bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of the integrative and conjugative element Tn916causes growth arrest and death of host bacteria
Authors: Bean Emily L. , McLellan Lisa K. , Grossman Alan D.
Published: April 2022

Integrative and conjugative elements (ICEs) serve as major drivers of bacterial evolution. These elements often confer some benefit to a host cell, including antibiotic resistance, metabolic capabilities, or pathogenic determinants. ICEs can also have negative impacts on their host cells. Here, we investigated the effects of the ICE (conjugative transposon) Tn916on host cells. Because Tn916is active in a relatively small subpopulation of host cells, we developed a fluorescent reporter system for monitoring activation of Tn916in single cells. We found that when active inBacillus subtilisand its natural hostEnterococcus faecalis, Tn916inhibited cell division and most cells died. We also observed these phenotypes on the population level inB. subtilisutilizing a modified version of Tn916that can be activated in the majority of cells. We identified two genes (orf17andorf16) in Tn916that were sufficient to cause host growth defects and identified a single gene,yqaR, that is found in a defective phage (skin) in theB. subtilischromosome that is required for this phenotype. However, these three genes are only partially responsible for the growth defect caused by Tn916, indicating that Tn916possesses multiple mechanisms to affect growth and viability of host cells. These results highlight the complex relationships that conjugative elements have with their host cells and the interplay between mobile genetic elements.
The behavioral signature of stepwise learning strategy and its neural correlate in the basal forebrain
Authors: Manzur Hachi E. , Vlasov Ksenia , Jhong You-Jhe , Chen Hung-Yen , Lin Shih-Chieh
Published: April 2022

Studies of associative learning have commonly focused on how rewarding outcomes are predicted by either sensory stimuli or animals’ actions. However, in many learning scenarios, reward delivery requires the occurrence of both sensory stimuli and animals’ actions in a specific order, in the form of behavioral sequences. How such behavioral sequences are learned is much less understood. Here we provide behavioral and neurophysiological evidence to show that behavioral sequences are learned using a stepwise strategy. In rats learning a new association, learning started from the behavioral event closest to the reward and sequentially incorporated earlier events. This led to the sequential refinement of reward-seeking behaviors, which was characterized by the stepwise elimination of ineffective and non-rewarded behavioral sequences. At the neuronal level, this stepwise learning process was mirrored by the sequential emergence of basal forebrain neuronal responses toward each event, which quantitatively conveyed a reward prediction error signal and promoted reward-seeking behaviors. Together, these behavioral and neural signatures revealed how behavioral sequences were learned in discrete steps and when each learning step took place.
The WalRK two-component system is essential for proper cell envelope biogenesis in Clostridioides difficile
Authors: Müh Ute , Ellermeier Craig D. , Weiss David S.
Published: April 2022

The WalR-WalK two-component regulatory system (TCS) is found in all Firmicutes, where it regulates the expression of multiple genes required for remodeling the cell envelope during growth and division. Unlike most TCSs, WalRK is essential for viability, so it has attracted interest as a potential antibiotic target. Here we used overexpression of WalR and CRISPR interference to investigate the Wal system of Clostridioides difficile, a major cause of hospital-associated diarrhea in high-income countries. We confirmed the wal operon is essential and identified morphological defects and cell lysis as the major terminal phenotypes of altered wal expression. We also used RNA-seq to identify over 150 genes whose expression changes in response to WalR levels. This gene set is enriched in cell envelope genes and includes several predicted PG hydrolases and proteins that could regulate PG hydrolase activity. A distinct feature of the C. difficile cell envelope is the presence of an S-layer and we found WalR affects expression of several genes which encode S-layer proteins. An unexpected finding was that some Wal-associated phenotypic defects were inverted in comparison to what has been reported in other Firmicutes. For example, down-regulation of Wal signaling caused C. difficile cells to become longer rather than shorter, as in Bacillus subtilis. Likewise, down-regulation of Wal rendered C. difficile more sensitive to vancomycin, whereas reduced Wal activity is linked to increased vancomycin resistance in Staphylococcus aureus.

Importance

The WalRK two-component system (TCS) is essential for coordinating synthesis and turnover of peptidoglycan in Firmicutes. Here we investigate the WalRK TCS in Clostridioides difficile, an important bacterial pathogen with an atypical cell envelope. We confirmed that WalRK is essential and regulates cell envelope biogenesis, although several of the phenotypic changes we observed were opposite to what has been reported in other Firmicutes. We also identified over 150 genes whose expression is controlled either directly or indirectly by WalR. Overall, our findings provide a foundation for future investigations of an important regulatory system and potential antibiotic target in C. difficile.
Building molecular band-pass filters via molecular sequestration
Authors: Zhang Yichi , Cuba Samaniego Christian , Carleton Katelyn , Qian Yili , Giordano Giulia , Franco Elisa
Published: April 2022

Engineered genetic circuits with tailored functions that mimic how cells process information in changing environments (e.g. cell fate decision, chemotaxis, immune response) have great applications in biomedicine and synthetic biology. Although there is a lot of progress toward the design of gene circuits yielding desired steady states (e.g. logic-based networks), building synthetic circuits for dynamic signal processing (e.g. filters, frequency modulation, and controllers) is still challenging. Here, we provide a model-based approach to build gene networks that can operate as band-pass filters by taking advantage of molecular sequestration. By suitably approximating the dynamics of molecular sequestration, we analyze an Incoherent Feed-Forward Loop (IFFL) and a Negative Feedback (NF) circuit and illustrate how they can achieve band-pass filter behavior. Computational analysis shows that a circuit that incorporates both IFFL and NF motifs improves the filter performance. Our approach facilitates the design of sequestration-based filters, and may support the synthesis of molecular controllers with desired specifications.
Profound phenotypic and epigenetic heterogeneity of the HIV-1 infected CD4+ T cell reservoir
Authors: Wu Vincent H. , Nguyen Son , Nordin Jayme M.L. , Joy Jaimy , Mampe Felicity , Tebas Pablo , Montaner Luis J. , Bar Katharine J. , Vella Laura A. , Betts Michael R.
Published: April 2022

Understanding the complexity of the long-lived HIV reservoir during antiretroviral therapy (ART) remains a major impediment for HIV cure research. To address this, we developed single-cell viral ASAPseq to precisely define the unperturbed peripheral blood HIV-infected memory CD4+ T cell reservoir from antiretroviral treated people living with HIV (ART-PLWH) via the presence of integrated accessible proviral DNA in concert with epigenetic and cell surface protein profiling. We identified profound reservoir heterogeneity within and between ART-PLWH, characterized by novel and known surface markers within total and individual memory CD4+ T cell subsets. We further uncovered novel epigenetic profiles and transcription factor motifs enriched in HIV-infected cells that suggest infected cells with accessible provirus, irrespective of reservoir distribution, are poised for reactivation during ART treatment. Together, our findings reveal the extensive inter- and intrapersonal cellular heterogeneity of the HIV reservoir, and establish an initial multiomic atlas to develop targeted reservoir elimination strategies.
Cotranslational folding and assembly of the dimeric E. coli inner membrane protein EmrE
Authors: Mermans Daphne , Nicolaus Felix , Fleisch Klara , von Heijne Gunnar
Published: April 2022

In recent years, it has become clear that many homo- and heterodimeric cytoplasmic proteins in both prokaryotic and eukaryotic cells start to dimerize cotranslationally, i.e., while at least one of the two chains is still attached to the ribosome. Whether this is possible also for integral membrane proteins is unknown, however. Here, we apply Force Profile Analysis (FPA) – a method where a translational arrest peptide (AP) engineered into the polypeptide chain is used to detect force generated on the nascent chain during membrane insertion – to demonstrate cotranslational interactions between a fully membrane-inserted monomer and a nascent, ribosome-tethered monomer of the E. coli inner membrane protein EmrE. Similar cotranslational interactions are also seen when the two monomers are fused into a single polypeptide. Further, we uncover an apparent intrachain interaction between E14 in TMH1 and S64 in TMH3 that forms at a precise nascent chain length during cotranslational membrane insertion of an EmrE monomer. Like soluble proteins, inner membrane proteins can thus both start to fold and start to dimerize during the cotranslational membrane-insertion process.

Significance statement

Many water-soluble proteins are known to fold and even dimerize cotranslationally, i.e., when still attached to the ribosome. Here, we show that an E. coli inner membrane protein can also start to fold and dimerize cotranslationally, establishing the generality of these cotranslational maturation processes.
Control of pancreatic islet function and glucose homeostasis by a novel microexon program misregulated in type 2 diabetes
Authors: Juan-Mateu Jonàs , Bajew Simon , Miret-Cuesta Marta , Íñiguez Luis P. , López-Pascual Amaya , Bonnal Sophie , Atla Goutham , Bonàs-Guarch Sílvia , Ferrer Jorge , Valcárcel Juan , Irimia Manuel
Published: April 2022

Pancreatic islets control glucose homeostasis by the balanced secretion of insulin and other hormones, and their abnormal function causes diabetes or hypoglycemia. Here, we uncover a conserved program of alternative microexons included in mRNAs of islet cells, particularly in genes involved in vesicle transport and exocytosis. Islet microexons (IsletMICs) are regulated by the RNA binding proteinSRRM3and represent a subset of the larger neural program that are particularly sensitive to the levels of this regulator. BothSRRM3and IsletMICs are induced by elevated glucose levels, and depletion ofSRRM3in beta cell lines and mouse islets, or repression of particular IsletMICs using antisense oligonucleotides, leads to inappropriate insulin secretion. Consistently,SRRM3mutant mice display defects in islet cell identity and function, leading to hyperinsulinemic hypoglycemia. Importantly, human genetic variants that influenceSRRM3expression and IsletMIC inclusion in islets are associated with fasting glucose variation and type 2 diabetes risk.
The optimal strategy of incompatible insect technique (IIT) using Wolbachia to control Malaria
Authors: Matsufuji Taiga , Seirin-Lee Sungrim
Published: April 2022

For decades, techniques to control vector population with low environmental impact have been widely explored in both field and theoretical studies. The incompatible insect method (IIT) using Wolbachia, based on cytoplasmic incompatibility, is a technique that Wolbachia-infected male mosquitoes are incapable of producing viable offspring after mating with wildtype female mosquitoes. While the IIT method experimentally ensured its effectiveness in several field works, the failure of female mosquito population control owing to the accidental contamination of Wolbachia-infected female mosquitoes has been a concern and an obstacle in implementing the IIT method in nature. In this study, we developed a population-based IIT mathematical model using cytoplasmic incompatibility and evaluated the effectiveness of the IIT method in scenarios where contamination was present or absent. In addition, by extending the model to assess the disease infection status of the human population with malaria, we evaluated the optimal release strategy and cost for successful disease control. Our study proves that IIT could be a promising method to control mosquito-borne diseases without perfect eradication of vector mosquito population regardless of contamination.
FCHO controls AP2’s critical endocytic roles through a PtdIns4,5P2 membrane-dependent switch
Authors: Zaccai Nathan R. , Kadlecova Zuzana , Dickson Veronica Kane , Korobchevskaya Kseniya , Kamenicky Jan , Kovtun Oleksiy , Umasankar Perunthottathu K. , Wrobel Antoni G. , Kaufman Jonathan G.G. , Gray Sally , Qu Kun , Evans Philip R. , Fritzsche Marco , Sroubek Filip , Höning Stefan , Briggs John A.G. , Kelly Bernard T. , Owen David J. , Traub Linton M.
Published: April 2022

Clathrin-mediated endocytosis (CME) is the main mechanism by which mammalian cells control their cell surface proteome. Proper operation of the pivotal CME cargo-adaptor AP2 requires membrane-localised FCHO. Here, live-cell eTIRF-SIM shows that FCHO marks sites of clathrin- coated pit (CCP) initiation, which mature into uniform sized CCPs comprising a central patch of AP2 and clathrin corralled by an FCHO/Eps15 ring. We dissect the network of interactions between the FCHO interdomain-linker and AP2, which concentrates, orients, tethers and partially destabilizes closed AP2 at the plasma membrane. AP2’s subsequent membrane deposition drives its opening, which triggers FCHO displacement through steric competition with PtdIns4,5P2, clathrin, cargo and CME accessory factors. FCHO can now relocate toward a CCP’s outer edge to engage and activate further AP2s to drive CCP growth/maturation.

125 character summary

FCHO primes AP2 for CCV incorporation, a process that triggers FCHO release to enable activation/recruitment of further AP2s
AcrNET: Predicting Anti-CRISPR with Deep Learning
Authors: Li Yunxiang , Wei Yumeng , Xu Sheng , Tan Qingxiong , Zong Licheng , Wang Jiuming , Wang Yixuan , Chen Jiayang , Hong Liang , Li Yu
Published: April 2022

As an important group of proteins discovered in phages, anti-CRISPR inhibits the activity of the immune system of bacteria (i.e., CRISPR-Cas), showing great potential for gene editing and phage therapy. However, the prediction and discovery of anti-CRISPR are challenging for its high variability and fast evolution. Existing biological studies often depend on known CRISPR and anti-CRISPR pairs, which may not be practical considering the huge number of pairs in reality. Computational methods usually struggle with prediction performance. To tackle these issues, we propose a novel deep neuralnetwork foranti-CRISPR analysis (AcrNET), which achieves impressive performance. On both the cross-fold and cross-dataset validation, our method outperforms the previous state-of-the-art methods significantly. Impressively, AcrNET improves the prediction performance by at least 15% regarding the F1 score for the cross-dataset test. Moreover, AcrNET is the first computational method to predict the detailed anti-CRISPR classes, which may help illustrate the anti-CRISPR mechanism. Taking advantage of a Transformer protein language model pre-trained on 250 million protein sequences, AcrNET overcomes the data scarcity problem. Extensive experiments and analysis suggest that Transformer model feature, evolutionary feature, and local structure feature complement each other, which indicates the critical properties of anti-CRISPR proteins. Combined with AlphaFold prediction, further motif analysis and docking experiments demonstrate that AcrNET captures the evolutionarily conserved pattern and the interaction between anti-CRISPR and the target implicitly. With the impressive prediction capability, AcrNET can serve as a valuable tool for anti-CRISPR study and new anti-CRISPR discovery, with a free webserver athttps://proj.cse.cuhk.edu.hk/aihlab/AcrNET/.
Computational design and construction of an Escherichia coli strain engineered to produce a non-standard amino acid
Authors: Zomorrodi Ali R. , Hemez Colin , Arranz-Gibert Pol , Wu Terrence , Isaacs Farren J. , Segrè Daniel
Published: April 2022

Introducing heterologous pathways into host cells constitutes a promising strategy for synthesizing nonstandard amino acids (nsAAs) to enable the production of proteins with expanded chemistries. However, this strategy has proven challenging as the expression of heterologous pathways can disrupt cellular homeostasis of the host cell. Here, we sought to optimize the heterologous production of the nsAA para-aminophenylalanine (pAF) in Escherichia coli. First, we incorporated a heterologous pAF biosynthesis pathway into a genome-scale model of E. coli metabolism, and computationally identified metabolic interventions in the host’s native metabolism to improve pAF production. Next, we explored different ways of imposing these flux interventions experimentally and found that the upregulation of flux in chorismate biosynthesis pathway through the elimination of feedback inhibition mechanisms could significantly raise pAF titers (∼20 fold) while maintaining a reasonable pAF yield-growth rate trade-off. Overall, this study provides a promising strategy for the biosynthesis of nsAAs in engineered cells.
High price premiums as barriers to organic meat demand? A hedonic analysis considering species, cut and retail outlet*
Authors: Staudigel Matthias , Trubnikov Aleksej
Published: April 2022

Rigid price setting and high organic price premiums have been perceived as major purchase barriers to organic meat products. While emerging price and product differentiation have been reported for organic products in other categories, empirical evidence for the organic fresh meat market is lacking. We estimate a hedonic pricing model based on German household scanner data for fresh red meat and poultry purchases from 2012 to 2014. We derive and test for differences in organic price premiums across distribution channels, species and product type. Our results indicate significant variation in organic premiums, which range from 14 per cent for minced beef to 108 per cent for chicken breasts, and are considerably lower than previously reported estimates. We also find substantial overlaps in the distributions of conventional and organic prices for selected products. Our results suggest that high price premiums can no longer serve as the dominant explanation for low market shares of organic red meat. Marketers and policymakers may instead communicate the benefits of organic meat over conventional premium alternatives more clearly or increase the availability of organic meat.
Smartphone‐based colorimetric determination of gamma‐butyrolactone and gamma‐hydroxybutyrate in alcoholic beverage samples
Authors: Procida Anselmo , Honeychurch Kevin C.
Published: April 2022

Gamma‐hydroxybutyrate (GBH) is a popular recreational drug. Its strong sedative and amnesic effects have led to drug‐facilitated sexual assaults, poisonings, overdose, and death. As a result, legislation has restricted its availability leading to GHB, consumers switching to its pro‐drug, gamma‐butyrolactone (GBL). Consequently, there is a growing need for methods capable of their determination in complex samples such as beverages. Previous studies have shown the possibility to colorimetrically qualitatively determine both GBH and GBL by the formation of the lactone and its reaction with hydroxylamine and ferric chloride to give a purple‐colored complex. In this present investigation, we have shown the possibility of using this approach to both quantify GBL and GHB using both UV/Vis spectrometry and by the application of the camera of a smartphone to record images of the purple color developed. Via subsequent use of a downloadable free App, to extract the numerical values of the Red, Green, and Blue (RGB) color components, it was shown possible to construct a calibration curve and to quantitatively determine the concentration of the drugs present in fortified alcoholic beverage samples. It was found that by simple mathematical normalization of the RGB values the effects of camera distance and elimination could be readily overcome. Using the smartphone approach, GBL determinations on a sample of lager beer gave a mean recovery of 103% (%CV = 0.70%, n = 5) at a concentration of 0.56 mg/ml indicating the method holds promise for the determination of GBL and GHB in such samples.
Phytochemical profile of differently processed tea: A review
Authors: Wong Melody , Sirisena Sameera , Ng Ken
Published: April 2022

Fresh tea leaves (Camellia sinensis (L.) O. Kuntze) are processed by various techniques to produce different types of tea. The most common way to classify tea types is based on the similarities in processing methods resulting in the five commonly recognized tea types: white, green, oolong, black, and pu‐erh teas. The differences in the degree and nature of fermentation of tea leaves lead to different chemical changes depending on the processing method. Understanding the phytochemical profile of differently processed tea is important, as tea types classified by processing methods are currently not well defined because the chemical parameters for these tea types are still not established. Therefore, any significant characteristics found for a tea type due to processing may be helpful in defining tea types. However, the evidence on the impact of tea processing on phytochemical profile and contents in differently processed tea is currently unclear. Therefore, this review aims to examine (1) the processing techniques of white, green, oolong, black, and pu‐erh tea, (2) the impact of tea processing on tea phytochemicals, and (3) the key characteristics associated with the phytochemical profiles of differently processed tea.

Practical Application

Tea (Camellia sinensis (L.) O. Kuntz) is the most widely consumed beverage in the world. Tea consumption has been demonstrated through in‐vitro experiments and in animal and human intervention studies to exhibit potential in preventing various oxidative stress‐related chronic diseases, such as cardiovascular diseases, Alzheimer.s disease, diabetes and certain cancers. Based on the processing methods, tea is commonly categorized into white, green, oolong, black and pu‐er tea. However, there are large overlap in processing methods between some teas and, more importantly, the chemical compositions of differently processed teas are highly variable. This review aims to examine (1) how white, green, oolong, black and Pu‐erh tea are processed, (2) what are the effects of tea processing on tea phytochemicals and (3) to identify whether there are key characteristics associated to the phytochemical profiles of differently processed teas. The review will contribute to tea research in collating in one article the state of knowledge on the chemical changes and composition of the differently processed teas, and point to future direction in this area of research.
In vitro digestion effect on CCK and GLP‐1 release and antioxidant capacity of some plant‐based milk substitutes
Authors: Aly Esmat , Sánchez‐Moya Teresa , Darwish Aliaa A. , Ros‐Berruezo Gaspar , López‐Nicolás Rubén
Published: April 2022

Recently, plant‐based milk substitutes, as an emerging industry, are receiving more attention. Despite that, these dairy alternatives have not been adequately studied for their functional properties. Thus, the current research was devoted to study the satiety potential through in vitro secretion of cholecystokinin (CCK) and glucagon‐like peptide‐1 (GLP‐1), and the antioxidant capacity of these dairy alternatives after in vitro digestion. The enteroendocrine cell line, STC‐1, was used to measure satiety hormones release (CCK and GLP‐1) by enzyme‐linked immunoassay (ELISA). Also, total phenolic and flavonoid contents and antioxidant capacity (using oxygen radical absorbance capacity [ORAC], ferric reducing antioxidant power [FRAP], and 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid [ABTS] assays) were measured before and after in vitro digestion. The results demonstrated that CCK secretion was significantly (p < 0.05) higher for cow's milk (350.64 pg ml–1) as compared to plant‐based milk substitutes. Among the plant‐based milk substitutes, tiger nut milk showed the highest CCK stimulant (228.96 pg ml–1), followed by hazelnut milk (220.04 pg ml–1). Concerning GLP‐1 release, the data exhibited that spelt milk was the food with the highest induction of GLP‐1 hormone secretion, followed by cow's milk (910.17 and 876.59 pg ml–1, respectively), but without any significant differences between them. total phenolic content (TPC) values strongly increased after in vitro digestion, cow's milk and soymilk being the samples with the highest TPC values after in vitro digestion (165.76 and 153.71 mg GAE/100 ml, respectively). In line with TPC values, soymilk had the highest ORAC, ABTS, and FRAP values after in vitro digestion (25.41, 8.17, and 2.51 µmol TE/ml, respectively). Thus, these dairy alternatives could be an adequate substitute for cow's milk, according to its satiety and antioxidant capacity.

Practical Application

The first study deals with the efficacy of plant‐based milk substitutes as satiating foods. Spelt milk was the highest stimulant for GLP‐1 secretion. Tiger nut milk showed the highest CCK stimulant, followed by hazelnut milk. TPC and total antioxidant capacity increased after digestion.
Collagen peptides from Acaudina molpadioides prevent CCl4‐induced liver injury via Keap1/Nrf2‐ARE, PI3K/AKT, and MAPKs pathways
Authors: Li Jie , Li Yan , Lin Saijun , Zhao Wei , Chen Yan , Jin Huoxi
Published: April 2022

Collagen peptide from Acaudina molpadioides (AMP) showed antioxidative activity in H2O2‐induced RAW264.7 cells in our pervious study. In this study, it was observed that AMP could effectively improve the morphology and function of liver in CCl4‐induced mice. After 200 mg/kg AMP treatment, the content of MDA in liver decreased by 62.3%, and the level of antioxidant enzymes (SOD, GSH‐Px, and CAT) increased by more than 65%. Western blot results disclosed that AMP (200 mg/kg) upregulated the Nrf2 level by 73.8% and downregulated Keap1 by 41.0% in CCl4‐induced mice liver. The levels of p‐ERK, p‐JNK, and p‐p38 in 200 mg/kg AMP treatment groups decreased by 57.3%, 40.9%, and 40.6%, but the levels of p‐PI3K and p‐AKT increased by 162.6% and 60.3%, respectively. Furthermore, the trends of Nrf2, Keap1, p‐ERK, p‐JNK, p‐p38, p‐PI3K, and p‐AKT levels in H2O2‐induced RAW264.7 cells after AMP treatment were similar to the results in CCl4‐induced mice liver. These findings provided evidence that AMP exerted antioxidant activity via Keap1/Nrf2‐ARE, PI3K/AKT, and MAPKs pathways in vivo and in vitro. Therefore, the collagen peptide from A. molpadioides might represent a novel functional food to prevent acute liver injury via attenuation of oxidative stress.
Admissions to substance use treatment facilities for cannabis use disorder, 2000–2017: Does legalization matter?
Authors: Rhee Taeho Greg , Rosenheck Robert A.
Published: April 2022

Background and Objectives

A growing number of US states have legalized marijuana use in the past decade. We examined if marijuana legalization is associated with increased marijuana‐related admissions to substance use treatment facilities between 2000 and 2017.

Methods

Data from the Treatment Episode Data Set‐Admissions were used to examine the relationship between marijuana‐related admissions among adults aged ≥18 by year and legalization status (i.e., fully legalized, medical use only [partially legalized], and illegal) (N = 35,457,854). Using interaction analyses, we further examined whether certain patient characteristics were associated with residence in states that legalized marijuana use as compared to those in which marijuana remained illegal.

Results

Overall, the proportion of marijuana‐related admissions in states with legalization decreased by 2.3% from 31.7% in 2000–2005 to 29.4% in 2012–2017 (odds ratio [OR], 0.90; 95% confidence intervals [CI], 0.89–0.90) with little difference from states where marijuana use remained illegal, in which marijuana use as any reason for admissions decreased by 0.3% from 39.8% in 2000–2005 to 39.5% in 2012–2017 (OR, 0.99; 95% CI, 0.98–0.99). We did not find any striking patient characteristics (e.g., referral by the police) associated with admissions in states that legalized compared to those that had not.

Discussion and Conclusions

While earlier studies suggested that marijuana legalization is associated with increased levels of use, emergency department visits, and traffic fatalities, our findings suggest that marijuana legalization did not increase marijuana‐related treatment use in the United States.

Scientific Significance

This is the first study to examine the association of marijuana legalization with marijuana‐related treatment use.
The effects of fire frequency on vegetation structure and mammal assemblages in a savannah‐woodland system
Authors: Nieman Willem A. , van Wilgen Brian W. , Radloff Frans G. T. , Tambling Craig J. , Leslie Alison J.
Published: April 2022

Fire frequency affects vegetation structure and composition in savannah‐ woodlands, with the potential indirect consequence of affecting the habitat choice and space use of large mammals. Understanding these responses can assist with the development of appropriate fire management policies to conserve co‐existing species with different habitat requirements. In a natural experiment in Majete Wildlife Reserve, Malawi, we compared vegetation composition, woody plant structure and large (>5 kg) mammal assemblages on 10 frequently and 10 infrequently burnt 30‐ha plots, that had fire return intervals of <2.5 and >6 years, respectively, between 2001 and 2019. Fire frequency had little effect on woody plant composition, but did affect grass species composition. Frequent burning reduced mean tree height from 4 to 3 m, woody plant cover from 59% to 35%, and resulted in the dominance of short‐statured, less‐palatable grasses. Many mammal species showed clear preferences for either frequently burnt (e.g. buffalo, zebra, kudu, impala and sable) or infrequently burnt (e.g. nyala, bush pig, baboon, common duiker and vervet monkey) areas, while others (e.g. elephants and black rhinoceros) were not selective. We conclude that establishing a mosaic of patches exposed to different fire frequencies would allow for the persistence of all mammal species in the area by creating an optimal range of habitat types.
Wildlife‐vehicle collisions in Moroccan Atlantic Sahara: Impact on resident species and Afro‐Palearctic birds for conservation purposes
Authors: Mansouri Ismail , Dakki Mohamed , Squalli Wafae , Achiban Hamid , Mounir Mohamed , El Ghadraoui Lahsen
Published: April 2022

In this study, we described the temporal and spatial patterns of wildlife‐vehicle collisions in Dakhla‐Laayoune regions, using counts from cars for two years (2018–2021). A total of 462 roadkills were documented (monthly average of 0.075 roadkills/km), comprising 16 species, including mammals (residents), reptiles (residents), and birds (residents and migrants). Seasonal abundance and diversity of roadkills revealed a high peak during breeding and migration periods for all species. The generalised linear mixed models indicated that wildlife‐vehicle accidents have a higher probability of occurrence close to breeding and feeding sites and road sections with increased vegetation cover. Similarly, road collisions were higher close to migration routes and during breeding periods. Our study provides the first and only detailed results on wildlife road collisions in Morocco. Data gathered from this study provide valuable information for conservation measures of the most affected Moroccan species and Palearctic migrant birds which are crossing between Europe and Africa. Moreover, our data provide a new window of large‐scale comparative studies addressing the impacts of the infrastructures on biodiversity in the entire Atlantic coasts of Northwest Africa. Detailed studies on the local population dynamics of highly affected species are urgently needed to conclude whether these levels of road mortality are supportable.
Export destination and the skill premium: Evidence from Chinese manufacturing industries
Authors: Wang Feicheng , Milner Chris , Scheffel Juliane
Published: April 2022

This paper examines the relationship between average income of export destinations and the skill premium using data of Chinese manufacturing industries from 1995 to 2008. To do so, we construct weighted average GDP per capita across destinations employing within‐industry export share to each destination as weights, and then link it with industry‐level wages and the skill premium. We find that industries that export more to high‐income destinations tend to pay a higher skill premium, suggesting that, on average, skilled workers benefit more from high‐income exports than unskilled workers. Our IV estimates confirm a causal relationship, and the results are robust to various specifications. Further results based on firm‐level data show consistent evidence. Our paper highlights the role of high‐income destination exports in shaping the uneven distributional effects of globalization for different types of workers.
IFNL4 rs368234815 polymorphism does not predict risk of BK virus associated nephropathy after living‐donor kidney transplant: A case‐control study
Authors: Tanriver Ursula , Emmerich Florian , Hummel Jonas Florian , Jänigen Bernd , Panning Marcus , Arnold Frederic , Tanriver Yakup
Published: April 2022

Background

BK polyoma virus (BKPyV) associated nephropathy (BKPyVAN) is a major cause of kidney graft loss in renal transplant patients. Interferons (IFNs) are an important innate immune response against viral infections and genetic polymorphisms of the IFN‐pathways can affect susceptibility and mortality during viral infection. Here, we investigated whether the dinucleotide polymorphism rs368234815 (ΔG/TT) in the IFNL4 gene contributed to BKPyV reactivation or BKPyVAN after living‐donor kidney transplantation.

Methods

This retrospective case‐control study determines the prevalence of IFNL4 variants in a Caucasian population of living‐donor kidney transplant recipients and donors and explores its association with BKPyV infection and BKPyVAN development. We included 28 recipients with BKPyV reactivation, 10 of which developed BKPyVAN and 30 BKPyV negative controls. Targeted sequencing of the IFNL4 gene from both recipients and their respective donors was performed.

Results

We found IFNL4 rs368234815 ΔG allele frequencies of 41.7% in BKPyV negative and 39.3% in BKPyV positive recipients (P = .85), and 41.7% and 40.4% (P>.99) in their respective donors. IFNL4 rs368234815 ΔG allele frequencies in BKPyVAN developing recipients and their respective donors were 50% and 43.7% (P = .60 and P>.99).

Conclusions

Our results indicate that the IFNL4 rs368234815 ΔG allele is not associated with BKPyV reactivation, nor the manifestation of BKPyVAN.
Dental education profile in COVID‐19 pandemic: A scoping review
Authors: Di Carvalho Melo Larissa , Bastos Silveira Bruna , Amorim dos Santos Juliana , Cena Jessica Alves de , Damé‐Teixeira Nailê , Martins Manoela Domingues , De Luca Canto Graziela , Guerra Eliete Neves Silva
Published: April 2022

Introduction

This scoping review aimed to determine the frequency of different teaching methodologies, tools and platforms applied in dental education during the COVID‐19 pandemic.

Materials and Methods

The search strategy was performed in six databases and grey literature. A total of 28 questionnaire‐based studies were included, without language or time restriction, from 20 different countries.

Results

Six thousand five hundred sixty‐five participants were assessed: 84% undergraduates, 9% of faculty members, 5% of postgraduate students/residents/trainees and 2% of dental schools/residency programs. The pooled eligible data for teaching methodologies were 62% of a combination of different methods (95% CI, 35.5% to 82.3%), 23% a combination of synchronous and asynchronous formats (95% CI, 8.2% to 50.2%) and 15% for only synchronous lectures (95% CI, 4.3% to 42.2%). The reported tools were laptops (40%), smartphones (40%), tablets (40%), desktops (20%), Blackboard (20%), Respondus Lockdown Browser (20%), eProctor (20%) and PowerPoint (20%). The most used platforms were Zoom (70.6%), Microsoft Teams (23.5%) and Cisco Webex (23.5%). A better time management (17.9%; 95% CI, 7.9% to 35.6%) and the possibility of revision with additional notes (14.3%; 95% CI, 5.7% to 31.5%) was the greatest advantages related to dental e‐learning, while the increased levels of anxiety/stress/burnout/exhaustion (35.7%; 95% CI, 21% to 54.2%) and internet connection problems (35.7%; 95% CI, 21% to 54.2%) was the most cited disadvantages.

Conclusion

This scoping review showed promising blended teaching methodologies, tools and platforms in the dental education profile. The evidence suggests that e‐learning technologies can widely contribute to dental education during the COVID‐19 pandemic. Therefore, this study makes a major contribution to research by assessing the impact of COVID restrictions on dental education and further studies are needed to identify how restrictions in dental practice will affect future professionals.
Internationalization in Russian universities during the pandemic of COVID‐19: Lessons for succeeding in the new reality
Authors: Minaeva Ekaterina , Taradina Larisa
Published: April 2022

The pandemic of COVID‐19 became a resilience test for internationalization in Russia and emphasized many systemic trends, both promising and concerning. The turbulence and instability during the pandemic initiated the growth of internationalization activities at the institutional level in two directions: first, it increased attention to the quality of work with current international students, including student support, adaptation issues, student engagement, and second, due to the risks in student enrolment, it brought universities to rethink their internationalization instruments and strategies for work with international applicants and future students. Indeed, the ongoing changes in global education call for reconsideration of the priorities and methods of internationalization: new forms of internationalization become widespread practices, new instruments are necessary for student recruitment, and new push and pull factors come into play. While internationalization of education in Russia during the pandemic was addressed at the national level to a degree, the universities carried out the key activities and had to come up with solutions “in the field”. The paper aims to provide a comprehensive analysis of Russia's transition through the pandemic and tackle the changes at the university level, based on a comparison of data of the survey of international departments of Russian universities conducted in 2020 and the survey of 2021, supported by semi‐structured interviews. The research offers insights on the capacity for change and resilience in Russian universities within the internationalization domain and can help to develop data‐driven approaches for improvement of organizational capacity of universities.
Effects of different high‐pressure syntheses on the magnetization reversal properties of Bi2FeMnO6 ceramics
Authors: Chen Zipeng , Liu Ronggang , Ma Zhengzheng , Du Jianhua , Li Kun , Chen Yi , Wang Yi
Published: April 2022

Bi2FeMnO6 ceramics were prepared under atmospheric pressure and a high pressure of 1–6 GPa. The effects of different high‐pressure syntheses on the microstructures were analyzed by X‐ray diffraction and Rietveld refinement, scanning electron microscopy–energy‐dispersive spectroscopy, X‐ray photoelectron spectrometer, and Raman spectroscopy test. The temperature dependence of magnetization was systematically investigated for all samples. There was a transition from rhombohedral R3c structure to orthorhombic phase Pnam with increasing synthetic pressure. The samples synthesized under atmospheric pressure are rhombohedral R3c with antiferromagnetic (AFM) magnetic temperature (M–T curves). The samples synthesized under a high pressure of 5–6 GPa are orthorhombic phase Pnam with the magnetization reversal effect, whereas the lower high‐pressure (1–3 GPa) synthesized samples might be in the transitional area between them. This structural transformation is accompanied by the transformation from normal AFM M–T curves to a typical magnetization reversal effect. The relationship between the lattice distortion and the internal magnetic competition mechanism of the material was discussed. The existence of magnetization reversal in these systems may ascribe to the competition between the single‐ion magnetic anisotropy and the Dzyaloshinsky–Moriya interaction.
Water safety, antifungal-resistant aflatoxigenic aspergillus flavus and other pathogenic fungi in a community hand-dug wells
Authors: Shittu Olufunke Bolatito , Iwaloye Opeoluwa Favour , Oloyede Adejare Rasak , Oni Eniola Oluyemisi , Ajibola Abiola Tosin , Arowosegbe Adediwura Oladunni , Oluwasanya Grace Olutope
Published: April 2022

Aim

To investigate hand-dug well water used for drinking and domestic purposes in a rural community in Southwest Nigeria for water safety and fungal presence as well as to determine the antifungal resistance and aflatoxigenic potentials of isolated fungi.

Methods and Results

Water samples were analysed for risk of contamination, bacteriological and mycological parameters using a standard sanitary survey checklist and microbiological culturing. Isolates were identified and subjected to antifungal resistance profiling using the diffusion method for susceptibility testing of filamentous fungi. Multidrug-resistant strains were confirmed with DNA barcoding identification. Fungal isolates were screened for aflatoxigenic potentials by culture methods and confirmed by densitometric analysis. From the 23 hand-dug wells assessed, 56.52% had a high risk of contamination (ROC) score, nitrate >50 mg/L (73.9%), and the presence of total coliforms (100%), Escherichia coli (43.48%) and fungi (91.3%). Spearman rank correlation coefficient gave a positive and strong correlation between Total Fungi and Faecal Coliform (r = 0.701; p = 0.016; n = 23) at 0.05 significance level (2-tailed). Aspergillus sp. (34%), Penicillium sp. (18%) and Rhizopus sp. (17%) were the most dominant fungal genera. Isolates were resistant to fluconazole (76.19%), ketoconazole (73.80%), clotrimazole (92.86%), griseofulvin (88.09%) and nystatin (100%). Penicillium and Aspergillus (50%) were positive for cultural mycotoxin screening. A strain of antifungal-resistant A. flavus produced aflatoxin B1 (752 ppb) and B2 (15 ppb).

Significance of the study

The existence of antifungal-resistant and aflatoxigenic fungi in water used for drinking and domestic purposes shows that filamentous fungi constitute greater threats than previously recognized and this call for a paradigm shift from the perceived safety of untreated hand-dug well-water.
Health status, healthcare, and access in children with long‐term medication use and difficulties with emotion, concentration, and behavior
Authors: Yang Yuyin , Reyes Beck L. , Jacob Eufemia
Published: April 2022

Problem

Children with chronic conditions often have difficulties with emotions, concentration, and behaviors (ECB) and are not recognized and treated adequately. In this paper, long‐term medication use (LTM) was adopted as a proxy for chronic illness due to the lack of consistent and standardized diagnostic criteria for chronic illnesses in children.

Methods

Children (8–12 years) were selected from the California Health Interview Survey (2017) based on: (1) households with children (<12 years), (2) parent/adult caregivers report about child's health indicating “yes” to, (3) “does your child require prescription medicine for a health condition that has lasted or is expected to last at least 12 months or more,” and (4) “difficulties with ECB in past 6 months.”

Findings

A total of 1600 children were included by the CHIS data set, and children whose parental report had met the selection criteria were children with LTM (n = 144; 7.4 ± 2.9 years), ECB (n = 233; 8.16 ± 2.14), and both LTM + ECB (n = 62; 8.61 ± 1.81). Children with LTM+ ECB were Caucasian (56.4%), Hispanic (19.3%), and males (64.5%). Children with both LTM + ECB had two to three (33.87%) or at least four (53.2%) physician visits, and/or receiving special therapy (45.1%). Children with LTM had prescription delays (n = 144; 5.6%) and were not able to get medical care due to lack of insurance (n = 144; 6.9%). The majority of the children with LTM (54.2%) and LTM + ECB (43.5%) had parental employment‐based insurance. More children that have both LTM and ECB (48.4%) than children with LTM, No ECB (32.9%) were on Medi‐Cal/Medicaid.

Conclusion

Children with LTM need further evaluation for difficulties with ECB. Future studies are required to examine health status, healthcare use, and access for children with LTM and ECB.
Nursing staff perspectives of continuous remote vital signs monitoring on surgical wards: Theory elicitation for a realist evaluation
Authors: Downey Candice , Brown Julia , Jayne David , Randell Rebecca
Published: April 2022

Rationale, Aims and Objectives

Continuous remote monitoring (CRM) provides a novel solution to the challenges of monitoring patients' vital signs in hospital, but the results of quantitative studies have been mixed. Acceptance by staff is a crucial determinant of the success of healthcare technologies and may explain these discrepancies. Drawing on the approach of realist evaluation, this paper aims to identify theories about how, why and in what conditions nursing staff perceptions vary regarding the CRM of patients' vital signs.

Methods

Multiple methods were used to elicit theories about factors likely to facilitate or impede the successful implementation of continuous remote vital signs monitoring. This included a literature review, consultation with patients and observational work conducted during a randomized controlled trial (RCT) of CRM. In addition, a priori theories developed through informal interactions with patients and ward staff during the day‐to‐day set‐up of the trial were included.

Results

The findings suggest that the perceptions of nursing staff regarding remote monitoring can be influenced by the type of patients under their care and their previous experience of telemetry. Factors which may undermine the engagement of staff are perceived staff burden, which can be dependent on contextual factors such as staffing levels, time of day and senior staff attitudes. Staff attitudes are also likely to be influenced by patient perspectives and the utility of the devices associated with remote monitoring. The successful implementation of CRM may be dependent on staff training, research staff input and hospital culture.

Conclusions

Theories regarding nursing staff engagement with remote monitoring are numerous, varied and contradictory. The theories elicited in this initial phase will be refined during interviews with the nursing staff involved with the RCT.