Specifically, weinvestigated the role of habitat and host identity on the diversity of algal biome. Results Here we used next-generation sequencing to identify the algal biome in the species A. lobifera , A. lessonii , and A. radiata , collected from shallow habitats in 16 sites, spanning from the Mediterranean Sea to French Polynesia. Results showed the consistent presence of Fragilariales as the main algal taxa associated with all species across sites analysed. However, we uncovered unprecedented diversity of algal phylotypes found in low abundance.We further found high variability in algal biomes both within and between species and sites, indicating a substantial level of flexibility in symbiont associations. The effect of site was significant in all species analysed, and showed that local habitat is the main factor influencing the identity of algal symbionts. Symbiotic associations are also not constrained by the species identity nor the phylogenetic relationship among closely related hosts, suggesting symbiont identity plays a limited role in the evolutionary history of the genus Amphistegina . Conclusions We found that species of Amphistegina form flexible symbiotic relationship with algal taxa, which are primarily shaped by their local habitat. These observations strongly suggest that the capacity of Amphistegina species to utilise a diverse array of available symbionts likely underpins the ecological success of these crucial calcifying organisms across their extensive geographic range.

This paper presents a mixed-integer programming approach to compute aircraft arrival routes in a terminal maneuvering area (TMA) with guaranteed temporal separation of all aircraft arriving within a given time period. Furthermore, the aircraft are assumed to be flying according to their optimal continous descent operation speed profile with idle thrust and no speed brakes usage. The arrival routes form a merge tree that satisfies several operational constraints; for example, all merge points are spatially separated. How the continuous descent operation speed profiles for different route lengths are computed is detailed. Experimental results are presented for calculation of fully automated continuous descent operation-enabled arrival routes during 1 h of operation on a busy day at a Stockholm terminal maneuvering area. The current framework successfully generates an arrival tree, merging the traffic from all TMA entry points to the runway for 30 min intervals. For a complete 1 h period, two trees (per 30 min) are computed that differ as little as possible.

In this study, hydrogen evolution reaction (HER) catalytic and corrosion data is determined for selected metal cathode materials. The HER data was gathered using cyclic voltammetry (CV) in electrolytes with several pH values and varying current densities. Of the tested materials, the stainless steel alloy EN 1.4401/AISI 316 generally had the lowest HER overpotentials at the pH values 0.25, 7 and 9. At the higher pH values of 11 and 14 a custom NiMoFe alloy with a m/m% composition of 60-30-10 showed the lowest overpotentials. After each CV experiment, the electrolyte solution was analyzed to determine the corrosion of the metal cathodes. Results of corrosion measurements showed that the stainless steels EN 1.4401 had the lowest corrosion losses on average across all tested pH values. Combining HER and corrosion data revealed that: In the pH 9 electrolyte solution, EN 1.4401 was not always the best catalyst in terms of its overpotential, but it incurs the least material costs due to its lack of corrosion, this balance thereby making it the “best choice” under the given conditions. The combination of HER and corrosion data provides a more effective framework for discussing economic viability than either data set alone.

Bacterial resistance to antibiotics is a major concern worldwide, leading to an extensive search for alternative drugs. Promising candidates are antimicrobial peptides (AMPs), innate immunity molecules, shown to be highly efficient against multidrug resistant bacteria. Therefore, it is essential to study bacterial resistance mechanisms against them. For that purpose, we used experimental evolution, and isolated a Salmonella enterica serovar typhimurium-resistant line to the AMP 4DK5L7. This AMP displayed promising features including widespread activity against Gram-negative bacteria and protection from proteolytic degradation. However, the resistance that evolved in the isolated strain was particularly high. Whole genome sequencing revealed that five spontaneous mutations had evolved. Of these, three are novel in the context of acquired AMP resistance. Two mutations are related to the AcrAB-TolC multidrug efflux pump. One occurred in AcrB, the substrate-binding domain of the system, and the second in RamR, a transcriptional regulator of the system. Together, the mutations increased the minimal inhibitory concentration (MIC) by twofold toward this AMP. Moreover, the mutation in AcrB induced hypersusceptibility toward ampicillin and colistin. The last mutation occurred in Skp, a periplasmic chaperone that participates in the biogenesis of outer membrane proteins (OMPs). This mutation increased the MIC by twofold to 4DK5L7 and by fourfold to another AMP, seg5D. Proteomic analysis revealed that the mutation abolished Skp expression, reduced OMP abundance, and increased DegP levels. DegP, a protease that was reported to have an additional chaperone activity, escorts OMPs through the periplasm along with Skp, but is also associated with AMP resistance. In conclusion, our data demonstrate that both loss of Skp and manipulation of the AcrAB-TolC system are alternative strategies of AMP acquired resistance in Salmonella typhimurium and might represent a common mechanism in other Gram-negative bacteria.

When can a polyomino piece of paper be folded into a unit cube? Prior work studied tree-like polyominoes, but polyominoes with holes remain an intriguing open problem. We present sufficient conditions for a polyomino with one or several holes to fold into a cube, and conditions under which cube folding is impossible. In particular, we show that all but five special \emph{simple} holes guarantee foldability., 24 pages, 21 figures

Photosymbiosis has played a key role in the diversification of foraminifera and their carbonate production throughout geologic history. However, identification of photosymbiosis in extinct taxa remains challenging, and even among the extant species the occurrence and functional relevance of photosymbiosis remain poorly constrained. Here, we investigate photosymbiosis in living planktonic foraminifera by measuring active chlorophyll fluorescence with fast repetition rate fluorometry. This method provides unequivocal evidence for the presence of photosynthetic capacity in individual foraminifera, and it allows us to characterize multiple features of symbiont photosynthesis including chlorophyll a (Chl a) content, potential photosynthetic activity (Fv∕Fm), and light-absorption efficiency (σPSII). To obtain robust evidence for the occurrence and importance of photosymbiosis in modern planktonic foraminifera, we conducted measurements on 1266 individuals from 30 species of the families Globigerinidae, Hastigerinidae, Globorotaliidae, and Candeinidae. Among the studied species, 19 were recognized as symbiotic and 11 as non-symbiotic. Of these, six species were newly confirmed as symbiotic and five as non-symbiotic. Photosymbiotic species have been identified in all families except the Hastigerinidae. A significant positive correlation between test size and Chl a content, found in 16 species, is interpreted as symbiont abundance scaled to the growth of the host and is consistent with persistent possession of symbionts through the lifetime of the foraminifera. The remaining three symbiont-bearing species did not show such a relationship, and their Fv∕Fm values were comparatively low, indicating that their symbionts do not grow once acquired from the environment. The objectively quantified photosymbiotic characteristics have been used to design a metric of photosymbiosis, which allows the studied species to be classified along a gradient of photosynthetic activity, providing a framework for future ecological and physiological investigations of planktonic foraminifera.

The dawn of animals remains one of the most mysterious milestones in the evolution of life. The fossil lipids 24-isopropylcholestane and 26-methylstigmastane are considered diagnostic for demosponges—arguably the oldest group of living animals. The widespread occurrence and high relative abundance of these biomarkers in Ediacaran sediments from 635–541 million years (Myr) ago have been viewed as evidence for the rise of animals to ecological importance approximately 100 Myr before their rapid Cambrian radiation. Here we show that the biosynthesis of 24-isopropylcholestane and 26-methylstigmastane precursors is common among early-branching unicellular Rhizaria—heterotrophic protists that play an important role in trophic cycling and carbon export in the modern ocean. Negating these hydrocarbons as sponge biomarkers, our study places the oldest evidence for animals closer to the Cambrian Explosion. Cambrian silica hexactine spicules that are approximately 535 Myr old now represent the oldest diagnostic sponge remains, whereas approximately 558-Myr-old Dickinsonia and Kimberella (Ediacara biota) provide the most reliable evidence for the emergence of animals. The proliferation of predatory protists may have been responsible for much of the ecological changes during the late Neoproterozoic, including the rise of algae, the establishment of complex trophic relationships and the oxygenation of shallow-water habitats required for the subsequent ascent of macroscopic animals. Fossil lipid biomarkers previously thought to be diagnostic of sponges (and thus indicative of animal life) are found to be preserved in unicellular Rhizarian protists, questioning a pre-Cambrian origin of sponges.

Epigenetic mechanisms of gene regulation, including DNA methylation and histone modifications, call increasing attention in the context of development and human health. Thereby, interactions between DNA methylating enzymes and histone modifications tremendously multiply the spectrum of potential regulatory functions. Epigenetic networks are critically involved in the establishment and functionality of neuronal circuits that are composed of gamma-aminobutyric acid (GABA)-positive inhibitory interneurons and excitatory principal neurons in the cerebral cortex. We recently reported a crucial role of the DNA methyltransferase 1 (DNMT1) during the migration of immature POA-derived cortical interneurons by promoting the migratory morphology through repression of Pak6. However, the DNMT1-dependent regulation of Pak6 expression appeared to occur independently of direct DNA methylation. Here, we show that in addition to its DNA methylating activity, DNMT1 can act on gene transcription by modulating permissive H3K4 and repressive H3K27 trimethylation in developing inhibitory interneurons, similar to what was found in other cell types. In particular, the transcriptional control of Pak6, interactions of DNMT1 with the Polycomb-repressor complex 2 (PCR2) core enzyme EZH2, mediating repressive H3K27 trimethylations at regulatory regions of the Pak6 gene locus. Similar to what was observed upon Dnmt1 depletion, inhibition of EZH2 caused elevated Pak6 expression levels accompanied by increased morphological complexity, which was rescued by siRNA-mediated downregulation of Pak6 expression. Together, our data emphasise the relevance of DNMT1-dependent crosstalk with histone tail methylation for transcriptional control of genes like Pak6 required for proper cortical interneuron migration.

We present an optimal, linear-time algorithm for the following version of terrain guarding: given a 1.5D terrain and a horizontal line, place the minimum number of guards on the line to see all of the terrain. We prove that the cardinality of the minimum guard set coincides with the cardinality of a maximum number of ``witnesses'', i.e., terrain points, no two of which can be seen by a single guard. We show that our results also apply to the Art Gallery problem in ``monotone mountains'', i.e., $x$-monotone polygons with a single edge as one of the boundary chains. This means that any monotone mountain is ``perfect'' (its guarding number is the same as its witness number); we thus establish the first non-trivial class of perfect polygons., 28 pages, 15 figures

We study the problem of folding a polyomino $P$ into a polycube $Q$, allowing faces of $Q$ to be covered multiple times. First, we define a variety of folding models according to whether the folds (a) must be along grid lines of $P$ or can divide squares in half (diagonally and/or orthogonally), (b) must be mountain or can be both mountain and valley, (c) can remain flat (forming an angle of $180^\circ$), and (d) must lie on just the polycube surface or can have interior faces as well. Second, we give all the inclusion relations among all models that fold on the grid lines of $P$. Third, we characterize all polyominoes that can fold into a unit cube, in some models. Fourth, we give a linear-time dynamic programming algorithm to fold a tree-shaped polyomino into a constant-size polycube, in some models. Finally, we consider the triangular version of the problem, characterizing which polyiamonds fold into a regular tetrahedron., 30 pages, 19 figures, full version of extended abstract that appeared in CCCG 2015. (Change over previous version: Fixed a missing reference.)

The Art Gallery Problem (AGP) asks for placing a minimum number of stationary guards in a polygonal region P, such that all points in P are guarded. The problem is known to be NP-hard, and its inherent continuous structure (with both the set of points that need to be guarded and the set of points that can be used for guarding being uncountably infinite) makes it difficult to apply a straightforward formulation as an Integer Linear Program. We use an iterative primal-dual relaxation approach for solving AGP instances to optimality. At each stage, a pair of LP relaxations for a finite candidate subset of primal covering and dual packing constraints and variables is considered; these correspond to possible guard positions and points that are to be guarded. Particularly useful are cutting planes for eliminating fractional solutions. We identify two classes of facets, based on Edge Cover and Set Cover (SC) inequalities. Solving the separation problem for the latter is NP-complete, but exploiting the underlying geometric structure, we show that large subclasses of fractional SC solutions cannot occur for the AGP. This allows us to separate the relevant subset of facets in polynomial time. We also characterize all facets for finite AGP relaxations with coefficients in {0, 1, 2}. Finally, we demonstrate the practical usefulness of our approach. Our cutting plane technique yields a significant improvement in terms of speed and solution quality due to considerably reduced integrality gaps as compared to the approach by Kr\"oller et al., Comment: 29 pages, 18 figures, 1 table

Infections of very young children or immunocompromised people with Salmonella of higher subspecies are a well-known phenomenon often associated with contact to cold-blooded animals. We describe the molecular characterization of three S. enterica subsp. diarizonae strains, isolated consecutively over a period of several months from a hospital patient suffering from diarrhea and sepsis with fatal outcome. With the initial isolate the first complete genome sequence of a member of subsp. diarizonae is provided and based on this reference we revealed the genomic differences between the three isolates by use of next-generation sequencing and confirmed by phenotypical tests. Genome comparisons revealed mutations within gpt, hfq and purK in the first isolate as a sign of clonal variation rather than host-directed evolution. Furthermore, our work demonstrates that S. enterica subsp. diarizonae possess, besides a conserved set of known Salmonella Pathogenicity Islands, a variable portfolio of additional genomic islands of unknown function.

Warming and changes in ocean carbonate chemistry alter marine coastal ecosystems at an accelerating pace. The interaction between these stressors has been the subject of recent studies on reef organisms such as corals, bryozoa, molluscs, and crustose coralline algae. Here we investigated the combined effects of elevated sea surface temperatures and pCO2 on two species of photosymbiont-bearing coral reef Foraminifera: Heterostegina depressa (hosting diatoms) and Marginopora vertebralis (hosting dinoflagellates). The effects of single and combined stressors were studied by monitoring survivorship, growth, and physiological parameters, such as respiration, photochemistry (pulse amplitude modulation fluorometry and oxygen production), and chl a content. Specimens were exposed in flow-through aquaria for up to seven weeks to combinations of two pCO2 (~790 and ~490 µatm) and two temperature (28 and 31 °C) regimes. Elevated temperature had negative effects on the physiology of both species. Elevated pCO2 had negative effects on growth and apparent photosynthetic rate in H.depressa but a positive effect on effective quantum yield. With increasing pCO2, chl a content decreased in H. depressa and increased in M. vertebralis. The strongest stress responses were observed when the two stressors acted in combination. An interaction term was statistically significant in half of the measured parameters. Further exploration revealed that 75 % of these cases showed a synergistic (= larger than additive) interaction between the two stressors. These results indicate that negative physiological effects on photosymbiont-bearing coral reef Foraminifera are likely to be stronger under simultaneous acidification and temperature rise than what would be expected from the effect of each of the stressors individually.

Site-directed scarless mutagenesis is an essential tool of modern pathogenesis research. We describe an optimized two-step protocol for genome editing in Salmonella enterica serovar Typhimurium to enable multiple sequential mutagenesis steps in a single strain. The system is based on the λ Red recombinase-catalyzed integration of a selectable antibiotics resistance marker followed by replacement of this cassette. Markerless mutants are selected by expressing the meganuclease I-SceI which induces double-strand breaks in bacteria still harboring the resistance locus. Our new dual-functional plasmid pWRG730 allows for heat-inducible expression of the λ Red recombinase and tet-inducible production of I-SceI. Methyl-accepting chemotaxis proteins (MCP) are transmembrane chemoreceptors for a vast set of environmental signals including amino acids, sugars, ions and oxygen. Based on the sensory input of MCPs, chemotaxis is a key component for Salmonella virulence. To determine the contribution of individual MCPs we sequentially deleted seven MCP genes. The individual mutations were validated by PCR and genetic integrity of the final seven MCP mutant WRG279 was confirmed by whole genome sequencing. The successive MCP mutants were functionally tested in a HeLa cell infection model which revealed increased invasion rates for non-chemotactic mutants and strains lacking the MCP CheM (Tar). The phenotype of WRG279 was reversed with plasmid-based expression of CheM. The complemented WRG279 mutant showed also partially restored chemotaxis in swarming assays on semi-solid agar. Our optimized scarless deletion protocol enables efficient and precise manipulation of the Salmonella genome. As demonstrated with whole genome sequencing, multiple subsequent mutagenesis steps can be realized without the introduction of unwanted mutations. The sequential deletion of seven MCP genes revealed a significant role of CheM for the interaction of S. Typhimurium with host cells which might give new insights into mechanisms of Salmonella host cell sensing.

Worldwide, huge amounts of mineral oil containing metalworking fluids (MWF) are applied for industrial metal machining. Future challenges in the field of lubricant usage are to overcome the consumption of finite resources and to solve problems like compatibility of MWFs to human health and environment as well as laborious deoiling and costly disposal. In this context, ecological and economic properties of a novel glycerol/water-based MWF are introduced. Investigations revealed that if a proportion of ≥35% of the biostatic trihydric alcohol glycerol was present in the MWF, the addition of biocides for fluid protection was unnecessary. Technical grade glycerol, a renewable by-product from the biodiesel market, proved a sufficient purity for application. Compared to common MWFs, the cleaning of metal surfaces just by rinsing with water was distinctly facilitated because of the water solubility of all fluid components. A disposal of the MWF at the end of service life or the wash waters had not to be considered because of the microbiological degradability of the organic components of the diluted MWF. The novel glycerol-fluid is available for energetic or even material recovery which contributes to cost reduction and covers the aspect of sustainability. Concerning the costs of application of the novel MWF in industrial production processes, the fluid even nowadays appears to be competitive to many common mineral oil based lubricants.