bluuebunny/crossref_metadata_2025 huggingface dataset:
Post-tuberculosis sequelae and their correlation with quality of life: An observational study at a tertiary care center of north India
Authors: Aggarwal Nishant , Ghosh Tamoghna , Bhan Munish , Dwarakanathan Vignesh , Sethi Prayas , Meena Ved Prakash , Sinha Sanjeev , Ray Animesh
Published: October 2021

Background

Lung impairment is a frequently recognised outcome in patients treated for pulmonary tuberculosis (TB). The impact of post-TB sequelae is not only restricted to clinical outcomes but also includes the quality of life and psycho-social well-being. However the magnitude of involvement of quality of life and the likely factors determining it are not clear. In this study, we assess the degree of compromise of quality of life and its determinants in patients of post-TB sequelae.

Methods

Patients >18 years of age with a history of pulmonary tuberculosis were included in the study. Clinical history, pulmonary function test (PFT) and chest radiographs were recorded. The severity of dyspnea was evaluated using mMRC; quality of life assessment (QoL) was done using two standardized questionnaires- St. George’s Respiratory Questionnaire (SGRQ) and Seattle Obstructive Lung Disease Questionnaire (SOLQ).

Results

A total of 90 participants (mean age 40.4±11.6 years; 60 [66.7%] males) were recruited in the study. Overall, 93.3% (95% CI: 86.1%-97.5%) were currently symptomatic. A total of 96.8% (61/63) patients had abnormal pulmonary function test results, out of which 61.9% (39/63) had a mixed type. Out of 65 patients with chest radiographs available, 60 (92.3%,95% CI:84.6-96.8) patients had abnormalities with 45 (69.2%,95% CI: 58.3-78.2) having bilateral chest radiographic abnormalities. On assessment of QoL by SGRQ, the average score obtained was 42.3±24.0 (95% CI:37.3-47.3), with ‘Symptoms’ being the most affected domain. On using SOLQ, ‘Treatment satisfaction’ (mean score 38.5±21.7, 95% CI:34-43) and ‘Physical function’ (mean score 66.6±23.7, 95% CI:61.6-71.6) were the most affected. Neither spirometry results nor chest radiograph severity score could significantly account for the reduction of QoL. There was also a significant correlation between most of the parameters of SGRQ and SOLQ questionnaires in these patients.

Conclusion

Persistent respiratory symptoms, radiographic and spirometric abnormalities, were present in most of the patients with post-tubercular sequelae. Quality of life, as measured by SGRQ and SOLQ, was found to be significantly impaired in the majority of patients.
Synergetic impacts of turbulence and fishing reduce ocean biomass
Authors: McKerral Jody C. , Seymour Justin R. , Lavery Trish J. , Rogers Paul J. , Jeffries Thomas C. , Paterson James S. , Roudnew Ben , Huveneers Charlie , Newton Kelly , van Dongen-Vogels Virginie , Cribb Nardi P. , Winn Karina M. , Smith Renee J. , Beckmann Crystal L. , Prime Eloise , Charlton Claire M. , Kleshnina Maria , Grigson Susanna R. , Takeuchi Marika , Seuront Laurent , Mitchell James G.
Published: October 2021

A universal scaling relationship exists between organism abundance and body size1,2. Within ocean habitats this relationship deviates from that generally observed in terrestrial systems2–4, where marine macro-fauna display steeper size-abundance scaling than expected. This is indicative of a fundamental shift in food-web organization, yet a conclusive mechanism for this pattern has remained elusive. We demonstrate that while fishing has partially contributed to the reduced abundance of larger organisms, a larger effect comes from ocean turbulence: the energetic cost of movement within a turbulent environment induces additional biomass losses among the nekton. These results identify turbulence as a novel mechanism governing the marine size-abundance distribution, highlighting the complex interplay of biophysical forces that must be considered alongside anthropogenic impacts in processes governing marine ecosystems.
Extracellular release of mitochondrial DNA is triggered by cigarette smoke and is detected in COPD
Authors: Giordano Luca , Gregory Alyssa D. , Verdaguer Mireia Perez , Ware Sarah A. , Harvey Hayley , DeVallance Evan , Brzoska Tomasz , Sundd Prithu , Zhang Yingze , Sciurba Frank C. , Shapiro Steven D. , Kaufman Brett A.
Published: October 2021

Chronic obstructive pulmonary disease (COPD) is characterized by continuous and irreversible inflammation frequently caused by persistent exposure to toxic inhalants such as cigarette smoke (CS). CS may trigger mitochondrial DNA (mtDNA) extrusion into the cytosol, extracellular space, or foster its transfer by extracellular vesicles (EVs). The present study aimed to elucidate whether mtDNA is released upon CS exposure and in COPD. We measured cell-free mtDNA (cf-mtDNA) in the plasma of former smokers affected by COPD, in the serum of mice that developed CS-induced emphysema, and in the extracellular milieu of human bronchial epithelial cells exposed to cigarette smoke extract (CSE). Further, we characterized cells exposed to sublethal and lethal doses of CSE by measuring mitochondrial membrane potential and dynamics, superoxide production and oxidative stress, cell cycle progression, and cytokine expression. Patients with COPD and mice that developed emphysema showed increased levels of cf-mtDNA. In cell culture, exposure to a sublethal dose of CSE decreased mitochondrial membrane potential, increased superoxide production and oxidative damage, dysregulated mitochondrial dynamics, and triggered mtDNA release in extracellular vesicles. The release of mtDNA into the extracellular milieu occurred concomitantly with increased expression of DNase III, DNA-sensing receptors (cGAS, NLRP3), proinflammatory cytokines (IL-1β, IL-6, IL-8, IL-18, CXCL2), and markers of senescence (p16, p21). Exposure to a lethal dose of CSE preferentially induced mtDNA and nuclear DNA release in cell debris. Our findings demonstrate that CS-induced stress triggers mtDNA release and is associated with COPD, supporting cf-mtDNA as a novel signaling response to CS exposure.
Genomic architecture and sexually dimorphic expression underlying immunity in the red mason bee, Osmia bicornis
Authors: Möllmann Jannik S. , Colgan Thomas J.
Published: October 2021

Insect pollinators provide crucial ecosystem services yet face increasing environmental pressures. The challenges posed by novel and reemerging pathogens on bee health means we need to improve our understanding of the immune system, an important barrier to infections and disease. Despite its importance, for certain ecologically important species, such as solitary bees, our understanding of the genomic basis and molecular mechanisms underlying immune potential, and how intrinsic and extrinsic factors may influence immune gene expression is lacking. Here, to improve our understanding of the genomic architecture underlying immunity of a key solitary bee pollinator, we characterised putative immune genes of the red mason bee, Osmia bicornis. In addition, we used publicly available RNA-seq datasets to determine how sexes differ in immune gene expression and splicing but also how pesticide exposure may affect immune gene expression in females. Through comparative genomics, we reveal an evolutionary conserved set of more than 500 putative immune-related genes. We found genome-wide patterns of sex-biased gene expression, including immune genes involved in antiviral-defence. Interestingly, the expression of certain immune genes were also affected by exposure to common neonicotinoids, particularly genes related to haemocyte proliferation. Collectively, our study provides important insights into the gene repertoire, regulation and expression differences in the sexes of O. bicornis, as well as providing additional support for how neonicotinoids can affect immune gene expression, which may affect the capacity of solitary bees to respond to pathogenic threats.
Addressing the Association Between Action Video Game Playing Experience and Visual Search in Naturalistic Multisensory scenes
Authors: Hamzeloo Mohammad , Kvasova Daria , Soto-Faraco Salvador
Published: October 2021

Prior studies investigating the effects of routine action video game playing have demonstrated improvements in a variety of cognitive processes, including improvements in attentional tasks. However, there is little evidence indicating that the cognitive benefits of playing action video games generalize from simplified unisensory stimuli to naturalistic multisensory scenes – a fundamental characteristic of natural, everyday life environments. In particular, it is unknown whether video game experience has an impact on cross-modal congruence effects when searching through such multisensory scenes. The present pre-registered compared the performance of action video game players (AVGPs) with non-video game players (NVGPs) on a visual search task for objects embedded in video clips of realistic scenes. We run two identical online experiments with gender-balanced samples, for a total N=130. Overall, the data replicated previous findings reporting search benefits when visual targets were accompanied by semantically congruent auditory events, compared to neutral or incongruent ones. However, according to the results, AVGPs did not consistently outperform NVGPs in the search task overall, nor they exploit multisensory cues more efficiently than NVGPs. Exploratory analyses with self-reported gender as a variable revealed a potential difference in response strategy between experienced male and female AVGPs when dealing with cross-modal cues. These findings suggest that the generalization of the advantage of AVG experience to realistic, cross-modal situations should be done with caution, and considering gender-related aspects.
Postsynaptic synucleins mediate vesicular exocytosis of endocannabinoids
Authors: Albarran Eddy , Sun Yue , Liu Yu , Raju Karthik , Dong Ao , Li Yulong , Wang Sui , Südhof Thomas C. , Ding Jun B.
Published: October 2021

Two seemingly unrelated questions have long motivated studies in neuroscience: How are endocannabinoids, among the most powerful modulators of synaptic transmission, released from neurons? What are the physiological functions of synucleins, key contributors to Parkinson’s Disease? Here, we report an unexpected convergence of these two questions: Endocannabinoids are released via vesicular exocytosis from postsynaptic neurons by a synuclein-dependent mechanism. Specifically, we find that deletion of all synucleins selectively blocks all endocannabinoid-dependent synaptic plasticity; this block is reversed by postsynaptic expression of wildtype but not of mutant α-synuclein. Loading postsynaptic neurons with endocannabinoids via patch-pipette dialysis suppressed presynaptic neurotransmitter release in wildtype but not in synuclein-deficient neurons, suggesting that the synuclein deletion blocks endocannabinoid release. Direct optical monitoring of endocannabinoid release confirmed the requirement of synucleins. Given the role of synucleins in vesicular exocytosis, the requirement for synucleins in endocannabinoid release indicates that endocannabinoids are secreted via exocytosis. Consistent with this hypothesis, postsynaptic expression of tetanus-toxin light chain, which cleaves synaptobrevin SNAREs, also blocked endocannabinoid-dependent plasticity and release. The unexpected finding that endocannabinoids are released via synuclein-dependent exocytosis assigns a function to synucleins and resolves a longstanding puzzle of how neurons release endocannabinoids to induce synaptic plasticity.
Nanoengineered DNA origami with repurposed TOP1 inhibitors targeting myeloid cells for the mitigation of neuroinflammation
Authors: Zhu Keying , Wang Yang , Sarlus Heela , Geng Keyi , Nutma Erik , Sun Jingxian , Kung Shin-Yu , Bay Cindy , Han Jinming , Lund Harald , Amor Sandra , Wang Jun , Zhang Xingmei , Kutter Claudia , Guerreiro Cacais André Ortlieb , Högberg Björn , Harris Robert A.
Published: October 2021

Targeting myeloid cells, especially microglia, for the treatment of neuroinflammatory diseases such as multiple sclerosis (MS), is underappreciated. Here, we screened a library of compounds and identified the topoisomerase 1 (TOP1) inhibitor camptothecin (CPT) as a promising drug candidate for microglial modulation. CPT and its FDA-approved analog topotecan (TPT) inhibited inflammatory responses in microglia and macrophages, and ameliorated neuroinflammation in mice. Transcriptomic analysis of sorted microglia revealed an altered transcriptional phenotype following TPT treatment, with Ikzf1 identified as a potential target. Importantly, TOP1 expression was found elevated in several neuroinflammatory conditions, including human MS brains. To achieve targeted delivery to myeloid cells we designed a nanosystem using DNA origami and loaded TPT into it (TopoGami). TopoGami also significantly suppressed the inflammatory response in microglia and mitigated disease progression in MS-like mice. Our findings suggest that TOP1 inhibition represents a therapeutic strategy for neuroinflammatory diseases, and the proposed nanosystem may foster future research and drug development with a demand to target myeloid cells.
Causal evidence for a domain-specific role of left superior frontal sulcus in human perceptual decision making
Authors: Barretto García Miguel , Grueschow Marcus , Moisa Marius , Polania Rafael , Ruff Christian C.
Published: October 2021

Humans and animals can flexibly choose their actions based on different information, ranging from objective states of the environment (e.g., apples are bigger than cherries) to subjective preferences (e.g., cherries are tastier than apples). Whether the brain instantiates these different choices by recruiting either specialised or shared neural circuitry remains debated. Specifically, domain-general accounts of prefrontal cortex (PFC) function propose that prefrontal areas flexibly process either perceptual or value-based evidence depending on what is required for the present choice, whereas domain-specific theories posit that PFC sub-areas, such as the left superior frontal sulcus (SFS), selectively integrate evidence relevant for perceptual decisions. Here we comprehensively test the functional role of the left SFS for choices based on perceptual and value-based evidence, by combining fMRI with a behavioural paradigm, computational modelling, and transcranial magnetic stimulation. Confirming predictions by a sequential sampling model, we show that TMS-induced excitability reduction of the left SFS selectively changes the processing of decision-relevant perceptual information and associated neural processes. In contrast, value-based decision making and associated neural processes remain unaffected. This specificity of SFS function is evident at all levels of analysis (behavioural, computational, and neural, including functional connectivity), demonstrating that the left SFS causally contributes to evidence integration for perceptual but not value-based decisions.
A causality-inspired feature selection method for cancer imbalanced high-dimensional data
Authors: Liu Yijun , Huang Qiang , Sun Huiyan , Chang Yi
Published: October 2021

It is significant but challenging to explore a subset of robust biomarkers to distinguish cancer from normal samples on high-dimensional imbalanced cancer biological omics data. Although many feature selection methods addressing high dimensionality and class imbalance have been proposed, they rarely pay attention to the fact that most classes will dominate the final decision-making when the dataset is imbalanced, leading to instability when it expands downstream tasks. Because of causality invariance, causal relationship inference is considered an effective way to improve machine learning performance and stability. This paper proposes a Causality-inspired Least Angle Nonlinear Distributed (CLAND) feature selection method, consisting of two branches with a class-wised branch and a sample-wised branch representing two deconfounder strategies, respectively. We compared the performance of CLAND with other advanced feature selection methods in transcriptional data of six cancer types with different imbalance ratios. The genes selected by CLAND have superior accuracy, stability, and generalization in the downstream classification tasks, indicating potential causality for identifying cancer samples. Furthermore, these genes have also been demonstrated to play an essential role in cancer initiation and progression through reviewing the literature.

Author Summary

Selecting trustworthy biomarkers from high-dimensional data is an important step to help researchers and clinicians understand which genes play key roles in cancer development and progression. A large number of machine learning-based feature selection algorithms have been generated in recent years for biomarker discovery. However, these methods usually show unstable results in the face of class-imbalanced biological data, making it seem unreliable for researchers. Here we introduce the causal theory with the property of causal invariance to aid in the design of feature selection algorithms, analyze how imbalanced distributions affect feature selection methods, and propose a novel causality-based feature selection method. The method with bilateral structure adjusts the data distribution from both class-wise and sample-wise to eliminate the effect of imbalance on the results. Additionally, CLAND can simultaneously address the nonlinearity and high-dimensionality of cancer data, which broaden its application scope. We conducted extensive experiments on six real imbalance cancer datasets and obtained efficient and stable results, while the obtained biomarker has significant biological significance.
Ferroptosis assassinates tumor (FAST)
Authors: Luo Tao , Wang Yile , Wang Jinke
Published: October 2021

In 2020, nearly 20 million peoples got cancer and nearly 10 million peoples died of cancer, indicating the current therapies do not meet the cancer treatment and cancer remains a great threat to human health and life. New therapies are still in urgent demand. In a recent study, we developed a new effective cancer therapy, gene-interfered ferroptosis therapy (GIFT), by combining cancer cell-specific knockdown of two iron efflux genes (FPN and LCN2) with iron nanoparticles (FeNPs). GIFT shows wide antitumor activity, high cancer specificity, certain cancer eradication potential, and biosafety. To further improve the therapy, we here develop an updated GIFT named as Ferroptosis ASsassinates Tumor (FAST) by knocking down five additional ferroptosis-resistance genes (FSP1, FTH1, GPX4, SLC7A11, NRF2). As a result, we found that FAST showed more significant antitumor activity than GIFT. Especially, FAST eradicated three different types of tumors (leukemia, colon cancer and lung metastatic melanoma) from over 50 percent of cancer mice, making the mice to survive up to 250 days without tumor relapse. FAST also significantly inhibited and prevented growth of spontaneous breast cancer and improved survival in mice. Additionally, FAST showed high pan-antitumor efficacy, high cancer specificity, and in vivo safety.
μ-Theraphotoxin-Pn3a inhibition of CaV3.3 channels reveals a novel isoform-selective drug binding site
Authors: McArthur Jeffrey R. , Wen Jierong , Hung Andrew , Finol-Urdaneta Rocio K. , Adams David J.
Published: October 2021

Low voltage-activated calcium currents are mediated by T-type calcium channels CaV3.1, CaV3.2, and CaV3.3, which modulate a variety of physiological processes including sleep, cardiac pace-making, pain, and epilepsy. CaV3 isoforms’ biophysical properties, overlapping expression and lack of subtype-selective pharmacology hinder the determination of their specific physiological roles in health and disease. Notably, CaV3.3’s contribution to normal and pathophysiological function has remained largely unexplored. We have identified Pn3a as the first subtype-selective spider venom peptide inhibitor of CaV3.3, with >100-fold lower potency against the other T-type isoforms. Pn3a modifies CaV3.3 gating through a depolarizing shift in the voltage dependence of activation thus decreasing CaV3.3-mediated currents in the normal range of activation potentials. Paddle chimeras of KV1.7 channels bearing voltage sensor sequences from all four CaV3.3 domains revealed preferential binding of Pn3a to the S3-S4 region of domain II (CaV3.3DII). This novel T-type channel pharmacological site was explored through computational docking simulations of Pn3a into all T-type channel isoforms highlighting it as subtype-specific pharmacophore with therapeutic potential. This research expands our understanding of T-type calcium channel pharmacology and supports the suitability of Pn3a as a molecular tool in the study of the physiological roles of CaV3.3 channels.
Ancient and modern geochemical signatures in the 13,500-year sedimentary record of Lake Cadagno
Authors: Berg Jasmine S. , Lepine Mathilde , Laymand Emile , Han Xingguo , Vogel Hendrik , Morlock Marina A. , Gajendra Niroshan , Gilli Adrian , Bernasconi Stefano , Schubert Carsten J. , Su Guangyi , Lever Mark A.
Published: October 2021

Although lake sediments are globally important organic carbon sinks and therefore important habitats for deep microbial life, the deep lacustrine biosphere has thus far been little studied compared to its marine counterpart. To investigate the impact of the underexplored deep lacustrine biosphere on the sediment geochemical environment and vice versa, we performed a comprehensive microbiological and geochemical characterization of a sedimentary sequence from Lake Cadagno covering its entire environmental history since formation following glacial retreat. We found that both geochemical gradients and microbial community shifts across the ∼13.5 kyr subsurface sedimentary record reflect redox changes in the lake, going from oxic to anoxic and sulfidic. Most microbial activity occurs within the top 40 cm of sediment, where millimolar sulfate concentrations diffusing in from the bottom water are completely consumed. In deeper sediment layers, organic carbon remineralization is much slower but microorganisms nonetheless subsist on fermentation, sulfur cycling, metal reduction, and methanogenesis. The most surprising finding was the presence of a deep, oxidizing groundwater source. This water source generates an inverse redox gradient at the bottom of the sedimentary sequence and could contribute to the remineralization of organic matter sequestered in the energy-limited deep subsurface.
Genome-wide mapping of Vibrio cholerae VpsT binding identifies a mechanism for c-di-GMP homeostasis
Authors: Guest Thomas , Haycocks James R.J. , Warren Gemma Z.L. , Grainger David C.
Published: October 2021

Many bacteria use cyclic dimeric guanosine monophosphate (c-di-GMP) to control changes in lifestyle. The molecule, synthesised by proteins having diguanylate cyclase activity, is often a signal to transition from motile to sedentary behaviour. In Vibrio cholerae, c-di-GMP can exert its effects via the transcription factors VpsT and VpsR. Together, these proteins activate genes needed for V. cholerae to form biofilms. In this work, we have mapped the genome-wide distribution of VpsT in a search for further regulatory roles. We show that VpsT binds 23 loci and recognises a degenerate DNA palindrome having the consensus 5’-W-5R-4[CG]-3Y-2W-1W+1R+2[GC]+3Y+4W+5-3’. Most genes targeted by VpsT encode functions related to motility, biofilm formation, or c-di-GMP metabolism. Most notably, VpsT activates expression of the vpvABC operon that encodes a diguanylate cyclase. This creates a positive feedback loop needed to maintain intracellular levels of c-di-GMP. Mutation of the key VpsT binding site, upstream of vpvABC, severs the loop and c-di-GMP levels fall accordingly. Hence, as well as relaying the c-di-GMP signal, VpsT impacts c-di-GMP homeostasis.
Inference of cell-type specific imprinted regulatory elements and genes during human neuronal differentiation
Authors: Liang Dan , Aygün Nil , Matoba Nana , Ideraabdullah Folami Y. , Love Michael I. , Stein Jason L.
Published: October 2021

Genomic imprinting results in gene expression biased by parental chromosome of origin and occurs in genes with important roles during human brain development. However, the cell-type and temporal specificity of imprinting during human neurogenesis is generally unknown. By detecting within-donor allelic biases in chromatin accessibility and gene expression that are unrelated to cross-donor genotype, we inferred imprinting in both primary human neural progenitor cells (phNPCs) and their differentiated neuronal progeny from up to 85 donors. We identified 43/20 putatively imprinted regulatory elements (IREs) in neurons/progenitors, and 133/79 putatively imprinted genes in neurons/progenitors. Though 10 IREs and 42 genes were shared between neurons and progenitors, most imprinting was only detected within specific cell types. In addition to well-known imprinted genes and their promoters, we inferred novel IREs and imprinted genes. We found IREs overlapped with CpG islands more than non-imprinted regulatory elements. Consistent with DNA methylation-based regulation of imprinted expression, some putatively imprinted regulatory elements also overlapped with differentially methylated regions on the maternal germline. Finally, we identified a progenitor-specific putatively imprinted gene overlap with copy number variation that is associated with uniparental disomy-like phenotypes. Our results can therefore be useful in interpreting the function of variants identified in future parent-of-origin association studies.
Regulation of Polyhomeotic condensates by intrinsically disordered sequences that affect chromatin binding
Authors: Kapur Ibani , Boulier Elodie L. , Francis Nicole J.
Published: October 2021

The Polycomb group (PcG) complex PRC1 localizes in the nucleus in the form of condensed structures called Polycomb bodies. The PRC1 subunit Polyhomeotic (Ph) contains an oligomerizing sterile alpha motif (SAM) that is implicated in both PcG body formation and chromatin organization in Drosophila and mammalian cells. A truncated version of Ph containing the SAM (mini-Ph), forms phase separated condensates with DNA or chromatin in vitro, suggesting PcG bodies may form by SAM-driven phase separation. In cells, Ph forms multiple small condensates, while mini-Ph typically forms a single large nuclear condensate. We therefore hypothesize that sequences outside of mini-Ph, which are predicted to be intrinsically disordered, are required for proper condensate formation. We identified three distinct low complexity regions in Ph based on sequence composition. We systematically tested the role of each of these sequences in Ph condensates using live imaging of transfected Drosophila S2 cells. Each sequence uniquely affects Ph SAM-dependent condensate size, number, and morphology, but the most dramatic effects occur when the central, glutamine rich IDR is removed, which results in large Ph condensates. Like mini-Ph condensates, these condensates exclude chromatin. Chromatin fractionation experiments indicate that removal of the glutamine rich IDR reduces chromatin binding, while removal of either of the other IDRs increases chromatin binding. Our data suggest all three IDRs, and functional interactions among them, regulate Ph condensate size and number. Our results can be explained by a model in which tight chromatin binding by Ph IDRs antagonizes Ph SAM driven phase separation and highlight the complexity of regulation of biological condensates housed in single proteins.
Low Temperatures Lead to Higher Toxicity of the Fungicide Folpet to Larval Stages of Rana temporaria and Bufotes viridis
Authors: Leeb Christoph , Schuler Laura , Brühl Carsten A. , Theissinger Kathrin
Published: October 2021

Pesticides are one of the main drivers of the worldwide amphibian decline. Their actual toxicity depends on a number of factors, like the species in focus or the developmental stage of exposed individuals. As ectothermic species, the metabolism of amphibians is influenced by ambient temperature. Therefore, temperature also affects metabolic rates and thus processes that might enhance or reduce toxic effects. Studies about the interactive effect of temperature and toxicity on amphibians are rare and deliver contrasting results. To investigate the temperature-dependent pesticide sensitivity of larvae of two European species we conducted acute toxicity tests for the viticultural fungicide Folpan® 500 SC with the active ingredient folpet at different temperatures (6°C, 11°C, 16°C, 21°C, 26°C). Sensitivity of Rana temporaria and Bufotes viridis was highly affected by temperature: early larvae (Gosner stage 20) were about twice more sensitive to Folpan® 500 SC at 6°C compared to 21°C. Next to temperature, species and developmental stage of larvae had an effect on sensitivity. The most sensitive individuals (early stages of R. temporaria at 6°C) were 14.5 times more sensitive than the least sensitive ones (early stages of B. viridis at 26°C). Our results raise concerns about typical ecotoxicological studies with amphibians that are often conducted at temperatures between 15°C and 20°C. We suggest that future test designs should be performed at temperatures that reflect the temperature range amphibians are exposed to in their natural habitats. Variations in the sensitivity due to temperature should also be considered as an uncertainty factor in upcoming environmental risk assessments for amphibians.
Non-coding function for mRNAs in Focal Adhesion Architecture and Mechanotransduction
Authors: Boraas Liana , Hu Mengwei , Thornton Lauren , Vejnar Charles E. , Zhen Gang , Giraldez Antonio J. , Mayr Christine , Wang Siyuan , Nicoli Stefania
Published: October 2021

Messenger RNA (mRNA) compartmentalization within the cytosol is well-recognized as a key mechanism of local translation-mediated regulation of protein levels, but whether such localization could be a means of exercising non-coding mRNA function is unknown. Here, we explore non-coding functions for mRNAs associated with focal adhesions (FAs), cellular structures responsible for mediating cell adhesion and response to changes in the extracellular matrix (ECM). Using high-throughput single molecule imaging and genomic profiling approaches, we find that mRNAs with distinct sequence characteristics localize to FAs in different human cell types. Notably, ∼85% of FA-mRNAs are not translationally active at steady state or under conditions of FA dissolution or activation. Untranslated mRNA sequences are anchored to FA based on their functional states by the RNA binding protein, G3BP1, forming biomolecular granules. Removing RNA or G3BP1, but not blocking new polypeptide synthesis, dramatically changes FA protein composition and organization, resulting in loss of cell contractility and cellular ability to adapt to changing ECM. We have therefor uncovered a novel, non-coding role for mRNAs as scaffolds to maintain FA structure and function, broadening our understating of noncanonical mRNA functions.
CRISPR-Cas9 induces large structural variants at on-target and off-target sitesin vivothat segregate across generations
Authors: Höijer Ida , Emmanouilidou Anastasia , Östlund Rebecka , van Schendel Robin , Bozorgpana Selma , Feuk Lars , Gyllensten Ulf , den Hoed Marcel , Ameur Adam
Published: October 2021

To investigate the extent and distribution of unintended mutations induced by CRISPR-Cas9in vivo,we edited the genome of fertilized zebrafish eggs and investigated DNA from >1100 larvae, juvenile and adult fish in the F0 and F1 generations. Four guide RNAs (gRNAs) were used, selected from 23 gRNAs with high on-target efficiencyin vivoin previous functional experiments. CRISPR-Cas9 outcomes were analyzed by long-read sequencing of on-target sites and off-target sites detectedin vitro.In founder larvae, on-target editing of the four gRNAs was 93-97% efficient, and three sites across two gRNAs were identified within vivooff-target editing. Seven percent of the CRISPR-Cas9 editing outcomes correspond to structural variants (SVs), i.e., insertions and deletions ≥50 bp. The adult founder fish displayed a mosaic pattern of editing events in somatic and germ cells. The F1 generation contained high levels of genome editing, with all alleles of 46 examined F1 juvenile fish affected by on-target mutations, including four cases of SVs. In addition, 26% of the juvenile F1 fish (n=12) carried off-target mutations. These CRISPR-induced off-target mutations in F1 fish were successfully validated in pooled larvae from the same founder parents. In conclusion, we demonstrate that large SVs and off-target mutations can be introducedin vivoand passed through the germline to the F1 generation. The results have important consequences for the use of CRISPR-Cas9 in clinical applications, where pre-testing for off-target activity and SVs on patient material is advisable to reduce the risk of unanticipated effects with potentially large implications.
Regression rate performance of paraffin wax and bees wax –Gox with varied grain configuration in a hybrid rocket motor
Authors: G. Saravanan , S. Shanmugam , A.R. Veerappan
Published: October 2021

Purpose

This paper aims to determine the regression rate using wax fuels for three different grain configurations and find a suitable grain port design for hybrid rocket application.

Design/methodology/approach

The design methodology of this work includes different grain port designs and subsequent selection of solid fuels for a suitable hybrid rocket application. A square, a cylindrical and a five-point star grained were designed and prepared using paraffin and beeswax fuels. They were tested in a laboratory-scale rocket with gaseous oxygen to study the effectiveness of solid fuels on these grain structures. The regression rate by static fire testing of these wax fuels was analyzed.

Findings

Beeswax performance is better than that of paraffin wax fuel for all three designs, and the five-slotted star fuel port grain attained the best performance. Beeswax fuel attained an average regression rate ≈of 1.35 mm/s as a function of oxidizer mass flux Gox ≈ 111.8 kg/m2 s and for paraffin wax 1.199 mm/s at Gox ≈ 121 kg/m2 s with gaseous oxygen. The local regression rates of fuels increased in the range of 0.93–1.194 mm/s at oxidizer mass flux range of 98–131 kg/m2 s for cylindrical grain, 0.99–1.21 mm/s at oxidizer mass flux range of 96–129 kg/m2s for square grain and 1.12–1.35 mm/s at oxidizer mass flux range of 91–126 kg/m2 s for a star grain. A complete set of the regression rate formulas is obtained for all three-grain designs as a function of oxidizer flux rate.

Research limitations/implications

The experiment has been performed for a lower chamber pressure up to 10 bar.

Originality/value

Different grain configurations were designed according to the required dimension of the combustion chamber, injector and exhaust nozzle of the design of a lab-scale hybrid rocket, and input parameters were selected and analyzed.
Ads in gaming apps: experiential value of gamers
Authors: Valaei Naser , Bressolles Gregory , Khan Hina , Low Yee Min
Published: October 2021

Purpose

Even though there is a noticeable market value in the mobile gaming apps industry, there has been limited research examining experiential value of gamers with respect to in-game ads in gaming apps. This study fills the void in the literature by examining factors associated with “experiential value of gamers through ads in gaming apps” as well as investigating its antecedents (cognitive and affective involvement) and consequences (positive word of mouth and intention to continue playing the mobile game).

Design/methodology/approach

A total of 600 valid responses from gamers was used to test the model fit, measurement and structural models, conditional probabilistic queries, and nonlinearity.

Findings

This study found that experiential value of gamers through ads in gaming apps is a second-order factor of four constructs: escapism, enjoyment, social affiliation and entertainment. Most of the structural paths between cognitive/affective involvement and dimensions of experiential value are supported. Surprisingly, only social affiliation and entertainment values predict positive word of mouth and intention to continue playing the mobile game, in a nonlinear way.

Originality/value

This study is the first to introduce “experiential value of gamers through ads in gaming apps”. The findings have important implications for companies to develop brand and communication strategies by leveraging specific advertisement formats and present their ads to the right audience in the right gaming apps and at the right time.
A non-parametric framework for evaluating governance–efficiency–productivity associations in commercial banking
Authors: Prakash Navendu , Singh Shveta , Sharma Seema
Published: October 2021

Purpose

Against the backdrop of an Indian banking sector that finds itself entangled in the triple deadlock of increasing competition, technological changes and strict regulatory compliance, the study aims to examine the need for reinforcing stringent corporate and risk governance mechanisms as an instrument for improving efficiency and productivity levels.

Design/methodology/approach

The authors construct three separate indices, namely, supervisory board index, audit index and risk governance index to measure the governance practices of commercial banks. A slacks-based data envelopment analysis technical efficiency (TE) measure, a variable returns to scale cost efficiency model and Malmquist productivity index are employed to determine TE, cost efficiency and productivity change, respectively. A two-step system-generalized method of moments estimation accounts for the dynamic relationship between governance and efficiency.

Findings

The authors show that strict audit and risk governance mechanisms are associated with better efficiency and productivity levels. However, consistent with the free-rider hypothesis, large, independent and diverse boards lead to cost inefficiencies. Strict risk governance structures circumvent the negative effects of high regulatory capital and improve efficiency and total factor productivity. However, friendly boards do not perform efficiently in the presence of regulatory capital, implying that incentives arising from maintaining high levels of equity capital make them more susceptible to risk-taking, and board composition is unable to sidestep this behaviour.

Originality/value

The paper contributes to the literature that explores the linkages between governance, efficiency and productivity. The inferences hold relevance in the post-COVID world, as regulators try to circumvent the additional stress on the banking system by adopting sound corporate and risk governance mechanisms.
The interplay between digital manufacturing and dynamic capabilities: an empirical examination of direct and indirect effects on firm performance
Authors: Savastano Marco , Cucari Nicola , Dentale Francesco , Ginsberg Ari
Published: October 2021

Purpose

The purpose of this paper is to identify and empirically examine the dynamic capabilities (DC) that drive the development of digital manufacturing capabilities (DMC) and the role of DMC in mediating their influence on firm performance.

Design/methodology/approach

Based on the dynamic capabilities view (DCV) of the firm, the authors develop a set of hypotheses that are tested through a survey of 110 managers in the manufacturing sector. The hypothesized model is tested through structural equation modeling.

Findings

The results indicate that although higher-order DC (HODC) have a strong influence on firm performance, their effects are partially mediated by the DMC that they generate, by positively affecting the extended production process.

Practical implications

The analysis contributes to a better understanding of the interplay between levels of the DC hierarchy by finding that DMC play an important role in translating HODC into enhanced firm performance.

Originality/value

By complementing the DCV with the disruptive innovation theory in a specific fast changing context, this study introduces a new construct (DMC) providing an original and considerable contribution to the literature. To the best of the authors’ knowledge, it is the first empirical study that includes and assesses all these elements together in the context of the manufacturing industry.
A study on consumer buying behaviour for fashion and luxury brands under emotional influence
Authors: Bishnoi Sushil Kumar , Singh Sukhvir
Published: October 2021

Purpose

Fashion and luxury brands struggle to make themselves distinguished by ever more apathetic consumers in this highly competitive market. Fashion and luxury retailers can use emotional branding as a way to get their customers involved to address the increasing trend of emotional relationships with a brand to become more competitive. Although brand technology, such as product attributes, characteristics and facts, is unforgettable, personal sensations and experiences better shape brand assessments of consumers. The purpose of this study is to illustrate the dominance of consumers’ emotions over objective analysis in selection among the brands in the field of fashion and luxury products for similar products.

Design/methodology/approach

A comprehensive literature study has been done to explore the various emotional associations that are identified by the advertising, marketing, psychology scholars and researchers. This study also analyses the relevance of consumers’ emotional associations with the fashion and luxury brands. Various online scholarly journal platforms have been used to find the relevant research papers, books and other publications on the basis of keywords of this study. Only recent studies and literature covering the basic concepts of branding, emotional buying and fashion consumer behaviour have been included after scrutinising carefully.

Findings

This study illustrates how emotional branding is crucial in a volatile market, particularly for fashion and luxury brands. This study will also be focussed on the possibility in which consumers buy the fashion and luxury products under the influence of emotional needs. The objective of this paper is to inform both consumers and brands about the emotional influence on the buying decision so that both can take better conscious decision.

Originality/value

Understanding the influence of emotional needs will help fashion brands in creating better customer value and satisfaction. A business or product will be successful only if it is chosen by the consumer to satisfy his needs. Understanding of emotional needs would result in enhancement of consumer’s loyalty for the brand with better satisfaction of needs. As huge part of marketing resources is involved into advertisement and celebrity endorsement, identifying the effective way of advertising and endorsement can help in efficient utilisation of resources.
Adequate sample sizes for improved accuracy of thermal trait estimates
Authors: Duffy Grant A. , Kuyucu Arda C. , Hoskins Jessica L. , Hay Eleanor M. , Chown Steven L.
Published: October 2021

Thermal traits, such as upper and lower critical thermal limits, are vital indicators of the vulnerability of populations and species to environmental change. Thus, accurate estimates of these traits are needed to explain biological patterns and forecast responses to the changing thermal environment. However, many thermal trait studies measure relatively few individuals to estimate traits for whole populations or species.

To ascertain if, and how, sample size affects the accuracy of reported trait means and variances, we applied a subsampling and equivalency testing approach to empirical and simulated trait data to investigate the accuracy of trait estimates relative to sample size and the skew and variance of the trait distribution in the source population.

Simulation results indicated that only 7.9% of the 428 critical thermal limit traits documented in a recent synthesis of thermal trait data reported sufficiently large sample sizes, relative to variance, to ensure confidence in the reported mean trait value with negligible (±0.25°C) error. Greater inter‐individual trait variance in the source population requires a larger number of individuals to be measured to accurately estimate the mean and variance of that trait. This pattern is mitigated somewhat by the tendency of thermal traits to exhibit skew‐normal distributions.

As measurements of few individuals from a population are unlikely to provide accurate estimates of thermal traits, the propensity towards small sample sizes in thermal trait studies is concerning. Macrophysiological syntheses often use these data to describe, explain and predict broad‐scale ecological patterns. Thus, insufficient sample sizes in the original studies could diminish the robustness of these patterns and predictions. For future studies, we recommend that preliminary data be used to estimate trait variance and calculate minimum sample sizes. If small sample sizes are unavoidable, larger error around the measured trait mean must be assumed and accounted for in subsequent analyses.

A free Plain Language Summary can be found within the Supporting Information of this article.
A Place for Women Only: Health, Healing and the Divine at an Islamic Shrine in Central Asia
Authors: Webster Jennifer R.
Published: October 2021

This article analyses the relationships between traditional healing and biomedical practices found in contemporary Central Asia from the late Soviet period into the early twenty‐first century. Gendered demarcation of space, the roles of women as caregivers and protectors of spiritual health in legends and emphasis on life cycle rituals position women at the centre of discussions of healing practices in Central Asia. Through historical and ethnographic work conducted in the Kyrgyz Republic, this article offers a view of women as practitioners and recipients of healing and as producers of knowledge about health and healing.
Changing patterns in medication prescription for gestational diabetes during a time of guideline change in the USA: a cross‐sectional study
Authors: Venkatesh KK , Chiang CW , Castillo WC , Battarbee AN , Donneyong M , Harper LM , Costantine M , Saade G , Werner EF , Boggess KA , Landon MB
Published: October 2021

Objective

To define patterns of prescription and factors associated with choice of pharmacotherapy for gestational diabetes mellitus (GDM), namely metformin, glyburide and insulin, during a period of evolving professional guidelines.

Desing

Cross‐sectional study.

Setting

US commercial insurance beneficiaries from Market‐Scan (late 2015 to 2018).

Study design

We included women with GDM, singleton gestations, 15–51 years of age on pharmacotherapy. The exposure was pharmacy claims for metformin, glyburide and insulin.

Main outcomes

Pharmacotherapy for GDM with either oral agent, metformin or glyburide, compared with insulin as the reference, and secondarily, consequent treatment modification (addition and/or change) to metformin, glyburide or insulin.

Results

Among 37 762 women with GDM, we analysed data from 10 407 (28%) with pharmacotherapy, 21% with metformin (n = 2147), 48% with glyburide (n = 4984) and 31% with insulin (n = 3276). From late 2015 to 2018, metformin use increased from 17 to 29%, as did insulin use from 26 to 44%, whereas glyburide use decreased from 58 to 27%. By 2018, insulin was the most common pharmacotherapy for GDM; metformin was more likely to be prescribed by 9% compared with late 2015/16, but glyburide was less likely by 45%. Treatment modification occurred in 20% of women prescribed metformin compared with 2% with insulin and 8% with glyburide.

Conclusions

Insulin followed by metformin has replaced glyburide as the most common pharmacotherapy for GDM among a privately insured US population during a time of evolving professional guidelines. Further evaluation of the relative effectiveness and safety of metformin compared with insulin is needed.

Tweetable abstract

Insulin followed by metformin has replaced glyburide as the most common pharmacotherapy for gestational diabetes mellitus in the USA.