bluuebunny/crossref_metadata_2025 huggingface dataset:
Comorbidity-Guided Text Mining and Omics Pipeline to Identify Candidate Genes and Drugs for Alzheimer’s Disease
Authors: Oviya Iyappan Ramalakshmi , Sankar Divya , Manoharan Sharanya , Prabahar Archana , Raja Kalpana
Published: May 2024

Alzheimer’s disease (AD), a multifactorial neurodegenerative disorder, is prevalent among the elderly population. It is a complex trait with mutations in multiple genes. Although the US Food and Drug Administration (FDA) has approved a few drugs for AD treatment, a definitive cure remains elusive. Research efforts persist in seeking improved treatment options for AD. Here, a hybrid pipeline is proposed to apply text mining to identify comorbid diseases for AD and an omics approach to identify the common genes between AD and five comorbid diseases—dementia, type 2 diabetes, hypertension, Parkinson’s disease, and Down syndrome. We further identified the pathways and drugs for common genes. The rationale behind this approach is rooted in the fact that elderly individuals often receive multiple medications for various comorbid diseases, and an insight into the genes that are common to comorbid diseases may enhance treatment strategies. We identified seven common genes—PSEN1, PSEN2, MAPT, APP, APOE, NOTCH, and HFE—for AD and five comorbid diseases. We investigated the drugs interacting with these common genes using LINCS gene–drug perturbation. Our analysis unveiled several promising candidates, including MG-132 and Masitinib, which exhibit potential efficacy for both AD and its comorbid diseases. The pipeline can be extended to other diseases.
Mitochondrial DNA: Inherent Complexities Relevant to Genetic Analyses
Authors: Ferreira Tomas , Rodriguez Santiago
Published: May 2024

Mitochondrial DNA (mtDNA) exhibits distinct characteristics distinguishing it from the nuclear genome, necessitating specific analytical methods in genetic studies. This comprehensive review explores the complex role of mtDNA in a variety of genetic studies, including genome-wide, epigenome-wide, and phenome-wide association studies, with a focus on its implications for human traits and diseases. Here, we discuss the structure and gene-encoding properties of mtDNA, along with the influence of environmental factors and epigenetic modifications on its function and variability. Particularly significant are the challenges posed by mtDNA’s high mutation rate, heteroplasmy, and copy number variations, and their impact on disease susceptibility and population genetic analyses. The review also highlights recent advances in methodological approaches that enhance our understanding of mtDNA associations, advocating for refined genetic research techniques that accommodate its complexities. By providing a comprehensive overview of the intricacies of mtDNA, this paper underscores the need for an integrated approach to genetic studies that considers the unique properties of mitochondrial genetics. Our findings aim to inform future research and encourage the development of innovative methodologies to better interpret the broad implications of mtDNA in human health and disease.
Transposable Element Expression Profiles in Premalignant Pigment Cell Lesions and Melanoma of Xiphophorus
Authors: Münch Luca , Helmprobst Frederik , Volff Jean-Nicolas , Chalopin Domitille , Schartl Manfred , Kneitz Susanne
Published: May 2024

Transposable elements (TEs) are characterized by their ability to change their genomic position. Through insertion or recombination leading to deletions and other chromosomal aberrations, they can cause genetic instability. The extent to which they thereby exert regulatory influence on cellular functions is unclear. To better characterize TEs in processes such as carcinogenesis, we used the well-established Xiphophorus melanoma model. By transcriptome sequencing, we show that an increasing total number in transposons correlates with progression of malignancy in melanoma samples from Xiphophorus interspecific hybrids. Further, by comparing the presence of TEs in the parental genomes of Xiphophorus maculatus and Xiphophorus hellerii, we could show that even in closely related species, genomic location and spectrum of TEs are considerably different.
Papillary Thyroid Cancer Remodels the Genetic Information Processing Pathways
Authors: Iacobas Dumitru Andrei , Iacobas Sanda
Published: May 2024

The genetic causes of the differentiated, highly treatable, and mostly non-fatal papillary thyroid cancer (PTC) are not yet fully understood. The mostly accepted PTC etiology blames the altered sequence or/and expression level of certain biomarker genes. However, tumor heterogeneity and the patient’s unique set of favoring factors question the fit-for-all gene biomarkers. Publicly accessible gene expression profiles of the cancer nodule and the surrounding normal tissue from a surgically removed PTC tumor were re-analyzed to determine the cancer-induced alterations of the genomic fabrics responsible for major functional pathways. Tumor data were compared with those of standard papillary and anaplastic thyroid cancer cell lines. We found that PTC regulated numerous genes associated with DNA replication, repair, and transcription. Results further indicated that changes of the gene networking in functional pathways and the homeostatic control of transcript abundances also had major contributions to the PTC phenotype occurrence. The purpose to proliferate and invade the entire gland may explain the substantial transcriptomic differences we detected between the cells of the cancer nodule and those spread in homo-cellular cultures (where they need only to survive). In conclusion, the PTC etiology should include the complex molecular mechanisms involved in the remodeling of the genetic information processing pathways.
Assessing DNA Degradation through Differential Amplification Efficiency of Total Human and Human Male DNA in a Forensic qPCR Assay
Authors: Chierto Elena , Aneli Serena , Nocco Nicola , Riem Alessia , Onofri Martina , Carnevali Eugenia , Robino Carlo
Published: May 2024

The assessment of degradation is crucial for the analysis of human DNA samples isolated from forensic specimens. Forensic quantitative PCR (qPCR) assays can include multiple targets of varying amplicon size that display differential amplification efficiency, and thus different concentrations, in the presence of degradation. The possibility of deriving information on DNA degradation was evaluated in a forensic qPCR assay not specifically designed to detect DNA fragmentation, the Plexor HY (Promega), by calculating the ratio between the estimated concentrations of autosomal (99 bp) and Y-chromosomal (133 bp) targets (“[Auto]/[Y]”). The [Auto]/[Y] ratio measured in 57 formalin-fixed, paraffin-embedded samples was compared to a quality score (QS) calculated for corresponding STR profiles using quantitative data (allele peak height). A statistically significant inverse correlation was observed between [Auto]/[Y] and QS (R = −0.65, p < 0.001). The [Auto]/[Y] values were highly correlated (R = 0.75, p < 0.001) with the “[Auto]/[D]” values obtained using the PowerQuant (Promega) assay, expressly designed to detect DNA degradation through simultaneous quantification of a short (Auto) and a long (D) autosomal target. These results indicate that it is possible to estimate DNA degradation in male samples through Plexor HY data and suggest an alternative strategy for laboratories lacking the equipment required for the assessment of DNA integrity through dedicated qPCR assays.
Kinematics and Controlling Factors of Slow-Moving Landslides in Central Texas: A Multisource Data Fusion Approach
Authors: Gebremichael Esayas , Hernandez Rosbeidy , Alsleben Helge , Ahmed Mohamed , Denne Richard , Harvey Omar
Published: May 2024

The Austin metropolitan area has experienced unprecedented economic and population growth over the past two decades. This rapid growth is leading communities to settle in areas susceptible to landslides, necessitating a comprehensive analysis of landslide risks and the development of early warning systems. This could be accomplished with better confidence for slow-moving landslides, whose occurrences could be forecasted by monitoring precursory ground displacement. This study employed a combination of ground- and satellite-based observations and techniques to assess the kinematics of slow-moving landslides and identify the controlling and triggering factors that contribute to their occurrence. By closely examining landslide events in the Shoal Creek area, potential failure modes across the study area were inferred. The findings revealed that landslide-prone areas are undergoing creep deformation at an extremely slow rate (up to −4.29 mm/yr). These areas lie on moderate to steep slopes (>22°) and are predominantly composed of clay-rich units belonging to the Del Rio and Eagle Ford formations. Based on the incidents at Shoal Creek, episodes of intense rainfall acting on the landslide-prone areas are determined to be the main trigger for landslide processes in the region.
Ladder Use Ability, Behavior and Exposure by Age and Gender
Authors: Pliner Erika M. , Sturnieks Daina L. , Beschorner Kurt E. , Redfern Mark S. , Lord Stephen R.
Published: May 2024

This study aimed to quantify and compare ladder use ability and behavior in younger and older men and women from three ladder use behavior experiments. The experimental tasks comprised (1) changing a lightbulb on a household stepladder under two cognitive demands (single and dual task), (2) clearing a simulated roof gutter on a straight ladder and (3) querying ladder choice in different exigency scenarios. Ladder use ability and behavior data were captured from recorded time, performance, motion capture and user choice data. In addition, this study surveyed ladder use frequency and habitual behaviors. The experimental findings indicate that older adults require more time to complete ladder tasks; younger adults display riskier ladder use behaviors; men and women display similar ladder use ability; and men are more willing to climb riskier ladders. The survey found older adults to report more frequent ladder use than younger adults, and men use straight ladders more frequently than women. These results suggest that the reported higher ladder fall rates experienced by older adults and men are linked to increased ladder use exposure and riskier ladder choice. This knowledge can help guide population-specific interventions to reduce ladder falls in both young and older people.
Chitin Synthases in Cordyceps militaris: Genome-Wide Gene Identification, Evolutionary Insights, and Life Cycle Transcript Profiling
Authors: Li Shoumian , Ren Huihui , Zhang Jie , Gao Shangpai , Chen Zixuan , Li Guojie , Tian Jinghua , Wang Junling , Li Ming , Li Xiao , Dong Caihong
Published: May 2024

Cordyceps militaris is one of the commercially cultivated mushrooms, valued for its medicinal and nutritional benefits. However, the fruiting body development mechanism has remained elusive. Chitin synthases (CHSs) are ubiquitous enzymes involved in the regulation of fungal growth, development and virulence. In this study, a total of eight CmChs genes were identified. Chromosomal localization analysis revealed an uneven distribution of CmCHSs across the C. militaris genome. Based on the phylogenetic analysis, 100 CHSs from Cordyceps sensu lato, encompassing C. militaris, were categorized into three divisions and seven classes, shedding light on their evolutionary relationships. There was no significant difference in the number of CHSs between ascomycetes and basidiomycetes in general (p = 0.067), as well as between pathogenic and saprotrophic fungi in general (p = 0.151 and 0.971 in Ascomycota and Basidiomycota fungi, respectively). This underscored the essential and conserved nature of these CHSs across various fungal lifestyles and ecological niches. The different transcript patterns of the eight CmChss during key life cycle stages, such as conidia germination, infection, and fruiting body development, indicated that each CHS gene may have a distinct role during specific stages of the life cycle. In conclusion, these findings indeed lay the groundwork for a further exploration of the functional roles of CHSs in the regulatory mechanism of fruiting body development in C. militaris.
Assessing the Influence of Viral Infection on ‘Tribidrag’ Grapevines: Insights from Two Vegetation Seasons
Authors: Čarija Mate , Likar Matevž , Černi Silvija , Radić Tomislav , Gaši Emanuel , Hančević Katarina
Published: May 2024

The objective of this study was to investigate the response of the grapevine variety ‘Tribidrag’ to virus infection over two vegetation seasons. Virus-free plants were greenhouse cultivated and green grafted with five different virus inocula composed of grapevine leafroll-associated virus 3 (GLRaV-3) singly or in coinfection with other most economically important grapevine viruses. Changes in nutrient status and photosynthesis-related parameters, along with symptom development, were measured. Using the quantitative PCR method, the relative concentration of five selected Vitis genes was determined. Cluster analysis and ANOVA revealed the reduction in phosphorus concentration (P) and photosynthesis-related parameters in infected plants in both seasons, even in the absence of symptom expression, indicating P and assimilation rate (Photo (A)) as stable markers of virus infection. Plants infected with inoculum Y composed of five different viruses provoked major significant changes in the first season while, in the second, fewer changes were measured. The sucrose synthase 3 gene was upregulated in infected plants confirming disturbed sugar metabolism related to virus-induced stress. This study showed that virus-induced changes in ‘Tribidrag’ plants even in the absence of symptoms are dependent on plant age, as well as on the composition of virus inocula.
Isolation and Identification of Lysinibacillus sp. and Its Effects on Solid Waste as a Phytate-Mineralizing Bacterium in an Aquaponics System
Authors: Riaño-Castillo Edna Rocio , Rodríguez-Ortiz Juan Carlos , Kim Hye-Ji , Guerrero González María de la Luz , Quintero-Castellanos María Fernanda , Delgado-Sánchez Pablo
Published: May 2024

Sedimentable solids generated in aquaponic systems are mainly composed of organic waste, presenting molecules such as phytate, which can be a potential source of inorganic nutrients through mineralization. This work aimed to isolate and identify phytase-producing bacteria and evaluate the inoculation effects of pure strains on mineralization and nutrient release from solid waste generated in aquaponic systems at different oxygen and temperature conditions. The bacteria were isolated from the settleable solids of a commercial aquaponic system and molecularly identified by amplifying the 16S rRNA gene. Subsequently, two tests were carried out: 1. Test for the biochemical identification of phytase-producing bacteria; 2. In vitro mineralization test, where the ability to mineralize phytate and release nutrients under different oxygen conditions [0 rpm (2.1 mg L−1) and 200 rpm (7.8 mg L−1)] and temperatures (24 and 37 °C) were evaluated. Our findings show that two pure strains of Lysinibacillus mangiferihumi can mineralize phytate under conditions of 200 rpm and 24 °C, mainly increasing the mineralization of PO4- and Ca, a property that has not yet been reported for this species. On the other hand, at 0 rpm and 24 °C, an increase in K was observed (control conditions), while the conditions of 200 rpm and 24 °C, regardless of bacterial inoculation, favored a rise in S, Mg, and Fe. The Lysinibacillus strains obtained in this investigation are of great importance due to their application in agriculture and the optimization of mineralization in aquaponic systems. A proper combination of oxygen and temperature will lead to a greater availability of nutrients for the growth and development of vegetables.
Water Use Efficiency in a Deficit-Irrigated Orange Orchard
Authors: Stagno Fiorella , Brambilla Massimo , Roccuzzo Giancarlo , Assirelli Alberto
Published: May 2024

Citrus is a subtropical fruit tree with high water requirements. This study aimed to determine the effects of water deficit on an orange orchard subjected to different water-saving strategies. The study was realised in an orange orchard in a semiarid area by adopting four different water management techniques: 100% crop evapotranspiration (control); SSDI—subsurface sustained deficit irrigation; RDI—regulated deficit irrigation; PRD—partial rootzone drying treatment during five growing seasons. The experimental design foresaw a randomised block design with six replicates per treatment (24 index plants). The results of the study showed that the water-saving strategies reduced irrigation water consumption by 25% (SSDI), 33% (RDI), and 49% (PRD) compared to the fully irrigated treatment without yield reduction, thus increasing water use efficiency. Mineral nutrition of the trees was slightly affected by irrigation treatments; element concentration in leaves was generally in the optimal range; only potassium showed values below the recommended leaf concentrations. Regarding fruit quality parameters, the vitamin C concentration in RDI showed significant differences with a value of 62.7 mg 100 mL−1 compared to 58.5 mg 100 mL−1 in the control. Plants subjected to SSDI and PRD strategies showed increased levels of pulp colour index with significant values of 10 and 9.90, respectively, compared to the control (8.44). By implementing targeted water management, citrus growers could save water and increase the ascorbic acid and sugar concentration in the fruits; anthocyanins also increased but not significantly. These findings open new market opportunities for citrus growers in marginal areas, where they cannot rely solely on producing citrus fruits to remain competitive.
The Effects of Prescribed Physical and Cognitive Exercise on Life Satisfaction, Self-Efficacy and Mood States in Adults with Down Syndrome: The MinDSets Study
Authors: Merzbach Viviane , Jewiss Matthew , Scruton Adrian , Gordon Dan
Published: May 2024

Down syndrome (DS) is characterised by a duplication of chromosome-21 and is linked to co-occurring physical and mental health conditions, including low self-efficacy and disturbed mood states. The purpose of this study was to investigate the effects of an eight-week prescribed physical and/or cognitive training intervention on measures of mood disturbance, life satisfaction and self-efficacy in a population of adults with DS. Eighty-three participants (age 27.1 ± 8.0 years) from across five continents volunteered. Participants were assigned using matched groups based upon performance in a modified six-minute walk test to either an exercise (EXE) 3 × 30 min of walking/jogging per week, cognitive training (COG) 6 × 20 min per week, a combined group (COM) or the control (CON) who did not complete any intervention. Profile of Mood States (POMS) were assessed using a five-point scale across 65 categories pre- and post-study as well as upon completion of each week of the intervention. In addition, Satisfaction with Life Scale (SWLS) and self-efficacy using the Generalised Self-Efficacy scale (GSE) were recorded before and after the intervention. GSE increased for all participants by 1.9 ± 5.2 (p = 0.002) from pre- to post-intervention, while POMS showed significant changes for the whole group from pre- to post-intervention for tension (p < 0.001), depression (p < 0.001) and for anger (p < 0.001). In addition, significant correlations were observed between SWLS and ΔTMD, Δtension, Δanger, and Δfatigue (p < 0.05) for EXE. Both COG and EXE provide a framework for empowering enhancements in life satisfaction, self-efficacy and mood states fostering improvements in quality of life.
Piloting a Measure of Segregation at the Census Tract Level: Associations with Place and Racial/Ethnic Disparities in Life Expectancy
Authors: Kitchens Katherine , Graaf Genevieve
Published: May 2024

This study considers residential segregation as a critical driver of racial/ethnic health disparities and introduces a proxy measure of segregation that estimates the degree of segregation at the census tract level with a metric capturing the overrepresentation of a racialized/ethnic group in a census tract in relation to that group’s representation at the city level. Using Dallas, Texas as a pilot city, the measure is used to investigate mean life expectancy at birth for relatively overrepresented Hispanic, non-Hispanic white, non-Hispanic Black, and Asian census tracts and examine for significant differences between mean life expectancy in relatively overrepresented census tracts and that group’s mean life expectancy at the state level. Multivariable linear regression analysis was utilized to assess how segregation measured at the census tract level associates with life expectancy across different racialized/ethnic groups, controlling for socioeconomic disparities. This study aimed to expose the need to consider the possibility of neighborhood mechanisms beyond socioeconomic characteristics as an important determinant of health and draw attention to the importance of critically engaging the experience of place in examinations of racial and ethnic health disparities. Multivariable linear regression modeling resulted in significant findings for non-Hispanic Black, non-Hispanic white, and Asian groups, indicating increased census tract-level life expectancy for Black and white residents in highly segregated census tracts and decreased life expectancy for residents of tracts in which the Asian community is overrepresented when compared to state means. Unadjusted models demonstrated socioeconomic inequities between first and fourth quartile census tracts and pointed to the importance of mixed methods in health disparities research and the importance of including the voice of community members to account for places of daily lived experience and people’s relationships with them.
Exploring the Relationship between Melioidosis Morbidity Rate and Local Environmental Indicators Using Remotely Sensed Data
Authors: Wongbutdee Jaruwan , Jittimanee Jutharat , Daendee Suwaporn , Thongsang Pongthep , Saengnill Wacharapong
Published: May 2024

Melioidosis is an endemic infectious disease caused by Burkholderia pseudomallei bacteria, which contaminates soil and water. To better understand the environmental changes that have contributed to melioidosis outbreaks, this study used spatiotemporal analyses to clarify the distribution pattern of melioidosis and the relationship between melioidosis morbidity rate and local environmental indicators (land surface temperature, normalised difference vegetation index, normalised difference water index) and rainfall. A retrospective study was conducted from January 2013 to December 2022, covering data from 219 sub-districts in Northeast Thailand, with each exhibiting a varying morbidity rate of melioidosis on a monthly basis. Spatial autocorrelation was determined using local Moran’s I, and the relationship between the melioidosis morbidity rate and the environmental indicators was evaluated using a geographically weighted Poisson regression. The results revealed clustered spatiotemporal patterns of melioidosis morbidity rate across sub-districts, with hotspots predominantly observed in the northern region. Furthermore, we observed a range of coefficients for the environmental indicators, varying from negative to positive, which provided insights into their relative contributions to melioidosis in each local area and month. These findings highlight the presence of spatial heterogeneity driven by environmental indicators and underscore the importance of public health offices implementing targeted monitoring and surveillance strategies for melioidosis in different locations.
Fair Funding Decisions: Consistency of the Time Horizons Used in the Calculation of Quality-Adjusted Life Years for Therapies for Very Rare Diseases by the National Institute for Health and Care Excellence in England
Authors: Barman-Aksözen Jasmin , Hentschel Nicole , Pettersson Mårten , Schupp Eva , Granata Francesca , Dechant Cornelia , Aksözen Mehmet Hakan , Falchetto Rocco
Published: May 2024

The National Institute for Health and Care Excellence (NICE) in England uses quality-adjusted life years (QALYs) to assess the cost-effectiveness of treatments. A QALY is a measure that combines the size of the clinical benefit of a treatment with the time the patient benefits from it, i.e., the time horizon. We wanted to know how consistently QALY gains are calculated at NICE. Therefore, we have analysed information on the time horizons used for the QALY calculations of the concluded evaluations conducted under the Highly Specialised Technologies programme for treatments of very rare diseases at NICE. For treatments with final guidance published by December 2023 (n = 29), a time horizon of median 97.5 years (range: 35 to 125 years) was used to calculate the QALY gains. For most QALY calculations, the accepted time horizon was longer than either the expected treatment duration or the estimated life expectancy. In contrast, for the only technology with a final negative funding decision, i.e., afamelanotide for treating the lifelong chronic disease erythropoietic protoporphyria, a time horizon that was shorter than the expected treatment duration was used. The fairness and consistency of the evaluation process of treatments for very rare diseases at NICE should be reviewed.
Characterization of Homicides in Mexico: Analysis of 2015–2022
Authors: López-Ortiz Eduardo , Altamirano Juan Manuel , Romero-Henríquez Luisa Fernanda , López-Ortiz Geovani
Published: May 2024

Background: In Mexico, homicides are the leading cause of death among men aged 15 to 44 years; however, despite their increase in recent decades, the study of this issue is insufficient, given its magnitude and impact. Therefore, this study aimed to characterize the spatial and temporal patterns and associated factors of homicides in Mexico from 2015 to 2022. Methods: An analytical cross-sectional study was conducted, analyzing death records from the National Institute of Statistics and Geography’s general mortality databases. Simple frequencies and incidence rates per 100,000 inhabitants by sex, year, and state of the Mexican Republic were calculated. Mortality was evaluated by age groups and geographic areas, and bivariate logistic regression models with sociodemographic variables were performed. Results: Records of 229,182 homicides in Mexico were analyzed, with a median age of 33 years, interquartile range 18. A total of 203,898 (88.96%) were men and 25,284 (11.04%) were women. The majority of deaths occurred in public places and were caused by firearms; women had a higher percentage of homicides at home. States with high incidence rates for both sexes were Chihuahua, Zacatecas, Michoacán, Colima, and Estado de México. The total years of life lost were 9.19 million years. The national incidence of homicides in men showed an upward trend from 2015 to 2019; however, in the case of women, this incidence increased in various age groups during the study period. Occupation, education, marital status, and place of occurrence had significant associations in the logistic regression models. Conclusions: This study provides a spatial-temporal characterization of homicides in Mexico between 2015 and 2022, highlighting the high incidence in men and the upward trend in certain age groups among women. These findings underscore the need for preventive measures and public policies to address this issue in a multisectoral manner.
Multiple Job Holding, Job Changes, and Associations with Gestational Diabetes and Pregnancy-Related Hypertension in the National Birth Defects Prevention Study
Authors: Omari Amel , Siegel Miriam R. , Rocheleau Carissa M. , Fujishiro Kaori , Van Buren Kristen , Shi Dallas , Agopian A.J. , Gilboa Suzanne M. , Romitti Paul A.
Published: May 2024

We used National Birth Defects Prevention Study data to investigate associations between working patterns shortly before and during pregnancy and gestational diabetes and pregnancy-related hypertension. We analyzed working patterns (multiple-job holders, job changers, single-job holders) during the three months before and during pregnancy for 8140 participants who delivered a live-born child without a birth defect. “Multiple-job holders” worked more than one job simultaneously, “job changers” worked more than one job with no overlap, and “single-job holders” (referent) worked one job. We used multivariable logistic regression to estimate associations between working pattern and each outcome, adjusting for maternal age and educational attainment at delivery. We explored effect measure modification by household income, peak weekly working hours, and maternal race/ethnicity. Multiple-job holders had higher odds of gestational diabetes (adjusted odds ratio [aOR]: 1.5; 95% confidence interval [CI]: 1.1–2.1) and pregnancy-related hypertension (aOR: 1.5; 95% CI: 1.0–2.2) compared with single-job holders. Multiple-job holders with a household income of more than 30,000 USD per year, 32–44 peak weekly working hours, and from racial/ethnic minority groups had higher odds of gestational diabetes compared with single-job holders in respective categories. Detailed occupational information is important for studies of occupation and maternal health.
A Question and Answering Service of Typhoon Disasters Based on the T5 Large Language Model
Authors: Xia Yongqi , Huang Yi , Qiu Qianqian , Zhang Xueying , Miao Lizhi , Chen Yixiang
Published: May 2024

A typhoon disaster is a common meteorological disaster that seriously impacts natural ecology, social economy, and even human sustainable development. It is crucial to access the typhoon disaster information, and the corresponding disaster prevention and reduction strategies. However, traditional question and answering (Q&A) methods exhibit shortcomings like low information retrieval efficiency and poor interactivity. This makes it difficult to satisfy users’ demands for obtaining accurate information. Consequently, this work proposes a typhoon disaster knowledge Q&A approach based on LLM (T5). This method integrates two technical paradigms of domain fine-tuning and retrieval-augmented generation (RAG) to optimize user interaction experience and improve the precision of disaster information retrieval. The process specifically includes the following steps. First, this study selects information about typhoon disasters from open-source databases, such as Baidu Encyclopedia and Wikipedia. Utilizing techniques such as slicing and masked language modeling, we generate a training set and 2204 Q&A pairs specifically focused on typhoon disaster knowledge. Second, we continuously pretrain the T5 model using the training set. This process involves encoding typhoon knowledge as parameters in the neural network’s weights and fine-tuning the pretrained model with Q&A pairs to adapt the T5 model for downstream Q&A tasks. Third, when responding to user queries, we retrieve passages from external knowledge bases semantically similar to the queries to enhance the prompts. This action further improves the response quality of the fine-tuned model. Finally, we evaluate the constructed typhoon agent (Typhoon-T5) using different similarity-matching approaches. Furthermore, the method proposed in this work lays the foundation for the cross-integration of large language models with disaster information. It is expected to promote the further development of GeoAI.
Investigating Distinct Skin Microbial Communities and Skin Metabolome Profiles in Atopic Dermatitis
Authors: Kim Suyeon , Cho Minah , Jung Eun Sung , Sim Inseon , Woo Yu Ri
Published: May 2024

Atopic dermatitis (AD) is a chronic inflammatory skin disorder influenced by genetic predisposition, environmental factors, immune dysregulation, and skin barrier dysfunction. The skin microbiome and metabolome play crucial roles in modulating the skin’s immune environment and integrity. However, their specific contributions to AD remain unclear. We aimed to investigate the distinct skin microbial communities and skin metabolic compounds in AD patients compared to healthy controls (HCs). Seven patients with AD patients and seven HCs were enrolled, from whom skin samples were obtained for examination. The study involved 16S rRNA metagenomic sequencing and bioinformatics analysis as well as the use of gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) to detect metabolites associated with AD in the skin. We observed significant differences in microbial diversity between lesional and non-lesional skin of AD patients and HCs. Staphylococcus overgrowth was prominent in AD lesions, while Cutibacterium levels were decreased. Metabolomic analysis revealed elevated levels of several metabolites, including hypoxanthine and glycerol-3-phosphate in AD lesions, indicating perturbations in purine metabolism and energy production pathways. Moreover, we found a positive correlation between hypoxanthine and glycerol-3-phosphate and clinical severity of AD and Staphylococcus overgrowth. These findings suggest potential biomarkers for monitoring AD severity. Further research is needed to elucidate the causal relationships between microbial dysbiosis, metabolic alterations, and AD progression, paving the way for targeted therapeutic interventions.
Mucolytic Drugs Ambroxol and Bromhexine: Transformation under Aqueous Chlorination Conditions
Authors: Sypalov Sergey A. , Varsegov Ilya S. , Ulyanovskii Nikolay V. , Lebedev Albert T. , Kosyakov Dmitry S.
Published: May 2024

Bromhexine and ambroxol are among the mucolytic drugs most widely used to treat acute and chronic respiratory diseases. Entering the municipal wastewater and undergoing transformations during disinfection with active chlorine, these compounds can produce nitrogen- and bromine-containing disinfection by-products (DBPs) that are dangerous for aquatic ecosystems. In the present study, primary and deep degradation products of ambroxol and bromhexine obtained in model aquatic chlorination experiments were studied via the combination of high-performance liquid and gas chromatography with high-resolution mass spectrometry. It was shown that at the initial stages, the reactions of cyclization, hydroxylation, chlorination, electrophilic ipso-substitution of bromine atoms with chlorine, and oxidative N-dealkylation occur. Along with known metabolites, a number of novel primary DBPs were tentatively identified based on their elemental compositions and tandem mass spectra. Deep degradation of bromhexine and ambroxol gives twenty-four identified volatile and semi-volatile compounds of six classes, among which trihalomethanes account for more than 50%. The specific class of bromhexine- and ambroxol-related DBPs are bromine-containing haloanilines. Seven of them, including methoxy derivatives, were first discovered in the present study. One more novel class of DBPs associated with bromhexine and ambroxol is represented by halogenated indazoles formed through dealkylation of the primary transformation products containing pyrazoline or tetrahydropyrimidine cycle in their structure.
Challenges of Robust RNAi-Mediated Gene Silencing in Aedes Mosquitoes
Authors: Figueiredo Prates Lucas Henrique , Fiebig Jakob , Schlosser Henrik , Liapi Eleni , Rehling Tanja , Lutrat Célia , Bouyer Jeremy , Sun Qiang , Wen Han , Xi Zhiyong , Schetelig Marc F. , Häcker Irina
Published: May 2024

In this study, we report the complexities and challenges associated with achieving robust RNA interference (RNAi)-mediated gene knockdown in the mosquitoes Aedes aegypti and Aedes albopictus, a pivotal approach for genetic analysis and vector control. Despite RNAi’s potential for species-specific gene targeting, our independent efforts to establish oral delivery of RNAi for identifying genes critical for mosquito development and fitness encountered significant challenges, failing to reproduce previously reported potent RNAi effects. We independently evaluated a range of RNAi-inducing molecules (siRNAs, shRNAs, and dsRNAs) and administration methods (oral delivery, immersion, and microinjection) in three different laboratories. We also tested various mosquito strains and utilized microorganisms for RNA delivery. Our results reveal a pronounced inconsistency in RNAi efficacy, characterized by minimal effects on larval survival and gene expression levels in most instances despite strong published effects for the tested targets. One or multiple factors, including RNase activity in the gut, the cellular internalization and processing of RNA molecules, and the systemic dissemination of the RNAi signal, could be involved in this variability, all of which are barely understood in mosquitoes. The challenges identified in this study highlight the necessity for additional research into the underlying mechanisms of mosquito RNAi to develop more robust RNAi-based methodologies. Our findings emphasize the intricacies of RNAi application in mosquitoes, which present a substantial barrier to its utilization in genetic control strategies.
Puerarin—A Promising Flavonoid: Biosynthesis, Extraction Methods, Analytical Techniques, and Biological Effects
Authors: Liga Sergio , Paul Cristina
Published: May 2024

Flavonoids, a variety of plant secondary metabolites, are known for their diverse biological activities. Isoflavones are a subgroup of flavonoids that have gained attention for their potential health benefits. Puerarin is one of the bioactive isoflavones found in the Kudzu root and Pueraria genus, which is widely used in alternative Chinese medicine, and has been found to be effective in treating chronic conditions like cardiovascular diseases, liver diseases, gastric diseases, respiratory diseases, diabetes, Alzheimer’s disease, and cancer. Puerarin has been extensively researched and used in both scientific and clinical studies over the past few years. The purpose of this review is to provide an up-to-date exploration of puerarin biosynthesis, the most common extraction methods, analytical techniques, and biological effects, which have the potential to provide a new perspective for medical and pharmaceutical research and development.
Special Issue “Bioinformatics of Unusual DNA and RNA Structures”
Authors: Bartas Martin , Brázda Václav , Pečinka Petr
Published: May 2024

Nucleic acids are not only static carriers of genetic information but also play vital roles in controlling cellular lifecycles through their fascinating structural diversity [...]
Differential Modulation of Catecholamine and Adipokine Secretion by the Short Chain Fatty Acid Receptor FFAR3 and α2-Adrenergic Receptors in PC12 Cells
Authors: Nagliya Deepika , Baggio Lopez Teresa , Del Calvo Giselle , Stoicovy Renee A. , Borges Jordana I. , Suster Malka S. , Lymperopoulos Anastasios
Published: May 2024

Sympathetic nervous system (SNS) hyperactivity is mediated by elevated catecholamine (CA) secretion from the adrenal medulla, as well as enhanced norepinephrine (NE) release from peripheral sympathetic nerve terminals. Adrenal CA production from chromaffin cells is tightly regulated by sympatho-inhibitory α2-adrenergic (auto)receptors (ARs), which inhibit both epinephrine (Epi) and NE secretion via coupling to Gi/o proteins. α2-AR function is, in turn, regulated by G protein-coupled receptor (GPCR)-kinases (GRKs), especially GRK2, which phosphorylate and desensitize them, i.e., uncouple them from G proteins. On the other hand, the short-chain free fatty acid (SCFA) receptor (FFAR)-3, also known as GPR41, promotes NE release from sympathetic neurons via the Gi/o-derived free Gβγ-activated phospholipase C (PLC)-β/Ca2+ signaling pathway. However, whether it exerts a similar effect in adrenal chromaffin cells is not known at present. In the present study, we examined the interplay of the sympatho-inhibitory α2A-AR and the sympatho-stimulatory FFAR3 in the regulation of CA secretion from rat adrenal chromaffin (pheochromocytoma) PC12 cells. We show that FFAR3 promotes CA secretion, similarly to what GRK2-dependent α2A-AR desensitization does. In addition, FFAR3 activation enhances the effect of the physiologic stimulus (acetylcholine) on CA secretion. Importantly, GRK2 blockade to restore α2A-AR function or the ketone body beta-hydroxybutyrate (BHB or 3-hydroxybutyrate), via FFAR3 antagonism, partially suppress CA production, when applied individually. When combined, however, CA secretion from PC12 cells is profoundly suppressed. Finally, propionate-activated FFAR3 induces leptin and adiponectin secretion from PC12 cells, two important adipokines known to be involved in tissue inflammation, and this effect of FFAR3 is fully blocked by the ketone BHB. In conclusion, SCFAs can promote CA and adipokine secretion from adrenal chromaffin cells via FFAR3 activation, but the metabolite/ketone body BHB can effectively inhibit this action.
Systems for Targeted Silencing of Gene Expression and Their Application in Plants and Animals
Authors: Motorina Daria M. , Galimova Yuliya A. , Battulina Nadezhda V. , Omelina Evgeniya S.
Published: May 2024

At present, there are a variety of different approaches to the targeted regulation of gene expression. However, most approaches are devoted to the activation of gene transcription, and the methods for gene silencing are much fewer in number. In this review, we describe the main systems used for the targeted suppression of gene expression (including RNA interference (RNAi), chimeric transcription factors, chimeric zinc finger proteins, transcription activator-like effectors (TALEs)-based repressors, optogenetic tools, and CRISPR/Cas-based repressors) and their application in eukaryotes—plants and animals. We consider the advantages and disadvantages of each approach, compare their effectiveness, and discuss the peculiarities of their usage in plant and animal organisms. This review will be useful for researchers in the field of gene transcription suppression and will allow them to choose the optimal method for suppressing the expression of the gene of interest depending on the research object.
MicroRNA-10 Family Promotes Renal Fibrosis through the VASH-1/Smad3 Pathway
Authors: Shuai Yichen , Xu Na , Zhao Chuan , Yang Fengrui , Ning Zhifen , Li Guoxia
Published: May 2024

Renal fibrosis (RF) stands as a pivotal pathological process in the advanced stages of chronic kidney disease (CKD), and impeding its progression is paramount for delaying the advancement of CKD. The miR-10 family, inclusive of miR-10a and miR-10b, has been implicated in the development of various fibrotic diseases. Nevertheless, the precise role of miR-10 in the development of RF remains enigmatic. In this study, we utilized both an in vivo model involving unilateral ureteral obstruction (UUO) in mice and an in vitro model employing TGF-β1 stimulation in HK-2 cells to unravel the mechanism underlying the involvement of miR-10a/b in RF. The findings revealed heightened expression of miR-10a and miR-10b in the kidneys of UUO mice, accompanied by a substantial increase in p-Smad3 and renal fibrosis-related proteins. Conversely, the deletion of these two genes led to a notable reduction in p-Smad3 levels and the alleviation of RF in mouse kidneys. In the in vitro model of TGF-β1-stimulated HK-2 cells, the co-overexpression of miR-10a and miR-10b fostered the phosphorylation of Smad3 and RF, while the inhibition of miR-10a and miR-10b resulted in a decrease in p-Smad3 levels and RF. Further research revealed that miR-10a and miR-10b, through binding to the 3’UTR region of Vasohibin-1 (VASH-1), suppressed the expression of VASH-1, thereby promoting the elevation of p-Smad3 and exacerbating the progression of RF. The miR-10 family may play a pivotal role in RF.
Anion-Binding Properties of Short Linear Homopeptides
Authors: Modrušan Matija , Glazer Lucija , Otmačić Lucija , Crnolatac Ivo , Cindro Nikola , Vidović Nikolina , Piantanida Ivo , Speranza Giovanna , Horvat Gordan , Tomišić Vladislav
Published: May 2024

A comprehensive thermodynamic and structural study of the complexation affinities of tetra (L1), penta (L2), and hexaphenylalanine (L3) linear peptides towards several inorganic anions in acetonitrile (MeCN) and N,N-dimethylformamide (DMF) was carried out. The influence of the chain length on the complexation thermodynamics and structural changes upon anion binding are particularly addressed here. The complexation processes were characterized by means of spectrofluorimetric, 1H NMR, microcalorimetric, and circular dichroism spectroscopy titrations. The results indicate that all three peptides formed complexes of 1:1 stoichiometry with chloride, bromide, hydrogen sulfate, dihydrogen phosphate (DHP), and nitrate anions in acetonitrile and DMF. In the case of hydrogen sulfate and DHP, anion complexes of higher stoichiometries were observed as well, namely those with 1:2 and 2:1 (peptide:anion) complexes. Anion-induced peptide backbone structural changes were studied by molecular dynamic simulations. The anions interacted with backbone amide protons and one of the N-terminal amine protons through hydrogen bonding. Due to the anion binding, the main chain of the studied peptides changed its conformation from elongated to quasi-cyclic in all 1:1 complexes. The accomplishment of such a conformation is especially important for cyclopeptide synthesis in the head-to-tail macrocyclization step, since it is most suitable for ring closure. In addition, the studied peptides can act as versatile ionophores, facilitating transmembrane anion transport.
IQGAP1 Regulates Actin Polymerization and Contributes to Bleomycin-Induced Lung Fibrosis
Authors: Akter Tanjina , Atanelishvili Ilia , Silver Richard M. , Bogatkevich Galina S.
Published: May 2024

We previously found IQ motif containing GTPase activating protein (IQGAP1) to be consistently elevated in lung fibroblasts (LF) isolated from patients with scleroderma (systemic sclerosis, SSc)-associated interstitial lung disease (ILD) and reported that IQGAP1 contributed to SSc by regulating expression and organization of α-smooth muscle actin (SMA) in LF. The aim of this study was to compare the development of ILD in the presence and absence of IQGAP1. Pulmonary fibrosis was induced in IQGAP1 knockout (KO) and wild-type (WT) mice by a single-intratracheal instillation of bleomycin. Two and three weeks later, mice were euthanized and investigated. We observed that the IQGAP1 KO mouse was characterized by a reduced rate of actin polymerization with reduced accumulation of actin in the lung compared to the WT mouse. After exposure to bleomycin, the IQGAP1 KO mouse demonstrated decreased contractile activity of LF, reduced expression of SMA, TGFβ, and collagen, and lowered overall fibrosis scores compared to the WT mouse. The numbers of inflammatory cells and expression of pro-inflammatory cytokines in lung tissue were not significantly different between IQGAP1 KO and WT mice. We conclude that IQGAP1 plays an important role in the development of lung fibrosis induced by bleomycin, and the absence of IQGAP1 reduces the contractile activity of lung fibroblast and bleomycin-induced pulmonary fibrosis. Thus, IQGAP1 may be a potential target for novel anti-fibrotic therapies for lung fibrosis.