bluuebunny/crossref_metadata_2025 huggingface dataset:
The anatomy of transcriptionally active chromatin loops inDrosophilaprimary spermatocytes using super-resolution microscopy
Authors: Ball Madeleine L. , Koestler Stefan A. , Muresan Leila , Rehman Sohaib Abdul , O’Holleran Kevin , White Robert
Published: July 2022

While the biochemistry of gene transcription has been well studied, our understanding of how this process is organised in 3D within the intact nucleus is less well understood. Here we investigate the structure of actively transcribed chromatin and the architecture of its interaction with active RNA polymerase.

For this analysis, we have used super-resolution microscopy to image theDrosophila melanogasterY loops which represent huge, several megabases long, single transcription units. The Y loops provide a particularly amenable model system for transcriptionally active chromatin. We find that, although these transcribed loops are decondensed they are not organised as extended 10nm fibres, but rather they largely consist of chains of nucleosome clusters. The average width of each cluster is around 50nm. We find that foci of active RNA polymerase are generally located off the main fibre axis on the periphery of the nucleosome clusters. Foci of RNA polymerase and nascent transcripts are distributed around the Y loops rather than being clustered in individual transcription factories. However, as the RNA polymerase foci are considerably less prevalent than the nucleosome clusters, the organisation of this active chromatin into chains of nucleosome clusters is unlikely to be determined by the activity of the polymerases transcribing the Y loops.

These results provide a foundation for understanding the topological relationship between chromatin and the process of gene transcription.
Modular Pooled Discovery of Synthetic Knockin Sequences to Program Durable Cell Therapies
Authors: Blaeschke Franziska , Chen Yan Yi , Apathy Ryan , Li Zhongmei , Mowery Cody T. , Nyberg William A. , To Angela , Yu Ruby , Bueno Raymund , Kim Min Cheol , Schmidt Ralf , Goodman Daniel B. , Feuchtinger Tobias , Eyquem Justin , Ye Chun Jimmie , Shifrut Eric , Roth Theodore L. , Marson Alexander
Published: July 2022

Chronic stimulation can cause T cell dysfunction and limit efficacy of cellular immunotherapies. CRISPR screens have nominated gene targets for engineered T cells, but improved methods are required to compare large numbers of synthetic knockin sequences to reprogram cell functions. Here, we developed Modular Pooled Knockin Screening (ModPoKI), an adaptable platform for modular construction of DNA knockin libraries using barcoded multicistronic adaptors. We built two ModPoKI libraries of 100 transcription factors (TFs) and 129 natural and synthetic surface receptors. Over 20 ModPoKI screens across human TCR and CAR T cells in diverse conditions identified a transcription factor AP4 (TFAP4) construct to enhance long-term T cell fitness and anti-cancer functionin vitroandin vivo. ModPoKI’s modularity allowed us to generate a ∼10,000-member library of TF combinations. Non-viral knockin of a combined BATF-TFAP4 polycistronic construct further enhanced functionin vivo. ModPoKI facilitates discovery of complex gene constructs to program cellular functions.

Highlights

Modular pooled knockins of hundreds of TF and surface receptor constructs combined with different antigen receptors

Chronic stimulation screens discover programs to improve T cell persistence

Combinatorial knockin screens with ∼10,000 transcription factor combinations

BATF-TFAP4 dual knockin construct improves CAR T cell functionin vitroandin vivo
Genetic and environmental circadian disruption induce metabolic impairment through changes in the gut microbiome
Authors: Altaha Baraa , Heddes Marjolein , Pilorz Violetta , Niu Yunhui , Gorbunova Elizaveta , Gigl Michael , Kleigrewe Karin , Oster Henrik , Haller Dirk , Kiessling Silke
Published: July 2022

Objective

Internal clocks time behavior and physiology, including the gut microbiome in a circadian (∼24 h) manner. Mismatch between internal and external time, e.g. during shift work, disrupts circadian system coordination promoting the development of obesity and type 2 diabetes (T2D). Conversely, body weight changes induce microbiota dysbiosis. The relationship between circadian disruption and microbiota dysbiosis in metabolic diseases, however, remains largely unknown.

Methods

Core and accessory clock gene expression in different gastrointestinal (GI) tissues were determined by qPCR in two different models of circadian disruption - mice with Bmal1 deficiency in the circadian pacemaker, the suprachiasmatic nucleus (Bmal1SCNfl/-), and wild-type mice exposed to simulated shift work (SSW). Body composition and energy balance were evaluated by nuclear magnetic resonance (NMR), bomb calorimetry, food intake and running-wheel activity. Intestinal permeability was measured in an Ussing chamber. Microbiota composition and functionality were evaluated by 16S rRNA gene amplicon sequencing, PICRUST2.0 analysis and targeted metabolomics. Finally, microbiota transfer was conducted to evaluate the functional impact of SSW-associated microbiota on the host’s physiology.

Results

Both chronodisruption models show desynchronization within and between peripheral clocks in GI tissues and reduced microbial rhythmicity, in particular in taxa involved in short-chain fatty acid (SCFA) fermentation and lipid metabolism. In Bmal1SCNfl/- mice, loss of rhythmicity in microbial functioning associates with previously shown increased body weight, dysfunctional glucose homeostasis and adiposity. Similarly, we observe an increase in body weight in SSW mice. Germ-free colonization experiments with SSW- associated microbiota mechanistically link body weight gain to microbial changes. Moreover, alterations in expression of peripheral clock genes as well as clock-controlled genes (CCGs) relevant for metabolic functioning of the host were observed in recipients, indicating a bidirectional relationship between microbiota rhythmicity and peripheral clock regulation.

Conclusions

Collectively, our data suggest that loss of rhythmicity in bacteria taxa and their products, which likely originates in desynchronization of intestinal clocks, promotes metabolic abnormalities during shift work.
Chemoenzymatic Synthesis of Heparan Sulfate Oligosaccharides having a Domain Structure
Authors: Sun Lifeng , Chopra Pradeep , Boons Geert-Jan
Published: July 2022

Heparan sulfate (HS) have domain structures in which regions that are substantially modified by epimerization and sulfation (NS domains) are interspersed by unmodified fragments (NA domains). There is data to support that the domain structure of HS can regulate protein binding, however, such a binding mode has been difficult to probe. Here, we report a chemoenzymatic methodology that can provide HS oligosaccharides composed of two or more NS domains separated by NA domains of different length. It is based on the chemical synthesis of a sulfated HS oligosaccharide that enzymatically could be extended by various GlcA-GlcNAc units and terminated in a GlcNAc-6N3 moiety. HS oligosaccharides having an azide and alkyne moiety could assembled by copper catalyzed alkyne-azide cycloaddition (CuAAC) to give compounds having various NS domains separated by unsulfated regions. Competition binding studies showed that the length of an NA domain modulates the binding of the chemokines CCL5 and CXCL8.
Genomic evaluation of BC4, a consortium of four Alkalihalobacillus clausii isolates, confirms its probiotic potential and safety in usage
Authors: Dhakephalkar Tanisha , Wagh Shilpa , Yadav Kunal , Engineer Anupama S. , Pore Soham D. , Dhakephalkar Prashant K.
Published: July 2022

Four strains of Alkalihalobacillus clausii B603/Nb (resistant to rifampicin), B619/R (resistant to streptomycin), B637/Nm (resistant to tetracyclin) and B106 (resistant to chloramphenicol) were isolated from various sources and used to prepare a consortium designated as BC4. Genomes of the constituent strains of the BC4 consortium were evaluated to investigate their genetic makeup and determine their probiotic potential. Gene prediction and functional annotation were performed using RAST. The data obtained was mined for genes encoding various phenotypic traits. This analysis revealed the presence of several genes encoding probiotic attributes like (i) survivability in the presence of low pH, bile, oxidative stress; (ii) bacterial aggregation and adhesion to gut epithelium, etc.; and (iii) enzymes/ molecules conferring health benefits. Further, the genome analysis also confirmed the genes required for enhancing the nutritional amenability, health-promoting, and disease-preventing traits were present. Several genes encoding multiple antibiotic resistance were detected; however, none of these genes was located on mobile elements such as plasmids, transposons, etc. The absence of genes encoding virulence factors, pathogenic islands, emetic toxins, etc., as well as mobile genetic elements, underscored the safety of BC4 isolates.
Sudan black lipid blot – a rapid and simple method for quantification of lipids in biological samples
Authors: Homolak Jan , Joja Mihovil , Markovic Pavel , Salkovic-Petrisic Melita
Published: July 2022

Bioanalytical techniques for the isolation and quantification of total lipids in biological samples are an integral part of lipidomic workflows and widely used tools for metabolic assessment at the cellular and organismic levels. The most widely used protocol for the isolation, extraction, and quantification of total lipids in biological tissues was originally introduced by Folch et al.. It requires a relatively large amount of tissue and large volumes of lipid extracts for reliable assessment of lipid content using the gravimetric technique. Here, we propose a new method to overcome the aforementioned challenges based on the hypothesis that the partitioning coefficient of the widely used lysochrome diazo dye Sudan Black B between the lipid extract and ethylene glycol can be used to indirectly estimate the absolute concentration of lipids. The proposed method demonstrates great precision and linearity, requires minimal equipment, and enables the analysis of total lipid content in biological specimens available only in limited amounts by reducing the requirements for the input quantity by >300-fold for some tissues (e.g. fecal samples).
Honey Bees Get Map Coordinates from the Dance
Authors: Wang Zhengwei , Chen Xiuxian , Becker Frank , Greggers Uwe , Walter Stefan , Werner Marleen , Gallistel Charles R. , Menzel Randolf
Published: July 2022

Honeybees (Apis mellifera carnica) communicate the rhumb line to a food source (its direction and distance from the hive) by means of a waggle dance. We ask whether bees recruited by the dance use it only as a flying instruction or also translate it into a location vector in a map-like memory, so that information about spatial relations of environmental cues informs their attempts to find the source. The flights of recruits captured on exiting the hive and released at distant sites were tracked by radar. The recruits performed first a straight flight in the direction of the rhumb line. However, the vector portions of their flights and the ensuing tortuous search portions were strongly and differentially affected by the release site. Searches were biased toward the true location of the food and away from the location specified by translating the rhumb line origin to the release site. We conclude that by following the dance a recruit gets two messages, a polar flying instruction (the rhumb line) and its conversion to Cartesian map coordinates.
The role of division stochasticity on the robustness of bacterial size dynamics
Authors: Nieto César , Arias-Castro Juan Carlos , Sánchez Carlos , Vargas-García César , Singh Abhyudai , Pedraza Juan Manuel
Published: July 2022

Variables of bacterial division such as size at birth, growth rate, division time, and the position of the septal ring, all vary from cell to cell. Currently, it is unknown how these random fluctuations can combine to produce a robust mechanism of homeostasis. To address this question, we studied the dynamics of the cell division process from both experimental and theoretical perspectives. Our model predicts robustness in division times as sustained oscillations in metrics of the cell size distribution, such as the mean, variability, and the cell size autocorrelation function. These oscillations do not get damped, even considering stochasticity in division timing and the cell size at the beginning of the experiment. Damping appears just after inducing stochasticity in either the septum position or the growth rate. We compare the predictions of the full model with the size dynamics of E. coli bacteria growing in minimal media using either glucose or glycerol as carbon sources. We observe that growth in poorer media increases the noise in both partitioning position and growth rate. This additional noise results in oscillations with more damping. Although intracellular noise is known as a source of phenotypic variation, our results show that it can play a similar but subtler role in maintaining population-level homeostasis by causing rapid desynchronization of cell cycles..
SEQUENCE VARIATIONS ASSOCIATED WITH NOVEL PURPLE-PERICARP SUPER-SWEETCORN COMPARED TO ITS PURPLE-PERICARP MAIZE AND WHITE SUPER-SWEETCORN PARENTS
Authors: Anirban Apurba , Masouleh Ardashir Kharabian , Henry Robert J , O’Hare Tim J
Published: July 2022

Recently, a novel purple-pericarp super-sweetcorn line, ‘Tim1’ (A1A1.sh2sh2) is derived from the purple-pericarp maize ‘Costa Rica’ (A1Sh2.A1Sh2) and white shrunken2 (sh2) super-sweetcorn ‘Tims-white’ (a1sh2.a1sh2), however information regarding purple colour controlling anthocyanin biosynthesis genes and sweetcorn gene is lacking. Specific sequence differences in the CDS (coding DNA sequence) and promoter regions of the anthocyanin biosynthesis structural genes, anthocyanin1 (A1), purple aleurone1 (Pr1) and regulatory genes, purple plant1 (Pl1), plant colour1 (B1), coloured1 (R1), and the sweetcorn structural gene, shrunken2 (sh2) were investigated using the publicly available annotated yellow starchy maize, B73 (NAM5.0) as a reference genome. In the CDS region, the A1, Pl1 and R1 gene sequence differences of ‘Tim1’ and ‘Costa Rica’ were similar, as they control purple-pericarp pigmentation, however the B1 gene showed similarity between the ‘Tim1’ and ‘Tims-white’ lines, which may indicate that it does not have a role in controlling pericarp colour, unlike a previous study. In case of Pr1 gene, unlike ‘Costa Rica’, 6- and 8-bp dinucleotide (TA) repeats were observed in the promoter region of the ‘Tims-white’ and ‘Tim1’ lines, respectively, indicating the defective functionality (redder colour in ‘Tim1’ than purple in ‘Costa Rica’) of the recessive pr1 allele. In the sweetcorn structural gene (sh2), sequence similarity was observed between purple-sweet ‘Tim1’ and its white-sweet parent ‘Tims-white’, as both display a shrunken phenotype in their mature kernels. These findings revealed that the developed purple-sweet line is different than the reference yellow-nonsweet line regarding both the anthocyanin biosynthesis and sweetcorn genes.
Bringing Plant Immunity to Light: A Genetically Encoded, Bioluminescent Reporter of Pattern Triggered Immunity inNicotiana benthamiana
Authors: Garcia Anthony G. K. , Steinbrenner Adam D.
Published: July 2022

Plants rely on innate immune systems to defend against a wide variety of biotic attackers. Key components of innate immunity include cell-surface pattern recognition receptors (PRRs), which recognize pest/pathogen-associated molecular patterns (PAMPs). Unlike other classes of receptors which often have visible cell death immune outputs upon activation, PRRs generally lack rapid methods for assessing function. Here, we describe a genetically encoded bioluminescent reporter of immune activation by heterologously-expressed PRRs in the model organismNicotiana benthamiana.We characterizedN. benthamianatranscriptome changes in response toAgrobacterium tumefaciens (Agrobacterium)and subsequent PAMP treatment to identify PTI-associated marker genes, which were then used to generate promoter-luciferase fusion fungal bioluminescence pathway (FBP) constructs. A reporter construct termedpFBP_2xNbLYS1::LUZallows for robust detection of PTI activation by heterologously expressed PRRs. Consistent with known PTI signaling pathways, activation by receptor-like protein (RLP) PRRs is dependent on the known adaptor of RLP PRRs, SOBIR1. This system minimizes the amount of labor, reagents, and time needed to assay function of PRRs and displays robust sensitivity at biologically relevant PAMP concentrations, making it ideal for high throughput screens. The tools described in this paper will be powerful for studying PRR function and investigations to characterize the structure-function of plant cell surface receptors.
MuMag2022: a software tool for analyzing magnetic field dependent unpolarized small-angle neutron scattering data of bulk ferromagnets
Authors: Adams Michael P. , Bersweiler Mathias , Jefremovas Elizabeth M. , Michels Andreas
Published: July 2022

The MATLAB-based software tool MuMag2022 is presented for the analysis of magnetic-field-dependent unpolarized small-angle neutron scattering (SANS) data of bulk ferromagnets such as elemental nanocrystalline ferromagnets, magnetic nanocomposites or magnetic steels. On the basis of the micromagnetic theory for the magnetic SANS cross section, the program analyzes unpolarized total (nuclear and magnetic) SANS data within the approach-to-saturation regime. The main features of MuMag2022 are the estimation of the exchange-stiffness constant, and of the strength and spatial structure of the magnetic anisotropy field and the magnetostatic field due to longitudinal magnetization fluctuations. MuMag2022 is open source and available as a standalone executable for Windows at https://mumag.uni.lu.
Quick and robust PDF data acquisition using a laboratory single-crystal X-ray diffractometer for study of polynuclear lanthanide complexes in solid form and in solution
Authors: Tsymbarenko Dmitry , Grebenyuk Dimitry , Burlakova Maria , Zobel Mirijam
Published: July 2022

Self-assembled polynuclear lanthanide hydroxo complexes are important objects in the reticular chemistry approach to the design of various functional materials. Revealing their structure in the solid state and understanding the molecular mechanism of self-assembly in solution require a universal and reliable structural method. Pair distribution function (PDF) analysis is a powerful technique which enables structural insight for a wide range of crystalline and amorphous materials on the nanoscale, but commonly measurements are performed at synchrotron X-ray sources or on specially designed laboratory diffractometers. In the present paper, a standard Bruker D8 QUEST single-crystal X-ray diffractometer equipped with a micro-focus Mo tube and CMOS Photon III detector was adapted to measure PDF data of high quality with Q
max = 16.97 Å–1 for solid and liquid samples. An improved data collection strategy and the original data reduction software FormagiX enable calibration and azimuthal full-frame integration of 2D frames, delivering reliable PDFs up to 80 Å with instrumental parameters Q
damp = 0.018 Å−1 and Q
broad = 0.010 Å−1. The effectiveness of the developed approach was demonstrated with reference samples and real-case studies of tetranuclear lanthanide hydroxocarboxylates in solid form and in solution.
Origin of irregular X-ray mirage fringes from a bent, thin crystal
Authors: Fukamachi Tomoe , Kawamura Takaaki
Published: July 2022

The dynamical theory of diffraction is used to analyse irregular X-ray mirage interference fringes observed in Si220 X-ray reflection topography from a weakly bent, thin crystal due to gravity. The origin of the irregular fringes is attributed to the interference between mirage diffracted beams and a reflected beam from the back surface, which is a new type of interference fringe. The irregular fringes are reproduced by calculating the reflected intensities numerically. The effects of absorption and thermal vibration are quite important for the reproduction. The result shows that the interference fringes depend on the strain as well as the thickness of the crystal, which indicates that the fringes should be useful for analysing weak strain in a crystal as an application.
Knowledge sharing processes and the role of attachment patterns
Authors: McLarnon Matthew J.W. , R. Gellatly Ian , A. Richards David , Arazy Ofer
Published: July 2022

Purpose

Past research on the motivational processes underpinning knowledge sharing has assumed that the sharing processes are similar for all individuals. Yet, sharing is a fundamental affiliative behavior, and the sharing processes can differ between people. This study aims to propose and test a model of the moderating influence that employee attachment patterns have on the theory of reasoned action (TRA)-defined knowledge sharing processes.

Design/methodology/approach

The authors administered a questionnaire to 1,103 employees from a range of industries who participated in an online Qualtrics survey. Advanced forms for structural equation modeling and latent profile analysis were used to assess the proposed model.

Findings

The results revealed that participants in the study exhibited the latent profiles corresponding to secure, dismissive, preoccupied and fearful patterns. The preoccupied cohort had the lowest knowledge sharing behavior, yet the strongest links within the sharing process. Secure, dismissive and fearful had similar sharing levels, but the strength of the TRA-defined processes differed. These findings underscore equifinality: although sharing may be approximately equal across different attachment patterns, the fundamental processes underpinning sharing differ.

Research limitations/implications

The authors used self-report data, given that sharing attitudes, norms and intentions may not be overly amenable to ratings even from well-acquainted others. Further, the use of advanced analytical methods helps to minimize common method concerns. Additionally, causal mechanisms underscoring the TRA have been demonstrated (Ajzen and Fishbein, 2005), allowing us to explore the moderating role of attachment patterns.

Practical implications

This study speaks to the importance of considering employees’ attachment patterns, and developing comprehensive intra-organizational norms, policies and systems that support and encourage knowledge sharing from employees with a variety of attachment patterns.

Originality/value

This study uniquely contributes to knowledge sharing literatures by incorporating attachment patterns as moderators within the TRA-defined sharing processes. The authors provide important insights on the role of individuals’ attachment patterns have for knowledge sharing behaviors, but also highlight how structure of knowledge sharing differed across subgroups of employees, determined based on their dispositional attachment pattern.
Analyst forecast quality and corporate social responsibility: the mediation effect of corporate governance
Authors: Shan Yuan George , Yang Joey Wenling , Zhang Junru , Chang Millicent
Published: July 2022

Purpose

This study aims to examine the mediating role played by corporate governance (CG) in the relationship between corporate social responsibility (CSR) and analyst forecast quality.

Design/methodology/approach

The authors raise three specific questions: Does CG play a mediating role in the relationship between CSR and analyst forecast quality? If so, is such mediation effect of CG reduced for firms with weak governance? Do firms with superior CSR performance experience higher analyst forecast quality through the mediation effect of CG?

Findings

The present results suggest that CG serves as a partial mediator that facilitates CSR’s positive influence on analyst forecast quality. However, further analyses show that in firms with a low governance score, CG does not have a mediation effect. Conversely, the authors find that firms with superior CSR performance have higher forecast quality through the mediation effect of CG. The authors also find that the mediation effect of CG is more pronounced for the environmental component than for the social component of CSR.

Originality/value

To the best of the authors’ knowledge, this study is the first to investigate the role of CG as a mediator between CSR and analyst forecast quality and to reveal that the strength of this effect varies depending on firms’ CG level and CSR commitment.
The evolution of carotenoid‐based plumage colours in passerine birds
Authors: Delhey Kaspar , Valcu Mihai , Dale James , Kempenaers Bart
Published: July 2022

Many birds use carotenoids to colour their plumage yellow to red. Because birds cannot synthesise carotenoids, they need to obtain these pigments from food, although some species metabolise dietary carotenoids (which are often yellow) into derived carotenoids (often red).

Here, we study the occurrence of yellow and red carotenoid‐based plumage colours in the passerines, the largest bird radiation and quantify the effects of potential ecological and life‐history drivers on their evolution.

We scored the presence/absence of yellow and red carotenoid‐based plumage in nearly 6,000 species and use Bayesian phylogenetic mixed models to assess the effects of carotenoid‐availability in diet, primary productivity, body size, habitat and sexual selection. We also test the widespread assumption that red carotenoid‐based colours are more likely to be the result of metabolization. Finally, we analyse the pattern of evolutionary transitions between yellow and red carotenoid‐based plumage colours to determine whether, as predicted, the evolution of yellow carotenoid‐based colours precedes red.

We show that, as expected, both colours are more likely to evolve in smaller species and in species with carotenoid‐rich diets. Yellow carotenoid‐based plumage colours, but not red, are more prevalent in species that inhabit environments with higher primary productivity and closed vegetation. In general, females were more likely to have yellow and males more likely to have red carotenoid‐based plumage colours, closely matching the effects of sexual selection. Our analyses also confirm that red carotenoid‐based colours are more likely to be metabolised than yellow carotenoid‐based colours. Evolutionary gains and losses of yellow and red carotenoid‐based plumage colours indicate that red colours evolved more readily in species that already deposited yellow carotenoids, while the reverse was rarely the case.

Our study provides evidence for a general, directional evolutionary trend from yellow to red carotenoid‐based colours, which are more likely to be the result of metabolization. This may render them potentially better indicators of quality, and thus favoured by sexual selection.
Radical shift in the genetic composition of New England chicory populations
Authors: Závada Tomáš , Malik Rondy J. , Mazumder Lisa , Kesseli Rick V.
Published: July 2022

Human activities have been altering the flora and fauna across the planet. Distributions and the diversity of species, and the phenotypes of individuals in those species are changing. New England with its rapidly changing human demographics is an ideal place to investigate these temporal changes in the habitat. The flora of New England consists of both native and nonnative species. Non‐indigenous plant species have been introduced since the first Europeans arrived in North America in the 15th century. Cichorium intybus (chicory), native to Eurasia, was first recorded in North America in 1774. Subsequently, chicory spread and became naturalized throughout much of the continent.

In this study, we used chloroplast DNA sequences and 12 microsatellite nuclear markers to assess the temporal genetic changes in New England populations of chicory. We analysed 84 herbarium specimens and 18 contemporary extant populations (228 individuals in total).

Three chloroplast DNA haplotypes were detected and all were present in New England prior to 1890; however, Hap3 was rare prior to the 1950s. The nuclear DNA markers showed a major shift in the genetic diversity and composition, with all historical herbarium collections belonging to a single genetic cluster and 16 out of 18 contemporary chicory populations belonging to different genetic clusters. This change occurred regionally and also on a local scale with contemporary populations being very different from herbarium specimens collected previously in the corresponding localities.

Synthesis. Our results indicate that the genetic diversity and structure of Cichorium intybus populations have changed substantially since the founding populations in New England. These changes may have contributed to the success of this nonnative species and helped to fuel its rapid expansion and adaptation to the changing landscapes in both New England and the rest of North America.
Inclusive recovery planning for incremental systemic change: A methodology, early outcomes, and limitations from the Falkland Islands' Covid‐19 recovery planning experience
Authors: Cochrane Kate , Cornish Flora , Murphy Annette , Denton Neil , Bracken Louise
Published: July 2022

Crises do not affect populations equally but expose and exacerbate long‐standing vulnerabilities and inequalities. Recovery language such as ‘build back better’, or ‘bounce forward’ has been criticised for neglecting underlying inequalities. This paper reports on the process and early outcomes of an inclusive Community Recovery Planning process for the Falkland Islands, in response to Covid‐19. The Falkland Islands is home to a complex community, with close ties and short power distances (due to its small size and remoteness), with differences institutionalised in citizenship statuses and entitlements, and shaped by geopolitical tensions. We aimed to use the ‘pandemic as a portal’, seeking out previously ‘less heard’ voices, to make visible previously hidden impacts, and initiate incremental systemic change to tackle them. Community Impact Assessments evidenced specific areas of vulnerability (e.g., housing and income insecurity) and inequalities, largely shaped by differing citizenship status. In tandem with other government currents, the Community Recovery Planning process has contributed to progressive policy changes in Equalities legislation and Income Support. We offer this paper as a demonstration of our methodology for inclusive recovery planning that could be adapted elsewhere. We argue that the inclusion of previously unheard voices contributed to incremental systemic change to reduce inequalities.
What is the accuracy of transvaginal ultrasound for endometriosis mapping prior to surgery when performed by a sonographer within an outpatient women's imaging centre?
Authors: Deslandes Alison , Parange Nayana , Childs Jessie T , Osborne Brooke , Hull M. Louise , Panuccio Catrina , Croft Anthea , Bezak Eva
Published: July 2022

Introduction

This study aimed to assess the accuracy of transvaginal ultrasound (TVUS) for the mapping of endometriosis before surgery when performed by sonographers in an outpatient women's imaging centre.

Methods

A prospective longitudinal cohort study was performed. The study group comprised of 201 women who underwent a comprehensive TVUS assessment, performed by a sonographer. Laparoscopy was performed as the reference standard. Complete TVUS and surgical data were available for 53 women who were included in the final analysis.

Results

Endometriosis was confirmed at a surgery in 50/53 (94.3%) participants, with 25/53 (47.2%) having deep endometriosis (DE) nodules and/or endometriomas present. TVUS for mapping of DE had an overall sensitivity of 84.0%, specificity of 89.3%, PPV of 87.5%, NPV of 86.2%, LR+ of 7.85, LR− of 0.18, and accuracy of 86.8% (P < 0.001). Ovarian immobility had poor sensitivity for detecting localised superficial endometriosis, DE, adhesions, and/or endometriomas (Left = 61.9% and right = 13.3%) but high specificities (left = 87.5% and right = 94.7%). Site‐specific tenderness had low sensitivities and moderate specificities for the same. All soft markers of endometriosis failed to reach statistical significance except for left ovarian immobility (P = <0.001).

Conclusion

Sonographers well experienced in obstetric and gynaecological imaging, working in an outpatient women's imaging setting can accurately map DE; however, the performance of soft markers for detection of SE was poor.
The optimal assortativity of teams inside the firm
Authors: Kambhampati Ashwin , Segura‐Rodriguez Carlos
Published: July 2022

How does a profit‐maximizing manager form teams and compensate workers when workers have private information about their productivity and exert hidden effort once in a team? We study a team‐production model in which positive assortative matching is both efficient and profit‐maximizing under pure adverse selection and pure moral hazard. We show that the interaction of adverse selection and moral hazard can lead to nonassortative matching if complementarities are sufficiently weak. When this is the case, the manager may prefer to delegate matching, allowing workers to sort themselves into teams.
The UN High‐Level Political Forum on Sustainable Development: An orchestrator, more or less?
Authors: Beisheim Marianne , Fritzsche Felicitas
Published: July 2022

The UN High‐level Political Forum on Sustainable Development (HLPF) is at the heart of the UN's follow‐up and review of the 2030 Agenda and the Sustainable Development Goals (SDGs). Analysing the first full cycle of the HLPF (2016–19), we ask what and how the HLPF delivers. In the early debates on its mandate, experts suggested that the HLPF could be an orchestrator, arguing that it would likely have to rely upon indirect and non‐hierarchical forms of governance. Others asked for more or expected less. For the analysis of the HLPF's (orchestration) qualities, we study the proceedings of the HLPF and specifically the HLPF's review of SDG 16 on peace, justice and strong institutions, one of the most contested goals and therefore an interesting hard case. Taken together, DESA as the secretariat of the HLPF does indeed use orchestration to make the most out of the forum's mandate, both through convening and shaping third actors' activities. Political conflicts and limited resources, however, negatively impact what they can do and what the HLPF can deliver. The results of the UN's recent negotiations on the review of the HLPF's ‘format and organizational aspects’ (2020–21) did not change that.
Prenatal methadone exposure leads to long‐term memory impairments and disruptions of dentate granule cell function in a sex‐dependent manner
Authors: Gamble Meredith E. , Marfatia Rhea , Diaz Marvin R.
Published: July 2022

Prenatal opioid exposures lead to extensive cognitive and emotion‐regulation problems in children, persisting at least through school‐age. Methadone, an opioid typically used for the treatment of opioid use disorder, has been approved for use in pregnant women for several decades. Importantly, however, the impacts of prenatal methadone exposure (PME), particularly on offspring as they progress into adulthood, has not been extensively examined. In recent years, children and young animal models have shown cognitive deficits related to PME, including evidence of hippocampal dysfunction. The present work aims to examine the persistent nature of these deficits, as well as determine how they may differ by sex. Pregnant Sprague–Dawley rats either received subcutaneous methadone or water injections twice daily from gestational days 3–20 or were left undisturbed. Following postnatal day 70, male and female offspring were behaviourally tested for impairments in recognition memory using the Novel Object Recognition task and working spatial memory through Spontaneous Alternation. Additionally, using whole‐cell patch‐clamp electrophysiology, hippocampal dentate granule cell function was examined in adult offspring. Results indicate that methadone‐exposed females showed decreased excitability and increased inhibition of dentate granule cells compared to naïve controls, while males did not. These findings were accompanied by impairments in female working spatial memory and altered behaviour in the Object Recognition task. Overall, this work supports the continued investigation of the long‐term effects of PME on adult male and female learning and memory, as well as promotes further exploration of adult hippocampal function as a neural mechanism impacted by this exposure.
Fetal heart block: Vaginal delivery an option
Authors: Gebara Sarah Asmaa , Melov Sarah Jane , Alahakoon Thushari Indika , Sholler Gary , Nayyar Roshini
Published: July 2022

Background

Fetal heart block (FHB) occurs in approximately 1:20 000 births and is associated with significant morbidity and mortality. Vaginal delivery with intrapartum fetal scalp lactate monitoring is offered as an option at our centre for selected cases, in contrast with the published literature advocating caesarean birth.

Aims

To review perinatal outcomes at delivery for FHB at a tertiary referral hospital.

Materials and Methods

Ours was a retrospective cohort study from 1 January, 2007 to 30 June, 2020. The infant outcomes are summarised in three delivery groups: vaginal delivery, planned caesarean section (CS) and unplanned CS.

Results

There were 23 newborns in the study period, with a median gestation at birth of 37.2 weeks and there was one antepartum fetal death in this cohort. Vaginal delivery was planned in 12 women: eight had normal births, three of these women progressed to an intrapartum (unplanned) CS and one woman had a planned CS. All live babies in the vaginal delivery cohort had an Apgar score greater than seven at five minutes. Of the 22 newborns, six required intubation, of which five had been delivered by a planned CS.

Conclusion

Our data suggest that planned vaginal delivery is a safe option for selected women carrying a fetus with FHB. Managing labour with serial fetal scalp lactates, and the involvement of senior clinicians are important factors in achieving a successful outcome.
Embolic phenomena to the limbs are an independent predictor of in‐hospital mortality from infective endocarditis
Authors: Lovelock Thomas , Zhu Michael Z. L. , Saran Ayushica , Vasudevan Thodur
Published: July 2022

Background

Infective endocarditis (IE) is a morbid condition with high mortality. We investigated predictors of in‐hospital mortality and embolic phenomena in a contemporary Australasian cohort.

Methods

We identified all patients with IE admitted between January 2017 and 30th April 2020 (40 months). Patient characteristics, risk factors and clinical outcomes were retrospectively collected and analysed.

Results

One hundred and seventy‐two consecutive patients (mean age: 56.8 ± 17.9 years, male: 63%, 114/172) were included. Causative organisms were Staphylococcus aureus (44%, 75/172), Enterococcus faecalis (15%, 26/172), Streptococcus mitis (6%, 10/172) and Staphylococcus epidermidis (3%, 6/172). In‐hospital mortality was 15% (25/172). Embolic complications were found among 57% (98/172) of patients, the most common being stroke (23%, 40/172), septic pulmonary emboli (17%, 29/172), splenic and/or renal emboli (17%, 26/172) and peripheral limb emboli (15%, 25/172). Sixty (35%, 60/172) patients underwent cardiac surgery. On multivariable analysis, independent predictors of in‐hospital mortality were: increased age (odds ratio: 1.064, per year older, P = 0.001), ICU admission independent of cardiac surgery (OR 9.81, P < 0.001), moderate or severe LV impairment (OR 5.19, P = 0.012) and any sign of embolic phenomena to limbs (OR 5.02, P = 0.006). Multivariable predictors of embolic complications were S. aureus bacteraemia (OR 3.22, P = 0.001) and large vegetation >10 mm (OR 3.04, P = 0.002).

Conclusion

We demonstrate predictors of in‐hospital mortality and embolic phenomena in our cohort. Though age remains a consistent predictor of mortality, surprisingly, signs of embolic phenomena to the limbs was established as an independent predictor of mortality. The mechanism of this is unclear and warrants further evaluation.
Patterns and controls on island‐wide aboveground biomass accumulation in second‐growth forests of Puerto Rico
Authors: Martinuzzi Sebastián , Cook Bruce D. , Helmer Eileen H. , Keller Michael , Locke Dexter H. , Marcano‐Vega Humfredo , Uriarte María , Morton Douglas C.
Published: July 2022

Understanding the heterogeneity of biomass accumulation in second‐growth tropical forests following land use abandonment is important for informing ecosystem carbon models and forest restoration efforts. There is an urgent need for a broad sample of second‐growth forests to enhance our knowledge of carbon accumulation in human‐dominated landscapes, especially for older forests. Puerto Rico has predominantly second‐growth forests, ranging in age from approximately 25 to more than 80 years. We used an island‐wide sample of airborne lidar from the NASA Goddard Lidar, Hyperspectral, and Thermal (G‐LiHT) Airborne Imager collected on March 2017, forest inventory data, and data on forest age, precipitation, soils, and land use to estimate aboveground biomass stocks in moist and wet, second‐growth tropical forests. Biomass accumulation rates in Puerto Rico were lower, on average, than in other Neotropical forests. Median biomass across >16,700 ha of older second‐growth forests was 105 Mg ha−1, and sampled biomass rarely surpassed 250 Mg ha−1. Differences in biomass by age were large and persistent across different substrates and land uses, with a plateau in the pattern of island‐wide biomass accumulation after about 33 years. A spatial regression model showed that multiple factors were related to biomass accumulation, including time since abandonment, geologic substrate, past land use as coffee or pasture, precipitation, topographic wetness index, and slope. Our findings have important consequences for the total carbon storage and expected climate mitigation benefits of large‐scale reforestation efforts, and highlight the value of airborne lidar for quantifying biomass variability in complex tropical landscapes.

Abstract in Spanish is available with online material.
Targeting upregulated RNA binding protein RCAN1.1: a promising strategy for neuroprotection in acute ischemic stroke
Authors: Yun Yan , Yang Xiaxin , Tan Shichuan , Wang Pin , Ji Yanbin , Sun Xiulian
Published: July 2022

Aims

To explore the expression changes and roles of the RNA‐binding protein RCAN1.1 in acute ischemic stroke (AIS), and to preliminarily confirm the medicinal value of the RNA aptamer R1SR13 in AIS by targeting RCAN1.1.

Methods

Two mouse AIS models of middle cerebral artery occlusion (MCAO) and right common carotid artery ligation (R‐CCAL) and oxygen glucose deprivation (OGD) model of AIS in primary neurons and SH‐SY5Y were performed. The expression pattern of RCAN1.1 was assessed using real‐time quantitative PCR (RT‐qPCR) and western blotting (WB) in vivo and in vitro. The underlying mechanism for the elevation of RCAN1.1 in the upstream was investigated. Lentiviruses were administrated and the effect of RCAN1.1 in AIS was assessed by ATP level, caspase 3/7 assay, TUNEL and WB. The protective function of R1SR13 in AIS was evaluated both in vivo and in vitro.

Results

In two mouse models of AIS, RCAN1.1 mRNA and RCAN1.1 L protein were significantly upregulated in the ischemic brain tissue. The same results were detected in the OGD model of primary neurons and SH‐SY5Y. The mechanistic analysis proved that hypoxia‐inducible factor‐1α (HIF1α) could specifically activate the RCAN1.1 gene promoter through combining with the functional hypoxia‐responsive element (HRE) site (−325 to −322 bp). The increased expression of RCAN1.1 L markedly depleted ATP production and aggravated neuronal apoptosis under OGD condition. R1SR13, an antagonizing RNA aptamer of RCAN1.1, was demonstrated to reduce neuronal apoptosis caused by the elevated RCAN1.1 L in the cellular and animal models of AIS.

Conclusion

RCAN1.1 is a novel target gene of HIF1α and the functional HRE in the RCAN1.1 promoter region is −325 to −322 bp. The marked upregulation of RCAN1.1 in AIS promoted neuronal apoptosis, an effect that could be reversed by its RNA aptamer R1SR13 in vivo and in vitro. Thus, R1SR13 represents a promising strategy for neuroprotection in AIS and our study lays a theoretical foundation for it to become a clinically targeted drug.
Climate matching and anthropogenic factors contribute to the colonization and extinction of local populations during avian invasions
Authors: Cardador Laura , Tella José L. , Louvrier Julie , Anadón José D. , Abellán Pedro , Carrete Martina
Published: July 2022

Aim

Concern about the impacts of biological invasions has generated a great deal of interest in understanding factors that determine invasion success. Most of our current knowledge comes from static approaches that use spatial patterns as a proxy of temporal processes. These approaches assume that species are present in areas where environmental conditions are the most favourable. However, this assumption is problematic when applied to dynamic processes such as species expansions when equilibrium has not been reached.

Location

Iberian Peninsula.

Taxon

Birds.

Methods

In our work, we analyse the roles played by human activities, climatic matching and spatial connectivity on the two main underlying processes shaping the spread of invasive species (i.e. colonization and extinction) using a dynamic modelling approach. We use a large data set that has recorded the occurrence of two invasive bird species—the ring‐necked (Psittacula krameri) and the monk (Myiopsitta monachus) parakeets—in the Iberian Peninsula from 1991 to 2016.

Results

Human activities and climate matching play a role on species range dynamics. Human influence and urbanization were the most relevant factors explaining colonization. Additionally, an effect of climate matching was found. Persistence (the inverse of extinction) was mainly affected by human influence for the monk parakeet and by the extent of urban environments for the ring‐necked parakeet.

Main conclusions

Human activities play a major role not only on colonization of new locations, but also on persistence during range expansion. Additionally, natural processes—notably climate matching—also affect new colonizations. These findings add to our understanding of the mechanisms that might allow alien species to expand their geographic range at new locations and might help to improve our capacity to assess invasion risks and impacts accurately.
The role of dual‐specificity phosphatase 3 in melanocytic oncogenesis
Authors: Chousakos Emmanouil , Katsoulas Nikolaos , Kavantzas Nikolaos , Stratigos Alexandros , Lazaris Andreas C.
Published: July 2022

Dual‐specificity phosphatase 3 (DUSP3), also known as Vaccinia H1‐related phosphatase, is a protein tyrosine phosphatase that typically performs its major role in the regulation of multiple cellular functions through the dephosphorylation of its diverse and constantly expanding range of substrates. Many of the substrates described so far as well as alterations in the expression or the activity of DUSP3 itself are associated with the development and progression of various types of neoplasms, indicating that DUSP3 may be an important player in oncogenesis and a promising therapeutic target. This review focuses exclusively on DUSP3's contribution to either benign or malignant melanocytic oncogenesis, as many of the established culprit pathways and mechanisms constitute DUSP3's regulatory targets, attempting to synthesize the current knowledge on the matter. The spectrum of the DUSP3 interactions analysed in this review covers substrates implicated in cellular growth, cell cycle, proliferation, survival, apoptosis, genomic stability/repair, adhesion and migration of tumor melanocytes. Furthermore, the speculations raised, based on the evidence to date, may be considered a fundament for potential research regarding the oncogenesis, evolution, management and therapeutics of melanocytic tumors.