bluuebunny/crossref_metadata_2025 huggingface dataset:
In Silico and In Vivo Analysis of Amino Acid Substitutions That Cause Laminopathies
Authors: Hinz Benjamin E. , Walker Sydney G. , Xiong Austin , Gogal Rose A. , Schnieders Michael J. , Wallrath Lori L.
Published: October 2021

Mutations in the LMNA gene cause diseases called laminopathies. LMNA encodes lamins A and C, intermediate filaments with multiple roles at the nuclear envelope. LMNA mutations are frequently single base changes that cause diverse disease phenotypes affecting muscles, nerves, and fat. Disease-associated amino acid substitutions were mapped in silico onto three-dimensional structures of lamin A/C, revealing no apparent genotype–phenotype connections. In silico analyses revealed that seven of nine predicted partner protein binding pockets in the Ig-like fold domain correspond to sites of disease-associated amino acid substitutions. Different amino acid substitutions at the same position within lamin A/C cause distinct diseases, raising the question of whether the nature of the amino acid replacement or genetic background differences contribute to disease phenotypes. Substitutions at R249 in the rod domain cause muscular dystrophies with varying severity. To address this variability, we modeled R249Q and R249W in Drosophila Lamin C, an orthologue of LMNA. Larval body wall muscles expressing mutant Lamin C caused abnormal nuclear morphology and premature death. When expressed in indirect flight muscles, R249W caused a greater number of adults with wing posturing defects than R249Q, consistent with observations that R249W and R249Q cause distinct muscular dystrophies, with R249W more severe. In this case, the nature of the amino acid replacement appears to dictate muscle disease severity. Together, our findings illustrate the utility of Drosophila for predicting muscle disease severity and pathogenicity of variants of unknown significance.
Sugar Transport, Metabolism and Signaling in Fruit Development of Litchi chinensis Sonn: A Review
Authors: Fan Shuying , Wang Dan , Xie Hanhan , Wang Huicong , Qin Yonghua , Hu Guibing , Zhao Jietang
Published: October 2021

Litchi chinensis Sonn. is an important evergreen fruit crop cultivated in the tropical and subtropical regions. The edible portion of litchi fruit is the aril, which contains a high concentration of sucrose, glucose, and fructose. In this study, we review various aspects of sugar transport, metabolism, and signaling during fruit development in litchi. We begin by detailing the sugar transport and accumulation during aril development, and the biosynthesis of quebrachitol as a transportable photosynthate is discussed. We then document sugar metabolism in litchi fruit. We focus on the links between sugar signaling and seed development as well as fruit abscission. Finally, we outline future directions for research on sugar metabolism and signaling to improve fruit yield and quality.
The Role of Nrf2 Transcription Factor and Sp1-Nrf2 Protein Complex in Glutamine Transporter SN1 Regulation in Mouse Cortical Astrocytes Exposed to Ammonia
Authors: Dąbrowska Katarzyna , Skowrońska Katarzyna , Popek Mariusz , Albrecht Jan , Zielińska Magdalena
Published: October 2021

Ammonia toxicity in the brain primarily affects astrocytes via a mechanism in which oxidative stress (OS), is coupled to the imbalance between glutamatergic and GABAergic transmission. Ammonia also downregulates the astrocytic N system transporter SN1 that controls glutamine supply from astrocytes to neurons for the replenishment of both neurotransmitters. Here, we tested the hypothesis that activation of Nrf2 is the process that links ammonia-induced OS formation in astrocytes to downregulation and inactivation of SN1 and that it may involve the formation of a complex between Nrf2 and Sp1. Treatment of cultured cortical mouse astrocytes with ammonia (5 mM NH4Cl for 24 h) evoked Nrf2 nuclear translocation, increased its activity in a p38 MAPK pathway-dependent manner, and enhanced Nrf2 binding to Slc38a3 promoter. Nrf2 silencing increased SN1 mRNA and protein level without influencing astrocytic [3H]glutamine transport. Ammonia decreased SN1 expression in Nrf2 siRNA treated astrocytes and reduced [3H]glutamine uptake. In addition, while Nrf2 formed a complex with Sp1 in ammonia-treated astrocytes less efficiently than in control cells, treatment of astrocytes with hybrid-mode inactivated Sp1-Nrf2 complex (Nrf2 silencing + pharmacological inhibition of Sp1) did not affect SN1 protein level in ammonia-treated astrocytes. In summary, the results document that SN1 transporter dysregulation by ammonia in astrocytes involves activation of Nrf2 but does not require the formation of the Sp1-Nrf2 complex.
Nanosecond Pulsed Electric Field Only Transiently Affects the Cellular and Molecular Processes of Leydig Cells
Authors: Kasprzycka Wiktoria , Trębińska-Stryjewska Alicja , Lewandowski Rafał Bogdan , Stępińska Małgorzata , Osuchowska Paulina Natalia , Dobrzyńska Monika , Achour Yahia , Osuchowski Łukasz Paweł , Starzyński Jacek , Mierczyk Zygmunt , Trafny Elżbieta Anna
Published: October 2021

The purpose of this study was to verify whether the nanosecond pulsed electric field, not eliciting thermal effects, permanently changes the molecular processes and gene expression of Leydig TM3 cells. The cells were exposed to a moderate electric field (80 quasi-rectangular shape pulses, 60 ns pulse width, and an electric field of 14 kV/cm). The putative disturbances were recorded over 24 h. After exposure to the nanosecond pulsed electric field, a 19% increase in cell diameter, a loss of microvilli, and a 70% reduction in cell adhesion were observed. Some cells showed the nonapoptotic externalization of phosphatidylserine through the pores in the plasma membrane. The cell proportion in the subG1 phase increased by 8% at the expense of the S and G2/M phases, and the DNA was fragmented in a small proportion of the cells. The membrane mitochondrial potential and superoxide content decreased by 37% and 23%, respectively. Microarray’s transcriptome analysis demonstrated a negative transient effect on the expression of genes involved in oxidative phosphorylation, DNA repair, cell proliferation, and the overexpression of plasma membrane proteins. We conclude that nanosecond pulsed electric field affected the physiology and gene expression of TM3 cells transiently, with a noticeable heterogeneity of cellular responses.
Structure of Lipopolysaccharide from Liberibacter crescens Is Low Molecular Weight and Offers Insight into Candidatus Liberibacter Biology
Authors: Black Ian M. , Heiss Christian , Jain Mukesh , Muszyński Artur , Carlson Russell W. , Gabriel Dean W. , Azadi Parastoo
Published: October 2021

Huanglongbing (HLB) disease, also known as citrus greening disease, was first reported in the US in 2005. Since then, the disease has decimated the citrus industry in Florida, resulting in billions of dollars in crop losses and the destruction of thousands of acres of citrus groves. The causative agent of citrus greening disease is the phloem limited pathogen Candidatus Liberibacter asiaticus. As it has not been cultured, very little is known about the structural biology of the organism. Liberibacter are part of the Rhizobiaceae family, which includes nitrogen-fixing symbionts of legumes as well as the Agrobacterium plant pathogens. To better understand the Liberibacter genus, a closely related culturable bacterium (Liberibacter crescens or Lcr) has attracted attention as a model organism for structural and functional genomics of Liberibacters. Given that the structure of lipopolysaccharides (LPS) from Gram-negative bacteria plays a crucial role in mediating host-pathogen interactions, we sought to characterize the LPS from Lcr. We found that the major lipid A component of the LPS consisted of a pentaacylated molecule with a β-6-GlcN disaccharide backbone lacking phosphate. The polysaccharide portion of the LPS was unusual compared to previously described members of the Rhizobiaceae family in that it contained ribofuranosyl residues. The LPS structure presented here allows us to extrapolate known LPS structure/function relationships to members of the Liberibacter genus which cannot yet be cultured. It also offers insights into the biology of the organism and how they manage to effectively attack citrus trees.
Molecular Pathways in Prolactinomas: Translational and Therapeutic Implications
Authors: Biagetti Betina , Simò Rafael
Published: October 2021

Prolactinoma has the highest incidence rate among patients with functional pituitary tumours. Although mostly benign, there is a subgroup that can be aggressive. Some clinical, radiological and pathology features have been associated with a poor prognostic. Therefore, it can be considered as a group of heterogeneous tumours. The aim of this paper is to give an overview of the molecular pathways involved in the behaviour of prolactinoma in order to improve our approach and gain deeper insight into the better understanding of tumour development and its management. This is essential for identifying patients harbouring aggressive prolactinoma and to establish personalised therapeutics options.
Ganoderma formosanum Exopolysaccharides Inhibit Tumor Growth via Immunomodulation
Authors: Kuo Hsing-Chun , Liu Yen-Wenn , Lum Chi-Chin , Hsu Kai-Di , Lin Shin-Ping , Hsieh Chang-Wei , Lin Hui-Wen , Lu Tze-Ying , Cheng Kuan-Chen
Published: October 2021

Ganoderma formosanum (GF) is a medicinal mushroom endemic to Taiwan. Previous research established the optimal culture conditions to produce exopolysaccharide rich in β-glucan (GF-EPS) from submerged fermentation of GF. The present study investigated the antitumor effects of GF-EPS in a Lewis lung carcinoma cell (LLC1) tumor-bearing mice model. In the preventive model, GF-EPS was orally administered to mice before LLC1 injection. In the therapeutic model, GF-EPS oral administration was initiated five days after tumor cell injection. The tumor size and body weight of the mice were recorded. After sacrifice, the lymphocyte subpopulation was analyzed using flow cytometry. Spleen tissues were used to analyze cytokine mRNA expression. The results showed that GF-EPS (80 mg/kg) effectively suppressed LLC1 tumor growth in both the preventive and therapeutic models. GF-EPS administration increased the proportion of natural killer cells in the spleen and activated gene expression of several cytokines. Our results provide evidence that GF-EPS promotes tumor inhibition through immunomodulation in tumor-bearing mice.
Polygodial and Ophiobolin A Analogues for Covalent Crosslinking of Anticancer Targets
Authors: Maslivetc Vladimir , Laguera Breana , Chandra Sunena , Dasari Ramesh , Olivier Wesley J. , Smith Jason A. , Bissember Alex C. , Masi Marco , Evidente Antonio , Mathieu Veronique , Kornienko Alexander
Published: October 2021

In a search of small molecules active against apoptosis-resistant cancer cells, including glioma, melanoma, and non-small cell lung cancer, we previously prepared α,β- and γ,δ-unsaturated ester analogues of polygodial and ophiobolin A, compounds capable of pyrrolylation of primary amines and demonstrating double-digit micromolar antiproliferative potencies in cancer cells. In the current work, we synthesized dimeric and trimeric variants of such compounds in an effort to discover compounds that could crosslink biological primary amine containing targets. We showed that such compounds retain the pyrrolylation ability and possess enhanced single-digit micromolar potencies toward apoptosis-resistant cancer cells. Target identification studies of these interesting compounds are underway.
Diverse Mechanisms of Antimicrobial Activities of Lactoferrins, Lactoferricins, and Other Lactoferrin-Derived Peptides
Authors: Gruden Špela , Poklar Ulrih Nataša
Published: October 2021

Lactoferrins are an iron-binding glycoprotein that have important protective roles in the mammalian body through their numerous functions, which include antimicrobial, antitumor, anti-inflammatory, immunomodulatory, and antioxidant activities. Among these, their antimicrobial activity has been the most studied, although the mechanism behind antimicrobial activities remains to be elucidated. Thirty years ago, the first lactoferrin-derived peptide was isolated and showed higher antimicrobial activity than the native lactoferrin lactoferricin. Since then, numerous studies have investigated the antimicrobial potencies of lactoferrins, lactoferricins, and other lactoferrin-derived peptides to better understand their antimicrobial activities at the molecular level. This review defines the current antibacterial, antiviral, antifungal, and antiparasitic activities of lactoferrins, lactoferricins, and lactoferrin-derived peptides. The primary focus is on their different mechanisms of activity against bacteria, viruses, fungi, and parasites. The role of their structure, amino-acid composition, conformation, charge, hydrophobicity, and other factors that affect their mechanisms of antimicrobial activity are also reviewed.
Toxic Effects of Indoxyl Sulfate on Osteoclastogenesis and Osteoblastogenesis
Authors: Shyu Jia-Fwu , Liu Wen-Chih , Zheng Cai-Mei , Fang Te-Chao , Hou Yi-Chou , Chang Chiz-Tzung , Liao Ting-Ying , Chen Yin-Cheng , Lu Kuo-Cheng
Published: October 2021

Uremic toxins, such as indoxyl sulfate (IS) and kynurenine, accumulate in the blood in the event of kidney failure and contribute to further bone damage. To maintain the homeostasis of the skeletal system, bone remodeling is a persistent process of bone formation and bone resorption that depends on a dynamic balance of osteoblasts and osteoclasts. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates the toxic effects of uremic toxins. IS is an endogenous AhR ligand and is metabolized from tryptophan. In osteoclastogenesis, IS affects the expression of the osteoclast precursor nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) through AhR signaling. It is possible to increase osteoclast differentiation with short-term and low-dose IS exposure and to decrease differentiation with long-term and/or high-dose IS exposure. Coincidentally, during osteoblastogenesis, through the AhR signaling pathway, IS inhibits the phosphorylation of ERK, and p38 reduces the expression of the transcription factor 2 (Runx2), disturbing osteoblastogenesis. The AhR antagonist resveratrol has a protective effect on the IS/AhR pathway. Therefore, it is necessary to understand the multifaceted role of AhR in CKD, as knowledge of these transcription signals could provide a safe and effective method to prevent and treat CKD mineral bone disease.
Synthesis and Inhibition Activity Study of Triazinyl-Substituted Amino(alkyl)-benzenesulfonamide Conjugates with Polar and Hydrophobic Amino Acids as Inhibitors of Human Carbonic Anhydrases I, II, IV, IX, and XII
Authors: Mikulová Mária Bodnár , Kružlicová Dáša , Pecher Daniel , Petreni Andrea , Supuran Claudiu T. , Mikuš Peter
Published: October 2021

Primary sulfonamide derivatives with various heterocycles represent the most widespread group of potential human carbonic anhydrase (hCA) inhibitors with high affinity and selectivity towards specific isozymes from the hCA family. In this work, new 4-aminomethyl- and aminoethyl-benzenesulfonamide derivatives with 1,3,5-triazine disubstituted with a pair of identical amino acids, possessing a polar (Ser, Thr, Asn, Gln) and non-polar (Ala, Tyr, Trp) side chain, have been synthesized. The optimized synthetic, purification, and isolation procedures provided several pronounced benefits such as a short reaction time (in sodium bicarbonate aqueous medium), satisfactory yields for the majority of new products (20.6–91.8%, average 60.4%), an effective, well defined semi-preparative RP-C18 liquid chromatography (LC) isolation of desired products with a high purity (>97%), as well as preservation of green chemistry principles. These newly synthesized conjugates, plus their 4-aminobenzenesulfonamide analogues prepared previously, have been investigated in in vitro inhibition studies towards hCA I, II, IV and tumor-associated isozymes IX and XII. The experimental results revealed the strongest inhibition of hCA XII with low nanomolar inhibitory constants (Kis) for the derivatives with amino acids possessing non-polar side chains (7.5–9.6 nM). Various derivatives were also promising for some other isozymes.
Biological Control of Leaf Blight Disease Caused by Pestalotiopsis maculans and Growth Promotion of Quercus acutissima Carruth Container Seedlings Using Bacillus velezensis CE 100
Authors: Won Sang-Jae , Moon Jae-Hyun , Ajuna Henry B. , Choi Su-In , Maung Chaw Ei Htwe , Lee Sangtae , Ahn Young Sang
Published: October 2021

Leaf blight disease caused by Pestalotiopsismaculans lead to deleterious losses in the quality of forest container seedlings. The use of plant growth-promoting bacteria provides a promising strategy to simultaneously control diseases and enhance forest seedling production. This study investigated the biocontrol of leaf blight disease and growth promotion potential of Bacillus velezensis CE 100 in Quercus acutissima Carruth seedlings. B. velezensis CE 100 produced cell wall degrading enzymes, such as chitinase, β-l,3-glucanase, and protease, which caused cell wall lysis and hyphae deformation of P. maculans, leading to mycelial growth inhibition by 54.94%. Inoculation of B. velezensis CE 100 suppressed P. maculans infection and increased seedling survival rate by 1.6-fold and 1.3-fold compared to chemical fertilizer and control, respectively. In addition, B. velezensis CE 100 produced indole-3-acetic acid, which improved root development and nutrient uptake compared to chemical fertilizer and control. Especially, inoculation with B. velezensis CE 100 increased the total nitrogen content of Q. acutissima seedlings, improved the chlorophyll index in the leaves, and increased seedling biomass by 1.3-fold and 2.2-fold compared to chemical fertilizer and control, respectively. Thus, B. velezensis CE 100 could be applied in the eco-friendly production of high-quality forest seedlings.
Irradiation Activates MZF1 to Inhibit miR-541-5p Expression and Promote Epithelial-Mesenchymal Transition (EMT) in Radiation-Induced Pulmonary Fibrosis (RIPF) by Upregulating Slug
Authors: Liang Xinxin , Yan Ziyan , Wang Ping , Liu Yuhao , Ao Xingkun , Liu Zheng , Wang Duo , Liu Xiaochang , Zhu Maoxiang , Gao Shanshan , Xie Dafei , Zhou Pingkun , Gu Yongqing
Published: October 2021

Understanding miRNAs regulatory roles in epithelial-mesenchymal transition (EMT) would help establish new avenues for further uncovering the mechanisms underlying radiation-induced pulmonary fibrosis (RIPF) and identifying preventative and therapeutic targets. Here, we demonstrated that miR-541-5p repression by Myeloid Zinc Finger 1 (MZF1) promotes radiation-induced EMT and RIPF. Irradiation could decrease miR-541-5p expression in vitro and in vivo and inversely correlated to RIPF development. Ectopic miR-541-5p expression suppressed radiation-induced-EMT in vitro and in vivo. Knockdown of Slug, the functional target of miR-541-5p, inhibited EMT induction by irradiation. The upregulation of transcription factor MZF1 upon irradiation inhibited the expression of endogenous miR-541-5p and its primary precursor (pri-miR-541-5p), which regulated the effect of the Slug on the EMT process. Our finding showed that ectopic miR-541-5p expression mitigated RIPF in mice by targeting Slug. Thus, irradiation activates MZF1 to downregulate miR-541-5p in alveolar epithelial cells, promoting EMT and contributing to RIPF by targeting Slug. Our observation provides further understanding of the development of RIPF and determines potential preventative and therapeutic targets.
Bioluminescence and Photoreception in Unicellular Organisms: Light-Signalling in a Bio-Communication Perspective
Authors: Timsit Youri , Lescot Magali , Valiadi Martha , Not Fabrice
Published: October 2021

Bioluminescence, the emission of light catalysed by luciferases, has evolved in many taxa from bacteria to vertebrates and is predominant in the marine environment. It is now well established that in animals possessing a nervous system capable of integrating light stimuli, bioluminescence triggers various behavioural responses and plays a role in intra- or interspecific visual communication. The function of light emission in unicellular organisms is less clear and it is currently thought that it has evolved in an ecological framework, to be perceived by visual animals. For example, while it is thought that bioluminescence allows bacteria to be ingested by zooplankton or fish, providing them with favourable conditions for growth and dispersal, the luminous flashes emitted by dinoflagellates may have evolved as an anti-predation system against copepods. In this short review, we re-examine this paradigm in light of recent findings in microorganism photoreception, signal integration and complex behaviours. Numerous studies show that on the one hand, bacteria and protists, whether autotrophs or heterotrophs, possess a variety of photoreceptors capable of perceiving and integrating light stimuli of different wavelengths. Single-cell light-perception produces responses ranging from phototaxis to more complex behaviours. On the other hand, there is growing evidence that unicellular prokaryotes and eukaryotes can perform complex tasks ranging from habituation and decision-making to associative learning, despite lacking a nervous system. Here, we focus our analysis on two taxa, bacteria and dinoflagellates, whose bioluminescence is well studied. We propose the hypothesis that similar to visual animals, the interplay between light-emission and reception could play multiple roles in intra- and interspecific communication and participate in complex behaviour in the unicellular world.
Dynamics of Choline-Containing Phospholipids in Traumatic Brain Injury and Associated Comorbidities
Authors: Javaid Sana , Farooq Talha , Rehman Zohabia , Afzal Ammara , Ashraf Waseem , Rasool Muhammad Fawad , Alqahtani Faleh , Alsanea Sary , Alasmari Fawaz , Alanazi Mohammed Mufadhe , Alharbi Metab , Imran Imran
Published: October 2021

The incidences of traumatic brain injuries (TBIs) are increasing globally because of expanding population and increased dependencies on motorized vehicles and machines. This has resulted in increased socio-economic burden on the healthcare system, as TBIs are often associated with mental and physical morbidities with lifelong dependencies, and have severely limited therapeutic options. There is an emerging need to identify the molecular mechanisms orchestrating these injuries to life-long neurodegenerative disease and a therapeutic strategy to counter them. This review highlights the dynamics and role of choline-containing phospholipids during TBIs and how they can be used to evaluate the severity of injuries and later targeted to mitigate neuro-degradation, based on clinical and preclinical studies. Choline-based phospholipids are involved in maintaining the structural integrity of the neuronal/glial cell membranes and are simultaneously the essential component of various biochemical pathways, such as cholinergic neuronal transmission in the brain. Choline or its metabolite levels increase during acute and chronic phases of TBI because of excitotoxicity, ischemia and oxidative stress; this can serve as useful biomarker to predict the severity and prognosis of TBIs. Moreover, the effect of choline-replenishing agents as a post-TBI management strategy has been reviewed in clinical and preclinical studies. Overall, this review determines the theranostic potential of choline phospholipids and provides new insights in the management of TBI.
β-Barrels and Amyloids: Structural Transitions, Biological Functions, and Pathogenesis
Authors: Sulatskaya Anna I. , Kosolapova Anastasiia O. , Bobylev Alexander G. , Belousov Mikhail V. , Antonets Kirill S. , Sulatsky Maksim I. , Kuznetsova Irina M. , Turoverov Konstantin K. , Stepanenko Olesya V. , Nizhnikov Anton A.
Published: October 2021

Insoluble protein aggregates with fibrillar morphology called amyloids and β-barrel proteins both share a β-sheet-rich structure. Correctly folded β-barrel proteins can not only function in monomeric (dimeric) form, but also tend to interact with one another—followed, in several cases, by formation of higher order oligomers or even aggregates. In recent years, findings proving that β-barrel proteins can adopt cross-β amyloid folds have emerged. Different β-barrel proteins were shown to form amyloid fibrils in vitro. The formation of functional amyloids in vivo by β-barrel proteins for which the amyloid state is native was also discovered. In particular, several prokaryotic and eukaryotic proteins with β-barrel domains were demonstrated to form amyloids in vivo, where they participate in interspecies interactions and nutrient storage, respectively. According to recent observations, despite the variety of primary structures of amyloid-forming proteins, most of them can adopt a conformational state with the β-barrel topology. This state can be intermediate on the pathway of fibrillogenesis (“on-pathway state”), or can be formed as a result of an alternative assembly of partially unfolded monomers (“off-pathway state”). The β-barrel oligomers formed by amyloid proteins possess toxicity, and are likely to be involved in the development of amyloidoses, thus representing promising targets for potential therapy of these incurable diseases. Considering rapidly growing discoveries of the amyloid-forming β-barrels, we may suggest that their real number and diversity of functions are significantly higher than identified to date, and represent only “the tip of the iceberg”. Here, we summarize the data on the amyloid-forming β-barrel proteins, their physicochemical properties, and their biological functions, and discuss probable means and consequences of the amyloidogenesis of these proteins, along with structural relationships between these two widespread types of β-folds.
An Equilibrium Analysis of a Secondary Mobile Data-Share Market
Authors: Blocher Jordan , Harris Frederick C.
Published: October 2021

Internet service providers are offering shared data plans where multiple users may buy and sell their overage data in a secondary market managed by the ISP. We propose a game-theoretic approach to a software-defined network for modeling this wireless data exchange market: a fully connected, non-cooperative network. We identify and define the rules for the underlying progressive second price (PSP) auction for the respective network and market structure. We allow for a single degree of statistical freedom—the reserve price—and show that the secondary data exchange market allows for greater flexibility in the acquisition decision making of mechanism design. We have designed a framework to optimize the strategy space using the elasticity of supply and demand. Wireless users are modeled as a distribution of buyers and sellers with normal incentives. Our derivation of a buyer-response strategy for wireless users based on second price market dynamics leads us to prove the existence of a balanced pricing scheme. We examine shifts in the market price function and prove that our network upholds the desired properties for optimization with respect to software-defined networks and prove the existence of a Nash equilibrium in the overlying non-cooperative game.
Evaluation of Reference Genes for Quantitative Reverse Transcription Polymerase Chain Reaction in Bactrocera dorsalis (Diptera: Tephritidae) Subjected to Various Phytosanitary Treatments
Authors: Cao Yue , Li Baishu , Chen Naizhong , Yang Ding , Li Li , Liu Tao
Published: October 2021

Bactrocera dorsalis is a major pest that causes serious damage to many fruits. Although phytosanitary treatment methods have been developed for Bactrocera control, there is a lack of information related to the gene expression pattern of B. dorsalis subjected to phytosanitary treatment conditions. Prior to quantitative reverse transcription polymerase chain reaction analysis of the most stable reference genes in B. dorsalis (Diptera: Tephritidae), B. dorsalis third-instar larvae were exposed to various phytosanitary treatments; seven candidate reference genes (18S, G6PDH, GAPDH, RPL-13, RPL-32, RPS-3, and α-Tub) were amplified and their expression stabilities were evaluated using geNorm, NormFinder, BestKeeper, and RefFinder algorithms. Different reference genes were found under different stress conditions. G6PDH was the most stable gene after heat treatment. After cold treatment, α-Tub exhibited the highest expression stability. G6PDH expression stability was the highest after fumigation with methyl bromide. RPL-32 showed the highest expression stability after irradiation treatment. Collectively, RefFinder analysis results revealed G6PDH and RPL-32 as the most suitable genes for analyzing phytosanitary treatment in B. dorsalis. This study provides an experimental basis for further gene expression analyses in B. dorsalis subjected to various phytosanitary treatments, which can aid in the development of novel phytosanitary treatments against insect pests.
First Population Study on Winter Breeding Monarch Butterflies, Danaus plexippus (Lepidoptera: Nymphalidae) in the Urban South Bay of San Francisco, California
Authors: James David G. , Schaefer Maria C. , Krimmer Easton Karen , Carl Annie
Published: October 2021

The western North American monarch butterfly population assessed by counts of non-reproductive overwintering butterflies at coastal sites in California declined to less than 2000 in 2020/21. Simultaneously, reports of reproductive monarchs increased in San Francisco urban areas, perhaps representing a shift in overwintering strategy. To better understand monarch winter breeding in the Bay area, we studied adult and immature populations in Santa Clara County during January–June 2021. Adult monarchs were common with numbers ranging from 0.23–1.54/min during ~30 min weekly surveys at one site, with lowest numbers late April to mid-May. Eggs and larvae, primarily on ornamental milkweeds, were found on nearly all survey dates with lowest numbers mid-late April to mid-May. Levels of infection of adults by the parasite Ophryocystis elektroscirrha were consistently high during the study (69.3–77.5%). From 499 monarchs tagged post-eclosion, recovery rates of 19.2–23.6% occurred from releases in January-February and May-June but only 11.9–13.0% from March-April releases. Although distances were small, butterflies tagged in April were recovered from greater distances than other months. Tagged monarchs flew primarily north or east. There were reduced numbers of adult monarchs during late April-mid-May with some evidence of northerly and easterly emigration at the same time from tagged butterflies, suggesting some movement out of the South Bay area, perhaps representing spring migration. We conclude that monarchs can successfully breed and maintain populations on ornamental milkweeds during winter at urban sites in the South Bay of San Francisco and may still migrate during spring to remain part of the wider western population.
Comparative Analysis of Eight Mitogenomes of Bark Beetles and Their Phylogenetic Implications
Authors: Du Huicong , Fang Jiaxing , Shi Xia , Zhang Sufang , Liu Fu , Yu Chunmei , Zhang Zhen , Kong Xiangbo
Published: October 2021

Many bark beetles of the subfamily Scolytinae are the most economically important insect pests of coniferous forests worldwide. In this study, we sequenced the mitochondrial genomes of eight bark beetle species, including Dendroctonus micans, Orthotomicus erosus, Polygraphus poligraphus, Dryocoetes hectographus, Ips nitidus, Ips typographus, Ips subelongatus, and Ips hauseri, to examine their structural characteristics and determine their phylogenetic relationships. We also used previously published mitochondrial genome sequence data from other Scolytinae species to identify and localize the eight species studied within the bark beetle phylogeny. Their gene arrangement matched the presumed ancestral pattern of these bark beetles. Start and stop codon usage, amino acid abundance, and the relative codon usage frequencies were conserved among bark beetles. Genetic distances between species ranged from 0.037 to 0.418, and evolutionary rates of protein-coding genes ranged from 0.07 for COI to 0.69 for ND2. Our results shed light on the phylogenetic relationships and taxonomic status of several bark beetles in the subfamily Scolytinae and highlight the need for further sequencing analyses and taxonomic revisions in additional bark beetle species.
Effect of Hypoxia on the Lethal Mortality Time of Adult Sitophilus oryzae L.
Authors: Kandel Pragya , Scharf Michael E. , Mason Linda J. , Baributsa Dieudonne
Published: October 2021

Sitophilus oryzae is one of the most destructive pests of stored grains. It leads to significant quantitative and qualitative losses, resulting in food and income insecurity among farmers. Chemical pesticides are the most common methods used by farmers and other grain value chain actors to manage this pest. However, pesticides are increasingly becoming unattractive for pest control due to health hazards posed to applicators, consumers, the environment, and insect resistance. Modified atmospheres have the potential to manage stored insect pests as an alternative to pesticides. There is limited understanding of when insect pests die when grain is stored in airtight containers. This experiment was conducted to assess the time required to reach mortality of adult S. oryzae when exposed to 1, 3, and 5% oxygen levels. Results revealed that the LT50 for 1, 3, and 5% of oxygen were reached after 69.7 h, 187.8 h, and 386.6 h of exposure, respectively. No adult emergence was observed on infested grains following exposure to 1 and 3% oxygen levels. This result provides vital rationale for storing grain in hermetic storage conditions for at least 39 days to achieve adult S. oryzae mortality and minimize grain reinfestation.
Characteristics of Prehospital Death in Trauma Victims
Authors: Gewiess Jan , Albers Christoph Emanuel , Pape Hans-Christoph , Bangerter Hannes , Zech Wolf-Dieter , Keel Marius Johann Baptist , Bastian Johannes Dominik
Published: October 2021

Background: Using Injury Severity Score (ISS) data, this study aimed to give an overview of trauma mechanisms, causes of death, injury patterns, and potential survivability in prehospital trauma victims. Methods: Age, gender, trauma mechanism, cause of death, and ISS data were recorded regarding forensic autopsies and whole-body postmortem CT. Characteristics were analyzed for injuries considered potentially survivable at cutoffs of (I) ISS ≤ 75 vs. ISS = 75, (II) ISS ≤ 49 vs. ISS ≥ 50, and (III) ISS < lethal dose 50% (LD50) vs. ISS > LD50 according to Bull’s probit model. Results: In n = 130 prehospital trauma victims (45.3 ± 19.5 years), median ISS was 66. Severity of injuries to the head/neck and chest was greater compared to other regions (p < 0.001). 52% died from central nervous system (CNS) injury. Increasing injury severity in head/neck region was associated with CNS-injury related death (odds ratio (OR) 2.7, confidence interval (CI) 1.8–4.4). Potentially survivable trauma was identified in (I) 56%, (II) 22%, and (III) 9%. Victims with ISS ≤ 75, ISS ≤ 49, and ISS < LD50 had lower injury severity across most ISS body regions compared to their respective counterparts (p < 0.05). Conclusion: In prehospital trauma victims, injury severity is high. Lethal injuries predominate in the head/neck and chest regions and are associated with CNS-related death. The appreciable amount (9–56%) of victims dying at presumably survivable injury severity encourages perpetual efforts for improvement in the rescue of highly traumatized patients.
The Predictive Role of Modified Early Warning Score in 174 Hematological Patients at the Point of Transfer to the Intensive Care Unit
Authors: Constantinescu Catalin , Pasca Sergiu , Iluta Sabina , Gafencu Grigore , Santa Maria , Jitaru Ciprian , Teodorescu Patric , Dima Delia , Zdrenghea Mihnea , Tomuleasa Ciprian
Published: October 2021

Introduction: The examination of vital signs and their changes during illness can alert physicians to possible impending deterioration and organ dysfunction. The Modified Early Warning Score (MEWS) is used worldwide as a track and trigger system that can help to identify patients at risk of critical illness. Thus, the current study aimed to assess the ability of MEWS to predict the mortality of hematologic patients at the point of transfer from the ward to the intensive care unit (ICU). Materials and Methods: The present study was retrospective, longitudinal, and observational, conducted at an oncology hospital in the city of Cluj-Napoca, Romania. We included 174 patients with hematological disorders transferred from the ward to the ICU between the 1st of January 2018 and the 1st of May 2020. We assessed the MEWS at the moment of admission in these patients in the ICU. The accuracy of MEWS in predicting mortality was assessed via the area under the receiver operating characteristic curves (AUC), and sensitivity, specificity, and hazard ratio (HR) were calculated for different MEWS cutoffs. MEWS values considering the status at discharge and frequency of death by MEWS were also analyzed. Results: We calculated MEWS values considering the status at discharge (p < 0.0001), and we assessed the frequency of death by MEWS. We also calculated the hazard ratio (HR) of death depending on the selected MEWS cutoff. The best cutoff point was found to be ≥6, with an accuracy of 0.667, sensitivity of 0.675, specificity of 0.646, and AUC of 0.731. Patients with higher MEWS had a higher probability of mortality. Conclusion: The MEWS and cutoff points were determined on a sample of hematologic patients at the moment of admission to the ICU. The final aim is to encourage physicians to use these scores to improve awareness of organ failure to admit patients to the ICU sooner and limit overall morbidity and mortality. The presence of an ICU physician on ward rounds might help in reducing the timeframe of access to a high-dependency unit (HDU) or ICU. An extension of these scores outside hematologic patients or considering hematologic patients outside ICU must be further studied.
Assessing Cognitive Function in Neuromuscular Diseases: A Pilot Study in a Sample of Children and Adolescents
Authors: D’Alessandro Rossella , Ragusa Neftj , Vacchetti Martina , Rolle Enrica , Rossi Francesca , Brusa Chiara , Davico Chiara , Vitiello Benedetto , Mongini Tiziana , Ricci Federica S.
Published: October 2021

Central nervous system (CNS) involvement has been variously studied in pediatric neuromuscular disorders (NMDs). The primary goal of this study was to assess cognitive functioning in NMDs, and secondary aims were to investigate possible associations of cognitive impairment with motor impairment, neurodevelopmental delay, and genotype. This was a cross-sectional study of 43 pediatric patients, affected by six NMDs. Myotonic dystrophy type 1 (DM1) and glycogen storage disease type 2 (GSD2) patients had a delay on the Bayley-III scales. On Wechsler scales, DMD and DM1 patients showed lower FSIQ scores, with an intellectual disability (ID) in 27% and 50%, respectively. FSIQ was normal in Becker muscular dystrophy (BMD), GSD2, and hereditary motor sensory neuropathy (HMSN) patients, while higher individual scores were found in the spinal muscular atrophy (SMA) group. In the DM1 cohort, lower FSIQ correlated with worse motor performance (ρ = 0.84, p < 0.05), and delayed speech acquisition was associated with ID (p = 0.048), with worse cognitive impairment in the congenital than in the infantile form (p = 0.04). This study provides further evidence of CNS in some NMDs and reinforces the need to include cognitive assessment in protocols of care of selected pediatric NMDs.
Clinical Analysis of the Diagnostic Accuracy and Time of Execution of a Transillumination Caries Detection Method Compared to Bitewing Radiographs
Authors: Pelliccioni Gian Andrea , Gatto Maria Rosaria Antonella , Bolognesi Silvia , Dal Fiume Daniele , Sebold Maicon , Breschi Lorenzo
Published: October 2021

Purposes: this clinical study evaluated the accuracy and execution time of a digital imaging fiber-optic transillumination (DIFOTI) technique for the detection of approximal caries in posterior teeth compared to intra-oral examination associated with bitewing radiographs. Methods: one hundred patients were selected and submitted to clinical inspection and bitewing radiographs. The outcomes of this process were converted into scores, according to the International Caries Detection and Assessment System (ICDAS): 0—sound tooth; 1, 2, and 3—carious lesion confined within enamel; 4, 5, and 6—dentin carious lesion. Subsequently, an independent investigator acquired digital images of the same teeth using a DIFOTI device (DIAGNOcam, Kavo Dental), which were also converted into ICDAS scores. The time required for executing diagnostic procedures was measured. The clinical sensitivity and specificity of DIFOTI were analyzed by receiver operating characteristic (ROC) curves. The time necessary to perform the diagnostic methods was evaluated by Mann–Whitney U (alfa = 0.05). Results: the overall test accuracy for the DIFOTI-based device ranged from 0.717 to 0.815 (area under the ROC curve) with p < 0.0001 for all ICDAS scores. Bitewing radiographs took almost twice the time required by DIFOTI (p < 0.001). Conclusions: the DIFOTI-based device DIAGNOcam provided accurate detection of approximal caries in posterior teeth, even at early stages. The technique employed for transillumination caries diagnosis by the same device took less time than conventional bitewing radiographs. Clinical Relevance: transillumination devices, such as DIAGNOcam, can be accurately used for caries diagnosis in approximal surfaces of posterior teeth, demanding less clinical time and without radiation-related risks.
Fertility-Sparing Treatment of Patients with Endometrial Cancer: A Review of the Literature
Authors: Leone Roberti Maggiore Umberto , Khamisy-Farah Rola , Bragazzi Nicola Luigi , Bogani Giorgio , Martinelli Fabio , Lopez Salvatore , Chiappa Valentina , Signorelli Mauro , Ditto Antonino , Raspagliesi Francesco
Published: October 2021

Endometrial cancer (EC) is currently the most common malignancy of the female genital tract in developed countries. Although it is more common in postmenopausal women, it may affect up to 25% in the premenopausal age and 3–5% under the age of 40 years. Furthermore, in the last decades a significant shift to pregnancy at older maternal ages, particularly in resource-rich countries, has been observed. Therefore, in this scenario fertility-sparing alternatives should be discussed with patients affected by EC. This study summarizes available literature on fertility-sparing management of patients affected by EC, focusing on the oncologic and reproductive outcomes. A systematic computerized search of the literature was performed in two electronic databases (PubMed and MEDLINE) in order to identify relevant articles to be included for the purpose of this systematic review. On the basis of available evidence, fertility-sparing alternatives are oral progestins alone or in combination with other drugs, levonorgestrel intrauterine system and hysteroscopic resection in association with progestin therapies. These strategies seem feasible and safe for young patients with G1 endometrioid EC limited to the endometrium. However, there is a lack of high-quality evidence on the efficacy and safety of fertility-sparing treatments and future well-designed studies are required.
The Effect of Risk, R&D Intensity, Liquidity, and Inventory on Firm Performance during COVID-19: Evidence from US Manufacturing Industry
Authors: Clampit Jack , Hasija Dinesh , Dugan Michael , Gamble John
Published: October 2021

Because prior knowledge may not generalize to the COVID-19 setting, scholars are racing to test the efficacy of existing theoretical frameworks during COVID-19. Most business studies are conceptual or surveys of damage. The main purpose of the paper is to extend the forthcoming stream that tests firm performance by examining it during COVID-19. We examine the sales growth of 1298 US manufacturers during COVID-19 compared to their pre-COVID-19 baselines. Riskier firms with higher R&D intensities performed better during COVID-19, especially when cash-to-inventory levels were low. This study is among the first to empirically identify actionable predictors of firm performance during COVID-19 via a quantitative analysis of strategies and performance outcomes. Understanding what type of firms perform at higher levels during COVID-19 will help decision makers make more informed decisions moving forward. Employing ordinary least squares (OLS) regression to test our hypotheses, our findings suggest that R&D intensive firms should pivot tactically regarding current asset management, if needed, but not strategically, while prioritizing inventory versus cash retention. The positive effect of inventory versus cash extends theory by suggesting a new boundary condition related to pandemics that reverses the positive link between cash and performance found during crises with more conventional levels of turbulence. Our most important contribution, however, is practical, via the testing of predictors that can help firms during COVID-19. For example, we found that firms with higher levels of operating risk experienced 60 percent more sales growth than risk-averse firms. This knowledge that risk-taking predicted performance during COVID-19 (especially when coupled with a focus on R&D intensity and inventory level) may encourage those that can adopt less risk-averse strategies, while others focus on tactical adjustments or mitigative measures during COVID-19 and future black swan events.
Fostering Carbon Credits to Finance Wildfire Risk Reduction Forest Management in Mediterranean Landscapes
Authors: Alcasena Fermín , Rodrigues Marcos , Gelabert Pere , Ager Alan , Salis Michele , Ameztegui Aitor , Cervera Teresa , Vega-García Cristina
Published: October 2021

Despite the need for preserving the carbon pools in fire-prone southern European landscapes, emission reductions from wildfire risk mitigation are still poorly understood. In this study, we estimated expected carbon emissions and carbon credits from fuel management projects ongoing in Catalonia (Spain). The planning areas encompass about 1000 km2 and represent diverse fire regimes and Mediterranean forest ecosystems. We first modeled the burn probability assuming extreme weather conditions and historical fire ignition patterns. Stand-level wildfire exposure was then coupled with fuel consumption estimates to assess expected carbon emissions. Finally, we estimated treatment cost-efficiency and carbon credits for each fuel management plan. Landscape-scale average emissions ranged between 0.003 and 0.070 T CO2 year−1 ha−1. Fuel treatments in high emission hotspots attained reductions beyond 0.06 T CO2 year−1 per treated ha. Thus, implementing carbon credits could potentially finance up to 14% of the treatment implementation costs in high emission areas. We discuss how stand conditions, fire regimes, and treatment costs determine the treatment cost-efficiency and long-term carbon-sink capacity. Our work may serve as a preliminary step for developing a carbon-credit market and subsidizing wildfire risk management programs in low-revenue Mediterranean forest systems prone to extreme wildfires.