bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of the ddt1 Mutant in Rice and Its Impact on Plant Height Reduction and Water Use Efficiency
Authors: Ruan Banpu , Jiang Yaohuang , Ma Yingying , Zhou Menghao , Chen Fei , Zhang Yanli , Yu Yanchun , Wu Limin
Published: July 2024

Rice (Oryza sativa L.), a fundamental global staple, nourishes over half of the world’s population. The identification of the ddt1 mutant in rice through EMS mutagenesis of the indica cultivar Shuhui527 revealed a dwarf phenotype, characterized by reduced plant height, smaller grain size, and decreased grain weight. Detailed phenotypic analysis and map-based cloning pinpointed the mutation to a single-base transversion in the LOC_Os03g04680 gene, encoding a cytochrome P450 enzyme, which results in a premature termination of the protein. Functional complementation tests confirmed LOC_Os03g04680 as the DDT1 gene responsible for the observed phenotype. We further demonstrated that the ddt1 mutation leads to significant alterations in gibberellic acid (GA) metabolism and signal transduction, evidenced by the differential expression of key GA-related genes such as OsGA20OX2, OsGA20OX3, and SLR1. The mutant also displayed enhanced drought tolerance, as indicated by higher survival rates, reduced water loss, and rapid stomatal closure under drought conditions. This increased drought resistance was linked to the mutant’s improved antioxidant capacity, with elevated activities of antioxidant enzymes and higher expression levels of related genes. Our findings suggest that DDT1 plays a crucial role in regulating both plant height and drought stress responses. The potential for using gene editing of DDT1 to mitigate the dwarf phenotype while retaining improved drought resistance offers promising avenues for rice improvement.
Interoceptive Processing in Functional Gastrointestinal Disorders
Authors: Karaivazoglou Katerina , Aggeletopoulou Ioanna , Triantos Christos
Published: July 2024

Functional gastrointestinal disorders (FGIDs) are characterized by chronic gastrointestinal symptoms in the absence of overt pathology and affect a significant percentage of the worldwide population. They are commonly accompanied by co-morbid psychiatric symptomatology and are associated with significant suffering and great healthcare services utilization. There is growing evidence that dysregulation of the gut–brain axis and disturbances in the processing of afferent interoceptive signals lie at the heart of these disorders. In this context, the aim of the current review was to detect and critically review original articles focusing on the role of interoception in the pathophysiology of FGIDs. Our search yielded 38 relevant studies. FGID patients displayed increased visceral sensitivity, enhanced attention to gastrointestinal interoceptive cues, and greater emotional arousal when coping with gut-derived sensations. Neuroimaging studies have shown significant structural and functional changes in regions of the interoceptive network, while molecular and genetic studies have revealed significant associations between interoceptive signaling and deficits in excitatory neurotransmission, altered endocrine and immune physiological pathways, and aberrant expression of transient receptor potential channel genes. Finally, there were emerging data suggesting that interoception-based interventions may reduce physical symptoms and improve quality of life and should be integrated into FGID clinical management practices.
Multi-Omics Characterization of E3 Regulatory Patterns in Different Cancer Types
Authors: Li Zhongyan , Wan Jingting , Li Shangfu , Tang Yun , Lin Yang-Chi-Dung , Ni Jie , Cai Xiaoxuan , Yu Jinhan , Huang Hsien-Da , Lee Tzong-Yi
Published: July 2024

Ubiquitination, a post-translational modification, refers to the covalent attachment of ubiquitin molecules to substrates. This modification plays a critical role in diverse cellular processes such as protein degradation. The specificity of ubiquitination for substrates is regulated by E3 ubiquitin ligases. Dysregulation of ubiquitination has been associated with numerous diseases, including cancers. In our study, we first investigated the protein expression patterns of E3 ligases across 12 cancer types. Our findings indicated that E3 ligases tend to be up-regulated and exhibit reduced tissue specificity in tumors. Moreover, the correlation of protein expression between E3 ligases and substrates demonstrated significant changes in cancers, suggesting that E3-substrate specificity alters in tumors compared to normal tissues. By integrating transcriptome, proteome, and ubiquitylome data, we further characterized the E3-substrate regulatory patterns in lung squamous cell carcinoma. Our analysis revealed that the upregulation of the SKP2 E3 ligase leads to excessive degradation of BRCA2, potentially promoting tumor cell proliferation and metastasis. Furthermore, the upregulation of E3 ubiquitin–protein ligase TRIM33 was identified as a biomarker associated with a favorable prognosis by inhibiting the cell cycle. This work exemplifies how leveraging multi-omics data to analyze E3 ligases across various cancers can unveil prognosis biomarkers and facilitate the identification of potential drug targets for cancer therapy.
The Structure–Antiproliferative Activity Relationship of Pyridine Derivatives
Authors: Villa-Reyna Ana-Laura , Perez-Velazquez Martin , González-Félix Mayra Lizett , Gálvez-Ruiz Juan-Carlos , Gonzalez-Mosquera Dulce María , Valencia Dora , Ballesteros-Monreal Manuel G. , Aguilar-Martínez Milagros , Leyva-Peralta Mario-Alberto
Published: July 2024

Pyridine, a compound with a heterocyclic structure, is a key player in medicinal chemistry and drug design. It is widely used as a framework for the design of biologically active molecules and is the second most common heterocycle in FDA-approved drugs. Pyridine is known for its diverse biological activity, including antituberculosis, antitumor, anticoagulant, antiviral, antimalarial, antileishmania, anti-inflammatory, anti-Alzheimer’s, antitrypanosomal, antimalarial, vasodilatory, antioxidant, antimicrobial, and antiproliferative effects. This review, spanning from 2022 to 2012, involved the meticulous identification of pyridine derivatives with antiproliferative activity, as indicated by their minimum inhibitory concentration values (IC50) against various cancerous cell lines. The aim was to determine the most favorable structural characteristics for their antiproliferative activity. Using computer programs, we constructed and calculated the molecular descriptors and analyzed the electrostatic potential maps of the selected pyridine derivatives. The study found that the presence and positions of the -OMe, -OH, -C=O, and NH2 groups in the pyridine derivatives enhanced their antiproliferative activity over the cancerous cellular lines studied. Conversely, pyridine derivatives with halogen atoms or bulky groups in their structures exhibited lower antiproliferative activity.
Long Non-Coding RNAs and Alzheimer’s Disease: Towards Personalized Diagnosis
Authors: Mosquera-Heredia Maria I. , Vidal Oscar M. , Morales Luis C. , Silvera-Redondo Carlos , Barceló Ernesto , Allegri Ricardo , Arcos-Burgos Mauricio , Vélez Jorge I. , Garavito-Galofre Pilar
Published: July 2024

Alzheimer’s disease (AD), a neurodegenerative disorder characterized by progressive cognitive decline, is the most common form of dementia. Currently, there is no single test that can diagnose AD, especially in understudied populations and developing countries. Instead, diagnosis is based on a combination of medical history, physical examination, cognitive testing, and brain imaging. Exosomes are extracellular nanovesicles, primarily composed of RNA, that participate in physiological processes related to AD pathogenesis such as cell proliferation, immune response, and neuronal and cardiovascular function. However, the identification and understanding of the potential role of long non-coding RNAs (lncRNAs) in AD diagnosis remain largely unexplored. Here, we clinically, cognitively, and genetically characterized a sample of 15 individuals diagnosed with AD (cases) and 15 controls from Barranquilla, Colombia. Advanced bioinformatics, analytics and Machine Learning (ML) techniques were used to identify lncRNAs differentially expressed between cases and controls. The expression of 28,909 lncRNAs was quantified. Of these, 18 were found to be differentially expressed and harbored in pivotal genes related to AD. Two lncRNAs, ENST00000608936 and ENST00000433747, show promise as diagnostic markers for AD, with ML models achieving > 95% sensitivity, specificity, and accuracy in both the training and testing datasets. These findings suggest that the expression profiles of lncRNAs could significantly contribute to advancing personalized AD diagnosis in this community, offering promising avenues for early detection and follow-up.
Preparation and Epitope Identification of Monoclonal Antibodies against the NS6 Protein of Porcine Deltacoronavirus (PDCoV)
Authors: Wu Huiguang , Sun Xian , Li Chen , Xie Sihan , Chen Zhenhai
Published: July 2024

Porcine deltacoronavirus (PDCoV) is an emerging enteric pathogen that causes substantial economic losses in the swine industry worldwide. The PDCoV NS6 protein is an accessory protein that plays a pivotal role in the viral life cycle and immune evasion. However, the functions of NS6 and its role in PDCoV pathogenesis remain largely unknown. In this study, we prepared a monoclonal antibody (mAb) 5-A11 that specifically recognizes the PDCoV NS6 protein. The mAb 5-A11 exhibited high specificity for PDCoV, with no cross-reactivity with several major porcine pathogenic viruses. Furthermore, the epitope recognized by mAb 5-A11 was precisely mapped to residues 70EYGSIYGKDFI80 of the NS6 protein using Western blot analysis. Notably, this epitope is highly conserved among different PDCoV isolates. Substantial variations were observed when comparing this epitope with the corresponding regions in the NS6 proteins of other δ coronaviruses, suggesting potential differences in the structure, function, and antigenicity of their NS6 proteins. Our findings provide valuable tools and insights for further elucidating the functions of the NS6 protein and its role in PDCoV pathogenesis, as well as for developing diagnostic and therapeutic strategies against PDCoV infection.
A Comparative Analysis of Two Automated Quantification Methods for Regional Cerebral Amyloid Retention: PET-Only and PET-and-MRI-Based Methods
Authors: Kim Sunghwan , Wang Sheng-Min , Kang Dong Woo , Um Yoo Hyun , Han Eun Ji , Park Sonya Youngju , Ha Seunggyun , Choe Yeong Sim , Kim Hye Weon , Kim Regina EY , Kim Donghyeon , Lee Chang Uk , Lim Hyun Kook
Published: July 2024

Accurate quantification of amyloid positron emission tomography (PET) is essential for early detection of and intervention in Alzheimer’s disease (AD) but there is still a lack of studies comparing the performance of various automated methods. This study compared the PET-only method and PET-and-MRI-based method with a pre-trained deep learning segmentation model. A large sample of 1180 participants in the Catholic Aging Brain Imaging (CABI) database was analyzed to calculate the regional standardized uptake value ratio (SUVR) using both methods. The logistic regression models were employed to assess the discriminability of amyloid-positive and negative groups through 10-fold cross-validation and area under the receiver operating characteristics (AUROC) metrics. The two methods showed a high correlation in calculating SUVRs but the PET-MRI method, incorporating MRI data for anatomical accuracy, demonstrated superior performance in predicting amyloid-positivity. The parietal, frontal, and cingulate importantly contributed to the prediction. The PET-MRI method with a pre-trained deep learning model approach provides an efficient and precise method for earlier diagnosis and intervention in the AD continuum.
Time-Restricted Feeding Protects against Renal Ischemia-Reperfusion Injury in Mice
Authors: Kim Do Kyun , Kim Young Suk , Kim Min Jeong , Kim Seo Rin , Lee Dong Won , Lee Soo Bong , Kim Il Young
Published: July 2024

Ischemia-reperfusion injury (IRI) in the kidneys is a major cause of acute kidney injury (AKI). Time-restricted feeding (TRF), known for its metabolic health benefits and alleviation of various chronic diseases without calorie restriction, was investigated for its potential protective effects against IRI-induced AKI. Male C57BL/6 mice underwent unilateral IRI, with their kidneys collected after two days. For two weeks before IRI induction, the TRF group had unlimited access to standard chow but within an 8-hour feeding window during the dark cycle. The study groups were Control, TRF, IRI, and TRF + IRI. In the TRF + IRI group, tubular damage scores significantly decreased compared to the IRI group. Furthermore, the TRF + IRI mice had lower levels of phosphorylated NF-κB and fewer F4/80-positive macrophages than the IRI group. Oxidative stress markers for lipids and proteins were also notably lower in the TRF + IRI group. Additionally, TUNEL-positive tubular cells and cleaved caspase-3 expression were reduced in the TRF + IRI group. Without calorie restriction, TRF mitigated renal damage by reducing inflammation, oxidative stress, and tubular apoptosis in renal IRI. This suggests that TRF could be a promising dietary strategy to prevent IRI-induced AKI.
Impact of Respiratory Dust on Health: A Comparison Based on the Toxicity of PM2.5, Silica, and Nanosilica
Authors: Hu Aoxiang , Li Rou , Chen Guo , Chen Shi
Published: July 2024

Respiratory dust of different particle sizes in the environment causes diverse health effects when entering the human body and makes acute or chronic damage through multiple systems and organs. However, the precise toxic effects and potential mechanisms induced by dust of different particle sizes have not been systematically summarized. In this study, we described the sources and characteristics of three different particle sizes of dust: PM2.5 (<2.5 μm), silica (<5 μm), and nanosilica (<100 nm). Based on their respective characteristics, we further explored the main toxicity induced by silica, PM2.5, and nanosilica in vivo and in vitro. Furthermore, we evaluated the health implications of respiratory dust on the human body, and especially proposed potential synergistic effects, considering current studies. In summary, this review summarized the health hazards and toxic mechanisms associated with respiratory dust of different particle sizes. It could provide new insights for investigating the synergistic effects of co-exposure to respiratory dust of different particle sizes in mixed environments.
Mannose-Binding Lectin Deposition in Membranous Nephropathy and Differentiation of Primary from Secondary Forms
Authors: Zdravkova Irina , Tilkiyan Eduard , Bozhkova Desislava
Published: July 2024

The differentiation between primary and secondary forms of membranous nephropathy (MN) is a cornerstone that is necessary for adequate decision making regarding the treatment options and behavior of each specific case. Kidney biopsy and antibody results can be controversial, and a unique biomarker has still not been found. Background and Objectives: We investigated the lack of mannose-binding lectin (MBL) deposition in patients with secondary MNs (sMNs) with the presence of IgG4 deposition in relation to the presence of MBL deposition in patients with primary MNs (pMNs). We also established a connection between the stage of MN and MBL deposition. Materials and Methods: Materials from 72 renal biopsies with proven MN were used for immunohistochemistry staining (IHC) for the phospholipase A2 receptor (PLA2R), immunoglobulin subtype IgG4, and MBL. Patients were separated into one of the following three groups: primary MN (pMN), idiopathic MN (iMN), and secondary MN (sMN). Serum antibodies for PLA2R and thrombospondin type-I-domain-containing 7A (THSD7A) were also used for the precise evaluation of the type of MN, as well as for detecting positivity for PLA2R using IHC. Which stage of MN was present in relation to the deposition of MBL was evaluated. Results: In total, 50 patients were positive for IgG4, 34 with pMN, 12 with iMN, and 4 with sMN. A total of 20 patients were positive for MBL, 14 with pMN and 6 with iMN; no MBL deposits were found in patients with sMN. MBL positivity was predominantly present in the first two stages of MN, with a gradual reduction in the later stages. Conclusions: The activation of the lectin–complement pathway occurs in the early stages of the disease and is associated with the deposition of IgG4; IgG4 deposition is present in sMN, but there is no MBL deposition. IgG4 cannot be used for the differentiation of primary from secondary MNs, but the lack of MBL can be used as a marker for sMN in the early stages of the disease.
MERTK Inhibition as a Targeted Novel Cancer Therapy
Authors: Tanim K.M. , Holtzhausen Alisha , Thapa Aashis , Huelse Justus M. , Graham Douglas K. , Earp H. Shelton
Published: July 2024

In this issue honoring the contributions of Greg Lemke, the Earp and Graham lab teams discuss several threads in the discovery, action, signaling, and translational/clinical potential of MERTK, originally called c-mer, a member of the TYRO3, AXL, and MERTK (TAM) family of receptor tyrosine kinases. The 30-year history of the TAM RTK family began slowly as all three members were orphan RTKs without known ligands and/or functions when discovered by three distinct alternate molecular cloning strategies in the pre-genome sequencing era. The pace of understanding their physiologic and pathophysiologic roles has accelerated over the last decade. The activation of ligands bridging externalized phosphatidylserine (PtdSer) has placed these RTKs in a myriad of processes including neurodevelopment, cancer, and autoimmunity. The field is ripe for further advancement and this article hopefully sets the stage for further understanding and therapeutic intervention. Our review will focus on progress made through the collaborations of the Earp and Graham labs over the past 30 years.
Immune Stimulation with Imiquimod to Best Face SARS-CoV-2 Infection and Prevent Long COVID
Authors: Pacheco-García Ursino , Varela-López Elvira , Serafín-López Jeanet
Published: July 2024

Through widespread immunization against SARS-CoV-2 prior to or post-infection, a substantial segment of the global population has acquired both humoral and cellular immunity, and there has been a notable reduction in the incidence of severe and fatal cases linked to this virus and accelerated recovery times for those infected. Nonetheless, a significant demographic, comprising around 20% to 30% of the adult population, remains unimmunized due to diverse factors. Furthermore, alongside those recovered from the infection, there is a subset of the population experiencing persistent symptoms referred to as Long COVID. This condition is more prevalent among individuals with underlying health conditions and immune system impairments. Some Long COVID pathologies stem from direct damage inflicted by the viral infection, whereas others arise from inadequate immune system control over the infection or suboptimal immunoregulation. There are differences in the serum cytokines and miRNA profiles between infected individuals who develop severe COVID-19 or Long COVID and those who control adequately the infection. This review delves into the advantages and constraints associated with employing imiquimod in human subjects to enhance the immune response during SARS-CoV-2 immunization. Restoration of the immune system can modify it towards a profile of non-susceptibility to SARS-CoV-2. An adequate immune system has the potential to curb viral propagation, mitigate symptoms, and ameliorate the severe consequences of the infection.
Transcriptome and Metabolome Analyses of Leaves from Cutting Rejuvenation of Ancient Cinnamomum camphora
Authors: Liu Lipan , Yang Aihong , Liu Tengyun , Liu Shujuan , Hu Ping , Chen Caihui , Zhou Hua , Wu Jingfang , Yu Faxin
Published: July 2024

Rejuvenation refers to the transition from the state of mature to juvenile. Many ancient Cinnamomum camphora have aged and died due to climatic and anthropic factors. Vegetative propagation can protect valuable germplasm resources. In this study, a 2000-year-old ancient C. camphora and its 2-year-old cutting plantlets were selected as experimental materials. The results indicated that the number of leaves with palisade tissue (Pal) cell layers was different between samples, with two layers in the rejuvenated leaves (RLs) and one layer in the mature leaves (MLs) and young leaves (YLs). Indole-3-acetic acid (IAA), isopentenyladenine (iP) and isopentenyladenosine (iPR) concentrations were significantly higher in RLs than in MLs and YLs, but the abscisic acid (ABA) concentration was lower. Targeted metabolome analysis identified 293 differentially accumulated metabolites (DAMs). Meanwhile, a total of 5241 differentially expressed genes (DEGs) were identified by transcriptome sequencing. According to the KEGG analysis, there were seven important enriched pathways in the MLs, RLs and YLs, including plant hormone signal transduction (57 DEGs), plant–pathogen interaction (56 DEGs) and MAPK signaling pathway–plant (36 DEGs). KEGG enrichment conjoint analyses of DEGs and DAMs identified 16 common pathways. Integrated analyses of cytological, hormone, metabolome and transcriptome elements can provide a research basis in regard to the rejuvenation regulatory mechanism of ancient C. camphora.
Genome-Wide Analysis of the WOX Family and Its Expression Pattern in Root Development of Paeonia ostii
Authors: Lou Xueyuan , Wang Jiange , Wang Guiqing , He Dan , Shang Wenqian , Song Yinglong , Wang Zheng , He Songlin
Published: July 2024

Tree peony (Paeonia suffruticosa Andr.) is a woody plant with high ornamental, medicinal, and oil values. However, its low rooting rate and poor rooting quality are bottleneck issues in the micropropagation of P. ostii. The WUSCHEL-related homeobox (WOX) family plays a crucial role in root development. In this study, based on the screening of the genome and root transcriptome database, we identified ten WOX members in P. ostii. Phylogenetic analysis revealed that the ten PoWOX proteins clustered into three major clades, the WUS, intermediate, and ancient clade, respectively. The conserved motifs and tertiary structures of PoWOX proteins located in the same clade exhibited higher similarity. The analysis of cis-regulatory elements in the promoter indicated that PoWOX genes are involved in plant growth and development, phytohormones, and stress responses. The expression analysis revealed that PoWOX genes are expressed in distinct tissues. PoWOX4, PoWOX5, PoWOX11, and PoWOX13b are preferentially expressed in roots at the early stage of root primordium formation, suggesting their role in the initiation and development of roots. These results will provide a comprehensive reference for the evolution and potential function of the WOX family and offer guidance for further study on the root development of tree peony.
Bhlhe40 Regulates Proliferation and Angiogenesis in Mouse Embryoid Bodies under Hypoxia
Authors: Acosta-Iborra Bárbara , Gil-Acero Ana Isabel , Sanz-Gómez Marta , Berrouayel Yosra , Puente-Santamaría Laura , Alieva Maria , del Peso Luis , Jiménez Benilde
Published: July 2024

Knowledge of the molecular mechanisms that underlie the regulation of major adaptive responses to an unbalanced oxygen tension is central to understanding tissue homeostasis and disease. Hypoxia-inducible transcription factors (HIFs) coordinate changes in the transcriptome that control these adaptive responses. Here, we focused on the functional role of the transcriptional repressor basic-helix-loop-helix family member e40 (Bhlhe40), which we previously identified in a meta-analysis as one of the most consistently upregulated genes in response to hypoxia across various cell types. We investigated the role of Bhlhe40 in controlling proliferation and angiogenesis using a gene editing strategy in mouse embryonic stem cells (mESCs) that we differentiated in embryoid bodies (EBs). We observed that hypoxia-induced Bhlhe40 expression was compatible with the rapid proliferation of pluripotent mESCs under low oxygen tension. However, in EBs, hypoxia triggered a Bhlhe40-dependent cell cycle arrest in most progenitor cells and endothelial cells within vascular structures. Furthermore, Bhlhe40 knockout increased the basal vascularization of the EBs in normoxia and exacerbated the hypoxia-induced vascularization, supporting a novel role for Bhlhe40 as a negative regulator of blood vessel formation. Our findings implicate Bhlhe40 in mediating key functional adaptive responses to hypoxia, such as proliferation arrest and angiogenesis.
Cosmic Ionizing Radiation: A DNA Damaging Agent That May Underly Excess Cancer in Flight Crews
Authors: Toprani Sneh M. , Scheibler Christopher , Mordukhovich Irina , McNeely Eileen , Nagel Zachary D.
Published: July 2024

In the United States, the Federal Aviation Administration has officially classified flight crews (FC) consisting of commercial pilots, cabin crew, or flight attendants as “radiation workers” since 1994 due to the potential for cosmic ionizing radiation (CIR) exposure at cruising altitudes originating from solar activity and galactic sources. Several epidemiological studies have documented elevated incidence and mortality for several cancers in FC, but it has not yet been possible to establish whether this is attributable to CIR. CIR and its constituents are known to cause a myriad of DNA lesions, which can lead to carcinogenesis unless DNA repair mechanisms remove them. But critical knowledge gaps exist with regard to the dosimetry of CIR, the role of other genotoxic exposures among FC, and whether possible biological mechanisms underlying higher cancer rates observed in FC exist. This review summarizes our understanding of the role of DNA damage and repair responses relevant to exposure to CIR in FC. We aimed to stimulate new research directions and provide information that will be useful for guiding regulatory, public health, and medical decision-making to protect and mitigate the risks for those who travel by air.
Structural Basis for the Interaction between the Ezrin FERM-Domain and Human Aquaporins
Authors: Strandberg Helin , Hagströmer Carl Johan , Werin Balder , Wendler Markus , Johanson Urban , Törnroth-Horsefield Susanna
Published: July 2024

The Ezrin/Radixin/Moesin (ERM) family of proteins act as cross-linkers between the plasma membrane and the actin cytoskeleton. This mechanism plays an essential role in processes related to membrane remodeling and organization, such as cell polarization, morphogenesis and adhesion, as well as in membrane protein trafficking and signaling pathways. For several human aquaporin (AQP) isoforms, an interaction between the ezrin band Four-point-one, Ezrin, Radixin, Moesin (FERM)-domain and the AQP C-terminus has been demonstrated, and this is believed to be important for AQP localization in the plasma membrane. Here, we investigate the structural basis for the interaction between ezrin and two human AQPs: AQP2 and AQP5. Using microscale thermophoresis, we show that full-length AQP2 and AQP5 as well as peptides corresponding to their C-termini interact with the ezrin FERM-domain with affinities in the low micromolar range. Modelling of the AQP2 and AQP5 FERM complexes using ColabFold reveals a common mode of binding in which the proximal and distal parts of the AQP C-termini bind simultaneously to distinct binding sites of FERM. While the interaction at each site closely resembles other FERM-complexes, the concurrent interaction with both sites has only been observed in the complex between moesin and its C-terminus which causes auto-inhibition. The proposed interaction between AQP2/AQP5 and FERM thus represents a novel binding mode for extrinsic ERM-interacting partners.
HIPK2 in Colon Cancer: A Potential Biomarker for Tumor Progression and Response to Therapies
Authors: Verdina Alessandra , Garufi Alessia , D’Orazi Valerio , D’Orazi Gabriella
Published: July 2024

Colon cancer, one of the most common and fatal cancers worldwide, is characterized by stepwise accumulation of specific genetic alterations in tumor suppressor genes or oncogenes, leading to tumor growth and metastasis. HIPK2 (homeodomain-interacting protein kinase 2) is a serine/threonine protein kinase and a “bona fide” oncosuppressor protein. Its activation inhibits tumor growth mainly by promoting apoptosis, while its inactivation increases tumorigenicity and resistance to therapies of many different cancer types, including colon cancer. HIPK2 interacts with many molecular pathways by means of its kinase activity or transcriptional co-repressor function modulating cell growth and apoptosis, invasion, angiogenesis, inflammation and hypoxia. HIPK2 has been shown to participate in several molecular pathways involved in colon cancer including p53, Wnt/β-catenin and the newly identified nuclear factor erythroid 2 (NF-E2) p45-related factor 2 (NRF2). HIPK2 also plays a role in tumor–host interaction in the tumor microenvironment (TME) by inducing angiogenesis and cancer-associated fibroblast (CAF) differentiation. The aim of this review is to assess the role of HIPK2 in colon cancer and the underlying molecular pathways for a better understanding of its involvement in colon cancer carcinogenesis and response to therapies, which will likely pave the way for novel colon cancer therapies.
The Biosynthesis Process of Small RNA and Its Pivotal Roles in Plant Development
Authors: Li Quan , Wang Yanan , Sun Zhihui , Li Haiyang , Liu Huan
Published: July 2024

In the realm of plant biology, small RNAs (sRNAs) are imperative in the orchestration of gene expression, playing pivotal roles across a spectrum of developmental sequences and responses to environmental stressors. The biosynthetic cascade of sRNAs is characterized by an elaborate network of enzymatic pathways that meticulously process double-stranded RNA (dsRNA) precursors into sRNA molecules, typically 20 to 30 nucleotides in length. These sRNAs, chiefly microRNAs (miRNAs) and small interfering RNAs (siRNAs), are integral in guiding the RNA-induced silencing complex (RISC) to selectively target messenger RNAs (mRNAs) for post-transcriptional modulation. This regulation is achieved either through the targeted cleavage or the suppression of translational efficiency of the mRNAs. In plant development, sRNAs are integral to the modulation of key pathways that govern growth patterns, organ differentiation, and developmental timing. The biogenesis of sRNA itself is a fine-tuned process, beginning with transcription and proceeding through a series of processing steps involving Dicer-like enzymes and RNA-binding proteins. Recent advances in the field have illuminated the complex processes underlying the generation and function of small RNAs (sRNAs), including the identification of new sRNA categories and the clarification of their involvement in the intercommunication among diverse regulatory pathways. This review endeavors to evaluate the contemporary comprehension of sRNA biosynthesis and to underscore the pivotal role these molecules play in directing the intricate performance of plant developmental processes.
Investigation of the Genetic Determinants of Telangiectasia and Solid Organ Arteriovenous Malformation Formation in Hereditary Hemorrhagic Telangiectasia (HHT)
Authors: Whitehead Kevin J. , Toydemir Doruk , Wooderchak-Donahue Whitney , Oakley Gretchen M. , McRae Bryan , Putnam Angelica , McDonald Jamie , Bayrak-Toydemir Pinar
Published: July 2024

Telangiectases and arteriovenous malformations (AVMs) are the characteristic lesions of Hereditary Hemorrhagic Telangiectasia (HHT). Somatic second-hit loss-of-function variations in the HHT causative genes, ENG and ACVRL1, have been described in dermal telangiectasias. It is unclear if somatic second-hit mutations also cause the formation of AVMs and nasal telangiectasias in HHT. To investigate the genetic mechanism of AVM formation in HHT, we evaluated multiple affected tissues from fourteen individuals. DNA was extracted from fresh/frozen tissue of 15 nasal telangiectasia, 4 dermal telangiectasia, and 9 normal control tissue biopsies, from nine unrelated individuals with HHT. DNA from six formalin-fixed paraffin-embedded (FFPE) AVM tissues (brain, lung, liver, and gallbladder) from five individuals was evaluated. A 736 vascular malformation and cancer gene next-generation sequencing (NGS) panel was used to evaluate these tissues down to 1% somatic mosaicism. Somatic second-hit mutations were identified in three in four AVM biopsies (75%) or half of the FFPE (50%) samples, including the loss of heterozygosity in ENG in one brain AVM sample, in which the germline mutation occurred in a different allele than a nearby somatic mutation (both are loss-of-function mutations). Eight of nine (88.9%) patients in whom telangiectasia tissues were evaluated had a somatic mutation ranging from 0.68 to 1.96% in the same gene with the germline mutation. Six of fifteen (40%) nasal and two of four (50%) dermal telangiectasia had a detectable somatic second hit. Additional low-level somatic mutations in other genes were identified in several telangiectasias. This is the first report that nasal telangiectasias and solid organ AVMs in HHT are caused by very-low-level somatic biallelic second-hit mutations.
Extended Isolation Forest for Intrusion Detection in Zeek Data
Authors: Moomtaheen Fariha , Bagui Sikha S. , Bagui Subhash C. , Mink Dustin
Published: July 2024

The novelty of this paper is in determining and using hyperparameters to improve the Extended Isolation Forest (EIF) algorithm, a relatively new algorithm, to detect malicious activities in network traffic. The EIF algorithm is a variation of the Isolation Forest algorithm, known for its efficacy in detecting anomalies in high-dimensional data. Our research assesses the performance of the EIF model on a newly created dataset composed of Zeek Connection Logs, UWF-ZeekDataFall22. To handle the enormous volume of data involved in this research, the Hadoop Distributed File System (HDFS) is employed for efficient and fault-tolerant storage, and the Apache Spark framework, a powerful open-source Big Data analytics platform, is utilized for machine learning (ML) tasks. The best results for the EIF algorithm came from the 0-extension level. We received an accuracy of 82.3% for the Resource Development tactic, 82.21% for the Reconnaissance tactic, and 78.3% for the Discovery tactic.
Exploring the Nature of Ag–Ag Interactions in Different Tellurides by Means of the Crystal Orbital Bond Index (COBI)
Authors: Weinelt Leander , Steinberg Simon
Published: July 2024

Over the decades, intensive explorations have been conducted to understand the nature of d10−d10 interactions. The recent establishment of a bonding indicator named the crystal orbital bond index stimulated our impetus to probe the capabilities of that approach for the examples of Ag–Ag interactions in different tellurides. In the framework of our quantum chemical explorations, we inspected the electronic structures of two tellurides which were previously reported to comprise d10−d10 interactions, while the third candidate material, i.e., RbCe2Ag3Te5, has been obtained from reactions of rubidium chloride, cerium, silver and tellurium for the very first time. The outcome of our explorations clearly shows that the nature of Ag–Ag interactions is well mirrored by the corresponding COBI.
Functional Morphology and Ultrastructure of the Peripheral Antennal Sensillar System of Graphosoma italicum (Müller, 1766) (Insecta: Hemiptera: Pentatomidae)
Authors: Brożek Jolanta , Poprawa Izabela , Wegierek Piotr , Stroiński Adam
Published: July 2024

The antennae of the shield bug Graphosoma italicum (Müller, 1766) were examined through scanning and transmission electron microscopy to reveal their general morphology, as well as the antennal sensilla’s distribution, size, and ultrastructure of their dendrites and function. The antennae comprise five antennomeres (one scape, two pedicels, and two flagellomeres). Different lengths of chaetic mechanosensilla (Ch1-Ch4) exist on all antennomeres, and several highly sensitive campaniform sensilla are embedded in the exoskeleton and measure cuticular strain. One pair of peg sensilla, the typical proprioceptive, is only on the proximal edge of the first pedicel and directed to the distal edge of the scapus. The antennal flagellum possesses two subtypes of trichoid and basiconic sensilla, each with one type of coeloconic olfactory sensilla. The distinctive characteristics of G. italicum are also apparent in two subtypes of coeloconic sensilla embedded in different cavities on both antennomeres of the flagellum, probably with a thermo-hypersensitive function. All studied morphological types of the sensilla and their function were supported by ultrastructural elements. The long and thin trichoid sensilla type 2 (TrS2) with an olfactive function was the most abundant sensilla localized on both flagellomeres. The peripheral antennal sensilla system consists of six main types of sensilla divided into twelve subtypes.
Approximate Closed-Form Solution of the Differential Equation Describing Droplet Flight during Sprinkler Irrigation
Authors: Friso Dario
Published: July 2024

Sprinkler irrigation is widely used in agriculture because it allows for rational use of water. However, it can induce negative effects of soil erosion and of surface waterproofing. The scholars of these phenomena use the numerical integration of the equation of motion, but if there was an analytical solution, the study would be facilitated, and this solution could be used as software for regulating sprinklers. Therefore, in this study, the solution of the differential equation of the flight of droplets produced by sprinklers in the absence of wind was developed. The impossibility of an exact analytical solution to the ballistic problem due to the variability of the drag coefficient of the droplets is known; therefore, to find the integrals in closed form, the following were adopted: a new formula for the drag coefficient; a projection of the dynamic’s equation onto two local axes, one tangent and one normal to the trajectory and some linearization. To reduce the errors caused by the latter, the linearization coefficients and their calculation formulas were introduced through multiple non-linear regressions with respect to the jet angle and the initial droplet speed. The analytical modeling obtained, valid for jet angles from 10° to 40°, was compared to the exact numerical solution, showing, for the total travel distance, a high accuracy with a mean relative error MRE of 1.8% ± 1.4%. Even the comparison with the experimental data showed high accuracy with an MRE of 2.5% ±1.1%. These results make the analytical modeling capable of reliably calculating the travel distance, the flight time, the maximum trajectory height, the final fall angle and the ground impact speed. Since the proposed analytical modeling uses only elementary functions, it can be implemented in PLC programmable logic controllers, which could be useful for controlling water waste and erosive effects on the soil during sprinkler irrigation.
Mathematical Modeling of Oxygen Transfer Using a Bubble Generator at a High Reynolds Number: A Partial Differential Equation Approach for Air-to-Water Transfer
Authors: Constantin Mihaela , Dobre Cătălina , Oprea Mugurel
Published: July 2024

This paper presents the mathematical modeling of the oxygen transfer process using partial differential equations (PDEs). This process is crucial in various environmental and engineering applications, such as wastewater treatment, aeration systems, and natural water bodies, in order to maintain water quality. The authors solved the typical PDE for describing the change in oxygen concentration over time and present the developed model of the differential equation with the term “source”, indicating that the model could be used to optimize oxygen transfer in various environmental and engineering applications, contributing to improved water quality and system efficiency.
Characterization and Long-Term Prognosis of Patients with Different Phenotypes of Dilated Cardiomyopathy
Authors: Zhang Shuyuan , Gao Shiqi , Tian Zhuang , Zhang Shuyang
Published: July 2024

Background: Long-term prognosis of dilated cardiomyopathy (DCM) in the Chinese population is lacking, and the left ventricular (LV) hypertrabeculation phenotype usually overlaps with DCM. Objectives: The study aims to investigate whether the presence of the LV hypertrabeculation phenotype confers additional adverse prognostic information for DCM patients. Methods: We retrospectively reviewed all DCM patients (≥18 years of age at diagnosis) hospitalized in the Peking Union Medical College Hospital between September 2002 and September 2022. The eligible patients were divided into two groups based on echocardiography at diagnosis: the isolated DCM (n = 353), and DCM with the LV hypertrabeculation phenotype (n = 97). The primary endpoint was major adverse cardiac events (MACEs), and multivariate Cox hazards regression models were used to compare the endpoints between the two groups. Results: During a mean follow-up time of 4.6 years, there was no significant difference in the primary endpoint between the isolated DCM and DCM with the LV hypertrabeculation phenotype (p = 0.19). The risk of MACEs in the first 5 years was significantly higher in DCM with the LV hypertrabeculation phenotype than isolated DCM (adjusted HR [95%CI]: 1.83 [1.21–2.77]) and after 5 years the effect of the LV hypertrabeculation phenotype as a prognostic attenuated. Subgroup analysis found a significant interaction for the incidence of MACEs between sex and DCM subtypes (p for interaction = 0.01). Conclusions: DCM with LV hypertrabeculation phenotypes had a higher early (first 5 years) risk of MACEs. For males, the presence of LV hypertrabeculation phenotypes might be an important clue for identifying high-risk DCM patients.
Hip Axis Length and Femoral Neck-Shaft Angle as Risk Factors for Proximal Femur Fractures in Octogenarians to Centenarians
Authors: Gumuchdjian Daniel Alexandre , Waltenspül Manuel , Dietrich Michael , Kabelitz Method
Published: July 2024

(1) Background: The prevention of proximal femoral fractures among people of very advanced age is relevant as they are common and increasing in number. The aim of this study was to determine if the hip axis length (HAL) and the neck-shaft angle (caput–collum–diaphyseal CCD) are risk factors for those fractures among people aged 80 years and over. Consequently, it was additionally analysed if these parameters are associated with a certain fracture type. (2) Methods: Anteroposterior radiographs of the pelvis were collected to form three groups (femoral neck fractures (FNFx), trochanteric fractures (TFx) and non-fractured femora (NFx)). Two independent blinded observers separately conducted each measurement of the HAL and CCD. Statistical analysis was performed to determine the association between the measured parameters and type of fracture. (3) Results: One hundred and fifty patients (50 per group) were examined, of which the mean age was 92.7 ± 3.5 (range 81–104) years. Both the HAL and CCD of the FNFx group were significantly larger than in the TFx group (p = 0.013, 0.003). The CCD was higher in the FNFx than that of the NFx group (p = 0.001). No further significant differences of HAL and CCD were observed between the groups. (4) Conclusions: For people aged 80 years and over, an increased HAL represented no risk factor for proximal femur fractures, and a large HAL was associated with an increased occurrence of FNFx instead of TFx. A large CCD was associated with an increased risk of suffering a femoral neck fracture, showing evidence of the CCD being a risk factor for the extremely old population.
Hidradenitis Suppurativa in the SARS-CoV-2 Pandemic: Investigation of Trigger Factors in a Single Center
Authors: Scholl Lisa , Abu Rached Nessr , Stockfleth Eggert , Cramer Philipp , Ocker Lennart , Stranzenbach René , Garcovich Simone , Hessam Schapoor , Bechara Falk G.
Published: July 2024

Background: Hidradenitis suppurativa (HS) is a debilitating, chronic inflammatory disease associated with multiple triggers. As the world struggles with the global COVID-19 pandemic, it is important to review the trigger factors for chronically ill HS patients during the COVID-19 pandemic. This work investigates the self-described trigger factors of HS patients that emerged during the COVID-19 outbreak. Methods: We anonymously surveyed 110 HS patients during the SARS-CoV-2 pandemic using a 25-question questionnaire that included trigger factors for deterioration. Demographic, personal, and HS-specific information was also collected to identify potential trigger factors for HS exacerbation. All HS patients were asked if their HS had worsened compared to the time before the pandemic. Results: Compared to before the pandemic, 20% of HS patients (n = 22) reported a worsening of HS. Patients with an HS exacerbation were significantly more likely to avoid contact with a doctor than those without an exacerbation (45.5% vs. 18.2%; p = 0.007). HS involvement, severity, exercise activity, and BMI had no association with worsening HS (p > 0.05). Interestingly, dietary changes and increased consumption of sweets and treats were associated with worsening HS (p = 0.011 and p = 0.013). Specifically, eating more sweets and treats was associated with a 6-fold increased risk of worsening HS. The results suggest that diet has an important influence on HS relapses. Further investigation is needed to determine whether diet is a triggering factor independent of the SARS-CoV-2 pandemic. In addition, gluteal HS involvement was associated with a more than 4.3-fold risk of HS exacerbation. Conclusions: In the management of HS patients, it is important to consider that gluteal involvement and the consumption of sweets are more often associated with deterioration.