bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of main components in Curcuma longa L. on hepatic fibrosis based on network pharmacology and molecular docking: A review
Authors: Han Qiang , Zhu Jiahui , Zhang Peng
Published: July 2023

Background:

Hepatic fibrosis is a great concern in public health. While effective drugs for its treatment are lacking,Curcuma longa L.(CL) has been reported as a promising therapeutic. We aimed to uncover the core components and mechanisms of CL against hepatic fibrosis via a network pharmacology approach.

Methods:

The main components of CL were obtained and screened. While targets of components and disease were respectively collected using SwissTargetPrediction and online databases, common targets were assessed. A protein–protein interaction (PPI) network was constructed, and core targets were identified. GO and KEGG pathway enrichment analyses were performed, and molecular docking was conducted to validate the binding of core components in CL on predicted core targets.

Results:

Nine main components from CL based on high-performance liquid chromatography (HPLC) and 63 anti-fibrosis targets were identified, and a PPI network and a component target-disease target network were constructed. Apigenin, quercetin, demethoxycurcumin, and curcumin are likely to become key phenolic-based components and curcuminoids for the treatment of hepatic fibrosis, respectively. KEGG pathway enrichment analysis revealed that the HIF-1 signaling pathway (hsa04066) was most significantly enriched. Considering core targets of the PPI network and a network of the common targets and pathways enriched, AKT1, MAPK1, EGFR, MTOR, and SRC may be the core potential targets of CL against hepatic fibrosis. Molecular docking was carried out to verify the binding of above core components to core targets.

Conclusions:

The therapeutic effect of CL on hepatic fibrosis may be attributed to multi-components, multi-targets, and multi-pathways.
Application of an OFA strategy to ERAS in a 102-year-old patient undergoing colon cancer surgery: A case report
Authors: Dai Jingwei , Yang Mengya , Li Shanliang
Published: July 2023

Rationale:

Colorectal cancer is the third most common cancer and the second leading cause of cancer-related deaths worldwide. Opioid-free anesthesia (OFA) is an opioid-sparing technique that focuses on multimodal or balanced analgesia, relying on non-opioid adjuncts and regional anesthesia. Enhanced recovery after surgery (ERAS) protocols, often under the auspices of a perioperative pain service, can help guide and promote opioid reduced and OFA, without negatively impacting perioperative pain management or recovery. Ultrasound-guided regional nerve block is currently a good option for OFA due to anesthesiologists’ mastery of ultrasound techniques. The safety of the OFA strategy for quadratus lumborum block (QLB) + transversus abdominis plane block (TAP) in the super-elderly patients has not been reported and remains unclear. We report a case of OFA anesthesia in a super-elderly patient with colon cancer.

Patient concerns:

A 102-year-old female was admitted to the hospital due to “abdominal pain for a week” and received conservative treatment for more than 20 days, with poor results.

Diagnoses:

The patient was diagnosed with colorectal cancer associated with bronchiectasis and infection, multiple nodules in the right lower lung, and sinus arrhythmia.

Interventions:

As the patient was a super-elderly patient with multiple diseases, we used an OFA strategy with general anesthesia combined with QLB and TAP.

Outcomes:

The patient awakened quickly and completely after surgery, and extubation was successful 2 min after surgery without anesthesia complications, which is in line with the concept of ERAS.

Lessons:

The OFA strategies of ultrasound guidance quadratus lumborum block (Ul-QLB) and ultrasound guidance transversus abdominis plane block (Ul-TAP) may be safe and effective for ERAS in super-elderly patients with colorectal cancer surgery.
Sentiment Analysis of Tweets on Soda Taxes
Authors: An Ruopeng , Yang Yuyi , Batcheller Quinlan , Zhou Qianzi
Published: July 2023

Context:

As a primary source of added sugars, sugar-sweetened beverage (SSB) consumption may contribute to the obesity epidemic. A soda tax is an excise tax charged on selling SSBs to reduce consumption. Currently, 8 cities/counties in the United States have imposed soda taxes.

Objective:

This study assessed people's sentiments toward soda taxes in the United States based on social media posts on Twitter.

Design:

We designed a search algorithm to systematically identify and collect soda tax–related tweets posted on Twitter. We built deep neural network models to classify tweets by sentiments.

Setting:

Computer modeling.

Participants:

Approximately 370 000 soda tax–related tweets posted on Twitter from January 1, 2015, to April 16, 2022.

Main Outcome Measure:

Sentiment associated with a tweet.

Results:

Public attention paid to soda taxes, indicated by the number of tweets posted annually, peaked in 2016, but has declined considerably ever since. The decreasing prevalence of tweets quoting soda tax–related news without revealing sentiments coincided with the rapid increase in tweets expressing a neutral sentiment toward soda taxes. The prevalence of tweets expressing a negative sentiment rose steadily from 2015 to 2019 and then slightly leveled off, whereas that of tweets expressing a positive sentiment remained unchanged. Excluding news-quoting tweets, tweets with neutral, negative, and positive sentiments occupied roughly 56%, 29%, and 15%, respectively, during 2015-2022. The authors' total number of tweets posted, followers, and retweets predicted tweet sentiment. The finalized neural network model achieved an accuracy of 88% and an F1 score of 0.87 in predicting tweet sentiments in the test set.

Conclusions:

Despite its potential to shape public opinion and catalyze social changes, social media remains an underutilized source of information to inform government decision making. Social media sentiment analysis may inform the design, implementation, and modification of soda tax policies to gain social support while minimizing confusion and misinterpretation.
A PREDICTION MODEL FOR SEPSIS IN INFECTED PATIENTS: EARLY ASSESSMENT OF SEPSIS ENGAGEMENT
Authors: Guo Siying , Guo Zhe , Ren Qidong , Wang Xuesong , Wang Ziyi , Chai Yan , Liao Haiyan , Wang Ziwen , Zhu Huadong , Wang Zhong ,   Regarding PSCC Union
Published: July 2023

Purpose: To evaluate significant risk variables for sepsis incidence and develop a predictive model for rapid screening and diagnosis of sepsis in patients from the emergency department (ED). Methods: Sepsis-related risk variables were screened based on the PIRO (Predisposition, Insult, Response, Organ dysfunction) system. Training (n = 1,272) and external validation (n = 568) datasets were collected from Peking Union Medical College Hospital (PUMCH) and Beijing Tsinghua Changgung Hospital (BTCH), respectively. Variables were collected at the time of admission. Sepsis incidences were determined within 72 h after ED admissions. A predictive model, Early Assessment of Sepsis Engagement (EASE), was developed, and an EASE-based nomogram was generated for clinical applications. The predictive ability of EASE was evaluated and compared with the National Early Warning Score (NEWS) scoring system. In addition, internal and external validations were performed. Results: A total of 48 characteristics were identified. The EASE model, which consists of alcohol consumption, lung infection, temperature, respiration rate, heart rate, serum urea nitrogen, and white blood cell count, had an excellent predictive performance. The EASE-based nomogram showed a significantly higher area under curve (AUC) value of 86.5% (95% CI, 84.2%–88.8%) compared with the AUC value of 78.2% for the NEWS scoring system. The AUC of EASE in the external validation dataset was 72.2% (95% CI, 66.6%–77.7%). Both calibration curves of EASE in training and external validation datasets were close to the ideal model and were well-calibrated. Conclusions: The EASE model can predict and screen ED-admitted patients with sepsis. It demonstrated superior diagnostic performance and clinical application promise by external validation and in-parallel comparison with the NEWS scoring system.
Evaluation of Tranexamic Acid and Calcium Chloride in Major Traumas in a Pre-hospital Setting: Narrative Review
Authors: Bell Kameron T. , Salmon Chase M. , Purdy Benjamin A. , Canfield Scott G.
Published: July 2023

Excessive blood loss in the pre-hospital setting poses a significant challenge and is one of the leading causes of death in the United States. In response, emergency medical services (EMS) have increasingly adopted the use of tranexamic acid (TXA) and calcium chloride (CaCl2) as therapeutic interventions for hemorrhagic traumas. TXA functions by inhibiting plasmin formation and restoring hemostatic balance, while calcium plays a pivotal role in the coagulation cascade, facilitating the conversion of factor X to factor Xa and prothrombin to thrombin. Despite the growing utilization of TXA and CaCl2 in both pre-hospital and hospital environments, a lack of literature exists regarding the comparative effectiveness of these agents in reducing hemorrhage and improving patient outcomes. Notably, Morgan County Indiana EMS, recently integrated the administration of TXA with CaCl2 into their treatment protocols, offering a valuable opportunity to gather insight and formulate updated guidelines based on patient-centered outcomes. This narrative review aims to comprehensively evaluate the existing evidence concerning the administration of TXA and CaCl2 in the pre-hospital management of hemorrhages, while also incorporating and analyzing data derived from the co-administration of these medications within the practices of Morgan County EMS. This represents the inaugural description of the concurrent use of both TXA and CaCl2 to manage hemorrhages in the scientific literature.
New body typology method based on the combination of coupling motion of pelvis, thorax, and cranium
Authors: Niitsuma Masahiro , Imai Sho , Mimuro Takahiko
Published: July 2023

The purpose of this study is to deepen the understanding of unconscious intrinsic individuality by proposing and verifying the hypothesis of “Integrated Spine Coupling” which is defined by the combination of the way of the coupling motion of 3 major units of our body: pelvis, thorax, and cranium. This paper, as the first step of the verification, examines how each of the three units — pelvis, thorax, and cranium as the representative units of cervical, thoracic, and lumber spines — produces a coupling motion during body rotational movement, and how the types of combinations are related to other movements such as breathing. The measurement results suggest that there exist only four types of coupling motion patterns and it significantly affects the way they breath and move their ankle and toe.
Cell viability is dominated by quantum effects
Authors: Yasuda Takeshi , Nakajima Nakako , Yanaka Tomoko , Gotoh Takaya , Kagawa Wataru , Sugasawa Kaoru , Tajima Katsushi
Published: July 2023

Quantum tunneling is a phenomenon in which small quantum particles pass through a reaction energy barrier, as if they were passing through a tunnel opened in the barrier. In this study, we analyzed the involvement of the quantum tunneling effect in enzymatic chemical reactions involving hydrolysisin vitro, by monitoring the kinetic isotope effects due to hydrogen isotopes and their temperature dependence as indicators. The results demonstrated that the quantum tunneling effect is involved in deacetylation, DNA cleavage, and protein cleavage reactions. These related reactions were also examined in terms of their effects on cells, which revealed that the quantum effect is even involved in cell survival, including the almost complete inhibition of DNA homologous recombinational repair.

One-Sentence Summary

Due to quantum effects in numerous enzymatic reactions mediated by hydrolysis, heavy water significantly impacts biological outcomes in cells.
NAPE-PLD in the ventral tegmental area regulates reward events, feeding and energy homeostasis
Authors: Castel Julien , Li Guangping , Onimus Oriane , Leishman Emma , Cani Patrice D. , Bradshaw Heather , Mackie Ken , Everard Amandine , Luquet Serge , Gangarossa Giuseppe
Published: July 2023

TheN-acyl phosphatidylethanolamine-specific phospholipase D (NAPE-PLD) catalyzes the production ofN-acylethanolamines (NAEs), a family of endogenous bioactive lipids, which are involved in various biological processes ranging from neuronal functions to energy homeostasis and feeding behaviors. Reward-dependent behaviors depend on the dopamine (DA) transmission between the ventral tegmental area (VTA) and the nucleus accumbens (NAc) which conveys reward-values and scales reinforced behaviors. However, whether and how NAPE-PLD may contribute to the regulation of feeding and reward-dependent behaviors has not been investigated yet. This biological question is of paramount importance since NAEs are altered in obesity and metabolic disorders.

Here, we show that transcriptomic meta-analysis highlights a potential role for NAPE-PLD within the VTA→NAc circuit. Using brain-specific invalidation approaches, we report that the integrity of NAPE-PLD is required for the proper homeostasis of NAEs within the midbrain VTA and it affects food-reward behaviors. Moreover, region-specific knock-down of NAPE-PLD in the VTA resulted in enhanced food-reward seeking and reinforced behaviors which were associated with increasedin vivoDA release dynamics in response to both food and non-food-related rewards together with heightened tropism towards food consumption. Furthermore, midbrain knock-down of NAPE-PLD, which led to increased energy expenditure and adapted nutrients partitioning, elicited a relative protection against high-fat diet-mediated body fat gain and obesity-associated metabolic features.

In conclusion, these findings unravel a new key role of VTA NAPE-PLD in shaping DA-dependent events, feeding behaviors and energy homeostasis, thus providing new insights on the regulation of body metabolism.

Highlights

- NAPE-PLD and NAEs are enriched in the VTA and regulate food-reinforced behaviors and reward processes.

- NAPE-PLD scalesin vivoVTA→NAc dopamine dynamics.

- NAPE-PLD in the VTA contributes to whole-body energy balance and metabolic efficiency.

- Downregulation of VTA NAPE-PLD ameliorates obesity-associated metabolic features.
Differential expression of miRNAs between Young-Onset and Late-Onset Indian colorectal carcinoma patients
Authors: Moiz Sumaiya , Mondal Varsha , Bishnu Debarati , Das Biswajit , Bose Bodhisattva , Das Soumen , Banerjee Nirmalya , Dutta Amitava , Chatterjee Krishti , Goswami Srikanta , Mukhopadhyay Soma , Basu Sudarshana
Published: July 2023

Early-Onset Colorectal Carcinoma (EOCRC) is a growing concern as reports indicate a worldwide increase in the incidence of CRC among young adults (<50 years old). In an effort to understand the different mode of pathogenesis in young-onset CRC, we performed a pilot study wherein we looked at colorectal tumors from both young (< 50 years old) and old patients (>55 years old) and screened them to eliminate tumors positive for Microsatellite Instability (MSI) and showing activation of the Wnt pathway, known canonical factors in CRC pathogenesis. RNA isolated from EOCRC and Late-Onset (LOCRC) tumors and paired normal tissues without MSI, nuclear β-catenin and APC mutations were sent for small RNA seq to identify miRNA alterations between the two subsets. Comparative analysis revealed differential expression of 23 miRNAs specific to EOCRC and 11 miRNAs specific to LOCRC. We validated the top 10 EOCRC DEMs in TCGA-COAD cohorts followed by validation in additional EOCRC and LOCRC cohorts. Our integrated analysis revealed upregulation of hsa-miR-1247-3p, hsa-miR-148a-3p and hsa-miR-27a-5p and downregulation of hsa-miR-326 between the two subsets. Experimentally validated targets of the above miRNAs were compared with differentially expressed genes in the TCGA dataset to identify targets with physiological significance in EOCRC development. Our analysis revealed downregulation of epithelial gene expression and intercellular junction proteins potentially leading to dissolution of epithelial intercellular junctions in EOCRC development and EMT progression. Upregulated targets included genes whose expression have been reported to correlate with CRC tumor invasion, liver metastasis, disease recurrence and poor prognosis.
EPIGENOMIC VARIABILITY AND TRANSCRIPTOMICS AS A NOVEL MULTIOMIC COMPLEMENTARY APPROACH FOR PERSONALIZED NUTRITION IN COLORECTAL CANCER PATIENTS
Authors: Laguna Teresa , Piette-Gómez Oscar , Garranzo Marco , Gómez de Cedrón Marta , Ramírez de Molina Ana , Carrillo de Santa Pau Enrique
Published: July 2023

Food natural compounds are of interest as modulators of cancer progression and prognosis, as they participate in cellular processes such as growth and differentiation, DNA repair, programmed cell death and oxidative stress. Here we select dietary biocompounds for specific subgroups of 285 colorectal adenocarcinoma (COAD) samples by finding bioactives with opposite transcriptomic profiles to the subgroup-specific tumoral transcriptomes, hypothesizing they may counteract the cancer gene-expression profiles. To establish a CRC classification based on epigenetic variability, we selected 2,189 CpGs based on their differentially variable methylation between tumor and normal samples by a combination of linear and Bartlett tests. Samples were meta-clustered by 1) classifying each sample by 8 different methods (including k-means and hierarchical clustering), 2) building a network and 3) meta-clustering it by theedge-betweennessmethod. We extracted 6 main subgroups, 2 of them with immune-affected transcriptomes. We compared the transcriptomes of the 6 subgroups with the ones of 56in vitrobioactive studies from GEO by Gene Set Enrichment Analysis (GSEA), resulting in a potential positive effect of resveratrol, japonicone A and vitamin D. In summary, we present a promisingin silicostrategy to suggest specific bioactives as co-adjuvants in cancer treatment.
Simulation of gap junction formation reveals critical role of cysteines in connexon coupling
Authors: Héja László , Simon Ágnes , Kardos Julianna
Published: July 2023

Despite the fundamental functions of connexin gap junctions (CxGJs), understanding of molecular mechanisms, governing intercellular CxGJ formation by coupling of connexon hemichannels (CxHCs, connexons) is still in infancy. In silico simulation of intercellular connexon coupling of two Cx43HC models, embedded in membrane bilayers (Cx43HC-HC) successfully modelled the emergence of trans-gap junctional (trans-GJ) stabilization centers (SCs). Investigating the molecular determinants shaping the HC-HC interface, we revealed that the exceptionally high number of cysteine residues located at the interface play a pivotal role in the stabilization of HC and GJ structures. Opening of the disulphide bonds between these cysteines resulted in disappearance of trans-GJ SCs in the Cx43GJ model. In contrast, the Cx43HC form was found to be consistent with open disulphide bonds. Finally, we have shown that the presence of an adjoining HC contributes to disulphide formation and consequently to the emergence of trans-GJ H-bonds.

Our results suggest that several connexon channels in vertebrates may undertake intercellular connexon coupling similarly and may bring forward to the targeting of CxGJ-specific coupling.
Complete Protection from SARS-CoV-2 Lung Infection in Mice Through Combined Intranasal Delivery of PIKfyve Kinase and TMPRSS2 Protease Inhibitors
Authors: Kant Ravi , Kareinen Lauri , Ojha Ravi , Strandin Tomas , Saber Saber Hassan , Lesnikova Angelina , Kuivanen Suvi , Sirnonen Tarja , Joensuu Merja , Vapalahti Olli , Kirchhausen Tom , Kipar Anja , Balistreri Giuseppe
Published: July 2023

Emerging variants of concern of SARS-CoV-2 can significantly reduce the prophylactic and therapeutic efficacy of vaccines and neutralizing antibodies due to mutations in the viral genome. Targeting cell host factors required for infection provides a complementary strategy to overcome this problem since the host genome is less susceptible to variation during the life span of infection. The enzymatic activities of the endosomal PIKfyve phosphoinositide kinase and the serine protease TMPRSS2 are essential to meditate infection in two complementary viral entry pathways. Simultaneous inhibition in cultured cells of their enzymatic activities with the small molecule inhibitors apilimod dimesylate and nafamostat mesylate synergistically prevent viral entry and infection of native SARS-CoV-2 and vesicular stomatitis virus (VSV)-SARS-CoV-2 chimeras expressing the SARS-CoV-2 surface spike (S) protein and of variants of concern. We now report prophylactic prevention of lung infection in mice intranasally infected with SARS-CoV-2 beta by combined intranasal delivery of very low doses of apilimod dimesylate and nafamostat mesylate, in a formulation that is stable for over 3 months at room temperature. Administration of these drugs up to 6 hours post infection did not inhibit infection of the lungs but substantially reduced death of infected airway epithelial cells. The efficiency and simplicity of formulation of the drug combination suggests its suitability as prophylactic or therapeutic treatment against SARS-CoV-2 infection in households, point of care facilities, and under conditions where refrigeration would not be readily available.
Genomic Characterisation of Multidrug-Resistant Pathogenic Enteric Bacteria from healthy children in Osun State, Nigeria
Authors: Uwanibe Jessica N. , Olawoye Idowu B. , Happi Christian T. , Folarin Onikepe A.
Published: July 2023

Antimicrobial resistance (AMR) has been established to be a significant driver for the persistence and spread of bacterial infections. It is, therefore, essential to conduct epidemiological surveillance of AMR in healthy individuals to understand the actual dynamics of AMR in Nigeria. Multi-drug resistantKlebsiella quasivariicola(n=1), Enterobacter hormaechei(n=1), andEscherichia coli(n=3) from stool samples of healthy children were subjected to whole genome sequencing using Illumina Nextseq1000/2000 and Oxford nanopore. Bioinformatics analysis reveals antimicrobial resistance, virulence genes, and plasmids. This pathogenic enteric bacteria harbored more than three plasmid replicons of either Col and/or Inc type associated with outbreaks and AMR resistant genepmrBresponsible for colistin resistance. Plasmid reconstruction revealed an integratedtetAgene responsible for tetracycline resistance, andcaagene responsible for toxin production in two of theE.coliisolates, and acusCgene known to induce neonatal meningitis in theK. quasivariicolaST3879. The global spread of MDR pathogenic enteric bacteria is a worrying phenomenon, and close surveillance of healthy individuals, especially children, is strongly recommended to prevent the continuous spread and achieve the elimination and eradication of these infections. Molecular epidemiological surveillance using whole genome sequencing (WGS) will improve the detection of MDR pathogens in Nigeria.
Denoising task-correlated head motion from motor-task fMRI data with multi-echo ICA
Authors: Reddy Neha A. , Zvolanek Kristina M. , Moia Stefano , Caballero-Gaudes César , Bright Molly G.
Published: July 2023

Motor-task functional magnetic resonance imaging (fMRI) is crucial in the study of several clinical conditions, including stroke and Parkinson’s disease. However, motor-task fMRI is complicated by task-correlated head motion, which can be magnified in clinical populations and confounds motor activation results. One method that may mitigate this issue is multi-echo independent component analysis (ME-ICA), which has been shown to separate the effects of head motion from the desired BOLD signal but has not been tested in motor-task datasets with high amounts of motion. In this study, we collected an fMRI dataset from a healthy population who performed a hand grasp task with and without task-correlated amplified head motion to simulate a motor-impaired population. We analyzed these data using three models: single-echo (SE), multi-echo optimally combined (ME-OC), and ME-ICA. We compared the models’ performance in mitigating the effects of head motion on the subject level and group level. On the subject level, ME-ICA better dissociated the effects of head motion from the BOLD signal and reduced noise. Both ME models led to increased t-statistics in brain motor regions. In scans with high levels of motion, ME-ICA additionally mitigated artifacts and increased stability of beta coefficient estimates, compared to SE. On the group level, all three models produced activation clusters in expected motor areas in scans with both low and high motion, indicating that group-level averaging may also sufficiently resolve motion artifacts that vary by subject. These findings demonstrate that ME-ICA is a useful tool for subject-level analysis of motor-task data with high levels of task-correlated head motion. The improvements afforded by ME-ICA are critical to improve reliability of subject-level activation maps for clinical populations in which group-level analysis may not be feasible or appropriate, for example in a chronic stroke cohort with varying stroke location and degree of tissue damage.
Modeling Mechanical Activation of Macrophages During Pulmonary Fibrogenesis for Targeted Anti-Fibrosis Therapy
Authors: Xu Ying , Ying Linxuan , Lang Jennifer K , Hinz Boris , Zhao Ruogang
Published: July 2023

Pulmonary fibrosis, as seen in idiopathic pulmonary fibrosis (IPF) and COVID-induced pulmonary fibrosis, is an often-fatal lung disease. Increased numbers of immune cells such as macrophages were shown to accumulate in the fibrotic lung, but it is unclear how they contribute to the development of fibrosis. To recapitulate the macrophage mechanical activation in the fibrotic lung tissue microenvironment, we developed a fibrotic microtissue model with cocultured human macrophages and fibroblasts. We show that profibrotic macrophages seeded on topographically controlled stromal tissue constructs become mechanically activated. The resulting co-alignment of macrophages, collagen fibers and fibroblasts promote widespread fibrogenesis in micro-engineered lung tissues. Anti-fibrosis treatment using pirfenidone disrupts the polarization and mechanical activation of profibrotic macrophages, leading to fibrosis inhibition. Pirfenidone inhibits the mechanical activation of macrophages by suppressing integrin αMβ2 (CD11b/CD18) and Rho-associated kinase 2, which is a previously unknown mechanism of action of the drug. Together, these results demonstrate a potential pulmonary fibrogenesis mechanism at the tissue level contributed by mechanically activated macrophages. We propose the coculture, force-sensing microtissue model as a powerful tool to study the complex immune-stromal cell interactions and the mechanism of action of anti-fibrosis drugs.
The complexity and dynamics ofin organellotranslation assessed by high-resolution mitochondrial ribosome profiling
Authors: Wakigawa Taisei , Mito Mari , Yamashiro Haruna , Tomuro Kotaro , Tani Haruna , Tomizawa Kazuhito , Chujo Takeshi , Nagao Asuteka , Suzuki Takeo , Wei Fan-Yan , Shichino Yuichi , Suzuki Tsutomu , Iwasaki Shintaro
Published: July 2023

Since mitochondrial translation serves the essential subunits of the OXPHOS complex that produces ATP, exhaustive, quantitative, and high-resolution delineation of mitoribosome traversal is needed. Here, we developed a technique for high-resolution mitochondrial ribosome profiling and revealed the intricate regulation of mammalsin organellotranslation. Our approach assessed the stoichiometry and kinetics of mitochondrial translation flux, such as the number of mitoribosomes on a transcript and the elongation rate, initiation rate, and lifetime rounds of translation of individual transcripts. We also surveyed the impacts of modifications at the anticodon stem loop in mt-tRNAs, including all possible modifications at the 34th position, by deleting the corresponding enzymes and harnessing patient-derived cells. Moreover, a retapamulin-assisted derivative and mito-disome profiling revealed cryptic translation initiation sites at subcognate codons and programmed mitoribosome collision sites across the mitochondrial transcriptome. Our work provides a useful platform for investigating protein synthesis within the energy powerhouse of the cell.
Cytosolic linear DNA plasmids inSaccharomycopsisspecies
Authors: Cinnéide Eoin Ó , Heneghan Padraic G. , Rajkumar Arun S. , Morrissey John P. , Wolfe Kenneth H.
Published: July 2023

Some budding yeast species contain cytosolic linear DNA plasmids (also called virus-like elements, VLEs) that code for killer toxins that can kill other yeasts. The toxins are anticodon nucleases that cleave a specific tRNA in the cells being attacked, stopping translation. The best known plasmids of this type are the pGKL1/pGKL2 system ofKluyveromyces lactis. pGKL1 is a killer plasmid encoding the toxin zymocin (γ-toxin) which cleaves tRNA-Glu, and pGKL2 is a helper plasmid required for replication and transcription of pGKL1. Here, we investigated similar plasmids in the genusSaccharomycopsisthat were originally described in the 1980s.Saccharomycopsishas undergone an evolutionary change of its genetic code, from CUG-Leu to CUG-Ser translation, which we hypothesized could have been driven by a tRNA-cleaving toxin encoded by a cytosolic plasmid. We sequenced a three-plasmid system inS. crataegensis, consisting of apparent killer, immunity, and helper plasmids. The killer plasmid contains genes coding for putative α/β (chitin-binding) and γ (ribonuclease) toxin subunits, but the γ-toxin gene is damaged in all the isolates we examined. We inferred the sequence of the intactS. crataegensisγ-toxin and expressed it inSaccharomyces cerevisiaeandKluyveromyces marxianus, but it did not cause a growth defect. We also identified free plasmids, or plasmids integrated into the nuclear genome, in nine otherSaccharomycopsisspecies, including a case of recent interspecies transfer of a plasmid. Our results show that many yeasts in the CUG-Ser2 clade contain, or have in the past contained, plasmids related to those that carry anticodon nucleases.
Characterization of thePlasmodium bergheiregulatory AAA-ATPase subunit Rpt3 as an activator of Protein Phosphatase 1: direct and indirect evidence
Authors: Lainé Claudianne , De Witte Caroline , Martoriati Alain , Farce Amaury , Metatla Inès , Guerrera Ida Chiara , Cailliau Katia , Khalife Jamal , Pierrot Christine
Published: July 2023

The 26S proteasome is the main proteolytic machine involved in protein degradation, thus contributing to homeostasis or stress response of eukaryotic cells. This macromolecular complex, consisting of a 20S core particle assembled with one or two 19S regulatory particles, is highly regulated by phosphorylation. Here we describe thePlasmodium bergheiproteasome AAA-ATPase regulatory subunit Rpt3 and show that it binds to protein phosphatase 1, the major parasite phosphatase. In addition, PbRpt3 regulates the activity of the phosphatase both in vitro and in a heterologous model ofXenopusoocytes. Using mutagenesis approaches, we observed that the RVXF motifs of PbRpt3 are involved in this binding and activity. Further use ofXenopusoocyte model and mutagenesis based on the 3D model that we established revealed that the binding capacity of PbRpt3 to ATP may also contribute to its phosphatase-regulating activity. In the parasite, reverse genetic studies suggested an essential role for PbRpt3 since no viable knock-out line could be obtained. Additionally, immunoprecipitation assays followed by mass spectrometry analyses using transgenic PbRpt3-tagged parasites not only confirmed that PbRpt3 belongs to the 19S regulatory particle of the proteasome, but also revealed potential interaction with proteins already shown to play a role in the phospholipid membrane dynamics.
Loss of REP1 impacts choroidal melanogenesis in choroideremia
Authors: Sakar Hajrah , Tracey-White Dhani , Hagag Ahmed M. , Burgoyne Thomas , Jensen Lasse D. , Edwards Malia M. , Moosajee Mariya
Published: July 2023

Choroideremia (CHM) is a rare X-linked chorioretinal dystrophy affecting the photoreceptors, retinal pigment epithelium (RPE) and choroid, however, the involvement of the choroid in disease progression is not fully understood. CHM is caused by mutations in theCHMgene, encoding the ubiquitously expressed Rab escort protein 1 (REP1). REP1 plays an important role in intracellular trafficking of vesicles, including melanosomes. In this study, we examined ultrastructure of the choroid inchmru848fish andChmnull/WTmouse models using transmission electron microscopy. Significant pigmentary disruptions were observed, with a lack of melanosomes in the choroid ofchmru848fish from 4 days post fertilisation (4dpf). Total melanin and expression of melanogenesis genestyr,tryp1a,mitf, dctandpmelwere also reduced from 4dpf. InChmnull/WTmice, choroidal melanosomes were significantly smaller at 1 month and at 1 year, eumelanin was reduced, and the choroid was thicker. The choroid in CHM patients was also examined using optical coherence tomography (OCT) and OCT- angiography (OCT-A) and the area of preserved choriocapillaris (CC) was found to be smaller than that of overlying photoreceptors, indicating that the choroid is degenerating at a faster rate. Histopathology of an enucleated eye from a 74-year-old CHM male patient revealed isolated areas of RPE but no associated underlying CC. Significant degenerative changes in the choroid of CHM patients and animal models are seen, highlighting the importance of administrative routes involving the choroid, such as suprachoroidal delivery. Pigmentary disruptions in CHM animal models reveal an important role for REP1 in melanogenesis, and drugs that improve melanin production represent a potential novel therapeutic avenue.
The hGIDGID4E3 ubiquitin ligase complex targets ARHGAP11A to regulate cell migration
Authors: Bagci Halil , Winkler Martin , Uliana Federico , Boulais Jonathan , Mohamed Weaam I , Park Sophia L , Côté Jean-François , Peter Matthias
Published: July 2023

The human CTLH/GID (hGID) complex emerged as an important E3 ligase regulating multiple cellular processes, including cell cycle progression and metabolic activity. However, the range of biological functions controlled by hGID remains unexplored. Here, we show that the hGID substrate receptor GID4 regulates cell growth and migration. Biochemical and cellular assays combined with proximity-dependent biotinylation (BioID2) revealed that the hGIDGID4E3-ligase targets the Rho-GAP ARHGAP11A for degradation. Depletion of GID4 or impeding the GID4 substrate binding pocket impairs motility and directed cell movement, whereas knockdown of ARHGAP11A significantly restores the cell migration defect. We found that GID4 controls cell migration by degrading ARHGAP11A thereby preventing its accumulation at the cell periphery where it inactivates RhoA activity. Together, we identified a unique function for GID4, as well as a wide range of substrate profiles beyond Pro/N-degron motifs, which pave the way for deciphering additional pathways regulated by hGID E3 ligase activity through its GID4 substrate receptor.
Hybrid strategy and firm performance: a time-series qualitative comparative analysis of the Chinese ICT sector
Authors: Tao Yan , Ke Hongyan , Zhang Ziye
Published: July 2023

Purpose

The paper examines whether the hybrid strategy can generate high performance and what hybrid strategy configurations are more conducive to high performance.

Design/methodology/approach

This paper explores the complex causal relationships between six strategic elements (marketing, growth, R&D, capital, efficiency, stability) and firm performance. From a configurational approach, the authors utilize necessary condition analysis, time-series qualitative comparative analysis, and typical case extraction techniques to analyze 944 balanced panel data from 118 Chinese ICT firms during 2013–2020.

Findings

Chinese ICT sector firms do not rely on pure strategies (prospector or defender) to achieve high performance. The hybrid strategy is conducive to high performance. Only specific hybrid strategy configurations, including stable growth, innovative efficiency, and two-way player types, could enable firms to perform well. Six strategic elements do not constitute a necessary condition for high performance.

Originality/value

This paper proposed an integrated qualitative comparative analysis scheme, proved the effectiveness of the hybrid strategy on firm performance, and revealed how hybrid strategy configurations generate high performance.
Diminishing returns or inverted U? The curvilinear relationship between eco-innovation and firms' sustainable business performance: the impact of market turbulence
Authors: Xuhua Hu , Larbi-Siaw Otu , Thompson Erika Tano
Published: July 2023

Purpose

Eco-innovations (EIs) are intended to benefit not only the environment but society and firms, but how the relationship is reconciled is unclear, particularly in emerging economies. The advancement of EI has resulted in both positive and negative relationships with sustainability, indicating that the association is more complex than a simple linear one.

Design/methodology/approach

Thus, the authors hypothesize that EI has a curvilinear relationship with sustainable business performance (SPB) and that market turbulence (MT) exerts stimulus that reinforces EIs. Accordingly, using the Stata software, the authors apply a moderated regression to a sample size data of 511 manufacturing firms to test the hypothesized assumptions.

Findings

Although the results attest to a positive relationship between EI and SBP, the results are synonymous with an inverted “U” shape that renders EIs unprofitable beyond a certain threshold (rebound effect). Additionally, the authors observe that the moderation stimulus of technology turbulence flattens the inverted U-shaped curve.

Originality/value

Built on the foundations of natural-resource-based view (NRBV) and contingency theory, the authors identify the rebound effect point of EI and SBP and the reinforcing stimulus of MT.
Minor‐focused sextortion by adult strangers: A crime script analysis of newspaper and court cases
Authors: O'Malley Roberta Liggett , Holt Karen , Holt Thomas J. , Rodriguez Joy
Published: July 2023

Sextortion is a form of image‐based sexual abuse in which an offender threatens to distribute sexually explicit images, videos, or information to gain victim compliance. In some sextortion incidents involving minor children, offenders are adult strangers who coerce victims into self‐producing child sexually abusive materials (CSAM). Despite the growing concern regarding minor victims of sextortion, there is a lack of empirical investigation of adult offenders who exclusively target minor children for the production of CSAM and the steps and decisions these offenders take to commit sextortion. Utilizing a sample of 130 minor‐focused sextortion cases gathered from news media and court documents, the current study employed crime script analysis and inductive qualitative methodology to investigate how adult offenders commit sextortion. The results indicated that adult offenders specifically targeting minor children move through several crime scripts: preparation, entry, instrumental actions, crime commission, and exit.

Policy Implications

Minor‐focused sextortion perpetrated by adult offenders is executed in stages, each with accompanying preventive solutions. Investing in education that teaches youth to recognize grooming, develops safety practices online, and removes barriers to reporting should be a priority for schools and parents. Increased adoption of technology and policies that would allow social media platforms to detect CSAM, remove fraudulent accounts, and streamline reporting would also disrupt these crimes.
Epidemiological characteristics of cases with scrub typhus and their correlation with chigger mite occurrence (2019–2021): A focus on case occupation and activity locations
Authors: Jeong Se‐Jin , Jeon Jin‐Hwan , Hwang Kyung won
Published: July 2023

Scrub typhus, transmitted through chigger mite bites, is a febrile disease associated with agricultural activities and primarily occurs in autumn. To address the increasing number of cases with scrub typhus over the past 3 years, we analyzed activity, visit history, and occupation data of 12,462 cases reported to the Korea Disease Control and Prevention Agency (KDCA) between January 2019 and December 2021. We examined changes in incidence and general characteristics by visualizing the incidence and eschar bite locations using population data and a geographic information system. Gyeongsangnam‐do had the highest overall incidence rate (22.7%), followed by Jeollanam‐do (19.0%) and Jeollabuk‐do (11.2%), during the study period. However, when considering the incidence rate per 100,000 people, Jeollanam‐do had the highest number of cases at 129.1, followed by Gyeongsangnam‐do (85.1 cases) and Jeollabuk‐do (78.1 cases). Most cases were women (61.0%) in their 70s (28.4%), and the highest incidence occurred in the agricultural worker group during autumn (October–December). Bites occurred most frequently in the abdomen (18.1%), and fever (79.2%) and muscle pain (49.8%) were the main symptoms. We also found a positive correlation (r = 0.848) between chigger mite populations and disease outbreaks over 3 years. In conclusion, it is crucial to provide education on identifying the habitats of chigger mites and rodents (vectors), as well as the appropriate application of repellents. Promoting awareness and preventive measures against infectious diseases is of utmost importance for rural areas and the general public who frequently come into contact with natural environments.
Measures of fetal growth and preterm birth and risk of endometriosis and adenomyosis in adult life: a systematic review and meta‐analysis
Authors: Brønd Marie , Breintoft Kjerstine , Forman Axel , Henriksen Tine Brink , Ramlau‐Hansen Cecilia Høst , Rytter Dorte , Arendt Linn Håkonsen
Published: July 2023

Introduction

Exposures in utero are suggested to play a role in the etiology of endometriosis and adenomyosis, although the current evidence is inconclusive. Knowledge about potential prenatal programming and early life exposures that may affect this risk is of high importance, to focus potential preventive strategies for the diseases already during pregnancy. The aim of this study was to review systematically the literature of the association between measures of fetal growth and preterm birth and endometriosis and adenomyosis in adult life.

Material and methods

A systematic review according to Preferred Reporting Items for Systematic Reviews and Meta‐analysis (PRISMA) guidelines and by search on PubMed and EMBASE was carried out. We included published case–control and cohort studies. We excluded studies without a reference group, eg case series, case reports as well as commentaries, letters and editorials. The quality of the studies was assessed using the Newcastle–Ottawa Scale. Meta‐analyses using a random‐effect inverse variance weighted model were performed. PROSPERO registration number is CRD42021249322.

Results

A total of 11 studies were included. In general, the quality scores of the studies were moderate. We found that the risk of endometriosis was 26% higher in women born with a birthweight <2.5 kg (pooled odds ratio [pOR] 1.26, 95% confidence interval [CI] 1.05–1.52) and 32% higher in women born preterm (pOR 1.32, 95% CI 1.01–1.72) than in the reference groups. The studies on adenomyosis pointed towards no association, but a meta‐analysis was unfeasible due to the small number of studies.

Conclusions

This systematic review and meta‐analysis found that low birthweight and being born preterm were associated with endometriosis in adult life, but the results must be interpreted cautiously. No solid conclusion could be made regarding adenomyosis due to a limited number of published studies, but the studies included found no association. The results support the hypothesis of a potential early programming effect of endometriosis. However, the body of evidence is sparse and this hypothesis needs to be investigated further.
Three‐dimensional endovaginal ultrasound assessment using the levator ani deficiency score in primiparas: A replication study
Authors: Rotstein Emilia , Ullemar Vilhelmina , Starck Marianne , Tegerstedt Gunilla
Published: July 2023

Introduction

It is essential to assess the levator ani properly as part of clinical care in patients presenting with pelvic floor dysfunction. The levator ani deficiency scoring system is a previously published method to assess levator ani defects with three‐dimensional endovaginal ultrasound. The primary aim of this study was to determine the intra‐ and interrater reliability of the levator ani deficiency score in a cohort of non‐instrumentally delivered primiparas.

Material and methods

Primiparas (n = 141) were examined at least 1 year after vaginal birth. Three‐dimensional endovaginal ultrasound volumes were acquired by a single examiner using two different automated ultrasound probes. The volumes were analyzed by two separate raters who were blinded to each other's assessments. Descriptive statistics were calculated for levator ani deficiency score and categorized into three levels (mild, moderate, severe). Kendall's tau‐b was calculated for intra‐ and interrater comparisons.

Results

Intrarater comparisons of levator ani deficiency score and levator ani deficiency category were high (Kendall's tau‐b ≥0.80 for Rater 1; >0.79 for Rater 2). Interrater comparisons of levator ani deficiency score and levator ani deficiency category were also high (Kendall's tau‐b >0.9 for assessment 1 and >0.78 for assessment 2). Varying by rater, probe and assessment, 75.9%–80.1% of the study population had no/mild deficiency, 6.4%–9.2% had moderate deficiency, and 4.3%–6.4% had severe levator ani deficiency.

Conclusions

The levator ani deficiency scoring system is a feasible method to assess defects of the levator ani muscle and can be reproduced with high intra‐ and interrater correlations. Using the scoring system in clinical practice may facilitate concordant assessment between different examiners. However, the system should be used to support clinical findings and symptomatology and not as a screening tool, as the score is lacking the category of no levator ani deficiency.