bluuebunny/crossref_metadata_2025 huggingface dataset:
A vitamin D-RelB/NF-κB pathway limits Chandipura virus multiplication by rewiring the homeostatic state of autoregulatory type 1 interferon-IRF7 signaling
Authors: Ratra Yashika , Kumar Naveen , Saha Manti K. , Bharadwaj Chandrima , Chongtham Chen , Bais Sachendra S. , Medigeshi Guruprasad , Arimbasseri Gopalakrishnan A. , Basak Soumen
Published: November 2021

Besides its functions in the skeletomuscular system, vitamin D also promotes protective immunity against viral pathogens. Viral sensing by mammalian cells triggers nuclear activation of RelA/NF-κB and IRF3 factors, which collaborate in mediating the early induction of antiviral type 1 interferons (T1-IFNs). Autocrine T1-IFN signaling further accumulates otherwise negligibly expressed IRF7 in virus-infected cells that then sustains T1-IFN production in a positive feedback. Surprisingly, prior cell-culture studies revealed that vitamin D actually suppresses signal-induced RelA activation. Indeed, it remains unclear how vitamin D limits viral multiplication in a cell-autonomous manner. Here, we examined the role of vitamin D in controlling cellular infections by the Chandipura virus (CHPV), a cytoplasmic RNA virus implicated in human epidemics. We found that vitamin D conditioning produced an altered cell state less permissive for CHPV multiplication because of the heightened expression of T1-IFNs. It is thought that viruses also induce a distinct RelB/NF-κB activity, which counteracts RelA-driven T1-IFN expressions in infected cells. Our analyses instead characterized a basal nuclear RelB activity, which was downregulated upon vitamin D-mediated suppression of RelB synthesis. Interestingly, this vitamin D-RelB pathway provoked IRF7-mediated positive autoregulation augmenting constitutive T1-IFN expressions even in the absence of viral infections. Accordingly, RelB deficiency rendered redundant, while IRF7 depletion abrogated antiviral vitamin D actions. In sum, our study suggests that the homeostatic state of the signaling circuitry comprising of the NF-κB and T1-IFN pathways connects micronutrients to antiviral immunity at the cellular level.

Significance statement

Vitamin D limits viral infections, but the underlying mechanism remains unclear. Linking micronutrients to antiviral immunity, Ratra et al. characterize an immune signaling circuitry engaged by vitamin D that generates a cellular state less permissive to infections by Chandipura virus, a pathogen of public health importance.
Act Natural: Functional Connectivity from Naturalistic Stimuli fMRI Outperforms Resting-State in Predicting Brain Activity
Authors: Gal Shachar , Coldham Yael , Tik Niv , Bernstein-Eliav Michal , Tavor Ido
Published: November 2021

The search for an ‘ideal’ approach to investigate the functional connections in the human brain is an ongoing challenge for the neuroscience community. While resting-state functional magnetic resonance imaging (fMRI) has been widely used to study individual functional connectivity patterns, recent work has highlighted the benefits of collecting functional connectivity data while participants are exposed to naturalistic stimuli, such as watching a movie or listening to a story. For example, functional connectivity data collected during movie-watching were shown to predict cognitive and emotional scores more accurately than resting-state-derived functional connectivity. We have previously reported a tight link between resting-state functional connectivity and task-derived neural activity, such that the former successfully predicts the latter. In the current work we use data from the Human Connectome Project to demonstrate that naturalistic-stimulus-derived functional connectivity predicts task-induced brain activation maps more accurately than resting-state-derived functional connectivity. We then show that activation maps predicted using naturalistic stimuli are better predictors of individual intelligence scores than activation maps predicted using resting-state. We additionally examine the influence of naturalistic-stimulus type on prediction accuracy. Our findings emphasize the potential of naturalistic stimuli as a promising alternative to resting-state fMRI for connectome-based predictive modelling of individual brain activity and cognitive traits.
Experimental evolution reveals the synergistic genomic mechanisms of adaptation to ocean warming and acidification in a marine copepod
Authors: Brennan Reid S. , deMayo James A. , Dam Hans G. , Finiguerra Michael , Baumann Hannes , Buffalo Vince , Pespeni Melissa H.
Published: November 2021

Metazoan adaptation to global change will rely on selection of standing genetic variation. Determining the extent to which this variation exists in natural populations, particularly for responses to simultaneous stressors, is therefore essential to make accurate predictions for persistence in future conditions. Here, we identify the genetic variation enabling the copepod Acartia tonsa to adapt to experimental ocean warming, acidification, and combined ocean warming and acidification (OWA) conditions over 25 generations. Replicate populations showed a strong and consistent polygenic response to each condition, targeting an array of adaptive mechanisms including cellular homeostasis, development, and stress response. We used a genome-wide covariance approach to partition the genomic changes into selection, drift, and lab adaptation and found that the majority of allele frequency change in warming (56%) and OWA (63%) was driven by selection but acidification was dominated by drift (66%). OWA and warming shared 37% of their response to selection but OWA and acidification shared just 1%. Accounting for lab adaptation was essential for not inflating a shared response to selection between all treatments. Finally, the mechanisms of adaptation in the multiple-stressor OWA conditions were not an additive product of warming and acidification, but rather a synergistic response where 47% of the allelic responses to selection were unique. These results are among the first to disentangle how the genomic targets of selection differ between single and multiple stressors and to demonstrate the complexity that non-additive multiple stressors will contribute to attempts to predict adaptive responses to complex environments.
Prophylactic Treatment of Undernourished Mice with Cotrimoxazole Induces a Different Profile of Dysbiosis with Functional Metabolic Alterations
Authors: Budziarek Eslabão Lívia , Gubert Gabriela Farias , Beltrame Lucas C. , de Mello Isis M. A. , Bruna-Romero Oscar , Zárate-Bladés Carlos R.
Published: November 2021

1.

Childhood malnutrition affects physiology and development, it increases infection rate which may not present clinical signs in severe cases. To overcome this issue, the World Health Organization recommends prophylactic treatment with Cotrimoxazole (SXT) along with nutritional recovery. This treatment is controversial since evidence of reduction in morbidity and mortality is not a consensus and could induce the development of antibiotic resistant bacteria. Moreover, the impact of the use of this wide-spectrum antibiotic on gut microbiota, in a critical period of development and weakness, is unknown. To understand how SXT prophylaxis could affect gut microbiota in undernutrition, we induced protein-energy undernutrition in weaning C57BL/6 mice for three weeks and treated animals with SXT for two weeks. Using 16S rRNA gene sequencing we compared the taxonomic composition and metabolic pathways of control mice, animals submitted to undernutrition (UND), treated with SXT, or undernourished and SXT treated (UND+SXT). Undernutrition protocol was responsible for increasing Bacteroidetes and decreasing Firmicutes abundance. We identified that UND mice had a significant increase in predicted pathways related to metabolic syndromes later in life. The prophylactic SXT treatment alone resulted in significant loss in community richness and beta diversity. In addition, we identified the reduction of 6 families in SXT treated mice, including the butyrate producers Lachnospiraceae and Ruminococcaceae. The double challenge (UND+SXT) resulted in a reduction in Clostridiaceae family and in the urea cycle pathway, both related to the fermentation of amino acids, the intestinal epithelial permeability, and the healthy gut environment. Our results show that SXT prophylaxis during an undernourishment period in young mice did not re-establish the undernourished microbiota community composition similar to healthy controls, but induces a distinct dysbiotic profile, with functional metabolic consequences.
mRNA Vaccines Induce Rapid Antibody Responses in Mice
Authors: Gebre Makda S. , Rauch Susanne , Roth Nicole , Gergen Janina , Yu Jingyou , Liu Xiaowen , Cole Andrew C. , Mueller Stefan O. , Petsch Benjamin , Barouch Dan H.
Published: November 2021

mRNA vaccines can be developed and produced quickly, making them attractive for immediate outbreak responses. Furthermore, clinical trials have demonstrated rapid protection following mRNA vaccination. We sought to investigate how quickly mRNA vaccines elicit antibody responses compared to other vaccine modalities. We first examined immune kinetics of mRNA and DNA vaccines expressing SARS-CoV-2 spike in mice. We observed rapid induction of antigen-specific binding and neutralizing antibodies by day 5 following mRNA, but not DNA, immunization. The mRNA vaccine also induced increased levels of IL-5, IL-6 and MCP-1. We then evaluated immune kinetics of an HIV-1 mRNA vaccine in comparison to DNA, protein, and rhesus adenovirus 52 (RhAd52) vaccines with the same HIV-1 envelope antigen in mice. Induction of envelope-specific antibodies was observed by day 5 following mRNA vaccination, whereas antibodies were detected by day 7-14 following DNA, protein, and RhAd52 vaccination. Eliciting rapid humoral immunity may be an advantageous property of mRNA vaccines for controlling infectious disease outbreaks.

IMPORTANCE

mRNA vaccines can be developed and produced in record time. Here we demonstrate induction of rapid antibody responses by mRNA vaccines encoding two different viral antigens by day 5 following immunization in mice. The rapid immune kinetics of mRNA vaccines can be an advantageous property that makes them well suited for rapid control of infectious disease outbreaks.
Genetic support of a causal relationship between Iron status and atrial fibrillation: a Mendelian randomization study
Authors: Wang Tianyi , Cheng Jun , Wang Yanggan
Published: November 2021

Background

Atrial fibrillation is the most common arrhythmia disease.Animal and observational studies have found a link between iron status and atrial fibrillation. However, the causal relationship between iron status and the risk of atrial fibrillation may be biased by confounding and reverse causality.The purpose of this investigation was to use Mendelian randomization (MR) analysis, which has been widely appied to estimate the causal effect,to reveal whether systemic iron status was causally related to atrial fibrillation.

Methods

Single nucleotide polymorphisms (SNPs) strongly associated (P < 5×10−8) with four biomarkers of systemic iron status were obtained from a genome-wide association study involving 48,972 subjects conducted by the Genetics of Iron Status consortium.

Summary-level data for the genetic associations with atrial fibrillation were acquired from AFGen (Atrial Fibrillation Genetics) consortium study(including 65,446 atrial fibrillation cases and 522,744 controls). We used a two-sample MR analysis to obtain a causal estimate, and further verified credibility through sensitivity analysis.

Results

Genetically instrumented serum iron [OR:1.09;95%; confidence interval (CI)1.02-1.16; p=0.01], ferritin [OR:1.16;95%CI:1.02-1.33; p=0.02], and transferrin saturation [OR:1.05;95%CI:1.01-1.11; p=0.01] had positive effects on atrial fibrillation. Genetically instrumented transferrin levels [OR:0.90;95%CI:0.86-0.97; p=0.006] was an inverse correlation with atrial fibrillation.

Conclusion

In conclusion,our results strongly elucidated a causal link between genetically determined higher iron status and increased the risk of atrial fibrillation.This provided new ideas for clinical prevention and treatment of atrial fibrillation.
CRISPR-Csx28 forms a Cas13b-activated membrane pore required for robust CRISPR-Cas adaptive immunity
Authors: VanderWal Arica R. , Park Jung-Un , Polevoda Bogdan , Kellogg Elizabeth H. , O’Connell Mitchell R.
Published: November 2021

Type VI CRISPR-Cas systems use the RNA-guided RNase Cas13 to defend bacteria against viruses, and some of these systems encode putative membrane proteins that have unclear roles in Cas13-mediated defense. Here we show that Csx28, of Type VI-B2 systems, forms membrane pore structures to slow cellular metabolism upon viral infection, and this activity drastically increases anti-viral defense. High- resolution cryo-EM reveals that Csx28 exists unexpectedly as a detergent-encapsulated octameric pore, and we then show these Csx28 pores are membrane localized in vivo. Activation of Csx28 in vivo strictly requires sequence-specific recognition of viral mRNAs by Cas13b, and this activation results in Csx28-mediated membrane depolarization, slowed metabolism, and inhibition of sustained viral infection. Together, our work reveals an unprecedented mechanism by which Csx28 acts as a downstream, Cas13b-activated, effector protein that uses membrane perturbation as an anti-viral defense strategy.
Xist-mediated silencing requires additive functions of SPEN and Polycomb together with differentiation-dependent recruitment of SmcHD1
Authors: Bowness Joseph S. , Nesterova Tatyana B. , Wei Guifeng , Rodermund Lisa , Almeida Mafalda , Coker Heather , Carter Emma J. , Kadaster Artun , Brockdorff Neil
Published: November 2021

X chromosome inactivation (XCI) is mediated by the non-coding RNA Xist which directs chromatin modification and gene silencing in cis. The RNA binding protein SPEN and associated corepressors have a central role in Xist-mediated gene silencing. Other silencing factors, notably the Polycomb system, have been reported to function downstream of SPEN. In recent work we found that SPEN has an additional role in correct localisation of Xist RNA in cis, indicating that its contribution to chromatin-mediated gene silencing needs to be reappraised. Making use of a SPEN separation-of-function mutation we show that SPEN and Polycomb pathways in fact function in parallel to establish gene silencing. Additionally, we find that differentiation-dependent recruitment of the chromosomal protein SmcHD1 is required for silencing many X-linked genes. Our results provide important insights into the mechanism of X inactivation and the coordination of chromatin-based gene regulation with cellular differentiation and development.
A tonic nicotinic brake controls spike timing in striatal spiny projection neurons
Authors: Matityahu Lior , Malgady Jeffrey M. , Schirelman Meital , Johansson Yvonne , Wilking Jennifer , Silberberg Gilad , Goldberg Joshua A. , Plotkin Joshua L.
Published: November 2021

Striatal spiny projection neurons (SPNs) transform convergent excitatory corticostriatal inputs into an inhibitory signal that shapes basal ganglia output. This process is fine-tuned by striatal GABAergic interneurons (GINs), which receive overlapping cortical inputs and mediate rapid corticostriatal feedforward inhibition of SPNs. Adding another level of control, cholinergic interneurons (CINs), which are also vigorously activated by corticostriatal excitation, can disynaptically inhibit SPNs by activating α4β2 nicotinic acetylcholine receptors (nAChRs) on various GINs. Measurements of this disynaptic inhibitory pathway, however, indicate that it is too slow to compete with direct GIN-mediated feed-forward inhibition. Moreover, functional nAChRs are also present on populations of GINs that respond only weakly to phasic activation of CINs, such as parvalbumin-positive fast-spiking interneurons (PV-FSIs), making the overall role of nAChRs in shaping striatal synaptic integration unclear. Using acute striatal slices we show that upon synchronous optogenetic activation of corticostriatal projections blockade of α4β2 nAChRs shortened SPN spike latencies and increased postsynaptic depolarizations. The nAChR-dependent inhibition was mediated by downstream GABA release, and data suggest that the GABA source was not limited to GINs that respond strongly to phasic CIN activation. In particular, the observed decrease in spike latency caused by nAChR blockade was associated with a diminished frequency of spontaneous inhibitory postsynaptic currents in SPNs, a parallel hyperpolarization of PV-FSIs, and was occluded by pharmacologically preventing cortical activation of PV-FSIs. Taken together, we describe a role for tonic (as opposed to phasic) activation of nAChRs in striatal function. We conclude that tonic activation of nAChRs by CINs maintains a GABAergic brake on cortically-driven striatal output by “priming” feedforward inhibition, a process that may shape SPN spike timing, striatal processing and synaptic plasticity.

Impact Statement

A novel mechanism describing how tonic activation of nicotinic acetylcholine receptors can modulate the timing of striatal output by priming feed forward inhibition.
Kv3.3 subunits control presynaptic action potential waveform and neurotransmitter release at a central excitatory synapse
Authors: Richardson Amy , Ciampani Victoria , Stancu Mihai , Newton Sherylanne , Steinert Joern R. , Pilati Nadia , Graham Bruce P. , Kopp-Scheinpflug Conny , Forsythe Ian D.
Published: November 2021

Kv3 potassium currents mediate rapid repolarization of action potentials (AP), supporting fast spikes and high repetition rates. Of the four Kv3 gene family members, Kv3.1 and Kv3.3 are highly expressed in the auditory brainstem and we exploited this to test for subunit-specific roles at the calyx of Held presynaptic terminal. Deletion of Kv3.3 (but not Kv3.1) increased presynaptic AP duration and facilitated transmitter release, which in turn enhanced short-term depression during high frequency transmission. The response to sound was delayed in the Kv3.3KO, with higher spontaneous and lower evoked firing, thereby reducing signal-to-noise ratio. Computational modelling showed that the enhanced EPSC and short-term depression in the Kv3.3KO reflected increased vesicle release probability and accelerated activity-dependent vesicle replenishment. We conclude that Kv3.3 is the presynaptic ‘delayed rectifier’, enabling short duration, precisely timed APs to maintain transmission at high frequencies and during sustained synaptic activity.
Creatine utilization as a sole nitrogen source in Pseudomonas putida KT2440 is transcriptionally regulated by CahR
Authors: Hinkel Lauren A. , Willsey Graham G. , Lenahan Sean M. , Eckstrom Korin , Schutz Kristin C. , Wargo Matthew J.
Published: November 2021

Glutamine amidotransferase-1 domain-containing AraC-family transcriptional regulators (GATRs) are present in the genomes of many bacteria, including all Pseudomonas species. The involvement of several characterized GATRs in amine-containing compound metabolism has been determined, but the full scope of GATR ligands and regulatory networks are still unknown. Here, we characterize Pseudomonas putida’s detection of the animal-derived amine compound, creatine, a compound particularly enriched in muscle and ciliated cells by a creatine-specific GATR, PP_3665, here named CahR (Creatine amidohydrolase Regulator). cahR is necessary for transcription of the gene encoding creatinase (PP_3667/creA) in the presence of creatine and is critical for P. putida’s ability to utilize creatine as a sole source of nitrogen. The CahR/creatine regulon is small and electrophoretic mobility shift demonstrates strong and specific CahR binding only at the creA promoter, supporting the conclusion that much of the regulon is dependent on downstream metabolites. Phylogenetic analysis of creA orthologs associated with cahR orthologs highlights a strain distribution and organization supporting likely horizontal gene transfer, particularly evident within the genus Acinetobacter. This study identifies and characterizes the GATR that transcriptionally controls P. putida metabolism of creatine, broadening the scope of known GATR ligands and suggesting GATR diversification during evolution of metabolism for aliphatic nitrogen compounds.
Detection of velogenic avian paramyxoviruses in rock doves in New York City, New York
Authors: Francisco Isabel , Bailey Shatoni , Bautista Teresa , Diallo Djenabou , Gonzalez Jesus , Gonzalez Joel , Roubidoux Ericka Kirkpatrick , Ajayi Paul K. , Albrecht Randy A. , McMahon Rita , Krammer Florian , Marizzi Christine
Published: November 2021

Avian paramyxovirus 1 (APMV-1), also known as Newcastle disease virus (NDV), causes severe and economically important disease in poultry around the globe. Although a limited amount of APMV-1 strains in urban areas have been characterized, the role of the urban wild bird population as an APMV-1 reservoir is unclear. Since urban birds may have an important role for long-term circulation of the virus, fecal and swab samples were collected by community scientists from wild birds in New York City (NYC), New York, United States. These samples were screened for APMV-1 and genotypically characterized by sequencing of the complete genome. A total of 885 samples were collected from NYC parks and from a local wildlife rehabilitation clinic from October 2020 through June 2021. Eight birds (1.1 %) screened positive for the APMV-1 nucleoprotein gene by conventional reverse transcription polymerase chain reaction (RT-PCR), and two live viruses were isolated via egg culture. The F protein cleavage site, an indicator of pathogenicity, was present in the two samples fully sequenced by next generation sequencing, and positioned 112R R K K R F117. Phylogenetic analysis of the F gene coding sequence classified both isolates into genotype VI, a diverse and predominant genotype responsible for NDV outbreaks in pigeon and dove species worldwide.

Importance

Here we describe the first large-scale effort to screen for APMV-1 in New York City’s wild bird population as part of the New York City Virus Hunters program, a community science initiative. We have characterized two isolates of NDV, with phylogenetic analyses suggesting diversity in established and circulating strains of pigeon paramyxoviruses. Our isolates are also domestic reference strains for future APMV-1 vaccine developments. Future surveillance in this region may contribute to our understanding of NDV’s evolution and genetic diversity, as well as inform poultry husbandry and vaccination practices in New York State.
Time-dependent regulation of cytokine production by RNA binding proteins defines T cell effector function
Authors: Popović Branka , Nicolet Benoît P. , Guislain Aurélie , Engels Sander , Jurgens Anouk P. , Paravinja Natali , Freen-van Heeren Julian J. , van Alphen Floris P.J. , van den Biggelaar Maartje , Salerno Fiamma , Wolkers Monika C.
Published: November 2021

Potent T cell responses against infections and malignancies depend on the release of effector molecules, such as pro-inflammatory cytokines. Because effector molecules can be toxic, their production is tightly regulated through post-transcriptional events at 3’ Untranslated Regions (3’UTRs). RNA binding proteins (RBPs) were shown to be key regulators herein. With an RNA aptamer-based capture assay from human T cells, we identified >130 RBPs interacting with theIFNG, TNFandIL23’UTRs in human T cells. T cell activation altered RBP-RNA interactions, revealing that RBP-target mRNA interactions rapidly respond to stimulation. Furthermore, we uncovered the intricate and time-dependent regulation of cytokine production by RBPs: whereas HuR supports early cytokine production, ZFP36L1, ATXN2L and ZC3HAV1 dampen and shorten the production duration, each at different time points. Strikingly, even though ZFP36L1 deletion did not phenotypically rescue T cell dysfunction in tumors, the increased production of cytokines and cytotoxic molecules resulted in superior anti-tumoral T cell responsesin vivo. Our findings thus show that identifying RBP-RNA interactions reveals key modulators of T cell responses in health and disease.
Differences in thermal expansion and motion ability for herringbone and face-to-face π-stacked solids
Authors: Ding Xiaodan , Zahid Ethan , Unruh Daniel K. , Hutchins Kristin M.
Published: November 2021

A series of aromatic organic molecules functionalized with different halogen atoms (I/ Br), motion-capable groups (olefin, azo or imine) and molecular length were designed and synthesized. The molecules self-assemble in the solid state through halogen bonding and exhibit molecular packing sustained by either herringbone or face-to-face π-stacking, two common motifs in organic semiconductor molecules. Interestingly, dynamic pedal motion is only achieved in solids with herringbone packing. On average, solids with herringbone packing exhibit larger thermal expansion within the halogen-bonded sheets due to motion occurrence and molecular twisting, whereas molecules with face-to-face π-stacking do not undergo motion or twisting. Thermal expansion along the π-stacked direction is surprisingly similar, but slightly larger for the face-to-face π-stacked solids due to larger changes in π-stacking distances with temperature changes. The results speak to the importance of crystal packing and intermolecular interaction strength when designing aromatic-based solids for organic electronics applications.
Efficient fitting of single-crystal diffuse scattering in interaction space: a mean-field approach
Authors: Schmidt Ella M. , Bulled Johnathan M. , Goodwin Andrew L.
Published: November 2021

The diffraction patterns of crystalline materials with strongly correlated disorder are characterized by the presence of structured diffuse scattering. Conventional analysis approaches generally seek to interpret this scattering either atomistically or in terms of pairwise (Warren–Cowley) correlation parameters. Here it is demonstrated how a mean-field methodology allows efficient fitting of diffuse scattering directly in terms of a microscopic interaction model. In this way the approach gives as its output the underlying physics responsible for correlated disorder. Moreover, the use of a very small number of parameters during fitting renders the approach surprisingly robust to data incompleteness, a particular advantage when seeking to interpret single-crystal diffuse scattering measured in complex sample environments. As the basis of this proof-of-concept study, a toy model is used based on strongly correlated disorder in diammine mercury(II) halides.
A systematic literature review on supply chain approaches
Authors: Sadeghi Asl Ramin , Bagherzadeh Khajeh Majid , Pasban Mohammad , Rostamzadeh Reza
Published: November 2021

Purpose

The purpose of this paper is to present green supply chain, resilient supply chain, agile supply chain, cold supply chain and lean supply chain (GRACL SC) procedures based on a detailed perspective, analyzing subjects in the past 19 years with a systematic literature review (SLR) of the papers reported from 2000 to 2019, and offering information and guidelines for further studies.

Design/methodology/approach

This research is based on 17 keywords in the title and topic of the articles and collects data from Web of Science (WOS) databases and objectively chooses 1,190 articles and performs meta-data analyses. Tables and statistical reports are based on the following three filters: publication year, authors and document type. At least, 39 publications from the ISI WOS has been examined for presenting information of categorization of the conducted research with regard to the content analysis, comprising the conceptual development and obstacles, cooperation with the supply chain elements, as well as mathematical and other optimization models.

Findings

Finally, this study answered three main questions in the research and demonstrates that the majority studies in the green supply chain (GSC) and a minimum number of studies on the cold supply chain have been conducted and 27 factors are chosen to achieve the 2000 to 2019 GRACL SCM model which robust and fit for Iranian food industries. The model shows that the agile, resilient and lean supply chain have direct effect on GSC and it can be said that all 27 groups which are selected for the final model of this research can be the main groups in the supply chain.

Originality/value

This paper was actually conducted by authors who reported it. To prevent plagiarized, redoubled efforts have been made and actually this paper is based on SLR methodology and the results are real and the researcher discusses the results appropriately. This investigation can have a positive impact within the field of expanding supply chain flexibility and lessening squander within the Iranian generation framework.
Volumetric adaptive slicing of manifold mesh for rapid prototyping based on relative volume error
Authors: Chen Qianyong , Xu Jinghua , Zhang Shuyou
Published: November 2021

Purpose

Compared with cusp height and area deviation ratio, volume error (VE) caused by the layer height could represent the stair-case effect more comprehensively. The proposed relative volume error (RVE)-based adaptive slicing method takes VE rather than cusp height as slicing criteria, which can improve part surface quality for functionalized additive manufacturing.

Design/methodology/approach

This paper proposes a volumetric adaptive slicing method of manifold mesh for rapid prototyping based on RVE. The pre-height sequences of manifold mesh are first preset to reduce the SE by dividing the whole layer sequence into several parts. A breadth-first search-based algorithm has been developed to generate a solid voxelization to get VE. A new parameter RVE is proposed to evaluate the VE caused by the sequence of the layer positions. The RVE slicing is conducted by iteratively adjusting the layer height sequences under different constraint conditions.

Findings

Three manifold models are used to verify the proposed method. Compared with uniform slicing with 0.2 mm layer height, cusp height-based method and area deviation-based method, the standard deviations of RVE of all three models are improved under the proposed method. The surface roughness measured by the confocal laser scanning microscope proves that the proposed RVE method can greatly improve part surface quality by minimizing RVE.

Originality/value

This paper proposes an RVE-based method to balance the surface quality and print time. RVE could be calculated by voxelized parts with required accuracy at a very fast speed by parallel.
A systematic review and meta‐analysis of the efficacy of processing stages and interventions for controllingCampylobactercontamination during broiler chicken processing
Authors: Dogan Onay B. , Aditya Anand , Ortuzar Juan , Clarke Jennifer , Wang Bing
Published: November 2021

Systematic review and meta‐analysis were conducted to quantify the effects of processing stages and interventions on the prevalence and concentration ofCampylobacteron broiler carcasses. To comprehensively capture relevant evidence, six databases were searched using the keywords “Campylobacter” and “broiler chicken.” The literature search yielded 10,450 unique citations, and after applying predetermined inclusion and exclusion criteria, 72 and 53 relevant citations were included in meta‐analyses for processing stages and interventions, respectively. As the two primary outcomes, log reduction and prevalence changes were estimated for each stage or intervention using a random‐effects meta‐analysis approach whenever possible. The outcome‐level quality assessment was conducted following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The analysis revealed that scalding and chilling majorly reduces the prevalence and concentration ofCampylobacter. Immersion chilling reduces the concentration regardless of chemical additives, but its effect on prevalence is not conclusive. The effects of carcass washing applications remain uncertain due to the inconsistency and imprecision of both outcomes. Defeathering and evisceration were identified as stages that can increase both prevalence and concentration. Both chemical and physical processing interventions provide limited efficacy in concentration and prevalence reduction. Major limitations of the review were inconsistency and imprecision at the outcome level and reporting issues and data gaps at the study level. The results are expected to inform quantitative microbial risk assessment model development and support evidence‐based decision‐making.
Policosanol alleviates hepatic lipid accumulation by regulating bile acids metabolism in C57BL6/mice through AMPK–FXR–TGR5 cross‐talk
Authors: Zhai Zhenya , Niu Kai‐Min , Liu Huiping , Lin Chong , Tu Yue , Liu Yichun , Cai Lichuang , Ouyang Kexian , Liu Jianping
Published: November 2021

Policosanol exhibits a lipid accumulation alleviating effect, but the underlying mechanisms remains unclear. Bile acids are a significant factor in regulating cholesterol and lipid metabolism homeostasis in mammals. This study was aimed to elucidate the alleviating effect and underlying mechanisms of policosanol on hepatic lipid accumulation through bile acid (BA) metabolism. Policosanol supplementation significantly reduced hepatic triglycerides (19.29%), cholesterol (30.38%) in high fat diet (HFD) induced obese mice (P < 0.05). Furthermore, compared with the control group, HFD decreased the levels of total BAs (TBAs, 37.67%) and cholic acid (CA, 62.74%) in the serum of mice (P < 0.05). Meanwhile, compared to HFD group, policosanol also increased the level of secondary BAs (SBAs) and muricholic acids (MCAs, P < 0.05). qRT‐PCR combined with protein level analysis revealed that policosanol significantly decreased sterol regulatory element‐binding protein (SREBP‐1c) and CD36, and increased the expression level of cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and cytochrome P450 Family 27 Subfamily A Member 1 (CYP27A1, P < 0.05). Additionally, in the liver, policosanol was found downregulated the expression of farnesoid X receptor (FXR)‐small heterodimer partner (SHP), and activate the Takeda G‐coupled protein receptor 5 (TGR5)‐adenosine‐monophosphate‐activated protein kinase (APMK) signaling pathway (P < 0.05). Peroxisome proliferator activated receptor (PPAR)‐α, hormone sensitive lipase (HSL), and carnitine palmitoyltransferase (CPT)‐1α also significantly increased in HP group (P < 0.05). The aforementioned results reveal that the potential mechanism of policosanol in alleviating liver lipid accumulation is to promote BA synthesis and lipolysis through regulating the cross‐talk of the AMPK–FXR–TGR5. New insight for the application of policosanol as an anti‐fatty liver functional food ingredient or supplement is also provided.

Practical Application

Policosanol is an important active component of cereals and insect waxes (15–80%). However, almost no policosanol in refined foods such as clear corn germ oil and wheat flour. This study showed that oral administration of policosanol can significantly reduce triglyceride and cholesterol levels in the liver through affecting AMPK–TGR5–FXR cross‐talk, whereas no significant toxicological effect is reported in human and mouse models. This study may provide theoretical support for the theory of dietary structure and the development of dietary supplements to improve lipid metabolism targeting the “bile acid–AMPK–TGR5” pathway.
Hexokinases II‐mediated glycolysis governs susceptibility to crizotinib in ALK‐positive non‐small cell lung cancer
Authors: Lin Caiyu , Chen Hengyi , Han Rui , Li Li , Lu Conghua , Hao Shuai , Wang Yubo , He Yong
Published: November 2021

Background

Activation of ALK leads to a high level of aerobic glycolysis related to crizotinib insensitivity in anaplastic lymphoma kinase‐positive non‐small cell lung cancer (ALK+ NSCLC). The strategy and mechanism of glycolysis inhibition in sensitizing ALK+ NSCLC cells to crizotinib requires further investigation.

Methods

The levels of glycolysis in H3122 and H2228 cells were evaluated through detection of glucose consumption and lactate production. MTT assay was used to explore the effects of glycolytic inhibitors on crizotinib sensitivity, and the potential mechanism of action were detected by colony formation, Ki67 incorporation assay, transwell assay, small interfering RNA technology and western blot analysis.

Results

ALK+ NSCLC cells exhibited significantly higher levels of glycolysis compared to ALK− NSCLC cells. Long‐term exposure to crizotinib could decrease the sensitivity of ALK+ NSCLC cells to crizotinib via increasing the levels of glycolysis related to hexokinases II (HK2). Crizotinib in combination with glycolysis inhibitor 2‐deoxy‐D‐glucose (2DG) synergistically inhibited proliferation, glycolysis, colony formation and invasion ability of ALK+ NSCLC cells. 2DG sensitization crizotinib might be associated with the inhibition of HK2‐mediated glycolysis and P‐ALK/AKT/mTOR signaling pathway in H3122 and H2228 cells.

Conclusions

These results indicate that HK2‐mediated glycolysis plays a crucial role in the increased tolerance of ALK+ NSCLC cells to crizotinib. 2DG may sensitize ALK+ NSCLC to crizotinib via suppression of HK2‐mediated glycolysis and the AKT/mTOR signaling pathway.
pyRSD‐CoEv: A python package for selective sweep detection and co‐evolutionary gene cluster identification
Authors: Zhu Xingxing , Zhang Haoyu , Tang Qianzi
Published: November 2021

Genes undergo distinct selective sweeps, and also interact and coevolve, forming the bases of complex phenotypic traits. Therefore, the identification of genes that coevolve or are under artificial selective sweeps is of great importance. However, previous computational methods have been designed for either populations of closely related breeds or individuals of distinct species. Approaches intended specifically for closely related individuals without replicate (i.e. each breed/strain is represented by only one individual) are long overdue. We present a free, powerful, open source package, pyRSD‐CoEv, that allows the identification of genes undergoing coevolution and/or selection‐based sweeps. pyRSD‐CoEv includes two main analysis workflows for genomic variant data: (i) the identification of selective sweeps using relative homozygous single nucleotide variant density (RSD); and (ii) the identification of coevolutionary gene clusters based on correlated evolutionary rates. The python package pyRSD‐CoEv is written using python 3.7 and is freely available from the github website at https://github.com/QianZiTang/pyRSD‐CoEv. It runs on Linux.
Women's and men's experiences in group therapy for substance use disorders: A qualitative analysis
Authors: Sugarman Dawn E. , Meyer Laurel E. , Reilly Meghan E. , Greenfield Shelly F.
Published: November 2021

Background and Objectives

This thematic analysis of qualitative interviews from participants in Stage II randomized controlled trial examined women's and men's experiences in group therapy for substance use disorders (SUDs).

Methods

Interviews were conducted with 77 women and 38 men after completion of either the gender‐specific Women's Recovery Group (WRG) or mixed‐gender Group Drug Counseling (GDC). Interviews were coded for themes using a deductive approach with a coding scheme modified from the Stage I trial. Satisfaction was measured quantitatively posttreatment.

Results

Participants had high satisfaction scores with no significant differences between groups. Women in GDC rated group gender composition as less helpful than those in WRG. In the GDC group, women more frequently discussed the theme of self‐perception (e.g., feelings of comfort, safety, shame) compared with men. Men overwhelmingly expressed the benefits of having women in the group, whereas women expressed advantages and disadvantages of mixed‐gender groups and preference for single‐gender groups. Guilt and shame were discussed by women and men; however, only women discussed stigma and its important role in their addiction and recovery.

Discussion and Conclusion

Men more frequently endorsed the helpfulness of mixed‐gender groups than did women while women appreciated the enhanced support in single‐gender SUD groups. Issues of stigma are especially salient for women.

Scientific Significance

Men and women express differences in their experiences of SUD group therapy. Only women endorse stigma as an obstacle to their treatment and recovery. Tailoring treatment to meet women's and men's needs may enhance engagement, retention, and clinical outcomes.
Associations between poor gross and fine motor skills in pre‐school and peer victimization concurrently and longitudinally with follow‐up in school age – results from a population‐based study
Authors: Øksendal Elise , Brandlistuen Ragnhild Eek , Holte Arne , Wang Mari Vaage
Published: November 2021

Background

Children with poor motor skills are at increased risk of peer victimization. However, it is unclear whether poor gross and fine motor skills are differently linked to peer victimization among pre‐school and schoolchildren.

Aims

To investigate associations between poor gross and fine motor skills measured in pre‐school and the associations to peer victimization measured concurrently and in school age.

Sample

Data from the Norwegian Mother, Father and Child Cohort Study (MoBa), and the Medical Birth Registry of Norway were used. Participants with complete questionnaires at 3, 5, and 8 years (n = 23 215) were included.

Methods

A longitudinal design and an autoregressive cross‐lagged model were used to investigate if poor gross and fine motor skills at 3 and 5 years predicted peer victimization at 5 and 8 years. Because emotional difficulties are associated with both motor skills and peer victimization, the results were adjusted for emotional difficulties.

Results

Only poor fine motor skills at 3 years had a significant association to peer victimization at 5 years. Poor gross motor skills at 5 years had a stronger association to peer victimization measured concurrently compared to poor fine motor skills, and only poor fine motor skills at 5 years was significantly linked to peer victimization at 8 years. No gender difference was found between these paths.

Conclusions

Teachers and parents should be aware that motor skills predict peer victimization, and that poor gross and fine motor skills have different associations to peer victimization measured at different ages.
Development co‐operation by European regions: Introducing the subnational donor governance dataset
Authors: Reinsberg Bernhard , Dellepiane Sebastian
Published: November 2021

Motivation

Interest in the international development co‐operation activities of subnational governments like Catalonia, Flanders, and Scotland has grown in recent years. Beyond these well‐known cases, however, we currently lack systematic evidence on the scope of the phenomenon.

Purpose

This article introduces a new dataset of 195 European regions to provide systematic information on which regions engage in international development co‐operation. The dataset includes information on institutional structures and governance modalities, aid motivations, aid modalities, and aid policies.

Methods and approach

To demonstrate the utility of our dataset, we provide descriptive insights into the phenomenon of subnational development co‐operation while at the same time suggesting questions for future research that can be addressed with the help of the dataset.

Findings

We find that subnational development co‐operation extends far beyond some well‐cited cases, given that around 70 regions have some institutional structure for development co‐operation. With relatively small budgets, regional aid delivery primarily relies on non‐governmental organizations (NGOs) and supports a variety of purposes in the sustainable development agenda, including human rights, environmental affairs, fair trade, sustainable consumption, and development education at home.

Policy implications

Being the first of its kind, the dataset advances our understanding of subnational governments as autonomous providers of development aid and their potential role in helping advance the Sustainable Development Goals in the multi‐level global development governance architecture.
Attentional sampling of visual and auditory objects is captured by theta‐modulated neural activity
Authors: Plöchl Michael , Fiebelkorn Ian , Kastner Sabine , Obleser Jonas
Published: November 2021

Recent evidence suggests that visual attention alternately samples two behaviourally relevant objects at approximately 4 Hz, rhythmically shifting between the objects. Whether similar attentional rhythms exist in other sensory modalities, however, is not yet clear. We therefore adapted and extended an established paradigm to investigate visual and potential auditory attentional rhythms, as well as possible interactions, on both a behavioural (detection performance, N = 33) and a neural level (EEG, N = 18). The results during unimodal attention demonstrate that both visual‐ and auditory‐target detection fluctuate at frequencies of approximately 4–8 Hz, confirming that attentional rhythms are not specific to visual processing. The EEG recordings provided evidence of oscillatory activity that underlies these behavioural effects. At right and left occipital EEG electrodes, we detected counter‐phasic theta‐band activity (4–8 Hz), mirroring behavioural evidence of alternating sampling between the objects presented right and left of central fixation, respectively. Similarly, alpha‐band activity as a signature of relatively suppressed sensory encoding showed a theta‐rhythmic, counter‐phasic change in power. Moreover, these theta‐rhythmic changes in alpha power were predictive of behavioural performance in both sensory modalities. Overall, the present findings provide a new perspective on the multimodal rhythmicity of attention.
Dentigerous cysts with exostosis of the temporal bone in horses – A new variant diagnosed by computed tomography
Authors: Heun F. , Schwieder A. , Hansmann F. , Bienert‐Zeit A. , Hellige M.
Published: November 2021

The dentigerous cyst or temporal teratoma in horses is a well‐known congenital malformation that occurs in the temporal region and usually contains dental tissue. This case report describes two horses with a previously unreported variant of the dentigerous cyst associated with an exostosis arising from the temporal bone. The principal clinical sign was a draining tract opening at the margin of the right pinna in both horses. There was no evidence of an ectopic tooth on the radiographs or at ultrasonographic examination. Computed tomography combined with positive contrast sinography of the draining tract revealed bone formation arising from the supramastoid crest of the right temporal bone extending towards a cyst‐like structure but without direct connection in both cases. This bone formation was located at a site on the supramastoid crest, close to the external acoustic meatus, where ectopic teeth may also occur. Both cysts were removed surgically with a good long‐term outcome.
The effect of risk aversion and financing source on a supply chain of in‐app products
Authors: Avinadav Tal , Bunker Adi Eyal
Published: November 2021

We study the decisions of a distribution platform and an app developer, both risk averse, which interact via a revenue‐sharing contract under the freemium business model with optional in‐app purchases. The model considers the random impact of quality on the demand potential of an in‐app product, and we conduct the analysis under the mean‐variance framework. We investigate two financing sources for the developer's activity: self‐financing and revenue‐based financing by an external investor. We reach three main findings: (i) The stochastic‐dominance property exists both for the platform's and the investor's profits with regard to their revenue shares; (ii) the more risk averse the developer is, the more he tends to use revenue‐based financing, but he will receive a lower financing amount; and (iii) the shift from self‐financing to revenue‐based financing lowers the platform's expected revenue.