bluuebunny/crossref_metadata_2025 huggingface dataset:
Were Notosuchia (Pseudosuchia: Crocodylomorpha) warm-blooded? A palaeohistological analysis suggests ectothermy
Authors: Cubo Jorge , Sena Mariana V A , Aubier Paul , Houee Guillaume , Claisse Penelope , Faure-Brac Mathieu G , Allain Ronan , Andrade Rafael C L P , Sayão Juliana M , Oliveira Gustavo R
Published: May 2020

Most Notosuchia were active terrestrial predators. A few were semi-aquatic, or were insectivorous, omnivorous or herbivorous. A question relative to their thermometabolism remains to be answered: were Notosuchia warm-blooded? Here we use quantitative bone palaeohistology to answer this question. Two variables were used as proxies to infer thermometabolism: resting metabolic rate and red blood cell dimensions. Resting metabolic rate was inferred using relative primary osteon area and osteocyte size, shape and density. Blood cell dimensions were inferred using harmonic mean canal diameter and minimum canal diameter. All inferences were performed using phylogenetic eigenvector maps. Both sets of analyses suggest that the seven species of Notosuchia sampled in this study were ectotherms. Given that extant Neosuchia (their sister group) are also ectotherms, and that archosaurs were primitively endotherms, parsimony suggests that endothermy may have been lost at the node Metasuchia (Notosuchia–Neosuchia) by the Early Jurassic. Semi-aquatic taxa such as Pepesuchus may have had thermoregulatory strategies similar to those of recent crocodylians, whereas the terrestrial taxa (Araripesuchus, Armadillosuchus, Iberosuchus, Mariliasuchus, Stratiotosuchus) may have been thermoregulators similar to active predatory varanids. Thermal inertia may have contributed to maintaining a stable temperature in large notosuchians such as Baurusuchus.
Invariant Synapse Density and Neuronal Connectivity Scaling in Primate Neocortical Evolution
Authors: Sherwood Chet C , Miller Sarah B , Karl Molly , Stimpson Cheryl D , Phillips Kimberley A , Jacobs Bob , Hof Patrick R , Raghanti Mary Ann , Smaers Jeroen B
Published: May 2020

Synapses are involved in the communication of information from one neuron to another. However, a systematic analysis of synapse density in the neocortex from a diversity of species is lacking, limiting what can be understood about the evolution of this fundamental aspect of brain structure. To address this, we quantified synapse density in supragranular layers II–III and infragranular layers V–VI from primary visual cortex and inferior temporal cortex in a sample of 25 species of primates, including humans. We found that synapse densities were relatively constant across these levels of the cortical visual processing hierarchy and did not significantly differ with brain mass, varying by only 1.9-fold across species. We also found that neuron densities decreased in relation to brain enlargement. Consequently, these data show that the number of synapses per neuron significantly rises as a function of brain expansion in these neocortical areas of primates. Humans displayed the highest number of synapses per neuron, but these values were generally within expectations based on brain size. The metabolic and biophysical constraints that regulate uniformity of synapse density, therefore, likely underlie a key principle of neuronal connectivity scaling in primate neocortical evolution.
Efficacy of Ceftazidime-avibactam Plus Aztreonam in Patients With Bloodstream Infections Caused by Metallo-β-lactamase–Producing Enterobacterales
Authors: Falcone Marco , Daikos George L , Tiseo Giusy , Bassoulis Dimitrios , Giordano Cesira , Galfo Valentina , Leonildi Alessandro , Tagliaferri Enrico , Barnini Simona , Sani Spartaco , Farcomeni Alessio , Ghiadoni Lorenzo , Menichetti Francesco
Published: May 2020

Background

In vitro data support the use of combination of aztreonam (ATM) with ceftazidime-avibactam (CAZ-AVI), but clinical studies are lacking. The aim of our study was to compare the outcome of patients with bloodstream infections (BSIs) due to metallo-β-lactamase (MBL)–producing Enterobacterales treated either with CAZ-AVI plus ATM or other active antibiotics (OAAs).

Methods

This was a prospective observational study including patients admitted to 3 hospitals in Italy and Greece. The primary outcome measure was 30-day all-cause mortality. Secondary outcomes were clinical failure at day 14 and length of stay after BSI diagnosis. Cox regression analysis including a propensity score (PS) for receiving CAZ-AVI + ATM was performed to evaluate primary and secondary outcomes. A PS-based matched analysis was also performed.

Results

We enrolled 102 patients with BSI; 82 had infections caused by NDM-producing (79 Klebsiella pneumoniae and 3 Escherichia coli) and 20 by VIM-producing (14 K. pneumoniae, 5 Enterobacter species, 1 Morganella morganii) strains. The 30-day mortality rate was 19.2% in the CAZ-AVI + ATM group vs 44% in the OAA group (P = .007). The PS-adjusted analysis showed that the use of CAZ-AVI + ATM was associated with lower 30-day mortality (hazard ratio [HR], 0.37 [95% confidence interval {CI}, .13–.74]; P = .01), lower clinical failure at day 14 (HR, 0.30 [95% CI, .14–.65]; P = .002), and shorter length of stay (subdistributional HR, 0.49 [95% CI, .30–.82]; P = .007). The PS-matched analysis confirmed these findings.

Conclusions

The CAZ-AVI + ATM combination offers a therapeutic advantage compared to OAAs for patients with BSI due to MBL-producing Enterobacterales. Further studies are warranted.
Obtaining extremely large and accurate protein multiple sequence alignments from curated hierarchical alignments
Authors: Neuwald Andrew F , Lanczycki Christopher J , Hodges Theresa K , Marchler-Bauer Aron
Published: May 2020

For optimal performance, machine learning methods for protein sequence/structural analysis typically require as input a large multiple sequence alignment (MSA), which is often created using query-based iterative programs, such as PSI-BLAST or JackHMMER. However, because these programs align database sequences using a query sequence as a template, they may fail to detect or may tend to misalign sequences distantly related to the query. More generally, automated MSA programs often fail to align sequences correctly due to the unpredictable nature of protein evolution. Addressing this problem typically requires manual curation in the light of structural data. However, curated MSAs tend to contain too few sequences to serve as input for statistically based methods. We address these shortcomings by making publicly available a set of 252 curated hierarchical MSAs (hiMSAs), containing a total of 26 212 066 sequences, along with programs for generating from these extremely large MSAs. Each hiMSA consists of a set of hierarchically arranged MSAs representing individual subgroups within a superfamily along with template MSAs specifying how to align each subgroup MSA against MSAs higher up the hierarchy. Central to this approach is the MAPGAPS search program, which uses a hiMSA as a query to align (potentially vast numbers of) matching database sequences with accuracy comparable to that of the curated hiMSA. We illustrate this process for the exonuclease–endonuclease–phosphatase superfamily and for pleckstrin homology domains. A set of extremely large MSAs generated from the hiMSAs in this way is available as input for deep learning, big data analyses. MAPGAPS, auxiliary programs CDD2MGS, AddPhylum, PurgeMSA and ConvertMSA and links to National Center for Biotechnology Information data files are available at https://www.igs.umaryland.edu/labs/neuwald/software/mapgaps/.
Early Transmural Response Assessed Using Magnetic Resonance Imaging Could Predict Sustained Clinical Remission and Prevent Bowel Damage in Patients with Crohn’s Disease Treated with Anti-Tumour Necrosis Factor Therapy
Authors: Messadeg L , Hordonneau C , Bouguen G , Goutorbe F , Reimund J M , Goutte M , Boucher A L , Scanzi J , Reymond M , Allimant C , Dapoigny M , Pereira B , Bommelaer G , Buisson A
Published: May 2020

Background

Magnetic resonance imaging [MRI] is a promising tool to evaluate therapeutic efficacy in ileocolonic Crohn’s disease [CD].

Aims

We aimed to assess the feasibility of early MRI evaluation (week 12 [W12]) to predict corticosteroid-free remission [CFREM] at W52 and prevent long-term bowel damage.

Methods

All patients with active CD needing anti-tumour necrosis factor [anti-TNF] therapy were consecutively enrolled in this multicentre prospective study. MRI was performed before starting therapy, at W12 and W52. CFREM was defined as Crohn’s Disease Activity Index < 150, C-reactive protein < 5 mg/L and faecal calprotectin < 250 µg/g, with no switch of anti-TNF agents, no bowel resection and no therapeutic intensification between W12 and W52.

Results

Among 46 patients, 22 [47.8%] achieved CFREM at W52. Anti-TNF agents were able to heal almost all CD lesions as soon as W12 [p < 0.05]. Early transmural response defined as a 25% decrease of either Clermont score (odds ratio [OR] = 7.7 [1.7–34.0], p < 0.001) or Magnetic Resonance Index of Activity (OR = 4.2 [1.3–13.3], p = 0.015) was predictive of CFREM at W52. Achieving at least two items on W12-MRI among ulceration healing, disappearance of enlarged lymph nodes or sclerolipomatosis, ΔADC [apparent diffusion coefficient] > +10% or ΔRCE [relative contrast enhancement] > −30% was associated with a likelihood of CFREM at W52 of 84.6% vs 37.5% in patients without transmural response [p < 0.001]. Early transmural response could prevent bowel damage progression over time using Clermont score (hazard ratio = 0.21 [0.0–0.9]; p = 0.037).

Conclusion

Evaluation of early transmural response by MRI is feasible and is a promising end point to monitor therapeutic efficacy in patients with CD.
Neither 1G nor 2G fuel ethanol: setting the ground for a sugarcane-based biorefinery using an iSUCCELL yeast platform
Authors: Bermejo Pamela Magalí , Raghavendran Vijayendran , Gombert Andreas Karoly
Published: May 2020

First-generation (1G) fuel ethanol production in sugarcane-based biorefineries is an established economic enterprise in Brazil. Second-generation (2G) fuel ethanol from lignocellulosic materials, though extensively investigated, is currently facing severe difficulties to become economically viable. Some of the challenges inherent to these processes could be resolved by efficiently separating and partially hydrolysing the cellulosic fraction of the lignocellulosic materials into the disaccharide cellobiose. Here, we propose an alternative biorefinery, where the sucrose-rich stream from the 1G process is mixed with a cellobiose-rich stream in the fermentation step. The advantages of mixing are 3-fold: (i) decreased concentrations of metabolic inhibitors that are typically produced during pretreatment and hydrolysis of lignocellulosic materials; (ii) decreased cooling times after enzymatic hydrolysis prior to fermentation; and (iii) decreased availability of free glucose for contaminating microorganisms and undesired glucose repression effects. The iSUCCELL platform will be built upon the robust Saccharomyces cerevisiae strains currently present in 1G biorefineries, which offer competitive advantage in non-aseptic environments, and into which intracellular hydrolyses of sucrose and cellobiose will be engineered. It is expected that high yields of ethanol can be achieved in a process with cell recycling, lower contamination levels and decreased antibiotic use, when compared to current 2G technologies.
Evolutionary and Ecological Correlates of Quiet Flight in Nightbirds, Hawks, Falcons, and Owls
Authors: Clark Christopher J , LePiane Krista , Liu Lori
Published: May 2020

Synopsis

Two hypotheses have been proposed for the evolution of structures that reduce flight sounds in birds. According to the stealth hypothesis, flying quietly reduces the ability of other animals (e.g., prey) to detect the animal’s approach from its flight sounds. This hypothesis predicts that animals hunting prey with acute hearing evolve silencing features. The self-masking hypothesis posits that reduced flight sounds permit the animal itself to hear better (such as the sounds of its prey, or its own echolocation calls) during flight. This hypothesis predicts that quieting features evolve in predators that hunt by ear, or in species that echolocate. Owls, certain hawks, and nightbirds (nocturnal Caprimulgiformes) have convergently evolved a sound-reducing feature: a velvety coating on the dorsal surface of wing and tail feathers. Here we document a fourth independent origin of the velvet, in the American kestrel (Falco sparverius). Among these four clades (hawks, falcons, nightbirds, and owls), the velvet is longer and better developed in wing and tail regions prone to rubbing with neighboring feathers, apparently to reduce broadband frictional noise produced by rubbing of adjacent feathers. We tested whether stealth or self-masking better predicted which species evolved the velvet. There was no support of echolocation as a driver of the velvet: oilbird(Steatornis caripensis) and glossy swiftlet (Collocalia esculenta) each evolved echolocation but neither had any velvet. A phylogenetic least squares fit of stealth and self-masking (to better hear prey sounds) provided support for both hypotheses. Some nightbirds (nightjars, potoos, and owlet-nightjars) eat flying insects that do not make much sound, implying the velvet permits stealthy approach of flying insects. One nightbird clade, frogmouths (Podargus) have more extensive velvet than other nightbirds and may hunt terrestrial prey by ear, in support of self-masking. In hawks, the velvet is also best developed in species known or suspected to hunt by ear (harriers and kites), supporting the self-masking hypothesis, but velvet is also present in reduced form in hawk species not known to hunt by ear, in support of the stealth hypothesis. American kestrel is not known to hunt by ear, and unlike the other falcons sampled, flies slowly (kite-like) when hunting. Thus the presence of velvet in it supports the stealth hypothesis. All owls sampled (n = 13 species) had extensive velvet, including the buffy fish-owl (Ketupa ketupu), contrary to literature claims that fish-owls had lost the velvet. Collectively, there is support for both the self-masking and stealth hypotheses for the evolution of dorsal velvet in birds.
Effects of temperature and hypoxia on respiration, photorespiration, and photosynthesis of seagrass leaves from contrasting temperature regimes
Authors: Rasmusson Lina M , Buapet Pimchanok , George Rushingisha , Gullström Martin , Gunnarsson Pontus C B , Björk Mats
Published: May 2020

In near-future climate change scenarios, elevated ocean temperatures with higher and more frequent peaks are anticipated than at present. Moreover, increased eutrophication and higher primary and secondary productivity will affect the oxygen levels of shallow-water coastal ecosystems, creating hypoxic conditions that can be experienced regularly, especially in dense vegetated systems. These climate-related events may impose detrimental effects on the primary productivity of seagrass. To evaluate such effects, this study combined gas exchange measurements with pulse amplitude-modulated fluorometry to assess the impact of short-time exposure to a range of water temperatures at ambient and low-oxygen levels on mitochondrial respiration, chlorophyll fluorescence (based on the Fv/F0 ratio), photosynthetic oxygen evolution, and photorespiration in leaf segments of the temperate seagrass Zostera marina and the tropical seagrass Thalassia hemprichii. We found that mitochondrial respiration in both Z. marina and T. hemprichii increased with higher temperatures up to 40°C and that low O2 caused significantly reduced respiration rates, particularly in T. hemprichii. Elevated water temperature had a clear negative effect on the Fv/F0 of both seagrass species, indicating damage or inactivation of the photosynthetic apparatus, even when light is not present. Moreover, damage to the photosynthetic apparatus was observed as an effect of elevated temperature combined with low O2 during darkness, resulting in subsequent lower photosynthesis in light. Photorespiration was present, but not promoted by increased temperature alone and will thus not further contribute to productivity losses during warmer events (when not carbon limited). This study demonstrates the negative impact of hypoxic stress and elevated temperatures on seagrass productivity, which may influence the overall health of seagrass plants as well as oxygen and carbon fluxes of shallow-water coastal ecosystems in warmer climate scenarios.
Dwork Crystals I
Authors: Beukers Frits , Vlasenko Masha
Published: May 2020

We present an elementary elaboration of Dwork’s idea of explicit $p$-adic limit formulas for zeta functions of toric hypersurfaces.
Bykovskii-Type Theorem for the Picard Manifold
Authors: Balog Antal , Biró András , Cherubini Giacomo , Laaksonen Niko
Published: May 2020

We generalise a result of Bykovskii to the Gaussian integers and prove an asymptotic formula for the prime geodesic theorem in short intervals on the Picard manifold. Previous works show that individually the remainder is bounded by $O(X^{13/8+\epsilon })$ and $O(X^{3/2+\theta +\epsilon })$, where $\theta$ is the subconvexity exponent for quadratic Dirichlet $L$-functions over $\mathbb{Q}(i)$. By combining arithmetic methods with estimates for a spectral exponential sum and a smooth explicit formula, we obtain an improvement for both of these exponents. Moreover, by assuming two standard conjectures on $L$-functions, we show that it is possible to reduce the exponent below the barrier $3/2$ and get $O(X^{34/23+\epsilon })$ conditionally. We also demonstrate a dependence of the remainder in the short interval estimate on the classical Gauss circle problem for shifted centres.
Quasimaps to Zero-Dimensional A∞-Quiver Varieties
Authors: Dinkins Hunter , Smirnov Andrey
Published: May 2020

We consider the moduli spaces of quasimaps to zero-dimensional $A_{\infty }$ Nakajima quiver varieties. An explicit combinatorial formula for the equivariant Euler characteristic of these moduli spaces is obtained and applications to symplectic duality are discussed.
Rabinowitz Floer Homology for Tentacular Hamiltonians
Authors: Pasquotto Federica , Vandervorst Robert , Wiśniewska Jagna
Published: May 2020

This paper extends the definition of Rabinowitz Floer homology to non-compact hypersurfaces. We present a general framework for the construction of Rabinowitz Floer homology in the non-compact setting under suitable compactness assumptions on the periodic orbits and the moduli spaces of Floer trajectories. We introduce a class of hypersurfaces arising as the level sets of specific Hamiltonians: strongly tentacular Hamiltonians for which the compactness conditions are satisfied, cf. [ 21], thus enabling us to define the Rabinowitz Floer homology for this class. Rabinowitz Floer homology in turn serves as a tool to address the Weinstein conjecture and establish existence of closed characteristics for non-compact contact manifolds.
Remembering and Enhancing the Impact of Women in Infectious Diseases
Authors: Gilsdorf Janet R , Zimmer Shanta M
Published: May 2020

Following the establishment of the Infectious Diseases Society of America (IDSA), women played a minor role as IDSA leaders, awards recipients, and presenters at the national meeting. Since the formation of the IDSA Women’s Committee in 1992, women have played an increasing role in all of these domains of the Society. Two subsequent IDSA task forces have emphasized the importance of women, and other unrepresented minorities, to the success of the core missions of the Society. Ongoing efforts to maintain the presence of women and their unique talents, experiences, and understandings in the Society will sustain the strengths of IDSA.
γ-Glutamyltransferase as a Novel Virulence Factor of Acinetobacter baumannii Inducing Alveolar Wall Destruction and Renal Damage in Systemic Disease
Authors: Elhosseiny Noha M , Elhezawy Nada B , Sayed Rehab M , Khattab Marwa S , El Far Miran Y , Attia Ahmed S
Published: May 2020

A thorough understanding of Acinetobacter baumannii pathogenicity is the key to identifying novel drug targets. In the current study, we characterize the γ-glutamyltransferase enzyme (GGT) as a novel virulence factor. A GGT assay showed that the enzyme is secreted via the type II secretion system and results in higher extracellular activity for the hypervirulent AB5075 than the laboratory-adapted strain American Type Culture Collection 17978. Enzyme-linked immunosorbent assay revealed that the former secretes larger amounts of GGT, and a rifampicin messenger RNA stability study showed that one reason for this could be the longer AB5075 ggt transcript half-life. Infection models confirmed that GGT is required for the virulence of A. baumannii. Finally, we show that clinical isolates with significantly higher extracellular GGT activity resulted in more severe infections, and assay of immune response and tissue damage markers confirm this correlation. The current findings establish for the first time the role of the GGT in the pathogenicity of A. baumannii.
How Far Can Rhynchophorus palmarum (Coleoptera: Curculionidae) Fly?
Authors: Hoddle Mark S , Hoddle Christina D , Milosavljević Ivan
Published: May 2020

The palm weevil, Rhynchophorus palmarum (L.), was first recorded in San Diego County, CA in 2011 and breeding populations were recovered from infested Canary Islands date palms, Phoenix canariensis, in San Ysidro, San Diego County, in 2015. This palm pest presents a significant threat to California’s edible date industry as Phoenix dactylifera is a recorded host for this weevil. The flight capabilities of R. palmarum are unknown which limits understanding of rates of natural dispersal. In response to this knowledge deficit, 24-h flight mill trials were conducted with field-collected male and female weevils. A total of 87 weevils (49 females and 38 males) were used in experiments, ~6% failed to fly >1 km in 24 h and were excluded from analyses. Of those 82 weevils flying >1 km in 24 h, the average distance flown by males and females was ~41 and ~53 km, respectively. Approximately 10% of females flew >100 km in 24 h, with two (~4%) females flying >140 km. The maximum recorded distance flown by a male weevil was 95 km. Flight activity was predominantly diurnal and flying weevils exhibited an average weight loss of ~18% while non-flying control weevils lost ~13% body weight in 24 h. The combined flight distances for male and female weevils exhibited a heavy-tailed platykurtic distribution. Flight mill data for R. palmarum are compared to similarly collected flight mill data for two other species of invasive palm weevil, Rhynchophorus ferrugineus (Olivier) and Rhynchophorus vulneratus (Panzer).
An unexpected diagnosis of paediatric subcutaneous sacrococcygeal extraspinal ependymoma: lessons learnt and review of the literature
Authors: Gupta Tanya , Patel Vikesh , El-Medani Faisal , Gupta Sanjay
Published: May 2020

This case describes a 9-year-old male who presented to general surgical clinic with a 3-year history of persistent natal cleft swelling, previously unsuccessfully treated as a pilonidal abscess in the community with multiple courses of antibiotics. In clinic, a 50 × 30-mm soft tissue swelling was found in the natal cleft and a clinical diagnosis of a pilonidal cyst was made. A cream-coloured solid mass measuring 50 × 35 × 30 mm was subsequently excised under general anaesthetic, with specialist histology and immunostaining confirming an unexpected diagnosis of a subcutaneous extraspinal myxopapillary ependymoma, a tumour usually found in the neuraxis. Given the atypical anatomical site of the tumour, the case presented a unique management challenge. Ultimately, the patient underwent a re-operation after specialist multi-disciplinary discussion and is currently disease free at 18 months post-surgery. The authors wish to contribute their experiences of managing this rare extraspinal ependymoma to the few existing reports in the literature.
Survey Costs: Where are We and What is the Way Forward?
Authors: Olson Kristen , Wagner James , Anderson Raeda
Published: May 2020

Survey costs are a major driver of survey design decisions and thought to be related to survey errors. Despite their importance, no common language exists for discussing survey costs, nor are there established criteria for identifying which cost metrics are useful for which purposes. Past efforts to study survey costs may have been hampered by the notion that more reporting is better reporting. This article starts by introducing a typology for survey cost metrics defined by the type of cost (estimated, observed in records, and actually incurred), currency versus non-currency measures, and level of aggregation (total, by components, per unit, relative). We also suggest a set of criteria – errors in costs, generalizability, and the degree to which a cost measure is informative about survey error sources – for evaluating the utility of cost metrics. We illustrate the evaluative criteria with the cost metrics. We argue that clearly articulating types of survey costs and resetting these baseline evaluative criteria for the utility of different types of costs will help us expand research in this critical area. We conclude with recommendations for future research in costs within and across organizations.
Scattered light may reveal the existence of ringed exoplanets
Authors: Sucerquia Mario , Alvarado-Montes Jaime A , Zuluaga Jorge I , Montesinos Matías , Bayo Amelia
Published: May 2020

Rings around giant exoplanets (hereafter ‘exorings’) are still a missing planetary phenomenon among the vast number of discovered planets. Despite the fact that there exist a large number of methods for identifying and characterizing these exorings, none of them has been successful to date. Most of those efforts focus on the photometric signatures produced by rings around transiting exoplanets; thus, little interest has been intended for the detectable signatures that non-transiting ringed planets might cause owing to the excess of scattered starlight from both their atmosphere and the considerably large surface of their (hypothetical) ring system. This extra scattering produced by exorings would occur at an orbital location defined here as ‘the summer solstice’ of a stellar light curve. In this letter, we develop a first-order model to estimate the photometric signatures of non-transiting exorings, and predict their detectability by using present and future facilities. We also show how, besides the discovery itself, our model can be used to constrain orbital and physical parameters of planet–ring systems.
Primed CRISPR DNA uptake in Pyrococcus furiosus
Authors: Garrett Sandra , Shiimori Masami , Watts Elizabeth A , Clark Landon , Graveley Brenton R , Terns Michael P
Published: May 2020

CRISPR-Cas adaptive immune systems are used by prokaryotes to defend against invaders like viruses and other mobile genetic elements. Immune memories are stored in the form of ‘spacers’ which are short DNA sequences that are captured from invaders and added to the CRISPR array during a process called ‘adaptation’. Spacers are transcribed and the resulting CRISPR (cr)RNAs assemble with different Cas proteins to form effector complexes that recognize matching nucleic acid and destroy it (‘interference’). Adaptation can be ‘naïve’, i.e. independent of any existing spacer matches, or it can be ‘primed’, i.e. spurred by the crRNA-mediated detection of a complete or partial match to an invader sequence. Here we show that primed adaptation occurs in Pyrococcus furiosus. Although P. furiosus has three distinct CRISPR-Cas interference systems (I-B, I-A and III-B), only the I-B system and Cas3 were necessary for priming. Cas4, which is important for selection and processing of new spacers in naïve adaptation, was also essential for priming. Loss of either the I-B effector proteins or Cas3 reduced naïve adaptation. However, when Cas3 and all crRNP genes were deleted, uptake of correctly processed spacers was observed, indicating that none of these interference proteins are necessary for naïve adaptation.
SNPnexus: a web server for functional annotation of human genome sequence variation (2020 update)
Authors: Oscanoa Jorge , Sivapalan Lavanya , Gadaleta Emanuela , Dayem Ullah Abu Z , Lemoine Nicholas R , Chelala Claude
Published: May 2020

SNPnexus is a web-based annotation tool for the analysis and interpretation of both known and novel sequencing variations. Since its last release, SNPnexus has received continual updates to expand the range and depth of annotations provided. SNPnexus has undergone a complete overhaul of the underlying infrastructure to accommodate faster computational times. The scope for data annotation has been substantially expanded to enhance biological interpretations of queried variants. This includes the addition of pathway analysis for the identification of enriched biological pathways and molecular processes. We have further expanded the range of user directed annotation fields available for the study of cancer sequencing data. These new additions facilitate investigations into cancer driver variants and targetable molecular alterations within input datasets. New user directed filtering options have been coupled with the addition of interactive graphical and visualization tools. These improvements streamline the analysis of variants derived from large sequencing datasets for the identification of biologically and clinically significant subsets in the data. SNPnexus is the most comprehensible web-based application currently available and these new set of updates ensures that it remains a state-of-the-art tool for researchers. SNPnexus is freely available at https://www.snp-nexus.org.
Molecular dynamics study of the recognition of ATP by nucleic acid aptamers
Authors: Xie Ya-chen , Eriksson Leif A , Zhang Ru-bo
Published: May 2020

Despite their great success in recognizing small molecules in vitro, nucleic acid aptamers are rarely used in clinical settings. This is partially due to the lack of structure-based mechanistic information. In this work, atomistic molecular dynamics simulations are used to study the static and dynamic supramolecular structures relevant to the process of the wild-type (wt) nucleic acid aptamer recognition and binding of ATP. The effects brought about by mutation of key residues in the recognition site are also explored. The simulations reveal that the aptamer displays a high degree of rigidity and is structurally very little affected by the binding of ATP. Interaction energy decomposition shows that dispersion forces from π-stacking between ATP and the G6 and A23 nucleobases in the aptamer binding site plays a more important role in stabilizing the supramolecular complex, compared to hydrogen-bond interaction between ATP and G22. Moreover, metadynamics simulations show that during the association process, water molecules act as essential bridges connecting ATP with G22, which favors the dynamic stability of the complex. The calculations carried out on three mutated aptamer structures confirm the crucial role of the hydrogen bonds and π-stacking interactions for the binding affinity of the ATP nucleic acid aptamer.
CryoEM structures of human CMG–ATPγS–DNA and CMG–AND-1 complexes
Authors: Rzechorzek Neil J , Hardwick Steven W , Jatikusumo Vincentius A , Chirgadze Dimitri Y , Pellegrini Luca
Published: May 2020

DNA unwinding in eukaryotic replication is performed by the Cdc45–MCM–GINS (CMG) helicase. Although the CMG architecture has been elucidated, its mechanism of DNA unwinding and replisome interactions remain poorly understood. Here we report the cryoEM structure at 3.3 Å of human CMG bound to fork DNA and the ATP-analogue ATPγS. Eleven nucleotides of single-stranded (ss) DNA are bound within the C-tier of MCM2–7 AAA+ ATPase domains. All MCM subunits contact DNA, from MCM2 at the 5′-end to MCM5 at the 3′-end of the DNA spiral, but only MCM6, 4, 7 and 3 make a full set of interactions. DNA binding correlates with nucleotide occupancy: five MCM subunits are bound to either ATPγS or ADP, whereas the apo MCM2-5 interface remains open. We further report the cryoEM structure of human CMG bound to the replisome hub AND-1 (CMGA). The AND-1 trimer uses one β-propeller domain of its trimerisation region to dock onto the side of the helicase assembly formed by Cdc45 and GINS. In the resulting CMGA architecture, the AND-1 trimer is closely positioned to the fork DNA while its CIP (Ctf4-interacting peptide)-binding helical domains remain available to recruit partner proteins.
Native de novo structural determinations of non-canonical nucleic acid motifs by X-ray crystallography at long wavelengths
Authors: Zhang Yashu , El Omari Kamel , Duman Ramona , Liu Sisi , Haider Shozeb , Wagner Armin , Parkinson Gary N , Wei Dengguo
Published: May 2020

Obtaining phase information remains a formidable challenge for nucleic acid structure determination. The introduction of an X-ray synchrotron beamline designed to be tunable to long wavelengths at Diamond Light Source has opened the possibility to native de novo structure determinations by the use of intrinsic scattering elements. This provides opportunities to overcome the limitations of introducing modifying nucleotides, often required to derive phasing information. In this paper, we build on established methods to generate new tools for nucleic acid structure determinations. We report on the use of (i) native intrinsic potassium single-wavelength anomalous dispersion methods (K-SAD), (ii) use of anomalous scattering elements integral to the crystallization buffer (extrinsic cobalt and intrinsic potassium ions), (iii) extrinsic bromine and intrinsic phosphorus SAD to solve complex nucleic acid structures. Using the reported methods we solved the structures of (i) Pseudorabies virus (PRV) RNA G-quadruplex and ligand complex, (ii) PRV DNA G-quadruplex, and (iii) an i-motif of human telomeric sequence. Our results highlight the utility of using intrinsic scattering as a pathway to solve and determine non-canonical nucleic acid motifs and reveal the variability of topology, influence of ligand binding, and glycosidic angle rearrangements seen between RNA and DNA G-quadruplexes of the same sequence.
Is milk and dairy intake a preventive factor for elderly cognition (dementia and Alzheimer’s)? A quality review of cohort surveys
Authors: Bermejo-Pareja Félix , Ciudad-Cabañas María José , Llamas-Velasco Sara , Tapias-Merino Ester , Hernández Gallego Jesús , Hernández-Cabria Marta , Collado-Yurrita Luis , López-Arrieta Jesús María
Published: May 2020

Milk and dairy (M&D) is a longstanding human food with widespread use. Many studies showed the preventive capacity of M&D in several human health disorders, but its utility in others is under discussion. Aging has been associated to elderly cognitive decline including dementia-Alzheimer syndrome (Dem-AD). The absence of a therapy to impede or postpone Dem-AD determines the need for its prevention, including nutritional factors. To evaluate the preventive capacity of M&D consumption in elderly Dem-AD we performed a systematic review in the main biomedical databases and information resources, but we present this study as a narrative review to discuss better the complexity of this subject. The elderly Dem-AD has a long pre-symptomatic period and the M&D intake has a widespread use. These determinants and the quality flaws of published studies impeach us to answer whether M&D consumption is preventive for Dem-AD. Moreover, two long Japanese cohorts suggest that M&D intake could prevent Dem-AD. Prospective cohorts beginning in midlife (or early life) could answer this question in the future.
Health Care–Seeking Behaviors and Perceptions of Provider-Initiated Discussion of Pre-exposure Prophylaxis Among PrEP-Naïve HIV-Negative Men Who Have Sex With Men in Atlanta, Georgia
Authors: Trost Susanna L , Onwubiko Udodirim N , Wilson Derick B , Holland David P , Chamberlain Allison T
Published: May 2020

Background

Given high rates of HIV among men who have sex with men (MSM) in the United States, there is a need to more effectively leverage the health care system to bolster promotion of pre-exposure prophylaxis (PrEP) to at-risk MSM.

Methods

Using data collected from a 2018 venue-based cross-sectional survey, we examined factors associated with health care–seeking behaviors, discussing PrEP with a provider, and barriers to PrEP uptake among MSM. Associations between outcomes and respondents’ sociodemographic characteristics and sexual behaviors were assessed using log binomial regression.

Results

Of 478 MSM, 247 (51%) were PrEP-naïve and HIV-negative. Although 85% of PrEP-naïve MSM reported visiting a health care provider in the past year, only 31% recalled having any provider discuss PrEP. The most frequently cited reasons for not taking PrEP were low perception of personal risk of acquiring HIV (37%) and not knowing enough about PrEP (35%). Those who saw a provider in the last year were less likely than those who did not to cite lack of knowledge as a barrier to use (prevalence rate, 0.66, 95% confidence interval, 0.45–0.96).

Conclusions

Despite the majority of PrEP-naïve MSM interfacing with the health care system, recollection of discussing PrEP with providers was limited. Increased efforts to equip providers with the tools to discuss PrEP and address pressing concerns with at-risk individuals may help improve PrEP uptake among priority populations.
Competition between vacuolated and mixotrophic unicellular plankton
Authors: Cadier Mathilde , Hansen Agnethe Nøhr , Andersen Ken H , Visser Andre W
Published: May 2020

Trait-based ecology allows much of the complexity of ecosystems to be projected onto a low-dimensional trait space. We conjecture that three key traits capture the main aspects of diversity of unicellular planktonic organisms: cell size, trophic strategies (relative investment in photosynthesis and phagotrophy) and vacuolation. The three selected traits are representative of two groups: mixotrophic protists, which in addition to phototrophy, use phagotrophic grazing as a food source, and diatoms that use fluid-filled vacuoles to increase their physical size relative to carbon biomass. We construct a trait-based model related to the three traits and determine the optimal trait values of cells of a given carbon size in a given environment. We also perform fully dynamic simulations to study the self-assembled trait distribution at steady state and throughout a seasonal cycle. Diatoms’ strategy is shown to be advantageous among small cells and under early spring conditions, in which highly vacuolated diatoms are simulated, while mixotrophy is dominant among larger cells when nutrients are limiting (summer conditions). The novelty of this approach lies in the mechanistic understanding of plankton physiology that is successfully used to capture how community trait structure emerges from trade-offs that constrain the different strategy among unicellular plankton.
First Impression Bias: Evidence from Analyst Forecasts*
Authors: Hirshleifer David , Lourie Ben , Ruchti Thomas G , Truong Phong
Published: May 2020

We present evidence of first impression bias among finance professionals in the field. Equity analysts’ forecasts, target prices, and recommendations suffer from first impression bias. If a firm performs particularly well (poorly) in the year before an analyst follows it, that analyst tends to issue optimistic (pessimistic) evaluations. Consistent with negativity bias, we find that negative first impressions have a stronger effect than positive ones. The market adjusts for analyst first impression bias with a lag. Finally, our findings contribute to the literature on experience effects. We show that a set of professionals in the field, equity analysts, apply U-shaped weights to their sequence of past experiences, with greater weight on first experiences and recent experiences than on intermediate ones.
DETERMINATION OF DIAGNOSTIC REFERENCE LEVEL IN ROUTINE EXAMINATIONS OF DIGITAL RADIOGRAPHY IN MAZANDARAN PROVINCE
Authors: Hoseini Motlagh Zeinab , Shabestani Monfared Ali , Deevband Mohammad Reza , Abedi-Firouzjah Razzagh , Ghaemian Naser , Abdi Rohollah , Ebrahimnejad Gorji Kourosh
Published: May 2020

Introduction

The main purpose of this study was to determine the diagnostic reference level (DRL) for routine digital radiography examinations in Mazandaran province.

Materials and methods

Thirteen digital radiographic examinations at 18 high-patient-load radiography centres were investigated. The indirect dosimetry method was performed based on the IAEA report. Average entrance skin dose (ESD) and the third quartile of ESD as the DRL were evaluated from the measurement made by a semiconductor dosemeter.

Results

DRL for the examinations of digital radiography was obtained as: Skull (postero-anterior [PA]): 2.2, skull (lateral [LAT]): 2.4, cervical spine (antero-posterior [AP]): 1.6, cervical spine (LAT): 1.7, thoracic spine (AP): 3.6, thoracic spine (LAT): 9.9, lumbar spine (AP): 5.3, lumbar spine (LAT): 11.8, chest (PA): 1.4, chest (LAT): 2.1, abdomen (AP): 4.3, pelvis (AP): 3.2 and hip (AP): 2.1 mGy.

Conclusion

Although DRL was not higher compared with the international organisations’ levels, it can be reduced by adequate training of radiographers.
INVESTIGATION OF XENON-FILLED TUBE BREAKDOWN VOLTAGE AND DELAY RESPONSE AS POSSIBLE DOSIMETRIC PARAMETERS FOR SMALL GAMMA RAY AIR KERMA RATES
Authors: Pejović Milić , Živanović Emilija , Živanović Miloš
Published: May 2020

This paper presents experimental results of dynamic breakdown voltage and delay response as functions of gamma ray air kerma rate for xenon-filled tube at 2.7 mbar pressure. Gamma ray air kerma rate range was considered from 123 nGy h–1 up to 12.3 mGy h–1 in order to investigate the possibility of the application of this tube in gamma radiation dosimetry. It was shown that the variations of the above-mentioned parameters are considerable up to the dose rate of 1.23 μGy h–1, which points to the possibility for application in small dose rate gamma ray dosimetry. Physical processes that make dominant impact to dynamic breakdown voltage and delay response during xenon-filled tube irradiation are also discussed in the paper.
Consistency of SVDQuartets and Maximum Likelihood for Coalescent-Based Species Tree Estimation
Authors: Wascher Matthew , Kubatko Laura
Published: May 2020

Numerous methods for inferring species-level phylogenies under the coalescent model have been proposed within the last 20 years, and debates continue about the relative strengths and weaknesses of these methods. One desirable property of a phylogenetic estimator is that of statistical consistency, which means intuitively that as more data are collected, the probability that the estimated tree has the same topology as the true tree goes to 1. To date, consistency results for species tree inference under the multispecies coalescent (MSC) have been derived only for summary statistics methods, such as ASTRAL and MP-EST. These methods have been found to be consistent given true gene trees but may be inconsistent when gene trees are estimated from data for loci of finite length. Here, we consider the question of statistical consistency for four taxa for SVDQuartets for general data types, as well as for the maximum likelihood (ML) method in the case in which the data are a collection of sites generated under the MSC model such that the sites are conditionally independent given the species tree (we call these data coalescent independent sites [CIS] data). We show that SVDQuartets is statistically consistent for all data types (i.e., for both CIS data and for multilocus data), and we derive its rate of convergence. We additionally show that ML is consistent for CIS data under the JC69 model and discuss why a proof for the more general multilocus case is difficult. Finally, we compare the performance of ML and SDVQuartets using simulation for both data types. [Consistency; gene tree; maximum likelihood; multilocus data; hylogenetic inference; species tree; SVDQuartets.]
The change in beneficial interest within the Liechtenstein Private Purpose Foundation—can the principles of solidification and flexibility coexist?
Authors: Schurr Francesco A
Published: May 2020

The article deals with the principles of solidification and flexibility within private foundations. Typically, private foundations are used as will substitutes or as essential elements within an overall asset protection strategy. One of the key advantages of foundations, as compared to other instruments, is the high level of stability combined with very limited instruments to change the purpose as well as the beneficial interest. An adjustment of the statutory provisions related to the purpose can be required due to a change of circumstances, but might violate the governance regime. The article deals with the different legal issues involved and tries to give some guidelines for practitioners by discussing a case study to illustrate the legal issues addressed in this article.
Partial Resistance Against Erysiphe pisi and E. trifolii Under Different Genetic Control in Lathyrus cicera: Outcomes from a Linkage Mapping Approach
Authors: Santos Carmen , Martins Davide , Rubiales Diego , Vaz Patto Maria Carlota
Published: May 2020

Powdery mildew infections are among the most severe foliar biotrophic fungal diseases in grain legumes. Several accessions of Lathyrus cicera (chickling pea) show levels of partial resistance to Erysiphe pisi, the causal agent of pea powdery mildew, and to E. trifolii, a powdery mildew pathogen recently confirmed to infect pea and Lathyrus spp. Nevertheless, the underlying L. cicera resistance mechanisms against powdery mildews are poorly understood. To unveil the genetic control of resistance against powdery mildews in L. cicera, a recombinant inbred line population segregating for response to both species was used in resistance linkage analysis. An improved L. cicera genetic linkage map was used in this analysis. The new higher-density linkage map contains 1,468 polymorphic loci mapped on seven major and two minor linkage groups, covering a total of 712.4 cM. The percentage of the leaf area affected by either E. pisi or E. trifolii was recorded in independent screenings of the recombinant inbred line population, identifying a continuous range of resistance-susceptibility responses. Distinct quantitative trait loci (QTLs) for partial resistance against each pathogen were identified, suggesting different genetic bases are involved in the response to E. pisi and E. trifolii in L. cicera. Moreover, through comparative mapping of L. cicera QTL regions with the pea reference genome, candidate genes and pathways involved in resistance against powdery mildews were identified. This study extended the previously available genetic and genomic tools in Lathyrus species, providing clues about diverse powdery mildew resistance mechanisms useful for future resistance breeding of L. cicera and related species.
Adjuvant chemotherapy in rectal cancer: state of the art and future perspectives
Authors: Glimelius Bengt
Published: May 2020

Purpose of review

The value of adjuvant chemotherapy in rectal cancer is controversial with opinions varying from ‘not be used’ since randomized trials have not shown significant gains to ‘be used as in colon cancer’ as the need is the same and colon and rectal cancers are quite similar. This review will look upon data critically and with open eyes.

Recent findings

With the exception of one randomized phase II trial (ADORE) revealing a significant gain in disease-free survival using one more effective regimen (mFOLFOX) than bolus 5-fluorouracil leucovorin, no new data have been presented. However, bringing up aspects in previous trials, either considered irrelevant for the present situation or overall negative, of what adjuvant treatment can achieve, a small reduction (hazard ratio about 0.8) in the risk of recurrence is present. This reduction is not fundamentally different from that in colon cancer considering that adjuvant treatment for rectal cancer cannot be initiated as rapidly as it can after a colon cancer diagnosis.

Adjuvant chemotherapy after rectal cancer surgery reduces recurrence risks but the benefit is limited and for most patients not clinically relevant. Neoadjuvant therapy can be more effective but results from randomized trials are not yet available.