bluuebunny/crossref_metadata_2025 huggingface dataset:
The continuing arc toward phototropic enlightenment
Authors: Liscum Emmanuel , Nittler Patrick , Koskie Katelynn
Published: January 2020

Phototropism represents a simple physiological mechanism—differential growth across the growing organ of a plant—to respond to gradients of light and maximize photosynthetic light capture (in aerial tissues) and water/nutrient acquisition (in roots). The phototropin blue light receptors, phot1 and phot2, have been identified as the essential sensors for phototropism. Additionally, several downstream signal/response components have been identified, including the phot-interacting proteins NON-PHOTOTROPIC HYPOCOTYL 3 (NPH3) and PHYTOCHROME SUBSTRATE 4 (PKS4). While the structural and photochemical properties of the phots are quite well understood, much less is known about how the phots signal through downstream regulators. Recent advances have, however, provided some intriguing clues. It appears that inactive receptor phot1 is found dispersed in a monomeric form at the plasma membrane in darkness. Upon light absorption dimerizes and clusters in sterol-rich microdomains where it is signal active. Additional studies showed that the phot-regulated phosphorylation status of both NPH3 and PKS4 is linked to phototropic responsiveness. While PKS4 can function as both a positive (in low light) and a negative (in high light) regulator of phototropism, NPH3 appears to function solely as a key positive regulator. Ultimately, it is the subcellular localization of NPH3 that appears crucial, an aspect regulated by its phosphorylation status. While phot1 activation promotes dephosphorylation of NPH3 and its movement from the plasma membrane to cytoplasmic foci, phot2 appears to modulate relocalization back to the plasma membrane. Together these findings are beginning to illuminate the complex biochemical and cellular events, involved in adaptively modifying phototropic responsiveness under a wide varying range of light conditions.
Lower bounds for the state complexity of probabilistic languages and the language of prime numbers
Authors: Fijalkow NathanaËl
Published: January 2020

This paper studies the complexity of languages of finite words using automata theory. To go beyond the class of regular languages, we consider infinite automata and the notion of state complexity defined by Karp. Motivated by the seminal paper of Rabin from 1963 introducing probabilistic automata, we study the (deterministic) state complexity of probabilistic languages and prove that probabilistic languages can have arbitrarily high deterministic state complexity. We then look at alternating automata as introduced by Chandra, Kozen and Stockmeyer: such machines run independent computations on the word and gather their answers through boolean combinations. We devise a lower bound technique relying on boundedly generated lattices of languages, and give two applications of this technique. The first is a hierarchy theorem, stating that there are languages of arbitrarily high polynomial alternating state complexity, and the second is a linear lower bound on the alternating state complexity of the prime numbers written in binary. This second result strengthens a result of Hartmanis and Shank from 1968, which implies an exponentially worse lower bound for the same model.
Power Kripke–Platek set theory and the axiom of choice
Authors: Rathjen Michael
Published: January 2020

While power Kripke–Platek set theory, ${\textbf{KP}}({\mathcal{P}})$, shares many properties with ordinary Kripke–Platek set theory, ${\textbf{KP}}$, in several ways it behaves quite differently from ${\textbf{KP}}$. This is perhaps most strikingly demonstrated by a result, due to Mathias, to the effect that adding the axiom of constructibility to ${\textbf{KP}}({\mathcal{P}})$ gives rise to a much stronger theory, whereas in the case of ${\textbf{KP}}$, the constructible hierarchy provides an inner model, so that ${\textbf{KP}}$ and ${\textbf{KP}}+V=L$ have the same strength.

This paper will be concerned with the relationship between ${\textbf{KP}}({\mathcal{P}})$ and ${\textbf{KP}}({\mathcal{P}})$ plus the axiom of choice or even the global axiom of choice, $\textbf{AC}_{\tiny {global}}$. Since $L$ is the standard vehicle to furnish a model in which this axiom holds, the usual argument for demonstrating that the addition of ${\textbf{AC}}$ or $\textbf{AC}_{\tiny {global}}$ to ${\textbf{KP}}({\mathcal{P}})$ does not increase proof-theoretic strength does not apply in any obvious way. Among other tools, the paper uses techniques from ordinal analysis to show that ${\textbf{KP}}({\mathcal{P}})+\textbf{AC}_{\tiny {global}}$ has the same strength as ${\textbf{KP}}({\mathcal{P}})$, thereby answering a question of Mathias. Moreover, it is shown that ${\textbf{KP}}({\mathcal{P}})+\textbf{AC}_{\tiny {global}}$ is conservative over ${\textbf{KP}}({\mathcal{P}})$ for $\varPi ^1_4$ statements of analysis.

The method of ordinal analysis for theories with power set was developed in an earlier paper. The technique allows one to compute witnessing information from infinitary proofs, providing bounds for the transfinite iterations of the power set operation that are provable in a theory.

As the theory ${\textbf{KP}}({\mathcal{P}})+\textbf{AC}_{\tiny {global}}$ provides a very useful tool for defining models and realizability models of other theories that are hard to construct without access to a uniform selection mechanism, it is desirable to determine its exact proof-theoretic strength. This knowledge can for instance be used to determine the strength of Feferman’s operational set theory with power set operation as well as constructive Zermelo–Fraenkel set theory with the axiom of choice.
Melatonin protects the mouse testis against heat-induced damage
Authors: Zhang Pengfei , Zheng Yi , Lv Yinghua , Li Fuyuan , Su Lihong , Qin Yuwei , Zeng Wenxian
Published: January 2020

Spermatogenesis, an intricate process occurring in the testis, is responsible for ongoing production of spermatozoa and thus the cornerstone of lifelong male fertility. In the testis, spermatogenesis occurs optimally at a temperature 2–4°C lower than that of the core body. Increased scrotal temperature generates testicular heat stress and later causes testicular atrophy and spermatogenic arrest, resulting in a lower sperm yield and therefore impaired male fertility. Melatonin (N-acetyl-5-methoxytryptamine), a small neuro-hormone synthesized and secreted by the pineal gland and the testis, is widely known as a potent free-radical scavenger; it has been reported that melatonin protects the testis against inflammation and reactive oxygen species generation thereby playing anti-inflammatory, -oxidative and -apoptotic roles in the testis. Nevertheless, the role of melatonin in the testicular response to heat stress has not been studied. Here, by employing a mouse model of testicular hyperthermia, we systematically investigated the testicular response to heat stress as well as the occurrence of autophagy, apoptosis and oxidative stress in the testis. Importantly, we found that pre-treatment with melatonin attenuated heat-induced apoptosis and oxidative stress in the testis. Also, post-treatment with melatonin promoted recovery of the testes from heat-induced damage, probably by maintaining the integrity of the Sertoli cell tight-junction. Thus, we for the first time provide the proof of concept that melatonin can protect the testis against heat-induced damage, supporting the potential future use of melatonin as a therapeutic drug in men for sub/infertility incurred by various testicular hyperthermia factors.
VERIFICATION AND OPTIMISATION OF PRESELECTED EXPOSURE PARAMETERS IN SCREENING MAMMOGRAPHY: A CENTRAL COMPOSITE DESIGN METHODOLOGY
Authors: Acho Sussan N , Stofile Caroline , Moller Mia , Morphis Michaella
Published: January 2020

In screening mammography, the automatic exposure control (AEC) device selects the optimum exposure parameters for each patient exposure. In practice, this device is calibrated to deliver an optimum figure of merit (FOM) for each set of exposure parameters. This study utilises the central composite design methodology to verify the operating level of the AEC performance for polymethyl methacrylate (PMMA) thicknesses of 4 and 5 cm. Quadratic surface plots reveal that the exposure parameters of the default AEC mode are optimised for the 4-cm thickness of the PMMA. However, the exposure parameters of the 5-cm thickness of PMMA need fine-tuning to obtain a maximum value for the FOM.
Multivariate neural signatures for health neuroscience: assessing spontaneous regulation during food choice
Authors: Cosme Danielle , Zeithamova Dagmar , Stice Eric , Berkman Elliot T
Published: January 2020

Establishing links between neural systems and health can be challenging since there is not a one-to-one mapping between brain regions and psychological states. Building sensitive and specific predictive models of health-relevant constructs using multivariate activation patterns of brain activation is a promising new direction. We illustrate the potential of this approach by building two ‘neural signatures’ of food craving regulation (CR) using multivariate machine learning and, for comparison, a univariate contrast. We applied the signatures to two large validation samples of overweight adults who completed tasks measuring CR ability and valuation during food choice. Across these samples, the machine learning signature was more reliable. This signature decoded CR from food viewing and higher signature expression was associated with less craving. During food choice, expression of the regulation signature was stronger for unhealthy foods and inversely related to subjective value, indicating that participants engaged in CR despite never being instructed to control their cravings. Neural signatures thus have the potential to measure spontaneous engagement of mental processes in the absence of explicit instruction, affording greater ecological validity. We close by discussing the opportunities and challenges of this approach, emphasizing what machine learning tools bring to the field of health neuroscience.
Exchange of information: the challenge ahead—Bermuda International Academy of Estate and Trust Law Tokyo May 2019
Authors: Robinson Keith
Published: January 2020

Bermuda has been engaging in tax information exchange with other jurisdictions since the 1980s. This article, which is based upon a paper presented at the annual meeting of the International Academy of Estate and Trusts Law in Tokyo, Japan in May 2019, looks at the historical trend towards information exchange. The article considers in detail the system now in place under Bermuda law for the production of information pursuant to tax information exchange agreements (TIEAs). This requires a court order and the reported case law dealing with challenges to these TIEA orders provides a useful insight into the nature and range of the requests being made by foreign tax authorities.
Pulmonary levels of biomarkers for inflammation and lung injury in protective versus conventional one-lung ventilation for oesophagectomy
Authors: van der Woude Margaretha C. , Bormans Laura , van der Horst Robrecht P. , Sosef Meindert N. , Belgers Henricus J. , Hemmes Sabrine N. , Tuip-de Boer Anita , Gama de Abreu Marcelo , Pelosi Paolo , Spronk Peter E. , Neto Ary Serpo , Schultz Marcus J.
Published: January 2020

BACKGROUND

It is uncertain whether protective ventilation reduces ventilation-induced pulmonary inflammation and injury during one-lung ventilation.

OBJECTIVE

To compare intra-operative protective ventilation with conventional during oesophagectomy with respect to pulmonary levels of biomarkers for inflammation and lung injury.

DESIGN

Randomised clinical trial.

SETTING

Tertiary centre for oesophageal diseases.

PATIENTS

Twenty-nine patients scheduled for one-lung ventilation during oesophagectomy.

INTERVENTIONS

Low tidal volume (V

T
) of 6 ml kg−1 predicted body weight (pbw) during two-lung ventilation and 3 ml kgpbw−1 during one-lung ventilation with 5 cmH2O positive end expired pressure versus intermediate V

T
of 10 ml kgpbw−1 during two-lung ventilation and 5 ml kgpbw−1 body weight during one-lung ventilation with no positive end-expiratory pressure.

OUTCOME MEASURES

The primary outcome was the change in bronchoalveolar lavage (BAL) levels of preselected biomarkers for inflammation (TNF-α, IL-6 and IL-8) and lung injury (soluble Receptor for Advanced Glycation End-products, surfactant protein-D, Clara Cell protein 16 and Krebs von den Lungen 6), from start to end of ventilation.

RESULTS

Median [IQR] V

T
in the protective ventilation group (n = 13) was 6.0 [5.7 to 7.8] and 3.1 [3.0 to 3.6] ml kgpbw−1 during two and one-lung ventilation; V

T
in the conventional ventilation group (n = 16) was 9.8 [7.0 to 10.1] and 5.2 [5.0 to 5.5] ml kgpbw−1 during two and one-lung ventilation. BAL levels of biomarkers for inflammation increased from start to end of ventilation in both groups; levels of soluble Receptor for Advanced Glycation End-products, Clara Cell protein 16 and Krebs von den Lungen 6 did not change, while levels of surfactant protein-D decreased. Changes in BAL biomarkers levels were not significantly different between the two ventilation strategies.

CONCLUSION

Intra-operative protective ventilation compared with conventional ventilation does not affect changes in pulmonary levels of biomarkers for inflammation and lung injury in patients undergoing one-lung ventilation for oesophagectomy.

TRIAL REGISTRATION

The ‘Low versus Conventional tidal volumes during one-lung ventilation for minimally invasive oesophagectomy trial’ (LoCo) was registered at the Netherlands Trial Register (study identifier NTR 4391).
Deep neuromuscular blockade during spinal surgery reduces intra-operative blood loss
Authors: Kang Woon-Seok , Oh Chung-Sik , Rhee Ka Y. , Kang Min H. , Kim Tae-Hoon , Lee Suk H. , Kim Seong-Hyop
Published: January 2020

BACKGROUND

Spinal surgery is usually performed in the prone position using a posterior approach. However, the prone position may cause venous engorgement in the back and thus increase surgical bleeding with interruption of surgery. The prone position also affects cardiac output since large vessels are compressed decreasing venous return to the heart.

OBJECTIVE

We hypothesised that deep neuromuscular blockade would be associated with less surgical bleeding during spinal surgery in the prone position.

DESIGN

Randomised, single blinded trial.

SETTING

University teaching hospital.

PARTICIPANTS

Eighty-eight patients in two groups.

INTERVENTIONS

Patients were randomly assigned to moderate neuromuscular blockade or deep neuromuscular blockade. In the moderate neuromuscular blockade group, administration of rocuronium was adjusted such that the train-of-four count was one to two. In the deep neuromuscular blockade group, rocuronium administration was adjusted such that the train-of-four count was zero with a posttetanic count 2 or less.

MAIN OUTCOME MEASURES

The primary outcome was the volume of intra-operative surgical bleeding. The surgeon's satisfaction with operating conditions, haemodynamic and respiratory status, and postoperative pain scores were evaluated.

RESULTS

The median [IQR] volume of intra-operative surgical bleeding was significantly less in the deep neuromuscular blockade group than in the moderate neuromuscular blockade group; 300 ml [200 to 494] vs. 415 ml [240 to 601]; difference: 117 ml (95% CI, 9 to 244; P = 0.044). The mean ± SD surgeon's satisfaction with the intra-operative surgical conditions was greater in the deep neuromuscular blockade group than in the moderate neuromuscular blockade group; 3.5 ± 1.0 vs. 2.9 ± 0.9 (P = 0.004). In intergroup comparisons of respiratory variables, peak inspiratory pressure was lower in the deep neuromuscular blockade group overall (P < 0.001). The median [IQR] postoperative pain score was lower in the deep neuromuscular blockade group than the moderate neuromuscular blockade group; 50 [36 to 60] vs. 60 [50 to 70], (P = 0.023).

CONCLUSION

Deep neuromuscular blockade reduced intra-operative surgical bleeding in patients undergoing spinal surgery. This may be related to greater relaxation in the back muscles and lower intra-operative peak inspiratory pressure when compared with moderate neuromuscular blockade.

TRIAL REGISTRATION

KCT0001264 (http://cris.nih.go.kr).
Nonadherence to antibiotic guidelines in patients admitted to ICU with sepsis is associated with increased mortality
Authors: Lindberg Oscar , De Geer Lina , Chew Michelle S.
Published: January 2020

BACKGROUND

Early appropriate antibiotic therapy is an important component of the Surviving Sepsis Guidelines bundles that are associated with decreased in-hospital mortality. National antibiotic guidelines for the treatment of sepsis in Sweden have been available since 2008. Compliance with these guidelines is largely unknown, and whether it translates to improved patient outcome has not been studied.

OBJECTIVE

To assess mortality and its relationship to compliance with Swedish antibiotic guidelines. A secondary aim was to assess the effect of timing of antibiotic administration and mortality.

DESIGN

A registry-based, retrospective cohort study. Registry data were supplemented by manual extraction of data on antibiotic treatment from patient charts. The association between guideline compliance and mortality was evaluated using multivariable analysis. Three levels of compliance were predefined: full compliance – correct antibiotics and dose; partial compliance – correct antibiotic but wrong dose and/or wrong initial antibiotic but corrected within 24 h and/or wrong combination in a combined regime that is at least one antibiotic not in line with the national antibiotic guideline; no compliance – incorrect antibiotic.

SETTING

Two general ICUs in Sweden between 1 January 2011 and 31 December 2015.

PATIENTS

Seven hundred and thirteen patients over the age of 18 with severe sepsis or septic shock identified through the Swedish ICU Registry.

MAIN OUTCOME MEASURES

The primary outcome was 30-day mortality.

RESULTS

Full compliance was observed in 47.0% of patients, partial compliance in 36.0%, and no compliance in 17.0%. Lack of compliance was independently associated with increased risk of 30-day mortality: the adjusted hazard ratio was 1.86 (95% CI 1.34 to 2.58 P < 0.001) for partial compliance and 2.18 (95% CI 1.34 to 3.40 P < 0.001) for no compliance. The time to first antibiotic administration was not associated with mortality.

CONCLUSION

Less than half of the patients with severe sepsis and septic shock received antibiotics according to Swedish national guidelines. Full compliance with the guidelines was associated with decreased mortality. The results of this study show that a strict approach to guideline compliance seems to be beneficial: half measures and inadequate doses should be avoided.
A highly contiguous genome for the Golden-fronted Woodpecker (Melanerpes aurifrons) via a hybrid Oxford Nanopore and short read assembly
Authors: Wiley Graham , Miller Matthew J.
Published: January 2020

Background

Woodpeckers are found in nearly every part of the world, absent only from Antarctica, Australasia, and Madagascar. Woodpeckers have been important for studies of biogeography, phylogeography, and macroecology. Woodpeckers hybrid zones are often studied to understand the dynamics of introgression between bird species. Notably, woodpeckers are gaining attention for their enriched levels of transposable elements (TEs) relative to most other birds. This enrichment of TEs may have substantial effects on woodpecker molecular evolution. The Golden-fronted Woodpecker (Melanerpes aurifrons) is a member of the largest radiation of New World woodpeckers. However, comparative studies of woodpecker genomes are hindered by the fact that no high-contiguity genome exists for any woodpecker species.

Findings

Using hybrid assembly methods that combine long-read Oxford Nanopore and short-read Illumina sequencing data, we generated a highly contiguous genome assembly for the Golden-fronted Woodpecker. The final assembly is 1.31 Gb and comprises 441 contigs plus a full mitochondrial genome. Half of the assembly is represented by 28 contigs (contig N50), each of these contigs is at least 16 Mb in size (contig L50). High recovery (92.6%) of bird-specific BUSCO genes suggests our assembly is both relatively complete and relatively accurate. Accuracy is also demonstrated by the recovery of a putatively error-free mitochondrial genome. Over a quarter (25.8%) of the genome consists of repetitive elements, with 287 Mb (21.9%) of those elements assignable to the CR1 superfamily of transposable elements, the highest proportion of CR1 repeats reported for any bird genome to date.

Conclusion

Our assembly provides a useful tool for comparative studies of molecular evolution and genomics in woodpeckers and allies, a group emerging as important for studies on the role that TEs may play in avian evolution. Additionally, the sequencing and bioinformatic resources used to generate this assembly were relatively low-cost and should provide a direction for the development of high-quality genomes for future studies of animal biodiversity.
Congruent population genetic structures and divergence histories in anther-smut fungi and their host plantsSilene italicaand theS. nutansspecies complex
Authors: Hartmann Fanny E. , Snirc Alodie , Cornille Amandine , Godé Cécile , Touzet Pascal , Van Rossum Fabienne , Fournier Elisabeth , Prieur Stéphanie Le , Shykoff Jacqui , Giraud Tatiana
Published: January 2020

The study of population genetic structure congruence between hosts and pathogens gives important insights into their shared phylogeographic and coevolutionary histories. We studied the population genetic structure of castrating anther-smut fungi (Microbotryumgenus) and of their host plants, theSilene nutansspecies complex, and the morphologically and genetically closeS. italica,which can be found in sympatry. Phylogeographic population genetic structure related to persistence in separate glacial refugia has been recently revealed in theS. nutansplant species complex across Western Europe, identifying several distinct lineages. We genotyped 171 associated plant-pathogen pairs of anther-smut fungi and their host plant individuals using microsatellite markers and plant chloroplastic SNPs. We found clear differentiation between fungal populations parasitizingS. nutansandS. italicaplants. The population genetic structure of fungal strains parasitizing theS. nutansplant species complex mirrored the host plant genetic structure, suggesting that the pathogen was isolated in glacial refugia together with its host and/or that it has specialized on the plant genetic lineages. Using random forest approximate Bayesian computation (ABC-RF), we found that the divergence history of the fungal lineages onS. nutanswas congruent with the one previously inferred for the host plant and likely occurred with ancient but no recent gene flow. Genome sequences confirmed the genetic structure and the absence of recent gene flow between fungal genetic lineages. Our analyses of host-pathogen individual pairs contribute to a better understanding of co-evolutionary histories between hosts and pathogens in natural ecosystems, in which such studies are still scarce.
Robotic Stereotaxic System based on 3D skull reconstruction to improve surgical accuracy and speed
Authors: Ly Phuong T. , Lucas Alexandra , Pun Sio Hang , Dondzillo Anna , Liu Chao , Klug Achim , Lei Tim C.
Published: January 2020

Some experimental approaches in neuroscience research require the precise placement of a recording electrode, pipette or other tool into a specific brain area that can be quite small and/or located deep beneath the surface. This process is typically aided with stereotaxic methods but remains challenging due to a lack of advanced technology to aid the experimenter. Currently, procedures require a significant amount of skill, have a high failure rate, and take up a significant amount of time.

We developed a next generation robotic stereotaxic platform for small rodents by combining a three-dimensional (3D) skull profiler sub-system and a full six degree-of-freedom (6DOF) robotic platform. The 3D skull profiler is based on structured illumination in which a series of horizontal and vertical line patterns are projected onto an animal skull. These patterns are captured by two two-dimensional (2D) CCD cameras which reconstruct an accurate 3D skull surface based on structured illumination and geometrical triangulation. Using the reconstructed 3D profile, the skull can repositioned using a 6DOF robotic platform to accurately align a surgical tool. The system was evaluated using mechanical measurement techniques, and the accuracy of the platform was demonstrated using brain phantoms. Additionally, small and deep brain nuclei were targeted in rodents for additional testing. The results indicate that this new stereotaxic system can improve the accuracy and speed of small-animal brain surgeries and reduce the failure rate of experiments.
Fine Sieving of Collected Atmospheric Particles using Oil Electrophoresis (iSCAPE)
Authors: Li Xinyue , Xu Siyu , Yao Maosheng
Published: January 2020

It is rather challenging to separate atmospheric particles from nano-to micro-metre mixed in a sample. Here, a system named iSCAPE was invented to efficiently sieve particles out from a mixture by employing an electrostatic field and a non-conductive mineral oil. Tests with atmospheric particles of different cities as well as soil and road dust samples demonstrated that the iSCAPEd particles under different operating conditions moved rapidly with different velocities and both directions. Particles of different sources such as ambient air, soil or road were shown to have different polarity-charged particle fractions, and exhibited clearly different particle electrical mobility graphs after the iSCAPE sieving from seconds to minutes. Data also revealed that after the sieving some particles were enriched at specific mobility ranges. Bacterial ATP measurements implied that the iSCAPE can be also used to efficiently separate bacteria of different sizes and charge polarity. Experimental data here suggest that the iSCAPE sieving strongly replies on the electrostatic field strength, mineral oil viscosity and the run time. In theory, the iSCAPE system can be used to extract any desired targets from a complex sample, thus opening up many outstanding opportunities for environmental, biomedical and life science fields.

TOC
Contrasting adaptations to synaptic physiology of prefrontal cortex interneuron subtypes in a mouse model of binge drinking
Authors: Joffe Max E. , Winder Danny G. , Jeffrey Conn P.
Published: January 2020

Alcohol use disorder (AUD) affects all sexes, however women who develop AUD may be particularly susceptible to cravings and other components of the disease. While many brain regions are involved in AUD etiology, proper function of the prefrontal cortex (PFC) is particularly important for top-down craving management and the moderation of drinking behaviors. Essential regulation of PFC output is provided by local inhibitory interneurons, yet the effects of chronic drinking on interneuron physiology remain poorly understood, particularly in female individuals. To address this gap, we generated fluorescent reporter transgenic mice to label the two major classes of interneuron in deep layer prelimbic PFC, based on expression of parvalbumin (PV-IN) or somatostatin (SST-IN). We then interrogated PV-IN and SST-IN membrane and synaptic physiology in a rodent model of binge drinking. Beginning in late adolescence, mice received 3-4 weeks of intermittent access (IA) ethanol. One day after the last drinking session, adaptations to PV-IN and SST-IN intrinsic physiology were observed in male mice but not in female mice. Furthermore, IA ethanol precipitated diametrically opposing changes to PV-IN synaptic physiology based on sex. IA ethanol decreased excitatory synaptic strength onto PV-INs from female mice and potentiated excitatory transmission onto PV-INs male mice. In contrast, decreased synaptic strength onto SST-INs was observed following IA ethanol in all groups of mice. Together, these findings illustrate novel sex differences in drinking-related PFC pathophysiology. Discovering means to restore PV-IN and SST-IN dysfunction following extended drinking provides opportunities for developing new treatments for all AUD patients.
Cryo-EM structures of the ATP release channel pannexin 1
Authors: Deng Zengqin , He Zhihui , Maksaev Grigory , Bitter Ryan M. , Rau Michael , Fitzpatrick James A.J. , Yuan Peng
Published: January 2020

The plasma membrane ATP release channel pannexin 1 has been implicated in numerous physiological and pathophysiological processes associated with purinergic signaling, including cancer progression, apoptotic cell clearance, inflammation, blood pressure regulation, oocyte development, epilepsy and neuropathic pain. Here, we present near-atomic resolution structures ofXenopus tropicalisandHomo sapiensPANX1 determined by cryo-electron microscopy that reveal a heptameric channel architecture. Compatible with ATP permeation, the transmembrane pore and cytoplasmic vestibule are exceptionally wide. An extracellular tryptophan ring located at the outer pore creates a constriction site, potentially functioning as a molecular sieve that restricts the size of permeable substrates. In combination with functional characterization, this work elucidates the previously unknown architecture of pannexin channels and establishes a foundation for understanding their unique channel properties as well as for developing rational therapies.
Identification of NLR-associated amyloid signaling motifs in filamentous bacteria
Authors: Dyrka Witold , Coustou Virginie , Daskalov Asen , Lends Alons , Bardin Thierry , Berbon Mélanie , Kauffmann Brice , Blancard Corinne , Salin Bénédicte , Loquet Antoine , Saupe Sven J.
Published: January 2020

NLRs (Nod-like receptors) are intracellular receptors regulating immunity, symbiosis, non-self recognition and programmed cell death in animals, plants and fungi. Several fungal NLRs employ amyloid signaling motifs to activate downstream cell-death inducing proteins. Herein, we identify in Archaea and Bacteria, short sequence motifs that occur in the same genomic context as fungal amyloid signaling motifs. We identify 10 families of bacterial amyloid signaling sequences (we term BASS), one of which (BASS3) is related to mammalian RHIM and fungal PP amyloid motifs. We find that BASS motifs occur specifically in bacteria forming multicellular structures (mainly inActinobacteriaandCyanobacteria). We analyze experimentally a subset of these motifs and find that they behave as prion forming domains when expressed in a fungal model. All tested bacterial motifs also formed fibrilsin vitro.We analyze by solid-state NMR and X-ray diffraction, the amyloid state of a protein fromStreptomyces coelicolorbearing the most common BASS1 motif and find that it forms highly ordered non-polymorphic amyloid fibrils. This work expands the paradigm of amyloid signaling to prokaryotes and underlies its relation to multicellularity.
Economic evaluation of a prospective Farm Animal Welfare program in Turkey
Authors: Turan Özlem , Gurluk Serkan , Madiyoh Abdulhakim
Published: January 2020

Purpose

The purpose of this paper is to examine producer preferences for changing Farm Animal Welfare (FAW) levels in regards to sheep and goat husbandry in Bursa-Turkey.

Design/methodology/approach

The paper tests “panel estimators” in a stated preference data by using the payment card question format. Probit panels are employed to measure individual effects on FAW levels by considering producers’ willingness to accept. Three different FAW levels were identified for valuation as “base” level, “better” level, and the “best” level. The current study suggests a protocol with WTA(P) nomenclature to resolve complexity issues in FAW studies by investigating producers rather than consumers because the scenarios regarding FAW levels include quite technical and difficult topics which are vague to consumers.

Findings

If half of the total number of the sheep and goats in Turkey are assumed to be in bad animal welfare conditions, which are worse than base level, the non-use benefits of bringing them to at least the base level would be about US$130.3m. Figures would be 166.2m US$/year and 175m US$/year for “better” and “best” FAW conditions, respectively.

Originality/value

This paper provides a contribution to the existing literature by examining the producers’ responses to new FAW schemes. Also it helps policy makers to understand producers’ environmental behavior as well as their sensitivity to FAW schemes.
Lack of vulnerability segmentation among woody species in a diverse dry sclerophyll woodland community
Authors: Smith‐Martin Chris M. , Skelton Robert Paul , Johnson Kate M. , Lucani Christopher , Brodribb Timothy J.
Published: January 2020

Recent findings suggest that tree mortality and post‐drought recovery of gas exchange can be predicted from loss of function within the water transport system. Understanding the susceptibility of plants to hydraulic damage requires knowledge about the vulnerability of different plant organs to stress‐induced hydraulic dysfunction. This is particularly important in the context of vulnerability segmentation between plant tissues which is believed to protect more energetically ‘costly’ tissues, such as woody stems, by sacrificing ‘cheaper’ leaves early under drought conditions.

Differences in vulnerability segmentation between co‐occurring plant species could explain divergent behaviours during drought, yet there are few studies considering how this characteristic may vary within a plant community. Here we investigated community‐wide vulnerability segmentation by comparing leaf/shoot and stem vulnerability in all coexistent dominant canopy and understory woody species in a diverse dry sclerophyll woodland community, including multiple angiosperms and one gymnosperm.

Previously published terminal leaf/shoot vulnerability to loss of water transport capacity was compared with stem xylem vulnerability to embolism measured on the same species at the same site. We calculated hydraulic safety margins for stems to determine variation in the risk of hydraulic failure during drought among species.

The xylem of all species was found to be highly resistant to hydraulic dysfunction, with only two of the eight species exhibiting significantly different vulnerability to the overall mean. No evidence of vulnerability segmentation between shoots/leaves and stems was found in seven of the eight species.

Phylogenetically diverse canopy and understory species in this evergreen sclerophyll woodland appear to have evolved similar strategies of drought resistance, including low xylem vulnerability to embolism and general lack of vulnerability segmentation. This convergence in hydraulic safety indicates a lack of hydraulic niche partitioning in this woodland community.

A free plain language summary can be found within the Supporting Information of this article.
Intrinsically altered lung‐resident γδT cells control lung melanoma by producing interleukin‐17A in the elderly
Authors: Cheng Min , Chen Yongyan , Huang Dake , Chen Wen , Xu Weiping , Chen Yin , Shen Guodong , Xu Tingjuan , Shen Gan , Tian Zhigang , Hu Shilian
Published: January 2020

Cancer is an age‐associated disease, potentially related to the altered immune system of elderly individuals. However, cancer has gradually decreased incidence in the eldest globally such as the most common lung cancer, the mechanisms of which remain to be elucidated. In this study, it was found that the number of lung‐resident γδT cells was significantly increased with altered gene expression in aged mice (20–24 months) versus young mice (10–16 weeks). Aged lung Vγ4+ and Vγ6+ γδT cells predominantly produced interleukin‐17A (IL‐17A), resulting in increased levels in the serum and lungs. Moreover, the aged mice exhibited smaller tumors and reduced numbers of tumor foci in the lungs after challenge with intravenous injection of B16/F10 melanoma cells compared with the young mice. Aged lung Vγ4+ and Vγ6+ γδT cells were highly cytotoxic to B16/F10 melanoma cells with higher expression levels of CD103. The markedly longer survival of the challenged aged mice was dependent on γδT17 cells, since neutralization of IL‐17A or depletion of indicated γδT cells significantly shortened the survival time. Consistently, supplementation of IL‐17A significantly enhanced the survival time of young mice with lung melanoma. Furthermore, the anti‐tumor activity of aged lung γδT17 cells was not affected by alterations in the load and composition of commensal microbiota, as demonstrated through co‐housing of the aged and young mice. Intrinsically altered lung γδT17 cells underlying age‐dependent changes control lung melanoma, which will help to better understand the lung cancer progression in the elderly and the potential use of γδT17 cells in anti‐tumor immunotherapy.
Age at migration and the risk of psychotic disorders: a systematic review and meta‐analysis
Authors: Anderson K. K. , Edwards J.
Published: January 2020

Objective

To conduct a systematic review and meta‐analysis of the existing evidence on the association between age at migration and the risk of psychotic disorders.

Methods

Observational studies were eligible for inclusion if they presented data on the association between age at migration and the risk of psychotic disorders among first‐generation migrant groups. We used two random effects meta‐analyses to pool effect estimates for each stratum of age at migration relative to (i) a native‐born reference category and (ii) the youngest age stratum (0 to 2 years).

Results

Ten studies met inclusion criteria, and five were included in the meta‐analysis. The risk of psychotic disorder among people who migrate prior to age 18 is nearly twice as high as the native‐born population, with no evidence of effect modification by age strata. People who migrate during early adulthood (19 to 29 years) have a similar risk of psychotic disorder as the native‐born population (IRR = 0.93, 95% CI = 0.60, 1.44) and a lower risk relative to those who migrate during infancy (0 to 2 years) (IRR = 0.58, 95% CI = 0.33, 1.04).

Conclusions

Migrant status is one of few well‐established risk factors for psychotic disorder, yet we have limited understanding of the underlying etiology. The findings of this review advance our understanding of this association and identify high‐risk groups to target for intervention.
More than just morbidity and mortality – quality of recovery and long‐term functional recovery after surgery
Authors: Myles P. S.
Published: January 2020

Traditional surgical outcome measures include minor and major complications, hospital length of stay and sometimes longer‐term survival. Each of these is important but there needs to be greater emphasis on patient‐reported outcome measures. Global measures of a patient's quality of recovery, avoidance of postoperative morbidities, early hospital discharge to home (without re‐admission) and longer term disability‐free survival can better define postoperative recovery. A patient's recovery pathway can be mapped through the immediate days or weeks after surgery with documentation of morbidity using the postoperative morbidity survey and/or a quality of recovery score, days alive and at home up to 30 days after surgery and then longer term disability‐free survival using the WHO Disability Assessment Schedule 2.0 scale. These can be used to define quality of recovery after surgery.
The association between genome‐wide polymorphisms and chronic postoperative pain: a prospective observational study
Authors: van Reij R. R. I. , Hoofwijk D. M. N. , Rutten B. P. F. , Weinhold L. , Leber M. , Joosten E. A. J. , Ramirez A. , van den Hoogen N. J. ,   the Italian Pain Group
Published: January 2020

Chronic postoperative pain is common and can have a negative impact on quality of life. Recent studies show that genetic risk factors are likely to play a role, although only gene‐targeted analysis has been used to date. This is the first genome‐wide association study to identify single‐nucleotide polymorphisms associated with the development of chronic postoperative pain based on two independent cohorts. In a discovery cohort, 330 women scheduled for hysterectomy were genotyped. A case–control association analysis compared patients without chronic postoperative pain and the 34 who had severe chronic postoperative pain 3 months after surgery. No single‐nucleotide polymorphisms reached genome‐wide significance, but several showed suggestive associations with chronic postoperative pain (p < 1 × 10−5). Single‐nucleotide polymorphisms with significance p < 1 × 10−5 were followed up in a replication cohort consisting of 203 men and women scheduled for orthopaedic or abdominal surgery. Ten of these patients developed severe chronic postoperative pain. A single‐nucleotide polymorphism in NAV3 was significantly replicated with chronic postoperative pain in the replication cohort (p = 0.009). Meta‐analysis revealed that two loci (IQGAP1 and CRTC3) were significantly associated with chronic postoperative pain at 3 months (IQGAP1 p = 3.93 × 10−6 β = 2.3863, CRTC3 p = 2.26 × 10−6, β = 2.4209). The present genome‐wide association study provides initial evidence for genetic risk factors of chronic postoperative pain and supports follow‐up studies.
Enhanced postoperative recovery: good from afar, but far from good?
Authors: Kehlet H.
Published: January 2020

Enhanced postoperative recovery programmes (ERAS) were developed about 20 years ago based on improved understanding of the pathophysiology of postoperative recovery within an integrated multidisciplinary approach. The results across surgical procedures have been extremely positive with a reduction in hospitalisation and medical complications, without increased re‐admission rates. However, several challenges lie ahead including improved implementation of existing scientific evidence, increased focus on post‐discharge recovery problems and a need for improved design of future ERAS studies. However, the most important challenges lie within a better understanding and control of undesirable peri‐operative pathophysiological responses with subsequent risk of organ dysfunction. These efforts should focus on: the inflammatory and neurohumoral surgical stress responses; fluid management; pain management; blood management; mechanisms of orthostatic intolerance; postoperative cognitive dysfunction; risk factors for thrombo‐embolic complications; and mechanisms and prevention of postoperative ileus. Finally, more focus should be made on the different barriers to post‐discharge functional recovery and the choice of (pre‐ and postoperative) rehabilitation. These efforts should be made on a procedure‐specific as well as on a patient‐specific basis.
The older surgical patient – to operate or not? A state of the art review
Authors: Santhirapala R. , Partridge J. , MacEwen C. J.
Published: January 2020

The increasing age and subsequent medical complexity of patients presenting for surgery grants the opportunity to examine the processes and delivery of peri‐operative care. There is a need to redesign peri‐operative pathways allowing room for shared decision making and personalised, evidence‐based care. In times of financial constraint, this is no easy task. However, neglecting to transform services now may lead to challenges in the sustainability of the provision of peri‐operative care in the long‐term. Challenges in redesigning peri‐operative care pathways include identification and optimisation of those at highest peri‐operative risk to inform the difficult conversations surrounding the appropriateness of surgery. The moral burden of these conversations on patient and professionals alike is increasingly recognised and managing this issue requires innovative models of collaborative, multidisciplinary and interprofessional working. To operate or not can be a challenging question to answer with a number of different perspectives to consider; not least that of the patient.
A narrative review of the impact of surgery and anaesthesia on acute kidney injury
Authors: Ostermann M. , Cennamo A. , Meersch M. , Kunst G.
Published: January 2020

The epidemiology of peri‐operative acute kidney injury varies depending on the definition, type of surgery and acute and chronic comorbidities. Haemodynamic instability, disturbance of the microcirculation, endothelial dysfunction, inflammation and tubular cell injury are the main factors contributing to the pathogenesis. There are no specific therapies. The most effective strategies to protect renal function during the peri‐operative period are: the avoidance of nephrotoxic insults; optimisation of haemodynamics; prevention of hypotension; and meticulous fluid management, including avoidance of both hypovolaemia and hypervolaemia. Peri‐operative acute kidney injury is associated with an increased risk of short‐ and long‐term postoperative complications, including a longer stay in hospital, development of premature chronic kidney disease and increased mortality. Resource utilisation and healthcare costs are also higher. In future, the development of advanced clinical prediction scores, new imaging and monitoring techniques and the application of new biomarkers for acute kidney injury have the prospect of identifying acute kidney injury earlier and allowing a more personalised management approach with the aim of reducing the global burden of acute kidney injury.
SOD2 genetic polymorphism (rs4880) has no impact on 6‐month response to antidepressant treatment and inflammatory biomarkers in depressed patients
Authors: Ait Tayeb Abd El Kader , Becquemont Laurent , El‐Asmar Khalil , Mahmoudi Kaïna , Colle Romain , Trabado Severine , Gressier Florence , Feve Bruno , Corruble Emmanuelle , Verstuyft Céline
Published: January 2020

Two thirds of patients suffering from a major depressive episode (MDE) do not reach a complete response with antidepressant drugs. This lack of response is due to several factors, including genetic determinants. Since major depressive disorder is associated with inflammatory and oxidative stress abnormalities, the metabolism of superoxide anions might be involved in non‐response to antidepressant drugs. Superoxide anions are metabolized by manganese‐dependent superoxide dismutase (SOD2) in the mitochondria. A functional genetic polymorphism (SOD2, rs4880), responsible of a 40% reduction in enzyme activity, is associated with anti‐inflammatory response of rosuvastatin. We investigated the association of ala‐allele of SOD2 rs4880 and both antidepressant efficacy and inflammatory parameters in patients treated for a MDE with antidepressant drugs. The Hamilton Depression Rating Scale (HDRS) score and levels of plasma CRP and inflammatory cytokines were assessed at baseline, one month (M1), 3 months (M3) and 6 months (M6) after antidepressant treatment. They were compared according to SOD2 genetic polymorphism. Of the 484 patients studied, 361 (74.6%) carried the ala‐allele (Ala group), 123 (25.4%) of them had Val/Val genotype (Val/Val group). No significant difference was observed between the Ala and Val/Val groups neither for baseline clinical characteristics, nor for HDRS scores, response/remission rates, plasma CRP and cytokine levels throughout the study. The rs4880 SOD2 genetic polymorphism was not associated with the clinical response and cytokines levels after antidepressant treatment. These data suggest that SOD2 is not a major genetic determinant of antidepressant response. Other genes of the oxidative stress pathways should be explored in further studies.