bluuebunny/crossref_metadata_2025 huggingface dataset:
Btbd11 is an inhibitory interneuron specific synaptic scaffolding protein that supports excitatory synapse structure and function
Authors: Bygrave Alexei M , Sengupta Ayesha , Jackert Ella P , Ahmed Mehroz , Adenuga Beloved , Nelson Erik , Goldschmidt Hana L , Johnson Richard C , Zhong Haining , Yeh Felix L , Sheng Morgan , Huganir Richard L
Published: November 2021

Synapses in the brain exhibit cell-type-specific differences in basal synaptic transmission and plasticity. Here, we evaluated cell-type-specific differences in the composition of glutamatergic synapses, identifying Btbd11, as an inhibitory interneuron-specific synapse-enriched protein. Btbd11 is highly conserved across species and binds to core postsynaptic proteins including Psd-95. Intriguingly, we show that Btbd11 can undergo liquid-liquid phase separation when expressed with Psd-95, supporting the idea that the glutamatergic post synaptic density in synapses in inhibitory and excitatory neurons exist in a phase separated state. Knockout of Btbd11 from inhibitory interneurons decreased glutamatergic signaling onto parvalbumin-positive interneurons. Further, both in vitro and in vivo, we find that Btbd11 knockout disrupts network activity. At the behavioral level, Btbd11 knockout from interneurons sensitizes mice to pharmacologically induced hyperactivity following NMDA receptor antagonist challenge. Our findings identify a cell-type-specific protein that supports glutamatergic synapse function in inhibitory interneurons—with implication for circuit function and animal behavior.
A metagenomic analysis of the wrackbed microbiome indicates a phylogeographic break along the North Sea - Baltic Sea transition zone
Authors: Berdan Emma L. , Roger Fabian , Kinnby Alexandra , Cervin Gunnar , Pereyra Ricardo , Töpel Mats , Wellenreuther Maren , Johannesson Kerstin , Butlin Roger K. , André Carl
Published: November 2021

Sandy beaches are biogeochemical hotspots that bridge marine and terrestrial ecosystems via the transfer of marine organic matter, such as seaweed (termed wrack). A keystone of this unique ecosystem is the microbial community, which helps to degrade wrack and re-mineralize nutrients. However, little is known about the wrackbed microbiome, its composition, trophic ecology, or how it varies over time and space. Here we characterize the wrackbed microbiome as well as the microbiome of a primary consumer, the seaweed fly Coelopa frigida, and examine how they change along one of the most studied ecological gradients in the world, the transition from the marine North Sea to the brackish Baltic Sea. We found that polysaccharide degraders dominated both the wrackbed and seaweed fly microbiomes but there were still consistent differences between wrackbed and fly samples. Furthermore, we observed a shift in both microbial communities and functionality between the North and Baltic Sea. These shifts were mostly due to changes in the frequency of different groups of known polysaccharide degraders (Proteobacteria and Bacteroidota). We hypothesize that microbes were selected for their abilities to degrade different polysaccharides corresponding to a shift in polysaccharide content in the seaweed communities of the North vs. Baltic Sea. Our results reveal the complexities of both the wracked microbial community, with different groups specialized to different roles, and the cascading trophic consequences of shifts in the near shore algal community.
Black-necked spitting cobra (Naja nigricollis) phospholipases A2 cause Trypanosoma brucei death by blocking endocytosis through the flagellar pocket
Authors: Martos-Esteban Andrea , Macleod Olivia J. S. , Maudlin Isabella , Kalogeropoulos Konstantinos , Jürgensen Jonas A. , Carrington Mark , Laustsen Andreas H.
Published: November 2021

African trypanosomes, such as Trypanosoma brucei, are flagellated protozoa which proliferate in mammals and cause a variety of diseases in people and animals. In a mammalian host, the external face of the African trypanosome plasma membrane is covered by a densely packed coat formed of variant surface glycoprotein (VSG), which counteracts the host adaptive immune response by antigenic variation. The VSG is attached to the external face of the plasma membrane by covalent attachment of the C-terminus to a glycosylphosphatidylinositol. As the trypanosome grows, newly synthesised VSG is added to the plasma membrane by vesicle fusion to the flagellar pocket, the sole location of exo- and endocytosis. Snake venoms contain dozens of components including proteases and phospholipases. Here, we investigated the effect of Naja nigricollis on T. brucei with the aim of describing the response of the trypanosome to hydrolytic attack on the VSG. We found no evidence for VGS hydrolysis however N. nigricollis venom caused: (i) an enlargement of the flagellar pocket, (ii) the Rab11 positive endosomal compartments to adopt an abnormal dispersed localisation, and (iii) a cell cycle arrest prior to cytokinesis. A single protein family, the phospholipases A2s present in N. nigricollis venom, was necessary and sufficient for the effects. This study provides new molecular insight into T. brucei biology and possibly describes mechanisms that could be exploited for T. brucei targeting.
Maize root-associated microbes likely under adaptive selection by the host to enhance phenotypic performance
Authors: Meier Michael A. , Xu Gen , Lopez-Guerrero Martha G. , Li Guangyong , Smith Christine , Sigmon Brandi , Herr Joshua R. , Alfano James R. , Ge Yufeng , Schnable James C. , Yang Jinliang
Published: November 2021

The root-associated microbiome (rhizobiome) plays a non-negligible role in determining plant health, stress tolerance, and nutrient use efficiency. However, it remains unclear to what extent the composition of the rhizobiome is governed by intraspecific variation in host plant genetics in the field and the degree to which host plant selection can reshape the composition of the rhizobiome. Here we quantify the rhizosphere microbial communities associated with a replicated diversity panel of 230 maize (Zea mays L.) genotypes grown in agronomically relevant conditions under high N (+N) and low N (-N) treatments. We show that the abundance of many root-associated microbes within a functional core microbial community of 150 abundant and consistently reproducible microbial groups is explainable by natural genetic variation in the host plant, with a greater proportion of microbial variance attributable to plant genetic variation in low N conditions. Population genetic approaches identify signatures of purifying selection in the maize genome associated with the abundance of several groups of microbes in the maize rhizobiome. Genome-wide association studies conducted using rhizobiome phenotypes identified n = 467 microbe-associated plant loci (MAPLs) in the maize genome linked to variation in the abundance of n = 115 microbial groups in the maize rhizosphere. In 62/115 cases, which is more than expected by chance, the abundance of these same microbial groups was correlated with variation in plant vigor indicators derived from high throughput phenotyping of the same field experiment. This study provides insights into harnessing the full potential of root-associated microbial symbionts in maize production.
Development of a novel bioluminescent activity assay for peptide ligases
Authors: Zhang Cong-Hui , Shao Xiao-Xia , Wang Xin-Bo , Shou Li-Li , Liu Ya-Li , Xu Zeng-Guang , Guo Zhan-Yun
Published: November 2021

In recent years, some peptide ligases have been identified, such as bacterial sortases and certain plant asparaginyl or prolyl endopeptidases. Peptide ligases have wide applications in protein labeling and cyclic peptide synthesis. To characterize known peptide ligases or identify new ones, we propose a novel bioluminescent activity assay via the genetic fusion of a recognition motif of a peptide ligase to the C-terminus of an inactive large NanoLuc fragment (LgBiT) and the chemical introduction of a nucleophilic motif preferred by the peptide ligase to the N-terminus of the low-affinity SmBiT complementation tag. When the inactive ligation version LgBiT protein was ligated with the low-affinity ligation version SmBiT tag by the expected peptide ligase, its luciferase activity would be restored and could be quantified sensitively according to the measured bioluminescence. In the present study, we first validated the novel bioluminescent activity assay using bacterial sortase A and plant butelase-1. Subsequently, we screened novel peptide ligases from crude extracts of selected plants using two LgBiT–SmBiT ligation pairs. Among 80 common higher plants, we identified that five of them likely express asparaginyl endopeptidase-type peptide ligase and four of them likely express prolyl endopeptidase-type peptide ligase, suggesting that peptide ligases are not so rare in higher plants and more of them await discovery. The novel bioluminescent activity assay is ultrasensitive, convenient for use, and resistant to protease interference, and thus would have wide applications for characterizing known peptide ligases or screening new ones from various sources in future studies.
The expression of essential selenoproteins during zebrafish development requires SECIS binding protein 2-like
Authors: Kiledjian Nora T. , Shah Rushvi , Vetick Michael B. , Copeland Paul R.
Published: November 2021

The dietary requirement for selenium is based on its incorporation into selenoproteins, which contain the amino acid selenocysteine (Sec). The Sec insertion sequence (SECIS) is an RNA structure found in the 3’ UTR of all selenoprotein mRNAs, and it is required to convert in-frame UGA codons from termination to Sec-incorporating codons. There are two proteins that bind to SECIS elements, but only one, SECIS binding protein 2 (Sbp2), has been shown to be required for Sec incorporation. The Sbp2 paralogue, SECIS binding protein 2-like (Secisbp2l) is conserved in all vertebrates and shares many features with Sbp2, but its function is unknown. Here we set out to determine the relative roles of Sbp2 and Secisbp2l by introducing CRISPR mutations in both genes in zebrafish. By monitoring selenoprotein synthesis with 75Se labeling during embryogenesis, we found that sbp2-/- embryos still make a select subset of selenoproteins but secisbp2l-/- embryos retain the full complement. Abrogation of both genes completely prevents selenoprotein synthesis and juveniles die at 14 days post fertilization. Embryos lacking Sbp2 are sensitive to oxidative stress and express the stress marker vtg1. We propose a model where Secisbp2l is required to promote essential selenoprotein synthesis during stress.
Oligomerization state of the functional bacterial twin arginine translocation (Tat) receptor complex
Authors: Sharma Ankith , Chowdhury Rajdeep , Musser Siegfried M.
Published: November 2021

The twin-arginine translocation (Tat) system transports folded proteins across bacterial and plastid energy transducing membranes. Ion leaks are generally considered to be mitigated by the creation and destruction of the translocation conduit in a cargodependent manner, a mechanism that enables tight sealing around a wide range of cargo shapes and sizes. In contrast to the variable stoichiometry of the active translocon, the oligomerization state of the receptor complex is considered more consistently stable, but has proved stubbornly difficult to establish. Here, using a single molecule photobleaching analysis of individual inverted membrane vesicles, we demonstrate that Tat receptor complexes are tetrameric in native membranes with respect to both TatB and TatC. This establishes a maximal diameter for a resting state closed pore. A large percentage of Tat-deficient vesicles explains the typical low transport efficiencies observed. This individual reaction chamber approach will facilitate examination of the effects of stochastically distributed molecules.
Adverse outcomes in SARS-CoV-2 infections are associated with a combination of variant genotypes at two loci in the APOL1 gene: a UK Biobank study
Authors: Adamson Walt E , Noyes Harry , Cooper Anneli , Beckett-Hill Georgia , Ogunsola John , Parekh Rulan , MacLeod Annette
Published: November 2021

Risk of hospitalisation or death from COVID-19 in the UK is disproportionately high in people of African ancestry. Two APOL1 haplotypes (G1 and G2) found at high frequency only in populations of African descent are associated with increased risk of non-communicable and infectious diseases. Here, we test the hypothesis that adverse COVID-19 outcomes are also associated with these APOL1 high-risk variants.
Within 9,433 individuals with African ancestry in the UK Biobank, there were 172 hospitalisations and 47 deaths attributed to COVID-19 as of December 2021. We examined APOL1 genotypes for association with hospitalisation and death while controlling for risk factors previously associated with poor COVID-19 outcomes.
We identified an association between carriage of two APOL1 high-risk variants and death from COVID-19 (OR=2.7, 95% CI: 1.2-6.4). Stratified by genotype, those with G1/G2 had a higher odds of COVID-19 hospitalisation (OR=2.1, 95% CI: 1.1-3.8) and death (OR=5.9, 95% CI: 2.2-15.3) than G0/G0. There was no significant association detected in carriers of G1/G1 and G2/G2.
These data suggest that the APOL1 G1/G2 genotype contributes to the increased rates of hospitalisation and mortality from COVID-19 in people of African ancestry, and could help to identify those at higher risk of severe COVID-19. This is especially relevant to geographical regions where APOL1 G1 and G2 high-risk variants are common, such as West and Central Africa and their diaspora.
E-cigarette aerosol exacerbates cardiovascular oxidative stress in mice with an inactive aldehyde dehydrogenase 2 enzyme
Authors: Yu Xuan , Zeng Xiaocong , Xiao Feng , Chen Ri , Sinharoy Pritam , Gross Eric R.
Published: November 2021

Aims

E-cigarette aerosol containing aldehydes, including acetaldehyde, are metabolized by the enzyme aldehyde dehydrogenase 2 (ALDH2). However, little is known how aldehyde exposure from e-cigarettes, when coupled with an inactivating ALDH2 genetic variant, ALDH2*2 (present in 8% of the world population), affects cardiovascular oxidative stress. The aim of this study was to determine how e-cigarette aerosol exposure, when coupled with genetics, impacts cardiovascular oxidative stress in wild type ALDH2 and ALDH2*2 knock-in mice.

Methods and Results

Using selective ion flow mass spectrometry, we determined that e-cigarette aerosol contains acetaldehyde that are 10-fold higher than formaldehyde or acrolein. Next, using wild type ALDH2 and ALDH2*2 knock-in rodents, we identified organ-specific differences in ALDH2 with the heart having ~1.5-fold less ALDH2 enzyme activity relative to the liver and lung. In isolated cardiac myocytes, acetaldehyde exposure (30 seconds, 0.1-1 μM) caused a 4-fold greater peak in calcium levels for ALDH2*2 relative to ALDH2 cardiomyocytes. ALDH2*2 cardiomyocytes exposed to acetaldehyde also demonstrated a 2-fold increase in ROS production and 2.5-fold increase in 4HNE protein adducts relative to ALDH2 cardiomyocytes. For intact rodents, ALDH2*2 knock-in mice exposed to e-cigarette aerosol had an increased heart rate beginning 5 days after exposure compared to wild type ALDH2 mice (775±30 bpm versus 679±33 bpm, respectively, *p<0.01, n=7-8/group). E-cigarette aerosol exposure also exacerbated oxidative stress in ALDH2*2 heart homogenates, including a 1.3-fold higher protein carbonyl level, a 1.7-fold higher lipid peroxide level and 1.5-fold greater phosphorylation of NF-κB relative to wild type ALDH2 homogenates.

Conclusions

The increased oxidative stress from e-cigarette aerosol aldehydes triggers the proinflammatory NF-κB pathway. As ALDH2 expression and activity is lower in the heart relative to the lung, the heart could be more susceptible to increases in cardiovascular oxidative stress from e-cigarette aerosol; particularly for those carrying an ALDH2*2 genetic variant which limits acetaldehyde metabolism.

Graphical Abstract

E-cigarette aerosol exposure triggers increases in ROS that lead to increased protein carbonylation, MDA production, and elevates phosphorylated NF-kB. This exposure to e-cigarette aerosol leads to increases in cardiovascular oxidative stress. For the ALDH2*2 variant, there is limited ability to metabolize the reactive aldehydes from e-cigarette aerosol and with increased levels of oxidative stress at baseline relative to wild type ALDH2, e-cigarette aerosol increased oxidative stress, protein carbonylation, and phosphorylation of NF-kB relative to wild type ALDH2 rodents.
Core circadian clock and light signaling genes brought into genetic linkage across the green lineage
Authors: Michael Todd P.
Published: November 2021

The circadian clock ensures that biological processes are phased to the correct time of day. In plants the circadian clock is conserved at both the level of transcriptional networks as well as core genes. In the model plantArabidopsis thaliana,the core circadiansingleMYB(sMYB) genesCCA1andRVE4are in genetic linkage with thePSEUDO-RESPONSE REGULATOR(PRR) genesPRR9andPRR7respectively. Leveraging chromosome-resolved plant genomes and syntenic ortholog analysis it was possible to trace this genetic linkage back to the basal angiospermAmborellaand identify an additional evolutionarily conserved genetic linkage betweenPIF3andPHYA. TheLHY/CCA1-PRR5/9, RVE4/8-PRR3/7andPIF3-PHYAgenetic linkages emerged in the bryophyte lineage and progressively moved within several genes of each other across an array of higher plant families representing distinct whole genome duplication and fractionation events. Soybean maintains all but two genetic linkages, and expression analysis revealed thePIF3-PHYAlinkage overlapping with the E4 maturity group locus was the only pair to robustly cycle with an evening phase in contrast to thesMYB-PRRmorning and midday phase. While most monocots maintain the genetic linkages, they have been lost in the economically important grasses (Poaceae) such as maize where the genes have been fractionated to separate chromosomes and presence/absence variation results in the segregation ofPRR7paralogs across heterotic groups. The evolutionary conservation of the genetic linkage as well as its loss in the grasses provides new insight in the plant circadian clock, which has been a critical target of breeding and domestication.

Summary Sentence

The genetic linkage of the core circadian clock components has evolutionary origins in bryophytes and sheds light on the current functioning and selection on the circadian clock in crops.
Logistic planning for pharmaceutical supply chain using multi-objective optimization model
Authors: Ershadi Mohammad Mahdi , Ershadi Mohamad Sajad
Published: November 2021

Purpose

Appropriate logistic planning for the pharmaceutical supply chain can significantly improve many financial and performance aspects. To this aim, a multi-objective optimization model is proposed in this paper that considers different types of pharmaceuticals, different vehicles with determining capacities and multi-period logistic planning. This model can be updated based on new information about resources and newly identified requests.

Design/methodology/approach

The main objective function of the proposed model in this paper is minimizing the unsatisfied prioritized requests for pharmaceuticals in the network. Besides, the total transportation activities of different types of vehicles and related costs are considered as other objectives. Therefore, these objectives are optimized hierarchically in the proposed model using the Lexicographic method. This method finds the best value for the first objective function. Then, it tries to optimize the second objective function while maintaining the optimality of the first objective function. The third objective function is optimized based on the optimality of other objective functions, as well. A non-dominated sorting genetic algorithm II-multi-objective particle swarm optimization heuristic method is designed for this aim.

Findings

The performances of the proposed model were analyzed in different cases and its results for different problems were shown within the framework of a case study. Besides, the sensitivity analysis of results shows the logical behavior of the proposed model against various factors.

Practical implications

The proposed methodology can be applied to find the best logistic plan in real situations.

Originality/value

In this paper, the authors have tried to use a multi-objective optimization model to guide and correct the pharmaceutical supply chain to deal with the related requests. This is important because it can help managers to improve their plans.
Financial crime in the decentralized finance ecosystem: new challenges for compliance
Authors: Wronka Christoph
Published: November 2021

Purpose

As decentralized finance (DeFi) has collected substantial promotion, investment and cryptographic development as a new model for numerous financial operations over the last months. As DeFi models and technology are quite unique, authorities have not been engaged much yet. However, these non-regulated financial markets will be overlooked for no long by the regulators. Therefore, the purpose of this paper is to analyse and evaluate the new challenges for financial crime compliance which need to be tackled very soon.

Design/methodology/approach

The research relied on secondary sources of data, using secondary research to collect archival data in the form of documents. Content and thematic analyses were used to synthesize the collected data

Findings

DeFi is considered to be one of the major steps towards adopting crypto masses. It is expected that DeFi will play a significant role in future and provide the present banking system with a feasible alternative. Therefore, it is crucial that the DeFi industry must address the main risks to ensure its “user” full compliance.

Originality/value

This research is the first to analyse the emerging challenges of fighting financial crime in the DeFi ecosystem.
Understanding the leaky pipeline system: behavioural ecological approach to the social marketing of women thriving in STEM careers
Authors: Çelik Hafize , Watson Forrest
Published: November 2021

Purpose

This paper aims to explore the complexity of the “leaky pipeline” of women in science, technology, engineering and maths (STEM) in the intriguing contexts where there are a high number of STEM graduates but a low number of women working in these fields.

Design/methodology/approach

The authors conducted in-depth interviews with eight STEM “leavers” and eight “persisters” in Turkey to understand the multi-level influences on their career paths.

Findings

The behavioural ecological model is applied to enrich the understanding of women’s attrition from STEM. The authors found a complex system of actors, relationships and influences that impact the negotiations of women’s felt misfit/love of their STEM career and changing self-actualisation.

Practical implications

The authors highlight that social marketers should consider the complex influences on even the most individualistic-looking decisions to produce systemic change.

Originality/value

This paper deepens the use of the behavioural ecological model in the ways that the layers of motivator and demotivator influences interact with women’s internal negotiations of career choice. The paper integrates classic theories (self-actualisation (Maslow, 1943) and two-factor model (Herzberg et al., 1959)) within systems social marketing.
Will the revisions to GRI 303 improve corporate water reporting? The challenges of defining and operationalising “water stress”
Authors: Hewawithana Dushyanthi , Hazelton James , Walkerden Greg , Tello Edward
Published: November 2021

Purpose

This paper aims to examine whether the disclosure obligations in areas of water stress required under the revised Global Reporting Initiative standard (GRI) 303 Water and Effluents, 2018 will improve the quality of corporate water reporting. As a key new requirement is to disclose the impact of water withdrawals from (and discharges to) areas experiencing water stress, the authors examine the ambiguity of the term “water stress” and the extent to which following the GRI’s guidance to use the Aqueduct Water Risk Atlas and/or the Water Risk Filter will enable quality corporate water reporting.

Design/methodology/approach

The study is informed by the notion of public interest reporting, on the basis that the provision of contextual water information is in the public interest. To explore the ambiguity of the term “water stress”, the authors conduct a semi-systematic review of hydrology literature on water stress and water stress indices. To explore the efficacy of using the Aqueduct Water Risk Atlas and/or the Water Risk Filter, the authors review the operation and underlying data sources of both databases.

Findings

The term “water stress” has a range of definitions and the indicators of water stress encompass a wide variety of differing factors. The Aqueduct Water Risk Atlas and the Water Risk Filter use a combination of different risk indicators and are based on source data of varying quality and granularity. Further, different weightings of water risk information are available to the user, which yield different evaluations of water stress. A variety of approaches are permitted under GRI 303.

Practical implications

Effective implementation of GRI 303 may be impeded by the ambiguity of the term “water stress”, varying quality and availability of the water stress information and the fact that different water stress calculation options are offered by the water databases. The authors suggest that the GRI closely monitor compliance, implementation approaches and scientific developments in relation to the water stress requirements with a view to providing further guidance and improving future iterations of the standard.

Originality/value

Whilst there have been many calls for improved contextual water reporting, few previous studies have explored the challenges to implementing reporting requirements related to the determination of “water stress”.
Developing rightly culture on TQM - evidence from SMEs in the context of emerging economy
Authors: Gorondutse Abdullahi Hassan , Ali Gamal Abdualmajed , Hilman Haim
Published: November 2021

Purpose

Total quality management (TQM) must include orientation towards quality awareness in the overall organisational processes in a firm. A successful TQM needs a supportive culture that can adapt to alterations and strengthen innovation. This study aims to confirm the association between the style of management known as organisational culture (OC) and TQM practices in manufacturing Small and Medium Enterprises (SMEs).

Design/methodology/approach

Data-driven research was drawn from self-assessment inquiries among 772 managers/owners of manufacturing SMEs of the Saudi Arabia Kingdom (KSA). The dominant culture was detected by means of a cross-sectional technique.

Findings

The findings enrich the literature by revealing a positive effect of OC on TQM execution in the manufacturing SMEs of KSA.

Research limitations/implications

Prior to the execution of TQM operations, administrators of manufacturing SMEs should be aware of the culture within organisations so that TQM may be implemented.

Practical implications

The study suggests that organisations, particularly manufacturing SMEs, should constantly strive to enhance the TQM culture.

Social implications

Amid intense competition among manufacturing SMEs, it is crucial to guarantee their high performance. This research assists society in evaluating the strength of a particular SME sector and further enables it to assess which SMEs really have a good OC–TQM relation.

Originality/value

The paper creates and presents various platforms of the OC and TQM as a unified body of knowledge.
BioF is a novel B2 metallo‐β‐lactamase from Pseudomonas sp. isolated from an on‐farm biopurification system
Authors: Cafiero Juan Hilario , Martini María Carla , Lozano Mauricio Javier , Vacca Carolina , Lagares Antonio , Tomatis Pablo Emiliano , Del Papa María Florencia
Published: November 2021

Antimicrobial resistance represents a major global health concern and environmental bacteria are considered a source of resistance genes. Carbapenems are often used as the last antibiotic option to treat multidrug‐resistant bacteria. Metallo‐β‐lactamases (MBLs) are able to render resistance to almost all β‐lactam antibiotics, including carbapenems. Unfortunately, there are no inhibitors against MBLs for clinical use. Subclass B2 MBLs are the only enzymes working as strict carbapenemases, under‐represented, encoded in chromosome genes and only functional as mono‐zinc enzymes. Despite current efforts in MBLs inhibitor development, B2 carbapenemase activity is especially difficult to suppress, even in vitro. In this study we characterized BioF, a novel subclass B2 MBL identified in a new environmental Pseudomonas sp. strain isolated from an on‐farm biopurification system (BPS). Although blaBioF is most likely a chromosomal gene, it is found in a genomic island and may represent a step previous to the horizontal transmission of B2 genes. The new B2 MBL is active as a mono‐zinc enzyme and is a potent carbapenemase with incipient activity against some cephalosporins. BioF activity is not affected by excess zinc and is only inhibited at high metal chelator concentrations. The discovery and characterization of B2 MBL BioF as a potent carbapenemase in a BPS bacterial isolate emphasizes the importance of exploring antibiotic resistances existing in the environmental microbiota under the influence of human activities before they could emerge clinically.
Getting high or getting low? the external effects of coffeeshops on house prices
Authors: Langen Mike , Aydin Erdal , Eichholtz Piet , Kok Nils
Published: November 2021

Cannabis legalization is a hotly contested policy topic. While beneficial to some, cannabis dispensaries may create negative externalities for others. This paper studies the external effects of coffeeshops—Dutch cannabis sales facilities—on house prices. We employ a difference‐in‐difference framework around a change in regulation, leading to exogenous coffeeshop closings. We find that closings have a negative effect on house prices. Compared to homes nearby remaining coffeeshops, homes nearby closing coffeeshops decrease on average 1.6–8.5% in value. The findings are robust to a battery of tests and unaffected by the subsequent use of coffeeshop locations.
Successful procedure with additional omentopexy to suture closure of gallbladder stump in laparoscopic subtotal cholecystectomy
Authors: Kato Hirotaka , Kinoshita Hiroyuki , Kawaguchi Masanori , Yamazaki Hirofumi , Sakata Yoshifumi
Published: November 2021

Laparoscopic subtotal cholecystectomy, a bailout surgery for cholecystitis, can result in postoperative bile leakage, so surgical ingenuity is required. An 88‐year‐old woman had pain at the right hypochondrium. Abdominal computed tomography showed swelling of the gallbladder and thickness of the gallbladder wall, leading to diagnosis of mild acute cholecystitis. Percutaneous transhepatic gallbladder drainage was performed to alleviate cholecystitis because the patient was taking antiplatelet medicine. Laparoscopic cholecystectomy was then performed within 72 hours from the onset. The gallbladder was operatively found to be strongly fibrotic, so the procedure was switched to laparoscopic subtotal cystectomy, dissecting the gallbladder at the infundibulum‐cystic duct level. The gallbladder stump was closed with barbed suture and omentopexy was added due to fragility. There was no significant postoperative bile leakage. Additional omentopexy to stump closure in laparoscopic subtotal cholecystectomy was thought to be useful in prevention of postoperative bile leakage.
COVID-19 vaccines and skin manifestations
Authors: Bataille V. , Puig S.
Published: November 2021

Linked Article:  Català et al. Br J Dermatol 2022; 186:142–152.
Risankizumab vs. fumaric acid esters: a direct comparison
Authors: Fleming P.
Published: November 2021

Linked Article:  Thaçi et al. Br J Dermatol 2022; 186:30–39.
Parenting and the development of children’s gratitude
Authors: Hussong Andrea M. , Coffman Jennifer L. , Halberstadt Amy G.
Published: November 2021

Fostering gratitude is often among the socialization goals parents hold for their children. In this article, we explore work that portrays gratitude as a complex socioemotional process that occurs during a moment in time and becomes more frequent, integrated, and rich with development. Researchers have identified at least four parent socialization practices that may foster children’s gratitude: modeling, daily scaffolding, niche selection, and conversations with children about gratitude moments and missed opportunities for gratitude. Parent training tools based on this work have yielded modest results. More work is needed to understand further the ways parenting and children’s gratitude are culturally embedded, place the work on gratitude socialization within the larger task of value socialization faced by parents, and explore gratitude as an ontogenetic tool for making meaning of the world around us.
Association between diabetes mellitus and chronic rhinosinusitis with nasal polyps: A population‐based cross‐sectional study
Authors: Nam Jae‐Sung , Roh Yun‐Ho , Kim Jungghi , Chang Suk‐Won , Ha Jong‐Gyun , Park Jeong‐Jin , Fahad Wasan Almazouq , Yoon Joo‐Heon , Kim Chang‐Hoon , Cho Hyung‐Ju
Published: November 2021

Objective

To investigate the association between physician‐diagnosed diabetes mellitus (DM) and chronic rhinosinusitis (CRS) phenotypes in a national population‐based study.

Study Design

Retrospective cross‐sectional study.

Setting

Population‐based survey data were collected by the Korean National Health and Nutrition Survey between January 2008 and December 2012.

Participants and Methods

A total of 34 670 participants aged over 19 years were enrolled in the Korea National Health and Nutrition Examination Surveys from 2008 to 2012. The relationship of CRS prevalence, with and without nasal polyps, with physician‐diagnosed DM and non‐DM were assessed. Differences in sinonasal symptoms between patients with and without DM were analysed in this cross‐sectional study.

Results

A significant association was observed between DM and CRS with nasal polyps after adjustment for multiple variables. No substantial association was observed between DM and CRS without nasal polyps. Among patients with CRS, olfactory dysfunction for >3 months was significantly more frequent in the DM group than in the non‐DM group.

Conclusion

We demonstrated significant associations between DM and CRS with nasal polyps and olfactory dysfunction among patients with CRS in a large national clinical cohort study. The direct mechanism of the association between DM and CRS with nasal polyps should be further investigated to clarify the pathogenesis of CRS with nasal polyps.
Rectal washout during abdominoperineal resection for rectal cancer has no impact on the oncological outcome
Authors: Svensson Neufert Rebecca , Jörgren Fredrik , Buchwald Pamela
Published: November 2021

Aim

Intraoperative rectal washout is performed to eliminate exfoliated intraluminal cancer cells and thereby decrease the risk of local recurrence. Rectal washout in abdominoperineal resection has not been studied. The aim of this study was to assess the oncological outcome after rectal washout in abdominoperineal resection for rectal cancer and to find evidence as to whether rectal washout should be performed or not.

Method

Data for all patients registered in the Swedish Colorectal Cancer Registry who underwent elective surgery with abdominoperineal resection for rectal cancer (TNM Stages I–III) between 2007 and 2013 were analysed using multivariable analysis.

Results

No significant differences were shown between the rectal washout group and the no rectal washout group for local recurrence [10/265 (3.8%) vs. 87/2160 (4.0%), p = 0.84], distant metastasis [51/265 (19.2%) vs. 476/2160 (22.0%), p = 0.29] or overall recurrence [53/265 (20.0%) vs. 505/2160 (23.4%), p = 0.21]. In multivariable analysis, rectal washout did not significantly affect the oncological outcome in terms of local recurrence, distant metastasis, overall recurrence or 5‐year overall or relative survival.

Conclusion

Our results do not support routine rectal washout during abdominoperineal resection in order to improve the oncological outcome.
Osteoblasts impair cholesterol synthesis in chondrocytes via Notch1 signalling
Authors: Yang Yueyi , Zhang Demao , Guo Daimo , Li Jiachi , Xu Siqun , Wei Jieya , Xie Jing , Zhou Xuedong
Published: November 2021

Objectives

Previous reports have proposed the importance of signalling and material exchange between cartilage and subchondral bone. However, the specific experimental evidence is still insufficient to support the effect of this interdependent relationship on mutual cell behaviours. In this study, we aimed to investigate cellular lipid metabolism in chondrocytes induced by osteoblasts.

Methods

Osteoblast‐induced chondrocytes were established in a Transwell chamber. A cholesterol detection kit was used to detect cholesterol contents. RNA sequencing and qPCR were performed to assess changes in mRNA expression. Western blot analysis was performed to detect protein expression. Immunofluorescence staining was conducted to show the cellular distribution of proteins.

Results

Cholesterol levels were significantly decreased in chondrocytes induced by osteoblasts. Osteoblasts reduced cholesterol synthesis in chondrocytes by reducing the expression of a series of synthetases, including Fdft1, Sqle, Lss, Cyp51, Msmo1, Nsdhl, Sc5d, Dhcr24 and Dhcr7. This modulatory process involves Notch1 signalling. The expression of ncstn and hey1, an activator and a specific downstream target of Notch signalling, respectively, were decreased in chondrocytes induced by osteoblasts.

Conclusions

For the first time, we elucidated that communication with osteoblasts reduces cholesterol synthesis in chondrocytes through Notch1 signalling. This result may provide a better understanding of the effect of subchondral bone signalling on chondrocytes.
Manchester Intermittent versus Daily Diet App Study (MIDDAS): A pilot randomized controlled trial in patients with type 2 diabetes
Authors: McDiarmid Sarah , Harvie Michelle , Johnson Rhona , Vyas Avni , Aglan Azza , Moran Jacqui , Ruane Helen , Hulme Amanda , Sellers Katharine , Issa Basil G.
Published: November 2021

Aims

To test the feasibility and potential efficacy of remotely supported intermittent low‐energy diets (ILEDs) and continuous low‐energy diets (CLEDs) in people with type 2 diabetes (T2D) and the feasibility of a randomized controlled trial comparing the two approaches.

Materials and methods

Seventy‐nine adults with overweight/obesity and T2D (≤8 years duration) were randomized 1:1 to CLED (8 weeks/56 days of daily Optifast 820 kcal (3430 kJ) diet) or isoenergetic ILED (2 days of Optifast and 5 days of a Mediterranean diet/week for 28 weeks). Weight maintenance/continued weight loss was undertaken for the remainder of the 52 weeks. Both groups received frequent telephone or the Oviva app support. Feasibility outcomes included study uptake, retention, app usage, dietary adherence, weight loss and change in glycated haemoglobin (HbA1c) at 52 weeks.

Results

We enrolled 39 ILED and 40 CLED participants and 27 (69%) ILED and 30 CLED (75%) attended the 52‐week follow‐up. Eighty‐nine per cent (70 of 79) started using the app and 86% (44 of 51) still used the app at 52 weeks. Intention‐to‐treat analysis at 52 weeks showed percentage weight loss was mean (95% confidence interval) −5.4% (−7.6, −3.1%) for ILED and −6.0% (−7.9, −4.0%) for CLED. HbA1c <48 mmol/mol was achieved in 42% of both groups. Mean (95% confidence interval) changes in the T2D medication effect score were 0.0008 (−0.3, 0.3) for ILED and −0.5 (−0.8, −0.3) for CLED.

Conclusion

The study shows the feasibility and potential efficacy of remotely delivered ILED and CLED programmes for weight loss and HbA1c reduction, and the feasibility of a randomized controlled trial comparing the two approaches.
Youth and family members make meaningful contributions to a randomized‐controlled trial: YouthCan IMPACT
Authors: Henderson Joanna , Courey Lynn , Relihan Jacqueline , Darnay Karleigh , Szatmari Peter , Cleverley Kristin , Cheung Amy , Hawke Lisa D.
Published: November 2021

Background

There are growing calls to engage service users in research about issues relevant to them. Youth and family members can make meaningful contributions to research projects, improving quality and relevance. However, more information is needed on the contributions that youth and family members can make to various study designs.

Objective

This paper describes the contributions that youth and family members have made to a multi‐site pragmatic randomized‐controlled trial, YouthCan IMPACT, and the way project‐based engagement learnings accelerated change at the institutional level and beyond.

Results

Youth and family members were full members of the project team, including the project's core governance and working groups. They contributed to project leadership, as funding co‐applicants and as equal members of the governance team. They were also engaged in study design. Youth defined the primary outcome measure and contributed to decisions on all secondary measures. The service pathway was co‐designed with youth and family members; for example, they guided the inclusion of peer support and a family member intervention as core service components. Study implementation contributions included ensuring a youth‐ and family‐friendly research process and training research staff on working with youth and family members. Knowledge translation activities have included youth and family members as co‐presenters and manuscript co‐authors. The learnings from this trial have been leveraged to expand youth and family engagement at the institution and beyond.

Conclusions

Youth and family members make substantial contributions to complex research projects, including randomized‐controlled trials, thereby improving project design, study implementation, associated interventions, and knowledge translation.
Genuine and non‐genuine smiles in individuals meeting criteria for a clinical high‐risk syndrome
Authors: Ricard Jordyn R. , Gupta Tina , Vargas Teresa , Haase Claudia M. , Mittal Vijay A.
Published: November 2021

Aim

Psychosis is characterized by both alterations in emotional functioning and environmental stressors including bullying victimization. Recent evidence suggests that some alterations in emotional functioning (e.g., blunted positive facial expressions) are already present in the psychosis risk period. Yet, some clinically relevant facial emotions have not been investigated such as genuine smiles (thought to reflect genuine positive emotions) and non‐genuine smiles (thought to fake positive or mask negative emotions) in individuals meeting criteria for a clinical high‐risk (CHR) syndrome. Further, despite a compelling conceptual basis to suggest a link between affective expression and exposure to environmental stress, to date, no investigations have sought to examine this association. Here, we aim to assess differences between a sample of CHR (N = 65) and control (N = 67) individuals in genuine and non‐genuine smiles and associations with bullying victimization.

Methods

Smiles (i.e., genuine; non‐genuine) were objectively coded on a second‐by‐second basis using the Facial Action Coding System during a digitally recorded clinical interview segment. Bullying victimization was measured via parent report.

Results

Findings revealed that the CHR group (1) showed blunted genuine (but not non‐genuine) smiles compared to controls. Moreover, (2) bullying victimization was related to blunted genuine smiles, but not non‐genuine smiles.

Conclusion

These findings expand our understanding of emotional alterations in this group with implications for diagnosis (highlighting blunted genuine smiles as a specific marker) and etiology (underscoring the role of bullying victimization in the etiology of emotional dysfunction).
Course of insight, depression and suicidality in inpatients with first‐episode schizophrenia who received group psychoeducation
Authors: Sato Kojiro , So Ryuhei , Yoshimura Bunta , Kitagawa Kohei
Published: November 2021

Aim

We aimed to investigate whether gaining insight through psychoeducation for first‐episode schizophrenia is associated with increased suicidality.

Methods

We conducted a secondary analysis of a prospective cohort study that included inpatients with first‐episode schizophrenia who attended a group psychoeducation program during their admission. The group psychoeducation program consisted of four weekly sessions provided by a multidisciplinary team. The primary outcome was the correlation between changes in insight and suicidality. We also examined whether change in insight was associated with changes in hopelessness and depression. We measured insight using the Birchwood Insight Scale. Suicidality, hopelessness and depression were measured using the Calgary Depression Rating Scale for Schizophrenia.

Results

A total of 125 people participated in the educational program. The Spearman's correlation coefficient between changes in insight and suicidality was −0.14 (95% confidence interval, −0.31 to 0.04; p = .12). Similarly, gain in insight did not significantly correlate with change in depression (0.01, 95% confidence interval, −0.17 to 0.18; p = .93) and change in hopelessness (0.01, 95% confidence interval, −0.16 to 0.19; p = .88).

Conclusions

We observed almost no association between gaining insight and suicidality after a group psychoeducation program in inpatients with first‐episode schizophrenia.
Pathogenesis of solar urticaria: Classic perspectives and emerging concepts
Authors: McSweeney Sheila Mary , Sarkany Robert , Fassihi Hiva , Tziotzios Christos , McGrath John Alexander
Published: November 2021

Solar urticaria is a rare, immunologically mediated photodermatosis in which activation of cutaneous mast cells is triggered by specific wavelengths of solar electromagnetic radiation. This manifests clinically as the rapid development of cutaneous itch, erythema and wheal formation after several minutes of sun exposure. Disease mechanisms in solar urticaria remain incompletely elucidated and there have been few recent investigations of its pathobiology. Historic passive transfer experiments performed during the twentieth century provide support for a ‘photoallergy’ model of disease pathogenesis, wherein molecular alteration of a putative chromophore by solar electromagnetic radiation produces mast cell activation via an IgE‐dependent mechanism. However, this model does not account for several observations made during passive transfer experiments nor does it explain a range of subsequent clinical and photobiological observations made in solar urticaria patients. Furthermore, increased understanding of the molecular dynamics underpinning cutaneous mast cell responses highlights the need to reformulate our understanding of solar urticaria pathogenesis in the context of this contemporary scientific landscape. In this review, we discuss the current understanding of solar urticaria pathogenesis and, by incorporating recent scientific and clinical observations, develop new hypotheses to drive future investigation into this intriguing disorder.