bluuebunny/crossref_metadata_2025 huggingface dataset:
Biochemical Correction of GM2 Ganglioside Accumulation in AB-Variant GM2 Gangliosidosis
Authors: Deschenes Natalie M. , Cheng Camilyn , Ryckman Alex E. , Quinville Brianna M. , Khanal Prem , Mitchell Melissa , Chen Zhilin , Sangrar Waheed , Gray Steven J. , Walia Jagdeep S.
Published: May 2023

GM2 gangliosidosis is a group of genetic disorders that result in the accumulation of GM2 ganglioside (GM2) in brain cells, leading to progressive central nervous system (CNS) atrophy and premature death in patients. AB-variant GM2 gangliosidosis (ABGM2) arises from loss-of-function mutations in the GM2 activator protein (GM2AP), which is essential for the breakdown of GM2 in a key catabolic pathway required for CNS lipid homeostasis. In this study, we show that intrathecal delivery of self-complementary adeno-associated virus serotype-9 (scAAV9) harbouring a functional human GM2A transgene (scAAV9.hGM2A) can prevent GM2 accumulation in in GM2AP-deficient mice (Gm2a−/− mice). Additionally, scAAV9.hGM2A efficiently distributes to all tested regions of the CNS within 14 weeks post-injection and remains detectable for the lifespan of these animals (up to 104 weeks). Remarkably, GM2AP expression from the transgene scales with increasing doses of scAAV9.hGM2A (0.5, 1.0 and 2.0 × 1011 vector genomes (vg) per mouse), and this correlates with dose-dependent correction of GM2 accumulation in the brain. No severe adverse events were observed, and comorbidities in treated mice were comparable to those in disease-free cohorts. Lastly, all doses yielded corrective outcomes. These data indicate that scAAV9.hGM2A treatment is relatively non-toxic and tolerable, and biochemically corrects GM2 accumulation in the CNS—the main cause of morbidity and mortality in patients with ABGM2. Importantly, these results constitute proof-of-principle for treating ABGM2 with scAAV9.hGM2A by means of a single intrathecal administration and establish a foundation for future preclinical research.
Rice OsMRG702 and Its Partner OsMRGBP Control Flowering Time through H4 Acetylation
Authors: Gong Feng , Zhang Kaixin , Wen Jing , Yu Shenbo , Li Wenjin , Du Gaofeng , Wu Cui , Zhu Kangjing , Xu Yifeng
Published: May 2023

MORF-RELATED GENE702 (OsMRG702) regulates flowering time genes in rice, but how it controls transcription is not well known. Here, we found that OsMRGBP can directly interact with OsMRG702. Both Osmrg702 and Osmrgbp mutants show the delayed flowering phenotype with the reduction in the transcription of multiple key flowering time genes, including Ehd1 and RFT1. Chromatin immunoprecipitation study showed that both OsMRG702 and OsMRGBP bind to the Ehd1 and RFT1 loci and the absence of either OsMRG702 or OsMRGBP leads to a decrease of H4K5 acetylation at these loci, indicating OsMRG702 and OsMRGBP cooperatively together to promote the H4K5 acetylation. In addition, whilst Ghd7 are upregulated in both Osmrg702 and Osmrgbp mutants, only OsMRG702 binds to the loci, together with the global increased and Ghd7 locus-specific increased H4K5ac levels in Osmrg702 mutants, suggesting an additional negative effect of OsMRG702 on H4K5 acetylation. In summary, OsMRG702 controls flowering gene regulation by altering H4 acetylation in rice; it works either together with OsMRGBP to enhance transcription by promoting H4 acetylation or with other unknown mechanisms to dampen transcription by preventing H4 acetylation.
Advances in Immunotherapeutic Approaches to Type 1 Diabetes
Authors: Cudini Annamaria , Fierabracci Alessandra
Published: May 2023

Type 1 diabetes mellitus (T1D) is a multifactorial autoimmune disease characterized by the selective destruction of pancreatic insulin-producing beta cells due to the aberrant activation of different immune effector cells (reviewed (rev [...]
Inflammation, Inflammatory Diseases, and Inflammasomes
Authors: Yi Young-Su
Published: May 2023

Inflammation represents the innate immune response of the body tissues against invading microbes and cellular danger signals, and, in this way, it is beneficial [...]
Progress towards Adjuvant Development: Focus on Antiviral Therapy
Authors: Brai Annalaura , Poggialini Federica , Pasqualini Claudia , Trivisani Claudia Immacolata , Vagaggini Chiara , Dreassi Elena
Published: May 2023

In recent decades, vaccines have been extraordinary resources to prevent pathogen diffusion and cancer. Even if they can be formed by a single antigen, the addition of one or more adjuvants represents the key to enhance the response of the immune signal to the antigen, thus accelerating and increasing the duration and the potency of the protective effect. Their use is of particular importance for vulnerable populations, such as the elderly or immunocompromised people. Despite their importance, only in the last forty years has the search for novel adjuvants increased, with the discovery of novel classes of immune potentiators and immunomodulators. Due to the complexity of the cascades involved in immune signal activation, their mechanism of action remains poorly understood, even if significant discovery has been recently made thanks to recombinant technology and metabolomics. This review focuses on the classes of adjuvants under research, recent mechanism of action studies, as well as nanodelivery systems and novel classes of adjuvants that can be chemically manipulated to create novel small molecule adjuvants.
α-Tocopherol-13′-Carboxychromanol Induces Cell Cycle Arrest and Cell Death by Inhibiting the SREBP1-SCD1 Axis and Causing Imbalance in Lipid Desaturation
Authors: Liao Sijia , Gollowitzer André , Börmel Lisa , Maier Charlotte , Gottschalk Luisa , Werz Oliver , Wallert Maria , Koeberle Andreas , Lorkowski Stefan
Published: May 2023

α-Tocopherol-13′-carboxychromanol (α-T-13′-COOH) is an endogenously formed bioactive α-tocopherol metabolite that limits inflammation and has been proposed to exert lipid metabolism-regulatory, pro-apoptotic, and anti-tumoral properties at micromolar concentrations. The mechanisms underlying these cell stress-associated responses are, however, poorly understood. Here, we show that the induction of G0/G1 cell cycle arrest and apoptosis in macrophages triggered by α-T-13′-COOH is associated with the suppressed proteolytic activation of the lipid anabolic transcription factor sterol regulatory element-binding protein (SREBP)1 and with decreased cellular levels of stearoyl-CoA desaturase (SCD)1. In turn, the fatty acid composition of neutral lipids and phospholipids shifts from monounsaturated to saturated fatty acids, and the concentration of the stress-preventive, pro-survival lipokine 1,2-dioleoyl-sn-glycero-3-phospho-(1′-myo-inositol) [PI(18:1/18:1)] decreases. The selective inhibition of SCD1 mimics the pro-apoptotic and anti-proliferative activity of α-T-13′-COOH, and the provision of the SCD1 product oleic acid (C18:1) prevents α-T-13′-COOH-induced apoptosis. We conclude that micromolar concentrations of α-T-13′-COOH trigger cell death and likely also cell cycle arrest by suppressing the SREBP1-SCD1 axis and depleting cells of monounsaturated fatty acids and PI(18:1/18:1).
Role of Bile-Derived Extracellular Vesicles in Hepatocellular Proliferation after Partial Hepatectomy in Rats
Authors: Sugahara Shinpei , Haga Hiroaki , Ikeda Chisaki , Makino Naohiko , Matsuda Akiko , Kakizaki Yasuharu , Hoshikawa Kyoko , Katsumi Tomohiro , Ishizawa Tetsuya , Kobayashi Toshikazu , Maki Keita , Suzuki Fumiya , Murakami Ryoko , Sato Hidenori , Ueno Yoshiyuki
Published: May 2023

Although liver regeneration has been extensively studied, the effects of bile-derived extracellular vesicles (bile EVs) on hepatocytes has not been elucidated. We examined the influence of bile EVs, collected from a rat model of 70% partial hepatectomy (PH), on hepatocytes. We produced bile-duct-cannulated rats. Bile was collected over time through an extracorporeal bile duct cannulation tube. Bile EVs were extracted via size exclusion chromatography. The number of EVs released into the bile per liver weight 12 h after PH significantly increased. Bile EVs collected 12 and 24 h post-PH, and after sham surgery (PH12-EVs, PH24-EVs, sham-EVs) were added to the rat hepatocyte cell line, and 24 h later, RNA was extracted and transcriptome analysis performed. The analysis revealed that more upregulated/downregulated genes were observed in the group with PH24-EVs. Moreover, the gene ontology (GO) analysis focusing on the cell cycle revealed an upregulation of 28 types of genes in the PH-24 group, including genes that promote cell cycle progression, compared to the sham group. PH24-EVs induced hepatocyte proliferation in a dose-dependent manner in vitro, whereas sham-Evs showed no significant difference compared to the controls. This study revealed that post-PH bile Evs promote the proliferation of the hepatocytes, and genes promoting cell cycles are upregulated in hepatocytes.
SUV3 Helicase and Mitochondrial Homeostasis
Authors: Chen Phang-Lang
Published: May 2023

SUV3 is a nuclear-encoded helicase that is highly conserved and localizes to the mitochondrial matrix. In yeast, loss of SUV3 function leads to the accumulation of group 1 intron transcripts, ultimately resulting in the loss of mitochondrial DNA, causing a petite phenotype. However, the mechanism leading to the loss of mitochondrial DNA remains unknown. SUV3 is essential for survival in higher eukaryotes, and its knockout in mice results in early embryonic lethality. Heterozygous mice exhibit a range of phenotypes, including premature aging and an increased cancer incidence. Furthermore, cells derived from SUV3 heterozygotes or knockdown cultural cells show a reduction in mtDNA. Transient downregulation of SUV3 leads to the formation of R-loops and the accumulation of double-stranded RNA in mitochondria. This review aims to provide an overview of the current knowledge regarding the SUV3-containing complex and discuss its potential mechanism for tumor suppression activity.
Ceramide AD™ Restores Skin Integrity and Function following Exposure to House Dust Mite
Authors: Bzioueche Hanene , Tamelghaghet Myriam , Chignon-Sicard Bérengère , Bazile Noémie , Hauchecorne Pauline , Barbero Calderón Maria , Meunier Pauline , Rocchi Stéphane , Passeron Thierry , Tulic Meri K.
Published: May 2023

Ceramides are epidermal lipids important for normal skin barrier function. Reduced Ceramide content is associated with atopic dermatitis (AD). House dust mite (HDM) has been localized in AD skin where it plays an exacerbator role. We set to examine the impact of HDM on skin integrity and the effect of three separate Ceramides (AD™, DS, Y30) on HDM-induced cutaneous damage. The effect was tested in vitro on primary human keratinocytes and ex vivo on skin explants. HDM (100 μg/mL) decreased the expression of adhesion protein E-cadherin, supra-basal (K1, K10) and basal (K5, K14) keratins and increased matrix metallopeptidase (MMP)-9 activity. The presence of Ceramide AD™ in topical cream inhibited HDM-induced E-cadherin and keratin destruction and dampened MMP-9 activity ex vivo which was not seen for the control cream or cream containing DS or Y30 Ceramides. The efficacy of Ceramide AD™ was tested in a clinical setting on moderate to very dry skin (as surrogate for environment-induced skin damage). When applied topically for 21 days, Ceramide AD™ significantly reduced transepidermal water loss (TEWL) in patients with very dry skin compared to their TEWL baseline data. Our study demonstrates Ceramide AD™ cream to be effective in restoring skin homeostasis and barrier function in damaged skin and warrants testing in larger clinical trials for possible treatment of AD and xerosis.
Effects of Flavonoids on Cancer, Cardiovascular and Neurodegenerative Diseases: Role of NF-κB Signaling Pathway
Authors: Barreca Maria Magdalena , Alessandro Riccardo , Corrado Chiara
Published: May 2023

Flavonoids are polyphenolic phytochemical compounds found in many plants, fruits, vegetables, and leaves. They have a multitude of medicinal applications due to their anti-inflammatory, antioxidative, antiviral, and anticarcinogenic properties. Furthermore, they also have neuroprotective and cardioprotective effects. Their biological properties depend on the chemical structure of flavonoids, their mechanism of action, and their bioavailability. The beneficial effects of flavonoids have been proven for a variety of diseases. In the last few years, it is demonstrated that the effects of flavonoids are mediated by inhibiting the NF-κB (Nuclear Factor-κB) pathway. In this review, we have summarized the effects of some flavonoids on the most common diseases, such as cancer, cardiovascular, and human neurodegenerative diseases. Here, we collected all recent studies describing the protective and prevention role of flavonoids derived from plants by specifically focusing their action on the NF-κB signaling pathway.
Flavones: The Apoptosis in Prostate Cancer of Three Flavones Selected as Therapeutic Candidate Models
Authors: Jeong Se Hyo , Kim Hun Hwan , Park Min Young , Bhosale Pritam Bhagwan , Abusaliya Abuyaseer , Won Chung Kil , Park Kwang Il , Kim Eunhye , Heo Jeong Doo , Kim Hyun Wook , Ahn Meejung , Seong Je Kyung , Kim Gon Sup
Published: May 2023

Cancer is a widespread but dangerous disease that can strike anyone and is the second 1leading cause of death worldwide. Prostate cancer, in particular, is a prevalent cancer that occurs in men, and much research is being done on its treatment. Although chemical drugs are effective, they have various side effects, and accordingly, anticancer drugs using natural products are emerging. To date, many natural candidates have been discovered, and new drugs are being developed as drugs to treat prostate cancer. Representative candidate compounds that have been studied to be effective in prostate cancer include apigenin, acacetin and tangeretin of the flavone family among flavonoids. In this review, we look at the effects of these three flavones on prostate cancer cells via apoptosis in vitro and in vivo. Furthermore, in addition to the existing drugs, we suggest the three flavones and their effectiveness as natural anticancer agents, a treatment model for prostate cancer.
IoT Health Devices: Exploring Security Risks in the Connected Landscape
Authors: Affia Abasi-amefon Obot , Finch Hilary , Jung Woosub , Samori Issah Abubakari , Potter Lucas , Palmer Xavier-Lewis
Published: May 2023

The concept of the Internet of Things (IoT) spans decades, and the same can be said for its inclusion in healthcare. The IoT is an attractive target in medicine; it offers considerable potential in expanding care. However, the application of the IoT in healthcare is fraught with an array of challenges, and also, through it, numerous vulnerabilities that translate to wider attack surfaces and deeper degrees of damage possible to both consumers and their confidence within health systems, as a result of patient-specific data being available to access. Further, when IoT health devices (IoTHDs) are developed, a diverse range of attacks are possible. To understand the risks in this new landscape, it is important to understand the architecture of IoTHDs, operations, and the social dynamics that may govern their interactions. This paper aims to document and create a map regarding IoTHDs, lay the groundwork for better understanding security risks in emerging IoTHD modalities through a multi-layer approach, and suggest means for improved governance and interaction. We also discuss technological innovations expected to set the stage for novel exploits leading into the middle and latter parts of the 21st century.
Transcatheter Aortic Valve Implantation: Addressing the Subsequent Risk of Permanent Pacemaker Implantation
Authors: Lauten Philipp , Costello-Boerrigter Lisa C. , Goebel Björn , Gonzalez-Lopez David , Schreiber Matthias , Kuntze Thomas , Al Jassem Mahmoud , Lapp Harald
Published: May 2023

Transcatheter aortic valve implantation (TAVI) is now a commonly used therapy in patients with severe aortic stenosis, even in those patients at low surgical risk. The indications for TAVI have broadened as the therapy has proven to be safe and effective. Most challenges associated with TAVI after its initial introduction have been impressively reduced; however, the possible need for post-TAVI permanent pacemaker implantation (PPI) secondary to conduction disturbances continues to be on the radar. Conduction abnormalities post-TAVI are always of concern given that the aortic valve lies in close proximity to critical components of the cardiac conduction system. This review will present a summary of noteworthy pre-and post-procedural conduction blocks, the best use of telemetry and ambulatory device monitoring to avoid unnecessary PPI or to recognize the need for late PPI due to delayed high-grade conduction blocks, predictors to identify those patients at greatest risk of requiring PPI, important CT measurements and considerations to optimize TAVI planning, and the utility of the MInimizing Depth According to the membranous Septum (MIDAS) technique and the cusp-overlap technique. It is stressed that careful membranous septal (MS) length measurement by MDCT during pre-TAVI planning is necessary to establish the optimal implantation depth before the procedure to reduce the risk of compression of the MS and consequent damage to the cardiac conduction system.
Prediction of Cervical Lymph Node Metastasis in Clinically Node-Negative T1 and T2 Papillary Thyroid Carcinoma Using Supervised Machine Learning Approach
Authors: Popović Krneta Marina , Šobić Šaranović Dragana , Mijatović Teodorović Ljiljana , Krajčinović Nemanja , Avramović Nataša , Bojović Živko , Bukumirić Zoran , Marković Ivan , Rajšić Saša , Djorović Biljana Bazić , Artiko Vera , Karličić Mihajlo , Tanić Miljana
Published: May 2023

Papillary thyroid carcinoma (PTC) is generally considered an indolent cancer. However, patients with cervical lymph node metastasis (LNM) have a higher risk of local recurrence. This study evaluated and compared four machine learning (ML)-based classifiers to predict the presence of cervical LNM in clinically node-negative (cN0) T1 and T2 PTC patients. The algorithm was developed using clinicopathological data from 288 patients who underwent total thyroidectomy and prophylactic central neck dissection, with sentinel lymph node biopsy performed to identify lateral LNM. The final ML classifier was selected based on the highest specificity and the lowest degree of overfitting while maintaining a sensitivity of 95%. Among the models evaluated, the k-Nearest Neighbor (k-NN) classifier was found to be the best fit, with an area under the receiver operating characteristic curve of 0.72, and sensitivity, specificity, positive and negative predictive values, F1 and F2 scores of 98%, 27%, 56%, 93%, 72%, and 85%, respectively. A web application based on a sensitivity-optimized kNN classifier was also created to predict the potential of cervical LNM, allowing users to explore and potentially build upon the model. These findings suggest that ML can improve the prediction of LNM in cN0 T1 and T2 PTC patients, thereby aiding in individual treatment planning.
Increased Alveolar Epithelial Damage Markers and Inflammasome-Regulated Cytokines Are Associated with Pulmonary Superinfection in ARDS
Authors: Peukert Konrad , Sauer Andrea , Seeliger Benjamin , Feuerborn Caroline , Fox Mario , Schulz Susanne , Wild Lennart , Borger Valeri , Schuss Patrick , Schneider Matthias , Güresir Erdem , Coburn Mark , Putensen Christian , Wilhelm Christoph , Bode Christian
Published: May 2023

Acute respiratory distress syndrome (ARDS) is a life-threatening form of respiratory failure defined by dysregulated immune homeostasis and alveolar epithelial and endothelial damage. Up to 40% of ARDS patients develop pulmonary superinfections, contributing to poor prognosis and increasing mortality. Understanding what renders ARDS patients highly susceptible to pulmonary superinfections is therefore essential. We hypothesized that ARDS patients who develop pulmonary superinfections display a distinct pulmonary injury and pro-inflammatory response pattern. Serum and BALF samples from 52 patients were collected simultaneously within 24 h of ARDS onset. The incidence of pulmonary superinfections was determined retrospectively, and the patients were classified accordingly. Serum concentrations of the epithelial markers soluble receptor for advanced glycation end-products (sRAGE) and surfactant protein D (SP-D) and the endothelial markers vascular endothelial growth factor (VEGF) and angiopoetin-2 (Ang-2) as well as bronchoalveolar lavage fluid concentrations of the pro-inflammatory cytokines interleukin 1ß (IL-1ß), interleukin 18 (IL-18), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-a) were analyzed via multiplex immunoassay. Inflammasome-regulated cytokine IL-18 and the epithelial damage markers SP-D and sRAGE were significantly increased in ARDS patients who developed pulmonary superinfections. In contrast, endothelial markers and inflammasome-independent cytokines did not differ between the groups. The current findings reveal a distinct biomarker pattern that indicates inflammasome activation and alveolar epithelial injury. This pattern may potentially be used in future studies to identify high-risk patients, enabling targeted preventive strategies and personalized treatment approaches.
Focus on the Prevention of Acute Limb Ischemia: Centrality of the General Practitioner from the Point of View of the Internist
Authors: Enea Iolanda , Martelli Eugenio
Published: May 2023

The thrombotic mechanism, being common to peripheral arterial disease (PAD), acute myocardial infarction (AMI), and stroke, is responsible for the highest number of deaths in the western world. However, while much has been done for the prevention, early diagnosis, therapy of AMI and stroke, the same cannot be said for PAD, which is a negative prognostic indicator for cardiovascular death. Acute limb ischemia (ALI) and chronic limb ischemia (CLI) are the most severe manifestations of PAD. They both are defined by the presence of PAD, rest pain, gangrene, or ulceration and we consider ALI if symptoms last less than 2 weeks and CLI if they last more than 2 weeks. The most frequent causes are certainly atherosclerotic and embolic mechanisms and, to a lesser extent, traumatic or surgical mechanisms. From a pathophysiological point of view, atherosclerotic, thromboembolic, inflammatory mechanisms are implicated. ALI is a medical emergency that puts both limb and the patient’s life at risk. In patients over age 80 undergoing surgery, mortality remains high reaching approximately 40% as well as amputation approximately 11%. The purpose of this paper is to summarize the scientific evidence on the possibilities of primary and secondary prevention of ALI and to raise awareness among doctors involved in the management of ALI, in particular by describing the central role of the general practitioner.
Guided Zygomatic Implantology for Oral Cancer Rehabilitation: A Case Report
Authors: Grecchi Francesco , D’Ambrogio Roberto Giuseppe , Stefanelli Luigi Vito , Grivetto Fabrizio , Goker Funda , Del Fabbro Massimo , Schreiber Alberto , Piazza Cesare , Salgarello Stefano , Dosio Camilla , Grecchi Emma
Published: May 2023

Oral rehabilitation after maxillary oncological resection is challenging. This case report presents the rehabilitation of a 65-year-old Caucasian male adenoid cystic carcinoma patient using a myo-cutaneous thigh flap, zygomatic implant placement, and an immediate fixed provisional prosthesis made with computer-aided technologies. The patient presented complaints of asymptomatic enlarged swelling of 5-mm on the right hard hemi-palate. There was an oro-antral communication deriving from a previous local excision. Preoperative radiographs showed the involvement of the right maxilla, maxillary sinus, and nose with a suspect involvement of the maxillary division of the trigeminal nerve. Treatment was planned through a fully digital workflow. A partial maxillectomy was performed endoscopically, and maxilla was reconstructed using an anterolateral thigh free flap. Two zygomatic implants were inserted simultaneously. A provisional fix full-arch prosthesis was manufactured preoperatively through a fully digital workflow and was placed in the operating room. Following post-operative radiotherapy, the patient received a final hybrid prosthesis. During the follow-up period of two years, the patient reported good function, aesthetics, and significant enhancement in quality of life. According to the results of this case, the protocol represented can be a promising alternative for oral cancer patients with large defects, and can lead to an improved quality of life.
Impaired Global Precedence Effect in Severe Alcohol Use Disorder and Korsakoff’s Syndrome: A Pilot Exploration through a Global/Local Visual Paradigm
Authors: Pitel Anne Lise , Laniepce Alice , Boudehent Céline , Poirel Nicolas
Published: May 2023

In healthy populations, visual abilities are characterized by a faster and more efficient processing of global features in a stimulus compared to local ones. This phenomenon is known as the global precedence effect (GPE), which is demonstrated by (1) a global advantage, resulting in faster response times for global features than local features and (2) interference from global distractors during the identification of local targets, but not vice versa. This GPE is essential for adapting visual processing in everyday life (e.g., extracting useful information from complex scenes). We investigated how the GPE is affected in patients with Korsakoff’s syndrome (KS) compared to patients with severe alcohol use disorder (sAUD). Three groups (including healthy controls, patients with KS and patients with sAUD) completed a global/local visual task in which predefined targets appeared at the global or local level during either congruent or incongruent (i.e., interference) situations. The results showed that healthy controls (N = 41) presented a classical GPE, while patients with sAUD (N = 16) presented neither a global advantage nor global interference effects. Patients with KS (N = 7) presented no global advantage and an inversion of the interference effect, characterized by strong interference from local information during global processing. The absence of the GPE in sAUD and the interference from local information in KS have implications in daily-life situations, providing preliminary data for a better understanding of how these patients perceive their visual world.
Genetic and Epigenetic Regulation of Drosophila Oocyte Determination
Authors: Cabrita Brigite , Martinho Rui Gonçalo
Published: May 2023

Primary oocyte determination occurs in many organisms within a germ line cyst, a multicellular structure composed of interconnected germ cells. However, the structure of the cyst is itself highly diverse, which raises intriguing questions about the benefits of this stereotypical multicellular environment for female gametogenesis. Drosophila melanogaster is a well-studied model for female gametogenesis, and numerous genes and pathways critical for the determination and differentiation of a viable female gamete have been identified. This review provides an up-to-date overview of Drosophila oocyte determination, with a particular emphasis on the mechanisms that regulate germ line gene expression.
Osteoderm Development during the Regeneration Process in Eurylepis taeniolata Blyth, 1854 (Scincidae, Sauria, Squamata)
Authors: Cherepanov Gennady O. , Gordeev Dmitry A. , Melnikov Daniel A. , Ananjeva Natalia B.
Published: May 2023

Osteoderms are bony structures that develop within the dermal layer of the skin in vertebrates and are very often found in different lizard families. Lizard osteoderms are diverse in topography, morphology, and microstructure. Of particular interest are the compound osteoderms of skinks, which are a complex of several bone elements known as osteodermites. We present new data on the development and regeneration of compound osteoderms based on the results of a histological and Computed Microtomography (micro-CT) study of a scincid lizard: Eurylepis taeniolata. The specimens studied are stored in the herpetological collections of the Saint-Petersburg State University and Zoological Institute of the Russian Academy of Sciences located in St. Petersburg, Russia. The topography of osteoderms in the integuments of the original tail area and its regenerated part was studied. A comparative histological description of the original and regenerated osteoderms of Eurylepis taeniolata is presented for the first time. The first description of the development of compound osteoderm microstructure in the process of caudal regeneration is also presented.
Transcription of HOX Genes Is Significantly Increased during Neuronal Differentiation of iPSCs Derived from Patients with Parkinson’s Disease
Authors: Fedoseyeva Viya B. , Novosadova Ekaterina V. , Nenasheva Valentina V. , Novosadova Lyudmila V. , Grivennikov Igor A. , Tarantul Vyacheslav Z.
Published: May 2023

Parkinson’s disease (PD) is the most serious movement disorder, but the actual cause of this disease is still unknown. Induced pluripotent stem cell-derived neural cultures from PD patients carry the potential for experimental modeling of underlying molecular events. We analyzed the RNA-seq data of iPSC-derived neural precursor cells (NPCs) and terminally differentiated neurons (TDNs) from healthy donors (HD) and PD patients with mutations in PARK2 published previously. The high level of transcription of HOX family protein-coding genes and lncRNA transcribed from the HOX clusters was revealed in the neural cultures from PD patients, while in HD NPCs and TDNs, the majority of these genes were not expressed or slightly transcribed. The results of this analysis were generally confirmed by qPCR. The HOX paralogs in the 3′ clusters were activated more strongly than the genes of the 5′ cluster. The abnormal activation of the HOX gene program upon neuronal differentiation in the cells of PD patients raises the possibility that the abnormal expression of these key regulators of neuronal development impacts PD pathology. Further research is needed to investigate this hypothesis.
Saddle Pressures Factors in Road and Off-Road Cyclists of Both Genders: A Narrative Review
Authors: Vicari Domenico Savio Salvatore , Patti Antonino , Giustino Valerio , Figlioli Flavia , Alamia Giuseppe , Palma Antonio , Bianco Antonino
Published: May 2023

The contact point of the pelvis with the saddle of the bicycle could generate abnormal pressure, which could lead to injuries to the perineum in cyclists. The aim of this review was to summarize in a narrative way the current literature on the saddle pressures and to present the factors that influence saddle pressures in order to prevent injury risk in road and off-road cyclists of both genders. We searched the PubMed database to identify English-language sources, using the following terms: “saddle pressures”, “pressure mapping”, “saddle design” AND “cycling”. We also searched the bibliographies of the retrieved articles. Saddle pressures are influenced by factors such as sitting time on the bike, pedaling intensity, pedaling frequency, trunk and hand position, handlebars position, saddle design, saddle height, padded shorts, and gender. The jolts of the perineum on the saddle, especially on mountain bikes, generate intermittent pressures, which represent a risk factor for various pathologies of the urogenital system. This review highlights the importance of considering these factors that influence saddle pressures in order to prevent urogenital system injuries in cyclists.
When Cognitive Reflection Leads to Less Overall but More Systematic Judgment Bias: The Case of the Base Rates Fallacy
Authors: Ferreira Mário B. , Assunção Hugo , Seruti Amanda
Published: May 2023

Although widely used in the judgment under uncertainty literature, the so-called Lawyer–Engineer problem does not have a Bayesian solution because the base rates typically oppose qualitative stereotypical information, which has an undefined diagnostic value. We propose an experimental paradigm that elicits participants’ subjective estimates of the diagnosticity of stereotypical information and allows us to investigate the degree to which participants are able to integrate both sources of information (base rates and stereotypical descriptions) according to the Bayesian rule. This paradigm was used to test the hypothesis that the responses (probability estimates) to the Lawyer–Engineer problem from more rational individuals deviate from normative Bayesian solutions in a way that shows smaller but more systematic bias. The results further suggest that the estimates of less rational participants are noisier (less reliable) but may be more accurate when aggregated across several problems.
An Adaptive Control Method with Disturbance Estimation for Underwater Manipulation
Authors: Wang Yiqun , Li Shuo , Tian Qiyan , Li Yiping , Sun Honglin , Zhang Yuexing
Published: May 2023

In this paper, an adaptive control scheme with disturbance estimation is proposed for the station keeping and trajectory tracking of an underwater vehicle-manipulator system (UVMS) in a task space. The control of UVMSs encounters time-varying and lumped disturbances introduced by the motion of the manipulator and currents. The proposed control scheme includes an observer to identify disturbances without introducing additional sensors. Using state-of-the-art UVMS control technologies, it alleviates the restriction of the feedforward control applied to the UVMS. In addition, the proposed control scheme is not designed based on the worst case. In other words, the robustness of the controller is not achieved at the price of performance, and the performance of the controller can be recovered in the absence of disturbance. Meanwhile, the controller can also realize quick responses to attenuating disturbance and closed-loop stability when encountering an unexpected disturbance. The effectiveness of the proposed control scheme was demonstrated by a series of spatial trajectory tracking experiments under various disturbances. A limitation of this study is that the proposed control scheme is specialized for the underwater manipulation of UVMSs.
Taxonomic Novelties and New Records of Amanita Subgenus Amanitina from Thailand
Authors: Liu Yuan S. , Liu Jian-Kui , Kumla Jaturong , Suwannarach Nakarin , Lumyong Saisamorn
Published: May 2023

The Amanita subgenus Amanitina contains six sections, and the species diversity of this subgenus has still not been explored in Thailand. Twenty samples collected in 2019 and 2020, which had the morphological characteristics of the Amanita subgen. Amanitina, were observed in this study. Both the microscopical characteristics and multi-gene phylogenetic analyses of the ITS, nrLSU, RPB2, TEF1-α, and TUB gene regions revealed that the 20 samples represented nine species and dispersed into four sections. Remarkably, three taxa were different from any other currently known species. Here, we describe them as new to science, namely A. albifragilis, A. claristriata, and A. fulvisquamea. Moreover, we also recognized six interesting taxa, including four records that were new to Thailand, viz. A. cacaina, A. citrinoannulata, A. griseofarinosa, and A. neoovoidea, as well as two previously recorded species, A. caojizong and A. oberwinkleriana. Moreover, we provide the first RPB2 and TEF1-α gene sequences for A. cacaina. Detailed descriptions, illustrations as line drawings, and comparisons with related taxa are provided.
Novel Pneumocystis Antigens for Seroprevalence Studies
Authors: Pungan Dora , Fan Jia , Dai Guixiang , Khatun Mst Shamima , Dietrich Monika L. , Zwezdaryk Kevin J. , Robinson James E. , Landry Samuel J. , Kolls Jay K.
Published: May 2023

Pneumocystis jirovecii is the most common cause of fungal pneumonia in children under the age of 2 years. However, the inability to culture and propagate this organism has hampered the acquisition of a fungal genome as well as the development of recombinant antigens to conduct seroprevalence studies. In this study, we performed proteomics on Pneumocystis-infected mice and used the recent P. murina and P. jirovecii genomes to prioritize antigens for recombinant protein expression. We focused on a fungal glucanase due to its conservation among fungal species. We found evidence of maternal IgG to this antigen, followed by a nadir in pediatric samples between 1 and 3 months of age, followed by an increase in prevalence over time consistent with the known epidemiology of Pneumocystis exposure. Moreover, there was a strong concordance of anti-glucanase responses and IgG against another Pneumocystis antigen, PNEG_01454. Taken together, these antigens may be useful tools for Pneumocystis seroprevalence and seroconversion studies.
Transcriptome and Metabolome Integration Reveals the Impact of Fungal Elicitors on Triterpene Accumulation in Sanghuangporus sanghuang
Authors: Zhou Linjiang , Fu Yan , Zhang Xinyuan , Wang Tong , Wang Guangyuan , Zhou Liwei , Yu Hailong , Tian Xuemei
Published: May 2023

Sanghuangporus sanghuang is a large wood-decaying mushroom highly valued in traditional Chinese medicine due to its medicinal properties, including hypoglycemic, antioxidant, antitumor, and antibacterial properties effects. Its key bioactive compounds include flavonoids and triterpenoids. Specific fungal genes can be selectively induced by fungal elicitors. To investigate the effect of fungal polysaccharides derived from Perenniporia tenuis mycelia on the metabolites of S. sanghuang, we conducted metabolic and transcriptional profiling with and without elicitor treatment (ET and WET, respectively). Correlation analysis showed significant differences in triterpenoid biosynthesis between the ET and WET groups. In addition, the structural genes associated with triterpenoids and their metabolites in both groups were verified using quantitative real-time polymerase chain reaction (qRT-PCR) and high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS). Through metabolite screening, three triterpenoids were identified: betulinol, betulinic acid, and 2-hydroxyoleanolic acid. Excitation treatment increased the level of betulinic acid by 2.62-fold and 2-hydroxyoleanolic acid by 114.67-fold compared to WET. The qRT-PCR results of the four genes expressed in secondary metabolic pathways, defense gene activation, and signal transduction showed significant variation between the ET and WET groups. Overall, our study suggests that the fungal elicitor induced the aggregation of pentacyclic triterpenoid secondary metabolites in S. sanghuang.
Biodegradation of Low Density Polyethylene by the Fungus Cladosporium sp. Recovered from a Landfill Site
Authors: Gong Zhu , Jin Long , Yu Xingye , Wang Baoteng , Hu Shuang , Ruan Honghua , Sung Yun-Ju , Lee Hyung-Gwan , Jin Fengjie
Published: May 2023

Low density polyethylene (LDPE) has been widely used commercially for decades; however, as a non-degradable material, its continuous accumulation has contributed to serious environmental issues. A fungal strain, Cladosporium sp. CPEF-6 exhibiting a significant growth advantage on MSM-LDPE (minimal salt medium), was isolated and selected for biodegradation analysis. LDPE biodegradation was analyzed by weight loss percent, change in pH during fungal growth, environmental scanning electron microscopy (ESEM), and Fourier transformed infrared spectroscopy (FTIR). Inoculation with the strain Cladosporium sp. CPEF-6 resulted in a 0.30 ± 0.06% decrease in the weight of untreated LDPE (U-LDPE). After heat treatment (T-LDPE), the weight loss of LDPE increased significantly and reached 0.43 ± 0.01% after 30 days of culture. The pH of the medium was measured during LDPE degradation to assess the environmental changes caused by enzymes and organic acids secreted by the fungus. The fungal degradation of LDPE sheets was characterized by ESEM analysis of topographical alterations, such as cracks, pits, voids, and roughness. FTIR analysis of U-LDPE and T-LDPE revealed the appearance of novel functional groups associated with hydrocarbon biodegradation as well as changes in the polymer carbon chain, confirming the depolymerization of LDPE. This is the first report demonstrating the capacity of Cladosporium sp. to degrade LDPE, with the expectation that this finding can be used to ameliorate the negative impact of plastics on the environment.
Determination of the Duplicated CYP2D6 Allele Using Real-Time PCR Signal: An Alternative Approach
Authors: Atiq Mazen A. , Peterson Sandra E. , Langman Loralie J. , Baudhuin Linnea M. , Black John L. , Moyer Ann M.
Published: May 2023

CYP2D6 duplication has important pharmacogenomic implications. Reflex testing with long-range PCR (LR-PCR) can resolve the genotype when a duplication and alleles with differing activity scores are detected. We evaluated whether visual inspection of plots from real-time-PCR-based targeted genotyping with copy number variation (CNV) detection could reliably determine the duplicated CYP2D6 allele. Six reviewers evaluated QuantStudio OpenArray CYP2D6 genotyping results and the TaqMan Genotyper plots for seventy-three well-characterized cases with three copies of CYP2D6 and two different alleles. Reviewers blinded to the final genotype visually assessed the plots to determine the duplicated allele or opt for reflex sequencing. Reviewers achieved 100% accuracy for cases with three CYP2D6 copies that they opted to report. Reviewers did not request reflex sequencing in 49–67 (67–92%) cases (and correctly identified the duplicated allele in each case); all remaining cases (6–24) were marked by at least one reviewer for reflex sequencing. In most cases with three copies of CYP2D6, the duplicated allele can be determined using a combination of targeted genotyping using real-time PCR with CNV detection without need for reflex sequencing. In ambiguous cases and those with >3 copies, LR-PCR and Sanger sequencing may still be necessary for determination of the duplicated allele.
Genetic Evaluation and Screening in Cardiomyopathies: Opportunities and Challenges for Personalized Medicine
Authors: Aiyer Sahana , Kalutskaya Emilia , Agdamag Arianne C. , Tang W. H. Wilson
Published: May 2023

Cardiomyopathy is a major cause of heart failure caused by abnormalities of the heart muscles that make it harder for it to fill or eject blood. With technological advances, it is important for patients and families to understand that there are potential monogenic etiologies of cardiomyopathy. A multidisciplinary approach to clinical genetic screening for cardiomyopathies involving genetic counseling and clinical genetic testing is beneficial for patients and families. With early identification of inherited cardiomyopathy, patients can initiate guideline-directed medical therapies earlier, resulting in a greater likelihood of improving prognoses and health outcomes. Identifying impactful genetic variants will also allow for cascade testing to determine at-risk family members through clinical (phenotype) screening and risk stratification. Addressing genetic variants of uncertain significance and causative variants that may change in pathogenicity is also important to consider. This review will dive into the clinical genetic testing approaches for the various cardiomyopathies, the significance of early detection and treatment, the value of family screening, the personalized treatment process associated with genetic evaluation, and current strategies for clinical genetic testing outreach.
The Effect of Ornamental Groundcover Habit and Irrigation Delivery on Dynamic Soil Conditions
Authors: McKeown Thomas M. , Fields Jeb S. , Abdi Damon E.
Published: May 2023

Sustainable landscapes provide environmental, social, and financial benefits, with interest and adoption increasing due to environmental awareness. Ornamental ground-cover systems have garnered interest in the landscape due to the reduced need for water, fertilizers, pesticides, and maintenance compared to typical landscapes; however, limited research on groundcover ability to modulate soil conditions or suppress weeds exists. This study explored how ornamental groundcover systems impact the sustainability of landscapes. The effects of ground-cover growth habit (matting; bunching) and irrigation delivery method (micro spray; overhead) on soil temperature, volumetric water content (VWC), and electric conductivity (EC), along with impacts on weed growth, soil microbial communities, and plant coverage, were measured. Soil temperatures were generally lower under groundcover species with a matting growth habit, and to a lesser extent, bunching growth habits, in comparison to the warmer fallow systems. Groundcovers with a matting form led to lower VWC values compared to taxa with other growth habits, particularly when micro-irrigated. Plant form did not significantly influence EC values; however, micro spray irrigated plots had significantly higher EC values, likely attributed to irrigation spray patterns. Micro spray irrigation in tandem with matting growth habit taxa decreased weed density more effectively than taxa with bunching growth habits or groundcovers maintained under overhead irrigation. Selection of groundcover species with greater foliar coverage along with implementing more efficient irrigation practices can decrease soil temperatures, soil moisture, and weed density. Incorporating groundcovers in the landscape can decrease maintenance requirements and water/chemical use, thus increasing sustainability and decreasing environmental consequences.
Analysis of Flow and Land Use on the Hydraulic Structure of Southeast Mexico City: Implications on Flood and Runoff
Authors: Bonasia Rosanna , Borselli Lorenzo , Madonia Paolo
Published: May 2023

The southeast of Mexico City is one of the last areas of environmental importance for the region. However, rapid urban expansion has led to a runoff increase in the presence of intense rainfall. This situation is common to many peri-urban centers close to large cities, where the urbanization of previously green areas has had a direct negative influence on the hydraulic structure. This work proposes a study that combines hydrological analysis for the definition of precipitation scenarios with hydrodynamic simulations based on the current land use. Reconstructed flood scenarios show that the runoffs descending from mountainous areas flow into cemented channels with hydraulic sections and characteristics not adequate to drain specific discharges that can reach 0.90 m2/s and water depths of the order of 2 m, caused by extreme weather phenomena, determining flooding in nearby areas. Runoffs are also intensified by the presence of non-urbanized open spaces in a state of abandonment, whose soil does not favor infiltration and promotes the flooding of residential centers with water levels higher than 1 m. The results indicate an urgent need to adopt actions to reduce flooding and favor infiltration in an area of the city that is also important for aquifer recharge.