bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-particle cryo-EM analysis of the shell architecture and internal organization of an intact α-carboxysome
Authors: Evans Sasha L. , Al-Hazeem Monsour M. J. , Mann Daniel , Smetacek Nicolas , Beavil Andrew J. , Sun Yaqi , Chen Taiyu , Dykes Gregory F. , Liu Lu-Ning , Bergeron Julien R. C.
Published: February 2022

Carboxysomes are proteaceous bacterial microcompartments (BMCs) that sequester the key enzymes for carbon fixation in cyanobacteria and some proteobacteria. They consist of a virus-like icosahedral shell, encapsulating carbonic anhydrase and ribulose 1,5-bisphosphate carboxylase/oxygenase (RuBisCO), which catalyses the dehydration of bicarbonate into CO2, the first step of the Calvin–Benson–Bassham cycle. Despite their significance in carbon fixation and great bioengineering potentials, the structural characterization of native carboxysomes, including the shell and the internal organization, is currently limited to low-resolution tomography studies. Notably, the degree of heterogeneity of the shell, and the internal arrangement of enzymes, remain poorly understood. Here, we report the structural characterization of a native α-carboxysome from a marine cyanobacterium by single-particle cryo-EM. We determine the structure of RuBisCO enzyme at 2.9 Å resolution. In addition, we obtain low-resolution maps of the icosahedral protein shell and the concentric interior organisation. In combination with artificial intelligence (AI)-driven modelling approaches, we exploited these maps to propose a complete atomic model of an intact carboxysome. This study provides insight into carboxysome structure and protein-protein interactions involved in carboxysome assembly. Advanced knowledge about carboxysome architecture and structural plasticity is critical for not only a better understanding of biological carbon fixation mechanism but also repurposing carboxysomes in synthetic biology for biotechnological applications.
Structural insights into Charcot-Marie-Tooth disease-linked mutations in human GDAP1
Authors: Sutinen Aleksi , Nguyen Giang Thi Tuyet , Raasakka Arne , Muruganandam Gopinath , Loris Remy , Ylikallio Emil , Tyynismaa Henna , Bartesaghi Luca , Ruskamo Salla , Kursula Petri
Published: February 2022

Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral polyneuropathy in humans, and its different subtypes are linked to mutations in dozens of different genes. Mutations in ganglioside-induced differentiation-associated protein 1 (GDAP1) cause two types of CMT, demyelinating CMT4A and axonal CMT2K. The GDAP1-linked CMT genotypes are mainly missense point mutations. Despite clinical profiling and in vivo studies on the mutations, the etiology of GDAP1-linked CMT is poorly understood. Here, we describe the biochemical and structural properties of the Finnish founding CMT2K mutation H123R as well as CMT2K-linked R120W, both of which are autosomal dominant mutations. The disease variant proteins retain close to normal structure and solution behaviour, but both present a large decrease in thermal stability. Using GDAP1 variant crystal structures, we identify a side chain interaction network between helices α3, α6, and α7, which is affected by CMT mutations, as well as a hinge in the long helix α6, which is linked to structural flexibility. Structural analysis of GDAP1 indicates that CMT may arise from disruption of specific intra- and intermolecular interaction networks, leading to alterations in GDAP1 structure and stability, and eventually, insufficient motor and sensory neuron function.
Systematic identification of conditionally folded intrinsically disordered regions by AlphaFold2
Authors: Alderson T. Reid , Pritišanac Iva , Kolarić Đesika , Moses Alan M. , Forman-Kay Julie D.
Published: February 2022

The AlphaFold Protein Structure Database contains predicted structures for millions of proteins. For the majority of human proteins that contain intrinsically disordered regions (IDRs), which do not adopt a stable structure, it is generally assumed these regions have low AlphaFold2 confidence scores that reflect low-confidence structural predictions. Here, we show that AlphaFold2 assigns confident structures to nearly 15% of human IDRs. By comparison to experimental NMR data for a subset of IDRs that are known to conditionally fold (i.e., upon binding or under other specific conditions), we find that AlphaFold2 often predicts the structure of the conditionally folded state. Based on databases of IDRs that are known to conditionally fold, we estimate that AlphaFold2 can identify conditionally folding IDRs at a precision as high as 88% at a 10% false positive rate, which is remarkable considering that conditionally folded IDR structures were minimally represented in its training data. We find that human disease mutations are nearly 5-fold enriched in conditionally folded IDRs over IDRs in general, and that up to 80% of IDRs in prokaryotes are predicted to conditionally fold, compared to less than 20% of eukaryotic IDRs. These results indicate that a large majority of IDRs in the proteomes of human and other eukaryotes function in the absence of conditional folding, but the regions that do acquire folds are more sensitive to mutations. We emphasize that the AlphaFold2 predictions do not reveal functionally relevant structural plasticity within IDRs and cannot offer realistic ensemble representations of conditionally folded IDRs.

Significance Statement

AlphaFold2 and other machine learning-based methods can accurately predict the structures of most proteins. However, nearly two-thirds of human proteins contain segments that are highly flexible and do not autonomously fold, otherwise known as intrinsically disordered regions (IDRs). In general, IDRs interconvert rapidly between a large number of different conformations, posing a significant problem for protein structure prediction methods that define one or a small number of stable conformations. Here, we found that AlphaFold2 can readily identify structures for a subset of IDRs that fold under certain conditions (conditional folding). We leverage AlphaFold2’s predictions of conditionally folded IDRs to quantify the extent of conditional folding across the tree of life, and to rationalize disease-causing mutations in IDRs.

Classifications: Biological Sciences; Biophysics and Computational Biology
Mechanisms of frustrated phagocytic spreading of human neutrophils on antibody-coated surfaces
Authors: Francis Emmet , Xiao Hugh , Teng Lay Heng , Heinrich Volkmar
Published: February 2022

Complex motions of immune cells are an integral part of diapedesis, chemotaxis, phagocytosis, and other vital processes. To better understand how immune cells execute such motions, we present a detailed analysis of phagocytic spreading of human neutrophils on flat surfaces functionalized with different densities of immunoglobulin G (IgG) antibodies. We visualize the cell-substrate contact region at high resolution and without labels using reflection interference contrast microscopy (RICM) and quantify how the area, shape, and position of the contact region evolves over time. We find that the likelihood of the cell commitment to spreading strongly depends on the surface density of IgG, but the rate at which the substrate-contact area of spreading cells increases does not. Validated by a theoretical companion study, our results resolve controversial notions about the mechanisms controlling cell spreading, establishing that active forces generated by the cytoskeleton rather than cell-substrate adhesion primarily drive cellular protrusion. Adhesion, on the other hand, aids phagocytic spreading by regulating the cell commitment to spreading, the maximum cell-substrate contact area, and the directional movement of the contact region.

The detailed analysis of immune-cell spreading on antibody-coated surfaces establishes that active cytoskeletal protrusion rather than passive substrate adhesion drives phagocytic spreading.
Synthetic lethality between toxic amino acids, retrograde target genes and chaperones in Saccharomyces cerevisiae
Authors: Druseikis Marina E. , Covo Shay
Published: February 2022

The toxicity of non-proteinogenic amino acids has been known for decades. Numerous reports describe their antimicrobial/anticancer potential. However, these molecules are often toxic to the host as well, therefore a synthetic lethality approach can be beneficial. Here we investigated the potential synthetic lethality between toxic amino acids, the retrograde pathway, and molecular chaperones. In Saccharomyces cerevisiae, mitochondrial retrograde (RTG) pathway activation induces transcription of RTG-target genes, which replenishes alpha- ketoglutarate and glutamate; both metabolites are required for arginine and lysine biosynthesis. We previously reported that tolerance of canavanine, a toxic arginine derivative, requires an intact RTG pathway, and low-dose canavanine exposure reduces the expression of RTG-target genes. At higher concentrations, canavanine causes protein misfolding. Here we show that in WT, low-dose thialysine exposure, a toxic lysine analog, has a similar effect as canavanine on RTG-target gene expression. To study if single amino acid deficiency and mild protein misfolding stress elicit a similar effect on RTG-target genes, we compared expression of heat shock protein (HSP) mutants grown without arginine or lysine to WT. Arginine deprivation induces RTG-target gene expression in sse2Δ, hsp78Δ, and mdj1Δ, but CIT2 and DLD3 are reduced in cpr7Δ. Lysine deprivation has the opposite effect on RTG-target gene expression in HSP mutants. Interestingly, exposure of HSP mutants to canavanine and thialysine reversed the trend of RTG-target gene expression in several cases. The RTG-target expression pattern in HSP mutants had a predictive value in canavanine sensitivity - the mutant with the lowest expression was the most sensitive - but this was not the case for thialysine. Some, but not all, mutants in RTG-target genes are sensitive to canavanine and thialysine; additional mutation in a certain HSP can exacerbate this sensitivity. Overall, we show that inhibiting molecular chaperones, RTG-target genes, or both can sensitize cells to low doses of toxic amino acids.
Detection of specific uncultured bacteriophages by fluorescence in situ hybridisation in pig microbiome
Authors: Ostenfeld Line Jensen , Munk Patrick , Aarestrup Frank M. , Otani Saria
Published: February 2022

Microbial communities have huge impacts on their ecosystems and local environments spanning from marine and soil communities to the mammalian gut. Bacteriophages (phages) are important drivers of population control and diversity in the community, but our understanding of complex microbial communities is halted by biased detection techniques. Metagenomics have provided a method of novel phage discovery independent of in vitro culturing techniques and have revealed a large proportion of understudied phages. Here, five large phage genomes, that were previously assembled in silico from pig faecal metagenomes, are detected and observed directly in their natural environment using a modified phageFISH approach, and combined with methods to decrease bias against large phages. These phages are uncultured with unknown hosts. The specific phages were detected by PCR and fluorescent in situ hybridisation in their original faecal samples as well as across other faecal samples. Co-localisation of bacterial signals and phage signals allowed detection of the different stages of phage life cycle. All phages displayed examples of early infection, advanced infection, burst, and free phages. To our knowledge, this is the first detection of jumbophages in faeces, which were investigated independently of culture, host identification, and size, and based solely on the genome sequence. This approach opens up opportunities for characterisation of novel in silico phages in vivo from a broad range of gut microbiomes.
With a pinch of salt: metagenomic insights into Namib Desert salt pan microbial mats and halites reveal functionally adapted and competitive communities
Authors: Martínez-Alvarez Laura , Ramond Jean-Baptiste , Vikram Surendra , León-Sobrino Carlos , Maggs-Kölling Gillian , Cowan Don A.
Published: February 2022

Salt pans or playas, which are saline-rich springs surrounded by halite evaporates in arid environments, have played an essential role in landscape erosion during the formation of the Namib Desert and are numerous in its central region. In this study, we used shotgun metagenomics to investigate the phylogenetic and functional capacities of the microbial communities from two salt pans (namely, Eisefeld and Hosabes) located in the Central Namib Desert, located in Southwest Africa. We studied the source and sink sediment mat communities of the saline streams, as well as those from two halites (crystallized structures on the stream margins). The microbial assemblages and potential functions were distinct in both niches. Independently from their localization (Eisfeld vs Hosabes and source vs sink), the sediment mat communities were dominated by members of theAlpha-andGamma-proteobacteriaclasses, while halites were Archaea-dominated and also contained high abundances of the extremely halophilic bacteriumSalinibactersp. (phylumBacteroidota). Photoheterotrophy and chemoheterotrophy were the principal lifestyles in both niches, with halite communities having a reduced diversity of metabolic pathways. Intense microbial-virus interactions in both niches were implied by the widespread detection of CRISPR-Cas defense systems. We identified a putatively novel clade of type II CRISPR-Cas systems, as well as novel candidate viral lineages of the class Caudoviricetes and of Halobacteriales-infecting haloviruses. Putative gene transfer agent-like sequences within theAlphaproteobacteriawere identified in the sediment mat communities. These horizontal gene transfer elements have the potential to drive genome plasticity and evolution of theAlphaproteobacteriain the Namib Desert salt pan microbiomes.

Importance

The hyperarid Namib Desert is one of the oldest deserts on Earth. It contains multiple clusters of playas which are saline-rich springs surrounded by halite evaporites. Playas are of great ecological importance and their indigenous (poly)extremophilic microorganisms are potentially involved in the precipitation of minerals such as carbonates and sulfates and have been of great biotechnological importance. While there has been a considerable amount of microbial ecology research preformed on various Namib Desert edaphic microbiomes, little is known about the microbial communities inhabiting its multiple playas. In this work, we therefore provide a comprehensive taxonomic and functional potential characterization of the microbial, including viral, communities of sediment mats and halites from two distant Namib Desert, contributing towards a better understanding of the ecology of this biome.
Reproducibility metrics for CRISPR screens
Authors: Billmann Maximilian , Ward Henry N. , Aregger Michael , Costanzo Michael , Andrews Brenda J. , Boone Charles , Moffat Jason , Myers Chad L.
Published: February 2022

CRISPR screens are used extensively to systematically interrogate the phenotype-to-genotype problem. In contrast to early CRISPR screens, which defined core cell fitness genes, most current efforts now aim to identify context-specific phenotypes that differentiate a cell line, genetic background or condition of interest, such as a drug treatment. While CRISPR-related technologies have shown great promise and a fast pace of innovation, a better understanding of standards and methods for quality assessment of CRISPR screen results is crucial to guide technology development and application. Specifically, many commonly used metrics for quantifying screen quality do not accurately measure the reproducibility of context-specific hits. We highlight the importance of reporting reproducibility statistics that directly relate to the purpose of the screen and suggest the use of metrics that are sensitive to context-specific signal.
Cohesin mutation sensitizes cancer cells to anti-PD-1 therapy through endogenous retrovirus-mediated PD-L1 upregulation
Authors: Han Yumin , Peng Fangfei , Chang Yunqi , Liu Tingting , Shen Jiayan , Chen Zizhuo , Dong Qian , Zhou Ping , Jiang Feng , Xiang Honggang , Zhu Hong , Qing Chen , Kong Xiangyin , Ding Jian , Lang Jing-Yu
Published: February 2022

Immune checkpoint therapy shows impressive and durable clinical responses in cancer patients, but the genetic determinants that enable cancer cells to respond to anti-PD-1 therapy are still elusive. Herein, we identified thatNIPBLdeficiency promotes endogenous retrovirus (ERV) expression in tumour cells, which in turn inactivates CD8+ tumour-infiltrating lymphocytes (TILs) via the PD-L1/PD-1 inhibitory checkpoint pathway. Mechanistically,NIPBLdeficiency impairs DNMT1 transcription, preventing DNMT1 from suppressing ERV expression in tumour cells; ERVs stimulate PD-L1 expression by inducing the STAT2-IRF9 complex, a downstream event of double-stranded RNA (dsRNA)-MAVS-IRF3 signalling, and thereby suppress CD8 TIL-mediated immunity. An anti-PD-1 monoclonal antibody achieved remarkable therapeutic effects inNipbl-deficient syngeneic tumour models and improved host survival by eliciting an antitumour memory immune response. Cancer patients harbouring mutations of cohesin subunits and regulators plus DNMT1 had significantly better responses to anti-PD-1 therapy than their non-mutated counterparts did. Our study reveals a novel mechanism by which cohesin complex deregulation stimulates ERV expression by impairing DNMT1 expression and fosters an immunosuppressive tumour microenvironment by activating the PD-L1/PD-1 inhibitory checkpoint.
Structural and Functional Characterization of Novel Phosphotyrosine Phosphatase Protein from Drosophila Melanogaster (Pupal Retina)
Authors: Naz Rubina , Iqbal Anwar , Saeed Asma , Khan Alamzeb , Shutaywi Meshal , Cioca Adriana Lavinia , Vrinceanu Narcisa
Published: February 2022

A novel pair of protein Tyrosine Phosphatases in Drosophila Melanogaster (pupal retina) has been identified. Phosphotyrosyl protein phosphatases (PTPs) are structurally diverse enzymes increasingly recognized having fundamental role in cellular processes including effects on metabolism, cell proliferation and differentiation. This study presents comparative homology modeling of low molecular weight phosphotyrosine protein phosphatase (PTPs) from Drosophila melanogaster (Dr-PTPs) and their complexation with potent inhibitor HEPES. The 3D structure was predicted based on sequence homology with bovine heart low molecular weight PTPs (Bh-PTPs). The sequence homology is approximately 50% identical to each other and to low molecular weight protein tyrosine phosphatases (PTPs) in other species. Comparison of the 3D structures of Bh-PTPs and Dr-PTPs (primo-2) reveals a remarkable similarity having a four stranded central parallel β sheet with flanking α helices on both sides, showing two right-handed β-α-β motifs. The inhibitor shows similar binding features as seen in other PTPs. The study also highlights the key catalytic residues important for target recognition and PTPs activation. The structure guided studies of both proteins clearly reveal a common mechanism of action, inhibitor binding at the active site and will expected to contribute towards the basic understanding of functional association of this enzyme with other molecules.
Alteration in long noncoding RNAs in response to oxidative stress and ladostigil in SH-SY5Y cells
Authors: Zohar Keren , Giladi Eliran , Eliyahu Tsiona , Linial Michal
Published: February 2022

Microglia activation causes neuroinflammation, which is a hallmark of neurodegenerative disorders, brain injury, and aging. Ladostigil, a bifunctional reagent with antioxidant and anti-inflammatory properties, reduced microglial activation and enhanced brain functioning in elderly rats. In this study, we studied SH-SY5Y, a human neuroblastoma cell line, and tested viability in the presence of hydrogen peroxide and Sin1 (3-morpholinosydnonimine), which generates reactive oxygen and nitrogen species (ROS/RNS). Both stressors caused significant apoptosis and necrotic cell death that was attenuated by ladostigil. Our results from RNA-seq experiments show that long non-coding RNAs (lncRNAs) account for 30% of all transcripts in SH-SY5Y cells treated with Sin1 for 24 hours. Altogether, we identify 94 differently expressed lncRNAs in the presence of Sin1, including MALAT1, a highly expressed lncRNA with anti-inflammatory and anti-apoptotic functions. Additional activities of Sin-1 upregulated lncRNAs include redox homeostasis (e.g., MIAT, GABPB1-AS1), energy metabolism (HAND2-AS1), and neurodegeneration (e.g., MIAT, GABPB1-AS1, NEAT1). Four lncRNAs implicated as enhancers were significantly upregulated in cells exposed to Sin1 and ladostigil. Finally, we show that H2O2 and Sin1 increased the expression of DJ-1, a redox sensor and modulator of Nrf2 (nuclear factor erythroid 2– related factor 2). Nrf2 (NFE2L2 gene) is a major transcription factor regulating antioxidant genes. In the presence of ladostigil, DJ-1 expression is restored to its baseline. The mechanisms governing SH-SY5Y cell survival and homeostasis are highlighted by the beneficial role of ladostigil in the crosstalk involving Nrf2, antioxidant transcription factor DJ-1, and lncRNAs. Stress-dependent induction of lncRNAs represents an underappreciated regulatory level that contributes to cellular homeostasis and the capacity of SH-SY5Y to cope with oxidative stress.
Use of sugarcane mosaic virus for virus-induced gene silencing in maize
Authors: Chung Seung Ho , Zhang Shudi , Song Hojun , Whitham Steven A. , Jander Georg
Published: February 2022

Previously, sugarcane mosaic virus (SCMV) was developed as a vector for transient expression of heterologous genes inZea mays(maize). Here we show that SCMV can also be applied for virus-induced gene silencing (VIGS) of endogenous maize genes. Comparison of sense and antisense VIGS constructs targeting maizePDS(phytoene desaturase) showed that antisense constructs resulted in a greater reduction in gene expression. In a time course of gene expression after infection with VIGS constructs targetingPDS, Les22(Lesion mimic 22), andIj1(Iodent japonica1), efficient expression silencing was observed two, three, and four weeks after infection with SCMV. However, at week five, expression ofLes22andIj1was no longer significantly reduced compared to control plants. The defense signaling molecule jasmonate-isoleucine (JA-Ile) can be inactivated by 12C-hydroxylation and hydrolysis, and knockout of these genes leads to increased herbivore resistance. JA-Ile hydroxylases and hydrolases have been investigated in Arabidopsis, rice, andNicotiana attenuata. To determine whether the maize homologs of these genes function in plant defense, we silenced expression ofZmCYP94B1(predicted JA-Ile hydroxylase) andZmJIH1(predicted JA-Ile hydrolase) by VIGS with SCMV. AlthoughZmCYP94B1andZmJIH1geneexpression silencing increased resistance toSpodoptera frugiperda(fall armyworm),Schistocerca americana(American birdwing grasshopper), andRhopalosiphum maidis(corn leaf aphid), there was no additive effect from silencing the expression of both genes. Further work will be required to determine the more precise functions of these enzymes in regulating maize defenses.
Pre-existing chromosomal polymorphisms in pathogenic E. coli potentiate the evolution of antibiotic resistance by MCR-1 plasmid acquisition
Authors: Jangir Pramod K. , Yang Qiue , Shaw Liam P. , Caballero Julio Diaz , Ogunlana Lois , Wheatley Rachel M. , Walsh Timothy R. , MacLean Craig
Published: February 2022

Bacterial pathogens show high levels of standing genetic diversity, but the influence of this diversity on the evolution of antibiotic resistance remains unclear. Here we address this problem in the context of colistin, a ‘last line of defense’ antibiotic. Using experimental evolution, we show that a plasmid carrying the MCR-1 colistin resistance gene dramatically increases the ability of E. coli populations to evolve high-level colistin resistance by acquiring mutations in lpxC, an essential chromosomal gene involved in lipopolysaccharide biosynthesis. Crucially, lpxC mutations increase colistin resistance in the presence of the MCR-1 gene, but decrease the resistance of wild-type cells, revealing positive sign epistasis for antibiotic resistance. Analysis of public genomic datasets shows that lpxC polymorphisms are common in pathogenic E. coli carrying MCR-1, highlighting the clinical relevance of this interaction. Importantly, lpxC diversity is high in pathogenic E. coli from regions with no history of MCR-1 acquisition, suggesting that pre-existing lpxC polymorphisms have potentiated the evolution of high-level colistin resistance by MCR-1 acquisition. More broadly, these findings highlight the importance of standing genetic variation and plasmid/chromosomal interactions in the evolutionary dynamics of antibiotic resistance.
Wasted pumpkins: a real Halloween horror story
Authors: Surucu-Balci Ebru , Berberoglu Bercim
Published: February 2022

Purpose

This study aims to understand pumpkin waste awareness among people by converting unstructured quantitative data into insightful information to understand the public's awareness of pumpkin waste during Halloween.

Design/methodology/approach

To fulfil the study's purpose, we extracted Halloween-related tweets by employing #halloween and #pumpkin hashtags and then investigated Halloween-related tweets via a topic modelling approach, specifically Latent Dirichlet Allocation. The tweets were collected from the UK between October 25th and November 7th, 2020. The analysis was completed with 11,744 tweets.

Findings

The topic modelling results revealed that people are aware of the pumpkin waste during Halloween. Furthermore, people tweet to reduce pumpkin waste by sharing recipes for using leftover pumpkins.

Originality/value

The study offers a novel approach to convert social media data into meaningful knowledge about public perception of food waste. This paper contributes to food waste literature by revealing people's awareness of pumpkin waste during Halloween using social media analytics. Norm activation model and communicative ecology theory are used for the theoretical underpinning of topic modelling.
Exploring the drivers of energetic seniors’ social reengagement intention: evidence from China’s Pearl River Delta region
Authors: Wei Chiou-Fong , Yu Jing , Ding Gwo-Hau , Wei Kai-Ting
Published: February 2022

Purpose

After retirement, energetic seniors still can contribute to social development. This paper aims to explore the structural relationship between energetic seniors’ social reengagement intention (SRI) and its five drivers. The antecedents of energetic seniors’ SRI were identified through extensive literature (including social marketing) review and focus group interviews.

Design/methodology/approach

Data was collected from Pearl River Delta region of Guangdong Province, China. The proposed model was tested using partial least squares structural equation modeling with a community-based valid sample size of 750 energetic seniors (ages 60+).

Findings

Results indicate that energetic seniors’ SRI is directly determined by their perceived social value and knowledge sharing intention, which are, in turn, directly determined by their individual social capital, social achievement motivation and perceived social risk.

Originality/value

To the best of the authors’ knowledge, this is the first study to provide a new approach toward reengagement social development for energetic seniors. The discussion provides implications and managerial new insights for research and practice of population aging.
Buying local food is not a question of attitude: an analysis of benefits and limitations
Authors: Peral-Peral Begoña , Arenas Gaitán Jorge , Reina-Arroyo Jesús
Published: February 2022

Purpose

This paper aims to explore the shopping intention of local products. Using the theory of planned behavior model, the authors study the effect of egoistic and altruistic benefits and the influence of contextual limitations and people’s own limitations on the intention to buy local fresh fruits and vegetables.

Methodology

This paper uses a sample of 1,200 consumers of a south European city to test the model using a structural equation modeling technique with partial least squares.

Findings

Although egoistic benefits have a direct effect on the shopping intention, altruistic benefits have a much higher total effect. Surprisingly, attitude does not influence shopping intention. This paper provides elements that favor the consumption of local products from a more global, social and sustainable perspective.

Value

This paper provides new empirical evidence on the influence of perceived benefits and personal limitations on local food consumption.
Soil heterogeneity tends to promote the growth of naturalized aliens when competing with native plant communities
Authors: Wei Guan‐Wen , van Kleunen Mark
Published: February 2022

Elton's diversity‐invasibility hypothesis predicts that diverse communities are more resistant against alien invaders. However, observational studies frequently find positive relationships between the numbers of alien and native species. It has been suggested, but rarely tested, that environmental heterogeneity may cause such positive relationships.

Here, we experimentally tested the effects of soil heterogeneity and diversity (species richness) on the invasibility of native communities. We first filled mesocosm pots with either a heterogeneous soil, consisting of one patch of sand, one patch of peat and one patch of an equal mixture of both substrates, or a homogeneous soil, consisting of the mixture only. Then, we planted those pots with 29 native communities consisting of one, four or eight species, and invaded them with populations of four individuals of one of five alien species.

In the heterogeneous soils, individual alien plants benefited more strongly from the resource‐rich peat soil than the native communities did. Moreover, in the mixture soil of the heterogeneous treatment, individual alien plant over‐proportionally produced more biomass than in the mixture soil of the homogeneous treatment. Consequently, the populations of naturalized alien plants in each pot benefited from heterogeneous soil conditions, and this tended to be particularly the case when a native community was present. The native communities did not respond to soil heterogeneity, but they had a negative effect on the naturalized plants, irrespective of their diversity.

Synthesis. Our results indicate that soil heterogeneity might alleviate the competitive effects of native communities on the alien invaders, as the latter took more advantage of the high resource patches than the natives did. The beneficial effect of heterogeneity on invasion success could thus explain why observational studies usually find positive relationships between the numbers of alien and native species.
Recovery of DNA from SERATECⓇ immunochromatographic PSA and saliva test strips
Authors: Conte Jillian , Ruddy Ashley , Domonoski Lindsey , Shanahan Aubrey , Daley Natalie , McDevitt Colleen , Roca Gabriela
Published: February 2022

There is an increased use of immunochromatographic test strips to presumptively identify bodily fluids of forensic interest, such as blood, semen, and saliva. Commonly, forensic samples are of low quantities. In the practice of conserving limited samples, it would be ideal to be able to recover the genetic material deposited on these testing membranes. This research aimed to determine whether DNA could be extracted from semen and saliva test strips, which part of the test strip is best to use, and to assess the quality of the DNA recovered. Semen and saliva samples were deposited on SERATEC® PSA Semiquant and Amylase Tests and analyzed. The testing membrane was then removed from the cassette and DNA extraction methods (forensicGEM Universal, forensicGEM Sperm, QIAamp® DNA Mini kit, Monarch® Nucleic Acid Purification kit, and organic extraction) were performed. Quality was evaluated by qPCR and STR analysis. DNA from semen was best extracted using the Monarch® Nucleic Acid Purification kit, while saliva was best extracted using the forensicGEM or QIAamp kits. No significant differences were observed between collection of the sample well pad and testing strip, thus use of the entire strip is encouraged. DNA from semen and saliva was quantifiable with a 1:1000 dilution. DNA quality analysis by qPCR showed that there is no difference in the DNA quality following elution from the test strip. However, degradation was noted in saliva samples and some semen samples by STR analysis. Scientists are encouraged to consider processed test strips for DNA profiling to preserve evidence.
A deep Generative Artificial Intelligence system to predict species coexistence patterns
Authors: Hirn Johannes , García José Enrique , Montesinos‐Navarro Alicia , Sánchez‐Martín Ricardo , Sanz Veronica , Verdú Miguel
Published: February 2022

Predicting coexistence patterns is a current challenge to understand diversity maintenance, especially in rich communities where these patterns' complexity is magnified through indirect interactions that prevent their approximation with classical experimental approaches.

We explore cutting‐edge Machine Learning techniques called Generative Artificial Intelligence (GenAI) to predict species coexistence patterns in vegetation patches, training generative adversarial networks (GAN) and variational AutoEncoders (VAE) that are then used to unravel some of the mechanisms behind community assemblage.

The GAN accurately reproduces real patches' species composition and plant species' affinity to different soil types, and the VAE also reaches a high level of accuracy, above 99%. Using the artificially generated patches, we found that high‐order interactions tend to suppress the positive effects of low‐order interactions. Finally, by reconstructing successional trajectories, we could identify the pioneer species with larger potential to generate a high diversity of distinct patches in terms of species composition.

Understanding the complexity of species coexistence patterns in diverse ecological communities requires new approaches beyond heuristic rules. Generative Artificial Intelligence can be a powerful tool to this end as it allows to overcome the inherent dimensionality of this challenge.
Microglial cathepsin E plays a role in neuroinflammation and amyloid β production in Alzheimer’s disease
Authors: Xie Zhen , Meng Jie , Kong Wei , Wu Zhou , Lan Fei , Narengaowa  , Hayashi Yoshinori , Yang Qinghu , Bai Zhantao , Nakanishi Hiroshi , Qing Hong , Ni Junjun
Published: February 2022

Regulation of neuroinflammation and β‐amyloid (Aβ) production are critical factors in the pathogenesis of Alzheimer's disease (AD). Cathepsin E (CatE), an aspartic protease, is widely studied as an inducer of growth arrest and apoptosis in several types of cancer cells. However, the function of CatE in AD is unknown. In this study, we demonstrated that the ablation of CatE in human amyloid precursor protein knock‐in mice, called APPNL−G−F mice, significantly reduced Aβ accumulation, neuroinflammation, and cognitive impairments. Mechanistically, microglial CatE is involved in the secretion of soluble TNF‐related apoptosis‐inducing ligand, which plays an important role in microglia‐mediated NF‐κB‐dependent neuroinflammation and neuronal Aβ production by beta‐site APP cleaving enzyme 1. Furthermore, cannula‐delivered CatE inhibitors improved memory function and reduced Aβ accumulation and neuroinflammation in AD mice. Our findings reveal that CatE as a modulator of microglial activation and neurodegeneration in AD and suggest CatE as a therapeutic target for AD by targeting neuroinflammation and Aβ pathology.
Impact of risk‐based sexually transmitted infection screening in the emergency department
Authors: Ahmad Fahd A. , Fischer Kayleigh , Gu Hongjie , Bailey Thomas C. , Jeffe Donna B. , Carpenter Christopher R. , Payne Philip R. O.
Published: February 2022

Objectives

Sexually transmitted infections (STIs), including chlamydia, gonorrhea, and human immunodeficiency virus (HIV) pose a significant health burden in adolescents. Many adolescents receiving care in the emergency department (ED) are in need of testing, regardless of their chief complaint. Our objective was to determine whether an electronic, risk‐based STI screening program in our ED was associated with an increase in STI testing among at‐risk adolescents.

Methods

We conducted a retrospective cohort analysis of patient outcomes in our pediatric ED after integrating an Audio‐enhanced Computer‐Assisted Self‐Interview (ACASI) as standard of care. It obtained a focused sexual history and generated STI testing recommendations. Patient answers and testing recommendations were integrated in real‐time into the electronic health record. Patients who tested positive received treatment according to our standard‐of‐care practices.

All patients 15–21 years of age were asked to complete this on an opt‐out basis, regardless of the reason for their ED visit. Exclusions included those unable to independently use a tablet, severe illness, sexual assault, or non‐English speaking. Our primary outcome was to describe STI‐testing recommendations and test results among ACASI participants. We also compared STI testing between ACASI participants and those who were eligible but did not use it.

Results

In the first 13 months, 28.9% (1788/6194) of eligible adolescents completed the ACASI and 44.2% (321/790) accepted recommended STI testing. The mean age of participants was 16.6 ± 1.3 years, with 65.4% (1169) being female.

Gonorrhea/chlamydia testing was significantly higher among participants vs. non‐participants (20.1% [359/1788] vs 4.8% [212/4406]; p < 0.0001). The proportion of positive STI tests was similar between the two groups: 24.8% (89/359) vs. 24.5% (52/212; p = 0.94) were positive for chlamydia and/or gonorrhea, while 0.6% (2/354) participants vs. 0% non‐participants (p > 0.99) were positive for HIV. Among participants whose chief complaints were unlikely to be related to STIs but accepted recommended testing, 20.9% (37/177) were positive for gonorrhea or chlamydia.

Conclusions

Our program facilitated STI testing in the ED and identified many adolescents with STIs, even when their ED complaint was for unrelated reasons. More rigorous implementation is needed to determine the impact of deployment of ACASI to all eligible adolescents and addressing barriers to accepting STI testing recommendations.
Grabbing hand or financial constraint mitigation effect? A reexamination of the relationship between institutional development and cash holdings
Authors: Zhang Xiang , Zhang Zongyi , Zhou Han
Published: February 2022

This study reexamines the impact of institutional development on corporate cash holdings. Our findings confirm that institutional development has a negative effect on corporate cash holdings, which may be partially explained by the financial constraint mitigation effect of institutional development. Our empirical evidence also shows that the corruption index, used as a proxy for the grabbing hand effect, does not mediate the negative effect of institutional development on corporate cash holdings. Furthermore, the impact of institutional development on corporate cash holdings is not significant for large firms and state‐owned enterprises. These results are robust to different measures of cash holdings.
Treatment of pemphigus in Australia: Aligning current practises with global recommendations
Authors: Somerville Erin , Gebauer Kurt , Mclean‐Tooke Andrew
Published: February 2022

Pemphigus encompasses of a group of rare, and often severe, intraepidermal bullous dermatoses that are mediated by autoantibodies that act against adhesion proteins of the desmosome. The current international consensus is that the use of intravenous CD20 inhibitors should be first‐line in the management of moderate‐to‐severe cases of pemphigus, however Australia is yet to adopt this. Systemic corticosteroids, combined with conventional corticosteroid‐sparing immunosuppressive agents such as azathioprine, mycophenolate mofetil, cyclosporin and methotrexate is still recommended as first‐line therapy in Australia despite overwhelming evidence that combining rituximab with a rapid corticosteroid tapering regime is more effective in the treatment of moderate‐to‐severe pemphigus, and leads to fewer severe adverse effects. We propose a therapeutic approach that echoes the international consensus and recommend that rituximab, an anti‐CD20 monoclonal antibody, be listed in the formularies of Australian Public Hospitals and on the Pharmaceutical Benefits Scheme for use in moderate to severe pemphigus.
Electrophysiological, structural, and functional disorders in patients with inflammatory cardiomyopathy secondary to inflammatory myopathy
Authors: Liu Yingxian , Hsu Jeffrey , Liu Xiaohang , Lin Xue , Zhu Yanlin , Jia Fuwei , Wu Wei , Chen Wei , Wang Qian , Fang Ligang
Published: February 2022

Background

Inflammatory cardiomyopathy (IC) is a syndrome with chronic myocarditis and cardiac remodeling. This study aimed to explore predicting factors of adverse outcomes in patients with IC secondary to idiopathic inflammatory myopathy (IIM‐IC).

Methods

By means of a single‐center retrospective study, 52 patients with IIM‐IC at Peking Union Medical College Hospital were identified from January 1999 to June 2019. Electrocardiogram and echocardiography data were analyzed for the primary outcome (defined as all‐cause death) and secondary outcomes (defined as re‐hospitalization of heart failure and all‐cause death), using regression and survival analysis.

Results

The prevalence of atrial fibrillation, ventricular tachycardia, Q‐wave abnormality, left ventricular conduction abnormalities, and reduced left ventricular ejection fraction (LVEF) (≤40%) were 65.4%, 67.3%, 67.3%, 61.6%, and 50.5%. After a median follow‐up of 2 years (IQR 0.8–3.0), 26 cases were readmitted due to heart failure. Twenty‐two deaths were recorded, including 20 cardiogenic deaths. Among the patients with adverse events, the incidence of poor R‐wave progression, low‐voltage of the limb leads, Q‐wave abnormality, QRS duration >130 ms, left ventricular enlargement, and impaired systolic function were higher. Kaplan–Meier analysis showed that Q‐wave abnormality, limb leads low‐voltage, LVEF ≤40%, and left ventricular end‐diastolic dimension >60 mm were correlated with shorter survival. However, multivariate Cox regression analysis revealed that only Q‐wave abnormality (HR = 12.315) and LVEF ≤40% (HR = 5.616) were independent risk factors for all‐cause death.

Conclusion

Q‐wave abnormality and reduced LVEF are predictive of poor prognosis in patients with IIM‐IC.
Influence of extracorporeal cytokine adsorption on hemodynamics in severe acute pancreatitis: Results of the matched cohort pancreatitis cytosorbents inflammatory cytokine removal (PACIFIC) study
Authors: Rasch Sebastian , Sancak Sengül , Erber Johanna , Wießner Johannes , Schulz Dominik , Huberle Christina , Algül Hana , Schmid Roland M. , Lahmer Tobias
Published: February 2022

Background

Outcome of severe acute pancreatitis (SAP) highly depends on the degree of systemic inflammation and organ failure. Although treatment approaches targeting the inflammatory cascade have failed in pancreatitis, recent studies suggest that extracorporeal cytokine adsorption effectively reduces concentrations of pro‐inflammatory cytokines and potentially improves the outcome of sepsis.

Methods

Sixteen patients with SAP, presenting within 7 days upon onset of pain, an APACHE‐II score of ≥10 and ≥1 marker of poor prognosis, received 2 consecutive 24‐h treatments with CytoSorb® extracorporeal cytokine adsorption (intervention group). Hemodynamics, organ failure, and mortality were compared with an APACHE‐II score‐matched retrospective control group of 32 patients.

Results

The primary objective (20% decrease in the vasopressor dependency index or 20% increase in the cardiac index) was reached in 68.8% of the intervention and 28.1% of the control patients (p = 0.007), respectively. The cytokine adsorption significantly reduced IL‐6 (−1998 pg/ml, p = 0.005) serum levels and resulted in stable CRP (p = 0.101) and decreased PCT (p = 0.003) levels in contrast to increased CRP (p = 0.014) and stable PCT levels (p = 0.695) in the control group. While mortality and improvement of respiratory failure were similar in both groups, renal failure significantly improved (change of KDIGO classification 72 h postcytokine adsorption [−1 vs. 0, p = 0.005]) and the SOFA score significantly decreased (day 5: −1.8 ± 2.0 vs. 1 ± 3.8, p = 0.013) in the intervention group.

Conclusion

Cytokine adsorption might be an effective treatment option to stabilize hemodynamics in SAP. It decreases levels of the pro‐inflammatory marker IL‐6 and stabilizes organ function according to serial SOFA score assessments.
Chest X‐rays are less sensitive than multiple breath washout examinations when it comes to detecting early cystic fibrosis lung disease
Authors: Svedberg Marcus , Imberg Henrik , Gustafsson Per , Brink Mela , Caisander Håkan , Lindblad Anders
Published: February 2022

Aim

Annual chest X‐ray is recommended as routine surveillance to track cystic fibrosis (CF) lung disease. The aim of this study was to investigate the clinical utility of chest X‐rays to track CF lung disease.

Methods

Children at Gothenburg's CF centre who underwent chest X‐rays, multiple breath washouts and chest computed tomography examinations between 1996 and 2016 were included in the study. Chest X‐rays were interpreted with Northern Score (NS). We compared NS to lung clearance index (LCI) and structural lung damage measured by computed tomography using a logistic regression model.

Results

A total of 75 children were included over a median period of 13 years (range: 3.0‐18.0 years). The proportion of children with abnormal NS was significantly lower than the proportion of abnormal LCI up to the age of 4 years (p < 0.05). A normal NS and a normal LCI at age 6 years were associated with a median (10‐90th percentile) total airway disease of 1.8% (0.4‐4.7%) and bronchiectasis of 0.2% (0.0‐1.5%).

Conclusion

Chest X‐rays were less sensitive than multiple breath washout examinations to detect early CF lung disease. The combined results from both methods can be used as an indicator to perform chest computed tomography less frequently.
Fewer maternal depression symptoms after the Close Collaboration with Parents intervention: Two‐year follow‐up
Authors: Ahlqvist‐Björkroth Sari , Axelin Anna , Setänen Sirkku , Huhtala Mira , Korja Riikka , Pape Bernd , Lehtonen Liisa
Published: February 2022

Aim

To test whether the implementation of the Close Collaboration with Parents intervention at a neonatal intensive care unit (NICU) decreases depression symptoms of mothers up to two years after the delivery of preterm infants.

Methods

We used a non‐equivalent two‐group design, comparing mothers of very low birthweight infants in the same NICU before (2001–2006) and after (2011–215) the intervention. The unit carried out the educational intervention (2009–2012) that was targeted at its healthcare team and aimed to improve their skills to collaborate with parents. Maternal depression symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS) six months and two years after the expected birth date of the infant.

Results

We found a median difference of 2.56 (95% CI from 1.64 to 3.48) in EPDS at the two‐year follow‐up between the pre‐intervention and post‐intervention groups, p < 0.001. Furthermore, we found no interaction between measurement time‐points and group, implying that the intervention effect on maternal depression symptoms was similar at the six‐month and two‐year time‐points.

Conclusion

The intervention seems to have long‐term preventive effects on maternal depressive symptoms. This effect is of clinical significance as prolonged maternal depression associates with adverse child outcomes.