bluuebunny/crossref_metadata_2025 huggingface dataset:
LncRNA MCM3AP-AS1 is downregulated in atherosclerosis and sponges miR-448 to suppress vascular smooth muscle cell proliferation
Authors: Liu Shiping , Qin Xiaoyi
Published: June 2023

Long noncoding RNA MCM3AP-AS1 plays critical roles in cancers, but its role in atherosclerosis is yet to be elucidated. The expression of MCM3AP-AS1 in atherosclerosis and control plasma samples were measured by RT-qPCR. IntaRNA was used to predict potential base pairings between MCM3AP-AS1 and miR-448, and the results were confirmed by a dual luciferase activity assay. Cell proliferation assay was performed to explore the role of overexpression of MCM3AP-AS1, miR-448, and myocyte enhancer factor 2 (MEF2)-C in the proliferation of human aortic smooth muscle cells (HAOSMCs). MCM3AP-AS1 was downregulated in atherosclerosis and directly interacted with miR-448, which is a critical player in the proliferation of HAOSMCs, indicating its involvement in atherosclerosis. However, MCM3AP-AS1 and miR-448 showed no role in regulating the expression of each other. In contrast, overexpression of MCM3AP-AS1 increased the expression levels of MEF2-C, which can be targeted by miR-448. Moreover, MCM3AP-AS1 was found to inhibit the effects of miR-448 overexpression on both HAOSMC proliferation and MEF2-C expression. MCM3AP-AS1 is downregulated in atherosclerosis and sponges miR-448 to suppress the proliferation of HAOSMCs.
Pneumonia caused by Schizophyllum commune in a patient with diabetes: A case report and comprehensive literature review
Authors: Chen Xing , Sun Jian , Chen YeFeng , Wang Jie , Liu ShuYing
Published: June 2023

Rationale:

Schizophyllum commune (S. commune) is a basidiomycete bracket fungus that rarely causes invasive fungal infections. It is often misdiagnosed as other invasive fungal disease because of its atypical clinical features. Here we report a case of pneumonia due to S commune and review the relevant literature.

Patient concerns and diagnoses:

A 55-year-old male with a history of diabetes and poor glycemic control presented with cough and sputum for half a month. Laboratory examination showed elevated peripheral blood eosinophils, bronchoalveolar lavage fluid eosinophils and increased serum total immunoglobulin E. Chest computed tomography revealed a gloved finger sign and consolidation in the middle lobe of the right lung and the upper lobe of the left lung. Bronchoscopy revealed thick white mucous plugs in the left lingular bronchus, which could be removed partially by suctioning. The culture of bronchoalveolar lavage fluid and bronchoscopy brush specimens grew cottony white mold in sabouraud dextrose agar. Pneumonia caused by S. commune was diagnosed based on clinical features and microbial methods.

Interventions and outcomes:

Voriconazole combined with inhaled budesonide and formoterol (inhaled corticosteroids + long-acting β-2 receptor agonist) were given, and his symptoms improved. The count of peripheral blood eosinophils and serum total immunoglobulin E decreased after 1 month. Repeated chest computed tomography showed remarkable improvement over the previous lesions.

Lessons:

Although rarely reported, infections in the lungs caused by S commune should be reminded especially in patients with immunocompromised. This case illustrates the risk factors, clinical symptoms and imaging features of the pneumonia caused by S. commune. It also further highlights the diagnosis and treatment of this disease through reviewing relevant literature.
Association between alcoholic beverage intake and hyperuricemia in Chinese adults: Findings from the China Health and Nutrition Survey
Authors: Wu Yueying , Shin Dayeon
Published: June 2023

While prior research has shown that consuming alcohol may raise the risk of hyperuricemia, little is known about how individual types of alcohol are linked to levels of uric acid in China. Therefore, this study aimed to investigate the independent impact of beer, wine, and liquor on serum uric acid (SUA) levels in the serum of Chinese adults. This study analyzed data from the 2009 China Health and Nutrition Survey and included 7083 participants (3418 men and 3665 women, ≥18 years of age). Multivariable logistic regression was used to analyze the potential association between alcohol intake and hyperuricemia risk, while linear regression analysis and general linear model were performed to examine the impact of alcohol consumption on SUA levels. This study revealed that men who drank alcohol daily had a greater odds ratio (1.68, 95% confidence interval: 1.01, 2.81) of hyperuricemia than those who drank alcohol no more than once a month. SUA levels of men significantly increased by 0.001 mg/dL for per additional gram of liquor consumed weekly. But men who drank ≤ 90.6 g of liquor per week had lower SUA levels compared with those in nondrinkers. SUA levels were inversely associated with wine intake in women (P = .03, P for trend = .02). Overall, consumption of beer, wine, and liquor differentially affected SUA levels in adult Chinese men and women.
Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and hemorrhoids: A nationwide, population-based study
Authors: Hu Wei-Syun , Lin Cheng-Li
Published: June 2023

The authors investigated whether there is an association between angiotensin-converting-enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB) users with hemorrhoids. A total of 21,670 ACEI users and 21,670 ARB users during 2000 − 2012 from a national health insurance database were included. Hemorrhoid incidences were monitored to the end of 2013. To examine the risk of hemorrhoids, the Cox proportional hazard model and the Kaplan–Meier method were used. The incidence rate of hemorrhoids in ARB users was 6.64 per 1000 person-years, which was higher than that of the ACEI users (5.48 per 1000 person-years). The adjusted hazard ratio of hemorrhoids in patients who received ACEI relative to those who received ARB was 0.83 (95% confidence intervals [CI] = 0.75, 0.92). Compared to ARB users, patients who used ACEI more than 740 days per year (adjusted hazard ratios = 0.44; 95% CI = 0.36, 0.54) and more than 7800 mg (adjusted hazard ratios = 0.54; 95% CI = 0.46, 0.65) had a lower risk of hemorrhoids. ACEI users who took a relatively long period or high cumulative dosage were found to less prone to develop hemorrhoids.
Validity and reliability of the single camera marker less motion capture system using RGB-D sensor to measure shoulder range-of-motion: A protocol for systematic review and meta-analysis
Authors: Lee Unhyung , Lee Suji , Kim Sung-A , Lee Jae-Dong , Lee Seunghoon
Published: June 2023

Background:

The range-of motion (ROM) is an essential component of joint mobility. Shoulder ROM measurement has been problematic due to its complexity. A marker less motion capture system can be a potential alternative for upper limb assessment. Currently, there is no systematic review to evaluate the validity of a marker less motion capture system for assessing shoulder ROM. This study aims to describe methods to evaluate the reliability and validity of a single camera marker less motion capture system that uses an RGB-depth sensor to measure shoulder ROM.

Methods:

Studies that measured shoulder ROM with a single camera marker less motion capture system using the RGB-depth sensor and assessed the intra- and/or inter-rater reliability, and/or validity of the device will be included. The search of electronic databases, such as MEDLINE, EMBASE, Cochran library, Cumulative Index to Nursing, and Allied Health Literature via EBSCO, IEEE Xplore, China National Knowledge Infrastructure, KoreaMed, Korean studies Information Service System, and Research Information Sharing Services will be performed for all relevant articles from inception to December 2022. Two authors will independently perform quality assessments using the Consensus-based Standards for the selection of health Measurement Instruments checklist for reliability, measurement error of outcome measurement instrument, and criterion validity. The primary outcomes will be the intra- and inter-rater reliability and validity of the markerless motion capture system measuring shoulder flexion, extension, abduction, adduction, internal rotation, or external rotation. A subgroup analysis would be performed if there are sufficient data to pool to identify an influencing factor in the measurement of ROM using a marker less motion capture system.

Results and Conclusion:

These findings will present tools to utilize and evaluate single camera motion capture systems for the medical use for clinicians and healthcare experts and can aid in further clinical research using such a system for different movements and other joints.
Comprehensive clinical evaluation of moxifloxacin: A retrospective study
Authors: Wang Hailiang , Liu Haiqiang , Lou Meimei , Xu Lanxia , Zhang Wei , Jing Lijun , Fu Min , Liu Bing
Published: June 2023

The objective was to provide a basis for the rational clinical application of moxifloxacin through its comprehensive clinical evaluation, and to serve as a reference for the clinical comprehensive evaluation of relevant drugs in the future. We obtained data from 91 community-acquired pneumonia patients admitted to Weifang people’s hospital from April 2020 to November 2021, including 46 in the evaluation group and 45 in the control group. Based on the requirements of the “Guidelines for the Management of Comprehensive Clinical Evaluation of Drugs” (for trial implementation), systematic evaluations are conducted in terms of drug safety, effectiveness, economy, innovation, suitability, and accessibility. The incidence of adverse drug reactions was low, drug quality, safety and stable efficacy; treatment efficiency was 91.3% and 93.3%, respectively (P > .05); the average total cost of the evaluation group was 9765.28RMB and 10250.69RMB, respectively; efficient cost-effectiveness ratio was 104.67 and 112.52 and cost-effectiveness ratio was 242.71. The economy of the evaluation group had a low price and was highly available.
HIV-1 genotypic profiling ensures effective response to third-line antiretroviral therapy in Cameroon
Authors: Mbouyap Pretty Rosereine , Fokam Joseph , Ngoufack Jagni Semengue Ezechiel , Mossiang Leonella , Takou Désiré , Ambe Chenwi Collins , Nka Alex Durand , Dambaya Beatrice , Teto Georges , Angong Beloumou Grâce , Djupsa Ndjeyep Sandrine Claire , Ka’e Aude Christelle , Kouanfack Charles , Ndjolo Alexis , Mbopi Keou François–Xavier
Published: June 2023

In order to limit the emergence of human immunodeficiency virus (HIV) drug resistance in a context of limited antiretroviral options, we sought to evaluate the efficacy of third-line (3L) regimens considering HIV genotypic resistance profile at initiation of 3L in Cameroon. A cohort-study was conducted from January-September 2020 among patients initiating a 3L antiretroviral therapy regimen at the Yaoundé Central Hospital. HIV-1 protease-reverse transcriptase was sequenced at the Chantal Biya international reference center for research on HIV/AIDS prevention and management and results were interpreted using Stanford HIVdbv8.3. Good virological response (viral load < 390 copies/mL) was assessed after 12 months using OPP-ERA platform. Statistical analyses were performed using Epi Info v7.2.2.6, with P < .05 considered statistically significant. Of the 38 patients initiating 3L with an available genotyping (42% female; median age, 49 [39–57] years), median cluster of differentiation type 4 count and viral load were 173 [34–374] cells/μL and 169,322 [30,382–551,826] copies/mL, respectively. At enrollment, all patients harbored resistance to reverse transcriptase inhibitors and 66% (25/38) to protease-inhibitors, although 63% (24/38) were still susceptible to darunavir/ritonavir. Preferred 3L regimen was dolutegravir + darunavir/r + tenofovir + lamivudine (51%) and median duration on 3L was 21 [17-32] months. Interestingly, 82% (31/38) of the participants achieved good virological response on 3L, regardless of genotypic profile at recruitment, variations in 3L regimens (P = .9) and baseline cluster of differentiation type 4 count (P = .3). Despite the high burden of reverse transcriptase inhibitor - and protease inhibitor boosted by ritonavir drug resistance, genotyping-guided 3L regimens is accompanied by virological success in most patients. This high efficacy, most likely due to use of high genetic barrier antiretrovirals, requires continuous adherence support alongside close monitoring for long-term effectiveness in similar programmatic settings.
Comparison of Short-Tau Inversion Recovery With Short-Tau Inversion Recovery–Slice Encoding for Metal Artifact Correction for Spine Imaging at 1.5 T in the Setting of Metallic Implants
Authors: Yang Jie-Yu , Hsieh Tsyh-Jyi , Chen Clement Kuen-Huang , Lin Chien-Hung , Chou Yi-Chen
Published: June 2023

Objective

To compare the image quality of short-tau inversion recovery (STIR) and the STIR-slice encoding for metal artifact correction (SEMAC) sequence for postsurgery spine magnetic resonance imaging (MRI).

Methods

Twenty-nine patients with metallic spinal implants who underwent spinal 1.5 T MRI with STIR and STIR-SEMAC sequences between July 2016 and November 2020 were retrospectively enrolled. Qualitative assessments were performed using 5-point scales; higher scores indicated better image quality. For screw metal artifact analysis, scores were obtained for artifacts on vertebral bodies and neural foramina, screw artifact widths, and bone marrow signal intensities. For patient-based analysis, scores were obtained for imaging quality and fat suppression quality, signal intensity, and cerebrospinal fluid noise. A paired t test was performed for statistical analyses.

Results

We analyzed 163 screws in 29 patients. In the screw metal artifact analysis, the vertebral body and neural foramen scores were significantly higher for the STIR-SEMAC images than for the STIR (all P < 0.001). The artifact width in the STIR-SEMAC images (9.8 ± 3.4 mm) was significantly smaller than that in the STIR images (16.0 ± 4.7 mm, P < 0.001). In patient-based analysis, the fat suppression and imaging quality scores were significantly higher for the STIR-SEMAC images than for the STIR images (all P < 0.001). The cerebrospinal fluid signal intensity, noise, and signal-to-noise ratios were significantly higher for the STIR images (all P < 0.005).

Conclusions

Short-tau inversion recovery–SEMAC sequences provide good metallic artifact reduction and fat suppression for postsurgery spine 1.5 T MRI.
EFFECTS OF TRANEXAMIC ACID ON NEUROPATHOLOGY, ELECTROENCEPHALOGRAPHY, AND CEREBRAL FIBRIN DEPOSITION IN A RAT MODEL OF POLYTRAUMA WITH CONCOMITANT PENETRATING TRAUMATIC BRAIN INJURY
Authors: Bailey Zachary S. , Yang Xiaofang , Cardiff Katherine , Wang Ping , Houchins Melonie , Lu Xi-Chun , Cao Ying , Gilsdorf Janice , Scultetus Anke , Shear Deborah
Published: June 2023

Several studies have demonstrated the clinical utility of tranexamic acid (TXA) for use in trauma patients presenting with significant hemorrhage. Tranexamic acid is an antifibrinolytic that inhibits plasminogen activation, and plasmin activity has been shown to mitigate blood loss and reduce all-cause mortality in the absence of adverse vascular occlusive events. Recent clinical developments indicate TXA is safe to use in patients with concomitant traumatic brain injury (TBI); however, the prehospital effects are not well understood. Importantly, TXA has been associated with seizure activity. Therefore, this study sought to evaluate the effects of early administration of TXA on neurological recovery and electroencephalogram (EEG) abnormalities following penetrating TBI with concomitant hypoxemia and hemorrhagic shock. We hypothesized that early administration of TXA will provide hemodynamic stabilization and reduce intracerebral hemorrhage, which will result in improved neurological function. To test this hypothesis, Sprague-Dawley rats received a unilateral, frontal penetrating ballistic-like brain injury by inserting a probe into the frontal cortex of the anesthetized rat. Five minutes following brain injury, animals underwent 30 min of respiratory distress and 30 min of hemorrhage. Upon completion of the hemorrhage phase, animals received the initial dose of drug intravenously over 10 min after which the prehospital phase was initiated. During the prehospital phase, animals received autologous shed whole blood as needed to maintain a MAP of 65 mm Hg. After 90 min, “in-hospital” resuscitation was performed by administering the remaining shed whole blood providing 100% oxygen for 15 min. Upon recovery from surgery, animals were administered their second dose of vehicle or TXA intravenously over 8 h. Tranexamic acid induced an early improvement in neurologic deficit, which was statistically significant compared with vehicle at 24, 48, and 72 h at three doses tested. Analysis of cerebral hemoglobin content and intracerebral lesion progression revealed 100 mg/kg provided the optimal effects for improvement of neuropathology and was continued for determination of adverse treatment effects. We observed no exacerbation of cerebral thrombosis, but TXA treatment caused an increased risk of EEG abnormalities. These results suggest that TXA following polytrauma with concomitant brain injury may provide mild neuroprotective effects by preventing lesion progression, but this may be associated with an increased risk of abnormal EEG patterns. This risk may be associated with TXA inhibition of glycine receptors and may warrant additional considerations during the use of TXA in patients with severe TBI.
Management and Outcomes of Wilms Tumor with Suprarenal Intravascular Extension
Authors: Naik-Mathuria Bindi , Utria Alan F. , Ehrlich Peter F , Aldrink Jennifer H. , Murphy Andrew J. , Lautz Timothy , Dasgupta Roshni , Short Scott S. , Lovvorn Harold N. , Kim Eugene S. , Newman Erica , Lal Dave R. , Rich Barrie S. , Piché Nelson , Kastenberg Zachary J. , Malek Marcus M. , Glick Richard D. , Petroze Robin T. , Polites Stephanie F. , Whitlock Richard , Alore Elizabeth , Sutthatarn Pattamon , Chen Stephanie Y. , Wong-Michalak Shannon , Romao Rodrigo LP , Al-Hadidi Ameer , Rubalcava Nathan S. , Marquart John P. , Gainer Hailey , Johnson Mike , Boehmer Chloe , Rinehardt Hannah , Seemann Natashia M. , Davidson Jacob , Polcz Valerie , Lund Sarah B. , McKay Katlyn G. , Correa Hernan , Rothstein David H.
Published: June 2023

Objective:

The purpose of this study was to describe management and outcomes from a contemporary cohort of children with Wilms Tumor (WT) complicated by inferior vena caval thrombus.

Summary Background Data:

The largest series of these patients was published almost two decades ago. Since then, neoadjuvant chemotherapy has been commonly used to manage these patients and outcomes have not been reported.

Methods:

Retrospective review from 19 North American centers between 2009-2019. Patient and disease characteristics, management, and outcomes were investigated and analyzed.

Results:

Of 124 patients, 81% had favorable histology (FH), and 52% were stage IV. IVC thrombus level was infrahepatic in 53 (43%), intrahepatic in 32 (26%), suprahepatic in 14 (11%), and cardiac in 24 (19%). Neoadjuvant chemotherapy using a 3-drug regimen was administered in 82% and post-resection radiation in 90%. Thrombus level regression was 45% overall, with suprahepatic level showing the best response (62%). Cardiopulmonary bypass (CPB) was potentially avoided in 67%. Peri-operative complication rate was significantly lower following neoadjuvant chemotherapy ([25%] vs. Upfront surgery [55%]; P=0.005). CPB was not associated with higher complications (CPB [50%] vs. no CPB [27%]; P=0.08). Two-year event-free survival (EFS) was 93% and overall survival (OS) was 96%, higher in FH cases (FH 98% vs. unfavorable histology/anaplastic 82%; P=0.73). Neither incomplete resection nor viable thrombus cells affected EFS or OS.

Conclusions:

Multimodal therapy resulted in excellent outcomes, even with advanced stage disease and cardiac extension. Neoadjuvant chemotherapy decreased the need for CPB to facilitate resection. Complete thrombectomy may not always be necessary.
Upregulated GRP78 and sFlt-1 in preeclampsia induces IRE1 and ATF6 arms of UPR leading to ER stress in placental cells
Authors: Mochan Sankat , Gupta Sunil k , Arora Pallavi , Rani Neerja , Bhatla Neerja , Dwivedi Sada Nand , Dhingra Renu
Published: June 2023

Introduction

Amongst vivid and diversified stresses which placenta in preeclampsia undergoes, ER stress has been a hal of the fame which is an insinuation of ill-fated UPR. In our previous study, we have already reported activation of PERK arm due to sFlt-1 present in preeclamptic mothers. The present study is an attempt to interpret rest of the two arms (IRE1 and ATF6) of UPR and ER stress subsequently byin vitrostudy using BeWo cells after upregulation of master regulator of UPR (GRP78) in placental tissue.

Materials and Methods

Part I: Serum analysis of circulating levels of GRP78 and sFlt-1 [in 50 pairs of preeclamptic and normotensive, non-proteinuric (control) pregnant women)] using ELISA.

Part II: Correlation analysis of levels of GRP78 and sFlt-1 in preeclamptic and control groups. Part III: Status of expression of GRP78 in placentae (n=10 each, preeclamptic and control groups) was reported using immunofluorescence.

Part IV:In vitroexperiments using BeWo cells were carried out to analyse the effect of GRP78 and sFlt-1 on IRE1 and ATF6 arms of UPR at protein (immunofluorescence and western blot) and transcript (qRT-PCR) levels.

Results

Protein expressions of GRP78 and sFlt-1 were found significantly elevated in preeclamptic patients as compared to controls. Enhanced expression of master regulator of UPR (GRP78) in placental tissue of preeclamptic women was reported. Up-regulated expression of XBP1 (IRE1 arm) and ATF6 markers of UPR was observed in trophoblast cells.

Conclusion

The upregulated expression of GRP78 in preeclamptic placentae and enhanced expression of XBP1 and ATF6 markers in BeWo cells at both protein and transcript levels connote role played by raised circulating levels of GRP78 and sFlt-1 in preeclampsia.
Discovery of medicinal herbal compounds with potential anti-cancer activities against microtubule affinity-regulating kinase (MARK4) in cancer therapy
Authors: Narayanan Nayana , Sivakumar K.C
Published: June 2023

MARK4 belongs to the serine/threonine family and is found to be involved in apoptosis and many other regulatory pathways. Therefore, MARK4 is considered a potential target for cancer therapy. HTVS and XP of LOTUS and NPACT revealed that Ligand 11 and Ligand 7 respectively show good binding affinity along with ADME properties towards MARK 4. Further MD simulations for 50 ns suggested that the binding mechanism of Ligand 11 and 7 stabilizes the MARK4 by forming a stable complex. Both the ligands were bound to the active site of MARK4. This work provides a new insight into the use of Ligand 7 and Ligand 11, which were obtained from herbal extracts belonging to the class of Flavonoids and Megastigmanes, respectively, showing anticancer activities. The MD simulation studies suggest that Ligand 11 and Ligand 7 can be considered as potential inhibitors to MARK 4. Overall, this study provides an experimental evaluation of the herbal compounds identified during the study against MARK 4-associated cancers
Serial KinderMiner (SKiM) Discovers and Annotates Biomedical Knowledge Using Co-Occurrence and Transformer Models
Authors: Millikin Robert J. , Raja Kalpana , Steill John , Lock Cannon , Tu Xuancheng , Ross Ian , Tsoi Lam C , Kuusisto Finn , Ni Zijian , Livny Miron , Bockelman Brian , Thomson James , Stewart Ron
Published: June 2023

Background

The PubMed database contains more than 34 million articles; consequently, it is becoming increasingly difficult for a biomedical researcher to keep up-to-date with different knowledge domains. Computationally efficient and interpretable tools are needed to help researchers find and understand associations between biomedical concepts. The goal of literature-based discovery (LBD) is to connect concepts in isolated literature domains that would normally go undiscovered. This usually takes the form of an A-B-C relationship, where A and C terms are linked through a B term intermediate. Here we describe Serial KinderMiner (SKiM), an LBD algorithm for finding statistically significant links between an A term and one or more C terms through some B term intermediate(s). The development of SKiM is motivated by the the observation that there are only a few LBD tools that provide a functional web interface, and that the available tools are limited in one or more of the following ways: 1) they identify a relationship but not the type of relationship, 2) they do not allow the user to provide their own lists of B or C terms, hindering flexibility, 3) they do not allow for querying thousands of C terms (which is crucial if, for instance, the user wants to query connections between a disease and the thousands of available drugs), or 4) they are specific for a particular biomedical domain (such as cancer). We provide an open-source tool and web interface that improves on all of these issues.

Results

We demonstrate SKiM’s ability to discover useful A-B-C linkages in three control experiments: classic LBD discoveries, drug repurposing, and finding associations related to cancer. Furthermore, we supplement SKiM with a knowledge graph built with transformer machine-learning models to aid in interpreting the relationships between terms found by SKiM. Finally, we provide a simple and intuitive open-source web interface (https://skim.morgridge.org) with comprehensive lists of drugs, diseases, phenotypes, and symptoms so that anyone can easily perform SKiM searches.

Conclusions

SKiM is a simple algorithm that can perform LBD searches to discover relationships between arbitrary user-defined concepts. SKiM is generalized for any domain, can perform searches with many thousands of C term concepts, and moves beyond the simple identification of an existence of a relationship; many relationships are given relationship type labels from our knowledge graph.
Cell wall pectic β-1,4-galactan contributes to increased plant freezing tolerance induced by cold acclimation
Authors: Takahashi Daisuke , Soga Kouichi , Sasaki Kazuma , Kikuchi Takuma , Kutsuno Tatsuya , Nishiyama Yui , Johnson Kim L. , Sampathkumar Arun , Bacic Antony , Kotake Toshihisa
Published: June 2023

Subzero temperatures are often lethal to plants. Many temperate plants have a mechanism called cold acclimation that allows them to sense a drop in temperature and prepare for freezing stress through accumulation of soluble sugars and cryoprotective proteins. Plant cells are surrounded by a cell wall and as ice formation primarily occurs in the extracellular matrix (the apoplast), cell wall properties are important for plant freezing tolerance. Although previous studies have shown that the amounts of constituent sugars of the cell wall, in particular those present in pectic polysaccharides, are altered by cold acclimation, the significance of this change during cold acclimation has not been clarified. We found that β-1,4-galactan, which forms neutral side chains of pectin, accumulates in the cell walls of Arabidopsis and various freezing tolerant vegetables during cold acclimation. Thegals1 gals2 gals3triple mutant, which has reduced β-1,4-galactan in the cell wall, exhibited reduced freezing tolerance compared with wild-type Arabidopsis during initial stages of cold acclimation. Expression of genes involved in the galactan biosynthesis pathway such asGALACTAN SYNTHASESandUDP-glucose 4-epimeraseswere induced during cold acclimation in Arabidopsis explaining galactan accumulation. Cold acclimation resulted in a decrease in extensibility and an increase in rigidity of the cell wall in the wild type, whereas these changes were not observed in thegals1 gals2 gals3triple mutant. These results indicate that the accumulation of pectic β-1,4-galactan contributes to acquired freezing tolerance by cold acclimationviachanges in cell wall mechanical properties.
Exome-wide analysis implicates rare protein-altering variants in human handedness
Authors: Schijven Dick , Soheili-Nezhad Sourena , Fisher Simon E. , Francks Clyde
Published: June 2023

Handedness is a manifestation of brain hemispheric specialization. Left-handedness occurs at increased rates in neurodevelopmental disorders. Genome-wide association studies have identified common genetic effects on handedness or brain asymmetry, which mostly involve variants outside protein-coding regions and may affect gene expression. Implicated genes include several that encode tubulins (microtubule components) or microtubule-associated proteins. Here we examined whether left-handedness is also influenced by rare coding variants (frequencies ≤ 1%), using exome data from 38,043 left-handed and 313,271 right-handed individuals (UK Biobank). The beta-tubulin geneTUBB4Bshowed exome-wide significant association, with a rate of rare coding variants 2.7 times higher in left-handers (0.076%) than right-handers (0.028%). TheTUBB4Bvariants were mostly heterozygous missense changes, but included two frameshifts found only in left-handers. OtherTUBB4Bvariants have been linked to sensorineural and/or ciliopathic disorders, but not the variants found here. Among genes previously implicated in autism or schizophrenia by exome screening,DSCAMandFOXP1showed evidence for rare coding variant association with left-handedness. The exome-wide heritability of left-handedness due to rare coding variants was 0.91%. This study revealed a role for rare, protein-altering variants in left-handedness, providing further evidence for the involvement of microtubules and disorder-relevant genes.
Development of rapid and affordable virus-mimicking artificial positive controls
Authors: Singh Shivani , Stainton Daisy , Tzanetakis Ioannis E.
Published: June 2023

A major bottleneck in the development of detection assays is the availability of positive controls. Their acquisition can be problematic; their maintenance is expensive and without them assays cannot be validated. Herein we present a novel strategy for the development of virus-mimicking positive controls (ViMAPCs). The time between design and application is less than five days, unlike alternatives which normally take several weeks to obtain and implement. The ViMAPCs provide a realistic representation of natural infection unlike alternatives and allow for an effortless recognition of lab-based contamination. The feasibility and adaptability of the strategy was evaluated using several RNA and DNA viruses. ViMAPCs can be used in diagnostics labs but also in monitoring of pathogen outbreaks where rapid response is of utmost importance.
Short-term heat stress assays provide a standardized screening tool to assess impacts of microbiome manipulation on Aiptasia thermal stress tolerance
Authors: Dörr Melanie , Denger Julia , Maier Céline S. , Kirsch Jana V. , Manns Hannah , Voolstra Christian R.
Published: June 2023

The ongoing loss of corals and their reef ecosystems hastens the need to develop approaches that mitigate the impacts of climate change. Given the strong reliance of corals on their associated prokaryotic and microalgal symbionts, microbiome-targeted interventions in the form of probiotics or microbiome transplants are emerging as potential solutions. Although inoculation with beneficial microorganisms was shown to improve coral bleaching recovery, the mechanistic underpinnings and extent to which microbiomes can be manipulated are largely unknown. Research progress in this regard is often hindered by coral holobiont complexity and a lack of standardized diagnostics to assess physiological and phenotypic changes following microbial manipulation. Here we address these shortcomings by establishing short-term acute thermal stress assays using the CBASS (Coral Bleaching Automated Stress System) as a standardized and reproducible experimental platform to assess the impact of microbiome manipulation on stress tolerance phenotypes of the coral model Aiptasia. We show that thermal tolerance phenotypes following acute heat stress assays are highly reproducible, host species-specific, and can exert legacy effects with consequences for long-term thermal resilience. We further demonstrate the ability to resolve phenotypic differences in thermal tolerance following microbiome manipulation through pathogen incubation. By employing acute heat stress assays in conjunction with a tractable model organism, we present a standardized experimental platform that allows functional screening for microbes that affect thermal stress tolerance. Such effort may accelerate the discovery of microbes and microbial mechanisms mediating thermal tolerance and our ability to harness them to increase stress resilience.
Beyond conflict: kinship theory of intragenomic conflict predicts individual variation in altruistic behavior
Authors: Bresnahan Sean T. , Galbraith David , Ma Rong , Anton Kate , Rangel Juliana , Grozinger Christina M.
Published: June 2023

Studies of the genetic basis of behavioral variation have emphasized gene cooperation within networks, often overlooking gene conflicts. The Kinship Theory of Intragenomic Conflict (KTIC) proposes that conflicts can occur within genes when parent-specific alleles have different strategies for maximizing reproductive fitness. Here, we test a prediction of the KTIC – that selection should favor alleles which promote “altruistic” behaviors that support the reproductive fitness of kin. In honey bee (Apis mellifera) colonies, workers act altruistically when tending to the queen by performing a “retinue” behavior, distributing the queen’s mandibular pheromone (QMP) throughout the hive. Workers exposed to QMP do not activate their ovaries, ensuring they care for the queen’s brood instead of competing to lay unfertilized eggs. Thus, the KTIC predicts that response to QMP should be favored by the maternal genome. Using a reciprocal cross design, we tested for parent-of-origin effects on the workers’ 1) responsiveness to QMP, 2) ovary activation, and 3) brain transcriptome. We hypothesized that QMP-responsive workers have smaller and less active ovaries, influenced by the workers’ parent-of-origin. With an allele-specific transcriptomic analysis, we tested whether QMP-responsive workers show enriched maternal allele-biased gene expression compared to QMP-unresponsive workers. Finally, we explored how parent-of-origin gene expression patterns are associated with overall gene expression patterns and regulatory networks. We report evidence in support of the KTIC for the retinue behavior and associated conflicts within gene networks. Our study provides new insights into the genetic basis of behavior and the potential for behavioral variation influenced by intragenomic conflict.
Covalent targeting as a common mechanism for inhibiting NLRP3 inflammasome assembly
Authors: Stanton Caroline , Sun Jie , Nutsch Kayla , Rosarda Jessica D. , Nguyen Thu , Li-Ma Chloris , Kutseikin Sergei , Saez Enrique , Teijaro John R. , Wiseman R. Luke , Bollong Michael J.
Published: June 2023

The NLRP3 inflammasome is a cytosolic protein complex important for the regulation and secretion of inflammatory cytokines including IL-1β and IL-18. Aberrant overactivation of NLRP3 is implicated in numerous inflammatory disorders. However, the activation and regulation of NLRP3 inflammasome signaling remains poorly understood, limiting our ability to develop pharmacologic approaches to target this important inflammatory complex. Here, we developed and implemented a high-throughput screen to identify compounds that inhibit inflammasome assembly and activity. From this screen we identify and profile inflammasome inhibition of 20 new covalent compounds across 9 different chemical scaffolds, as well as many known inflammasome covalent inhibitors. Intriguingly, our results indicate that NLRP3 possesses numerous reactive cysteines on multiple domains whose covalent targeting blocks activation of this inflammatory complex. Specifically, focusing on compound VLX1570, which possesses multiple electrophilic moieties, we demonstrate that this compound allows covalent, intermolecular crosslinking of NLRP3 cysteines to inhibit inflammasome assembly. Our results, along with the recent identification of numerous covalent molecules that inhibit NLRP3 inflammasome activation, suggests that NLRP3 serves as a cellular electrophile sensor important for coordinating inflammatory signaling in response to redox stress. Further, our results support the potential for covalent cysteine modification of NLRP3 for regulating inflammasome activation and activity.
Expression of RcrB confers resistance to hypochlorous acid in uropathogenicEscherichia coli
Authors: Crompton Mary E. , Gaessler Luca F. , Tawiah Patrick O. , Pfirsching Lisa , Camfield Sydney K. , Johnson Colton , Meurer Kennadi , Bennis Mehdi , Roseberry Brendan , Sultana Sadia , Dahl Jan-Ulrik
Published: June 2023

To eradicate bacterial pathogens, neutrophils are recruited to the sites of infection, where they engulf and kill microbes through the production of reactive oxygen and chlorine species (ROS/RCS). The most prominent RCS is antimicrobial oxidant hypochlorous acid (HOCl), which rapidly reacts with various amino acids side chains, including those containing sulfur and primary/tertiary amines, causing significant macromolecular damage. Pathogens like uropathogenicEscherichia coli(UPEC), the primary causative agent of urinary tract infections (UTIs), have developed sophisticated defense systems to protect themselves from HOCl. We recently identified the RcrR regulon as a novel HOCl defense strategy in UPEC. The regulon is controlled by the HOCl-sensing transcriptional repressor RcrR, which is oxidatively inactivated by HOCl resulting in the expression of its target genes, includingrcrB.rcrBencodes the putative membrane protein RcrB, deletion of which substantially increases UPEC’s susceptibility to HOCl. However, many questions regarding RcrB’s role remain open including whether(i)the protein’s mode of action requires additional help,(ii) rcrARBexpression is induced by physiologically relevant oxidants other than HOCl, and(iii)expression of this defense system is limited to specific media and/or cultivation conditions. Here, we provide evidence that RcrB expression is sufficient toE. coli’s protection from HOCl and induced by and protects from several RCS but not from ROS. RcrB plays a protective role for RCS-stressed planktonic cells under various growth and cultivation conditions but appears to be irrelevant for UPEC’s biofilm formation.

IMPORTANCE

Bacterial infections pose an increasing threat to human health exacerbating the demand for alternative treatment options. UPEC, the most common etiological agent of urinary tract infections (UTIs), are confronted by neutrophilic attacks in the bladder, and must therefore be well equipped with powerful defense systems to fend off the toxic effects of RCS. How UPEC deal with the negative consequences of the oxidative burst in the neutrophil phagosome remains unclear. Our study sheds light on the requirements for the expression and protective effects of RcrB, which we recently identified as UPEC’s most potent defense system towards HOCl-stress and phagocytosis. Thus, this novel HOCl-stress defense system could potentially serve as an attractive drug target to increase the body’s own capacity to fight UTIs.
Optimization of RNA Pepper sensors for the detection of arbitrary RNA targets
Authors: Tang Anli , Afasizheva Anna , Cano Clara , Plath Kathrin , Black Douglas , Franco Elisa
Published: June 2023

The development of fluorescent light up RNA aptamers (FLAPs) has paved the way for the creation of sensors to track RNA in live cells. A major challenge with FLAP sensors is their brightness and their limited signal-to-background ratio bothin vivoandin vitro. To address this, we develop sensors using the Pepper aptamer, which exhibits superior brightness and photostability when compared to other FLAPs. The sensors are designed to fold into a low fluorescence conformation, and to switch to a high fluorescence conformation through toehold or loop-mediated interactions with their RNA target. Our sensors detect RNA targets as short as 20 nucleotides in length with a wide dynamic range over 300-foldin vitro, and we describe strategies for optimizing the sensor’s performance for any given RNA targets. To demonstrate the versatility of our design approach, we generate Pepper sensors for a range of specific, biologically relevant RNA sequences. Our design and optimization strategies are portable to other FLAPs, and offer a promising foundation for future development of RNA sensors with high specificity and sensitivity for detecting RNA biomarkers with multiple applications.
Comparison of colorimetric, fluorometric, and liquid chromatography-mass spectrometry assays for acetyl-coenzyme A
Authors: Kantner Daniel S. , Megill Emily , Bostwick Anna , Yang Vicky , Bekeova Carmen , Van Scoyk Alexandria , Seifert Erin , Deininger Michael W. , Snyder Nathaniel W.
Published: June 2023

Acetyl-Coenzyme A is a central metabolite in catabolic and anabolic pathways as well as the acyl donor for acetylation reactions. Multiple quantitative measurement techniques for acetyl-CoA have been reported, including commercially available kits. Comparisons between techniques for acetyl-CoA measurement have not been reported. This lack of comparability between assays makes context-specific assay selection and interpretation of results reporting changes in acetyl-CoA metabolism difficult. We compared commercially available colorimetric ELISA and fluorometric enzymatic-based kits to liquid chromatography-mass spectrometry-based assays using tandem mass spectrometry (LC-MS/MS) and high-resolution mass spectrometry (LC-HRMS). The colorimetric ELISA kit did not produce interpretable results even with commercially available pure standards. The fluorometric enzymatic kit produced comparable results to the LC-MS-based assays depending on matrix and extraction. LC-MS/MS and LC-HRMS assays produced well-aligned results, especially when incorporating stable isotope-labeled internal standards. In addition, we demonstrated the multiplexing capability of the LC-HRMS assay by measuring a suite of short-chain acyl-CoAs in a variety of acute myeloid leukemia cell lines and patient cells.
Do credit market incentives drive classification shifting in emerging markets?
Authors: Bansal Manish
Published: June 2023

Purpose

To report inflated operating performance indicators, such as operating revenue and operating profit, managers vertically reposition revenue and expense items inside the income statement. This study aims to investigate the relationship between credit market incentives and these practices.

Design/methodology/approach

This study examined a sample of 1,592 Bombay Stock Exchange-listed companies from 2009 to 2021 and tested them using panel data regression models. The propensity score matching method and different measurements of classification shifting practices are used to validate the results.

Findings

The conclusions drawn from the empirical data show that firms prefer revenue shifting over expense shifting to prevent debt covenant violations. It shows that the firm’s classification-shifting practices are driven by credit market incentives. This finding is consistent with the notion of positive accounting theory that firms engage in classification shifting (earnings management) to avoid violation of debt covenants. Further, the firm’s preference for revenue shifting is in line with the ease-need-advantage-based shifting framework where firms choose the shifting tool based on costs and constraints associated with each tool.

Practical implications

The finding suggests that if managers heavily rely on revenue shifting to avoid debt covenant violations, the firm may end up breaking these covenants based on its actual operating performance. Managers may use aggressive accounting techniques to prevent covenant violations, which can be a warning indicator of financial difficulties or operational problems. It highlights the necessity for creditors and investors to carefully evaluate a company’s financial stability outside of the financial statements that are publicly disclosed. Authorities should create separate forensic accounting standards for auditors to check revenue items and stop the corporate misfeasance of revenue shifting.

Originality/value

The study is among the earlier attempts to provide empirical evidence on credit market incentives behind classification shifting practices. It is the first study that documents the substitution relationship between classification shifting forms for avoiding violation of debt covenants.
Analyzing the linkage between Islamic financial literacy and Islamic banking services adoption: evidence from Turkey
Authors: Pala Fahrettin , Erdoğdu Aylin , Ali Muhammad , Alnori Faisal , Barut Abdulkadir
Published: June 2023

Purpose

The purpose of this study is twofold. First, this research explores the level of Islamic financial literacy of customers in the context of Islamic banking. Second, this study examines the determinants of customer adoption of Islamic banking in Turkey.

Design/methodology/approach

This study gathered sample data from 409 participants determined using the purposive sampling method. In the study, first, the reflective measurement model is used to examine the reliability, validity and multicollinearity problems of the variables. Then, AMOS structural equation model (SEM) is used to reveal the relationship between Islamic financial literacy and Islamic banking services. Additionally, this study performed both descriptive and inferential analysis to understand customer literacy about Islamic banking and their adoption behavior of Islamic banking.

Findings

The results obtained from descriptive assessment indicate that Turkish customers of Islamic banking possess sufficient literacy about Islamic banking. Moreover, the results from SEM indicate that the adoption of Islamic banking by customers is significantly predicted by the role of Sharia Board management, Islamic banking and purpose of financial institution, religious factor and legitimacy of Islamic financial system.

Research limitations/implications

This study focuses only on the level of knowledge and perceptions of customers who have accounts in Islamic banks or financial institutions in Turkey. It does not focus on the level of knowledge and perception of Muslims who do not have accounts in Islamic banks and financial institutions.

Originality/value

Previous studies on Islamic banking are mostly studies that investigate customers’ perceptions of the Islamic banking system and why individuals prefer Islamic banks. In particular, studies examining the relationship between individuals’ Islamic financial literacy level and Islamic banking preferences are limited. This study is considered to be an original study as it investigates the relationship between the Islamic financial literacy level of individuals and their adoption of Islamic banking services in Turkey.