bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual-specificity protein phosphatase 6 (DUSP6) overexpression reduces amyloid load and improves memory deficits in male 5xFAD mice
Authors: Pan Allen L. , Audrain Mickael , Sakakibara Emmy , Joshi Rajeev , Zhu Xiaodong , Wang Qian , Wang Minghui , Beckmann Noam D. , Schadt Eric E. , Gandy Sam , Zhang Bin , Ehrlich Michelle E. , Salton Stephen R.
Published: June 2024

Introduction

Dual specificity protein phosphatase 6 (DUSP6) was recently identified as a key hub gene in a causal VGF gene network that regulates late-onset Alzheimer’s disease (AD). Importantly, decreased DUSP6 levels are correlated with an increased clinical dementia rating (CDR) in human subjects, and DUSP6 levels are additionally decreased in the 5xFAD amyloidopathy mouse model.

Methods

To investigate the role of DUSP6 in AD, we stereotactically injected AAV5-DUSP6 or AAV5-GFP (control) into the dorsal hippocampus (dHc) of both female and male 5xFAD or wild type mice, to induce overexpression of DUSP6 or GFP.

Results

Barnes maze testing indicated that DUSP6 overexpression in the dHc of 5xFAD mice improved memory deficits and was associated with reduced amyloid plaque load, Aß1–40 and Aß1–42 levels, and amyloid precursor protein processing enzyme BACE1, in male but not in female mice. Microglial activation, which was increased in 5xFAD mice, was significantly reduced by dHc DUSP6 overexpression in both males and females, as was the number of “microglial clusters,” which correlated with reduced amyloid plaque size. Transcriptomic profiling of female 5xFAD hippocampus revealed upregulation of inflammatory and extracellular signal-regulated kinase pathways, while dHc DUSP6 overexpression in female 5xFAD mice downregulated a subset of genes in these pathways. Gene ontology analysis of DEGs (p < 0.05) identified a greater number of synaptic pathways that were regulated by DUSP6 overexpression in male compared to female 5xFAD.

Discussion

In summary, DUSP6 overexpression in dHc reduced amyloid deposition and memory deficits in male but not female 5xFAD mice, whereas reduced neuroinflammation and microglial activation were observed in both males and females, suggesting that DUSP6-induced reduction of microglial activation did not contribute to sex-dependent improvement in memory deficits. The sex-dependent regulation of synaptic pathways by DUSP6 overexpression, however, correlated with the improvement of spatial memory deficits in male but not female 5xFAD.
Non-coding RNAs involved in the molecular pathology of Alzheimer’s disease: a systematic review
Authors: Canoy Reynand Jay , Sy Jenica Clarisse , Deguit Christian Deo , Castro Caitlin Bridgette , Dimaapi Lyoneil James , Panlaqui Beatrice Gabrielle , Perian Wenzel , Yu Justine , Velasco John Mark , Sevilleja Jesus Emmanuel , Gibson Anna
Published: June 2024

Alzheimer’s disease (AD) is the leading cause of dementia globally, having a pathophysiology that is complex and multifactorial. Recent findings highlight the significant role of non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and piwi-interacting RNAs (piRNAs) in the molecular mechanisms underlying AD. These ncRNAs are involved in critical biological processes such as cell proliferation, apoptosis, oxidative stress, amyloid-beta aggregation, tau phosphorylation, neuroinflammation, and autophagy, which are pivotal in AD development and progression. This systematic review aims to consolidate current scientific knowledge on the role of ncRNAs in AD, making it the first to encompass the four types of ncRNAs associated with the disease. Our comprehensive search and analysis reveal that ncRNAs not only play crucial roles in the pathogenesis of AD but also hold potential as biomarkers for its early detection and as novel therapeutic targets. Specifically, the findings underscore the significance of miRNAs in regulating genes involved in key AD pathways such as activin receptor signaling pathway, actomyosin contractile ring organization, and advanced glycation endproducts-receptor advanced glycation endproducts (AGE-RAGE) signaling pathway. This review also highlights the potential of ncRNAs in unveiling novel diagnostic and therapeutic strategies, emphasizing the need for further research to validate their clinical utility. Our systematic exploration provides a foundation for future bioinformatic analyses and the development of ncRNA-based precision medicine approaches for AD, offering new insights into the disease’s molecular pathology and paving the way for innovative treatment strategies.

Systematic review registration

PROSPERO, https://www.crd.york.ac.uk/prospero/, CRD42022355307.
Survival pattern in male breast cancer: distinct from female breast cancer
Authors: Gwark Sungchan , Kim Jisun , Chung Il Yong , Kim Hee Jeong , Ko Beom Seok , Lee Jong Won , Son Byung Ho , Ahn Sei Hyun , Lee Sae Byul
Published: June 2024

Introduction

Male breast cancer (MBC) is a rare condition, and recent research has underscored notable distinctions between MBC and breast cancer in women. This study aimed to assess and contrast the long-term survival outcomes and disease patterns of MBC patients with those of their female counterparts.

Methods

We analyzed data from 113,845 patients diagnosed with breast cancer who had undergone curative surgery from the Korean Breast Cancer Registry (KBCR) between January 1990 and August 2014 in Seoul, Korea. The five-year overall survival was analyzed according to clinicopathological characteristics.

Results

Among 113,845 patients with breast cancer, 473 MBC cases were included. The median duration of follow-up was 72 months. The median age at diagnosis was 60 and 48 years for MBC and female breast cancer, respectively. Most male patients (92.6%) underwent total mastectomy, while 50.4% of female patients underwent breast-conserving surgery. Among MBC, 63.2% received chemotherapy, and 83.9% of hormone receptor-positive male patients received endocrine therapy. In survival analysis, MBC demonstrated distinct 5-year overall survival patterns compared with female breast cancer, according to age at diagnosis. In women with breast cancer, the younger age group (≤40 years) demonstrated worse 5-year overall survival than did the older age group (>40 years) (91.3% vs 92.7%, p <0.05). While in MBC, the younger age group (≤40 years) demonstrated better 5-year overall survival than did the older age group (>40 years) (97.4% vs 86.4%, p <0.05).

Discussion

In conclusion within this extensive cohort, we have revealed unique survival patterns in MBC that diverge from those observed in women with breast cancer. This study enhances our comprehension of MBC prognosis and can potentially shed light on unresolved questions, paving the way for future research in the realm of MBC.
Psyllium fiber improves hangovers and inflammatory liver injury by inhibiting intestinal drinking
Authors: Yang Keungmo , Ryu Tom , Chung Beom Sun
Published: June 2024

Introduction: Excessive alcohol intake often results in hangovers and inflammatory liver damage, posing a significant health concern. Current treatment options for hangovers are still insufficient, highlighting the urgent need for new therapeutic approaches. Psyllium fiber (PF) is well-known for its gastrointestinal benefits, but its effect on hangovers is less explored.

Methods: We utilized a mouse model with a single binge drinking (4 g/kg) to induce hangover and inflammatory liver injury. Intestine and liver injury were serologically and histologically estimated. Hangover symptoms were assessed using cylinder and footprint tests to objectively quantify hangover symptoms in mice.

Results: Binge drinking significantly activated alcohol-metabolizing enzymes in the small intestine and liver, leading to inflammatory damage. Concurrently, there was a rise in alcohol metabolites such as acetaldehyde and acetone, which exhibited a positive correlation with hangover symptoms in mice. Interestingly, the oral administration of PF (100 mg/kg) alongside alcohol consumption significantly reduced the activity of these enzymes and lowered the levels of alcohol metabolites. Mice treated with PF exhibited a considerable improvement in hangover symptoms and a reduction in hepatic inflammation, compared to control groups. Furthermore, in vitro experiments using HepG2 cell lines and semipermeable membranes demonstrated that PF effectively inhibits alcohol absorption into the body.

Discussion: In conclusion, PF demonstrates a potential protective effect against alcohol-induced hangover and liver injury by inhibiting the absorption of alcohol and lowering hangover-related alcohol metabolites. This study suggests that PF could serve as an effective therapeutic option for mitigating the adverse effects of excessive alcohol consumption.
Foliar application of various biostimulants produces contrasting response on yield, essential oil and chemical properties of organically grown sage (Salvia officinalis L.)
Authors: Farruggia Davide , Di Miceli Giuseppe , Licata Mario , Leto Claudio , Salamone Francesco , Novak Johannes
Published: June 2024

Sage (Salvia officinalis L.) is a medicinal and aromatic plant (MAP) belonging to the Lamiaceae family. Its morphological, productive and chemical characteristics are affected by abiotic and biotic factors. The use of biostimulants seems to be one of the most interesting innovative practices due to fact they can represent a promising approach for achieving sustainable and organic agriculture. Despite a large application in horticulture, the use of biostimulants on MAPs has been poorly investigated. On this basis, a field experiment in a 2-year study was done to assess the effect of foliar treatments with different types of biostimulants (containing seaweeds, fulvic acids and protein hydrolysates) and two frequencies of application on morphological, productive, and chemical characteristics of S. officinalis grown organically in Mediterranean environment. Morphological, productive, and chemical parameters were affected by the factors. The biostimulant application generated higher plant height, chlorophyll content, relative water content, biomass yield and essential oil yield compared to control plants. In addition, more frequent application of biostimulants produced higher biomass and essential oil yield. The application of fulvic acid and protein hydrolysates every week produced the highest total fresh yields (between 3.9 and 8.7 t ha-1) and total dry yields (between 1.3 and 2.5 t ha-1). The essential oil yield almost doubled (33.9 kg ha-1) with a higher frequency of protein hydrolysates application. In this study, 44 essential oil compounds were identified, and the frequency factor significantly influenced the percentage of 38 compounds. The highest percentage of some of the most representative monoterpenes, such as 1,8-cineole, α-thujone and camphor, were observed in biostimulated plants, with average increases between 6% and 35% compared to control plants. The highest values for total phenolics, rosmarinic acid, antioxidant activity were obtained in control plants and with a lower frequency of biostimulant applications. This study emphasizes how biostimulant applications may be used to improve sage production performance and essential oil parameters when produced in agricultural organic system. At the same time, biostimulants application caused a decrease in total phenolic, antioxidant activity and rosmarinic acid values.
Effects of different types of physical exercise on executive function of older adults: a scoping review
Authors: Cai Zhidong , Cai Ruibao , Sen Li
Published: June 2024

Objective

This scoping review examined the impact of physical exercise on executive function (EF) in older adults and investigated the moderating effects of exercise types.

Methods

We systematically searched four electronic databases for randomized controlled trials (RCTs) investigating the effects of exercise on EF, published until November 26, 2023. The proportions of positive and null/negative effects across all studies were calculated.

Results

In total, 91 studies were included in the analysis. Among these, 27 (29.7%) studies employed aerobic exercise interventions for older adults’ EF, with 19 (70.4%) studies reporting positive effects. Additionally, 18 (19.8%) studies utilized strength exercise interventions for older adults’ EF, with 15 (83.3%) studies demonstrating positive benefits. Furthermore, 32 (35.2%) studies employed coordination exercise interventions for older adults’ EF, with 25 (78.1%) studies showing positive benefits. Similarly, 30 (33%) studies applied mixed exercise interventions for older adults’ EF, with 25 (83.3%) studies indicating positive benefits.

Conclusion

Overall, all four types of physical exercise enhance EF in older adults, with mixed exercises being the most effective.
The mediating role of mentalization and integrative self-knowledge in the relationship between childhood trauma and fear of intimacy
Authors: Riazi Seyyedeh Sara , Manouchehri Mehdi
Published: June 2024

Introduction

Since intimacy is a fundamental human need within social relationships, and recognizing that a fear of intimacy correlates with various negative consequences, it becomes crucial to examine the origins and factors that contribute to addressing this issue. This research aimed to investigate the mediating roles of mentalization and integrative self-knowledge in the link between childhood trauma and the fear of intimacy.

Methods

Conducted as correlational descriptive research, our study incorporates a total sample of 303 adult women and men participants aged 20 to 50 in Tehran using the convenience sampling method. They completed the Fear of Intimacy Scale (FIS), the Childhood Trauma Questionnaire (CTQ), the Mentalization Scale (MentS), and the Integrative Self-Knowledge Scale (ISK). To analyze the research data at the descriptive level, frequency, percentage, standard deviation, and Pearson’s correlation coefficient were used, while path analysis tested our hypotheses in SPSS version 26 and AMOS version 24. Fit indices were used to check the model’s fit, and the mediation test was performed using the bootstrapping method. The fit indices revealed an excellent fit of the model with the data (χ2 = 1.51, χ2/df = 1.51, p = 0.219; RMSEA = 0.05; SRMR = 0.02; CFI = 0.99; NFI = 0.99; TLI = 0.99).

Results

Results indicate mentalization fully mediates the childhood trauma-fear of intimacy relationship (β = 0.14, p < 0.01). However, the indirect relationship between childhood trauma and fear of intimacy through integrative self-knowledge was insignificant. The results also showed that the path coefficient from mentalization to fear of intimacy was negative and significant (β = −0.41, p < 0.001), while the path coefficient from integrative self-knowledge to fear of intimacy was not significant (β = −0.02, p > 0.05).

Discussion

Based on the current findings indicating the complete mediation of mentalization and the insignificance of the mediation of integrative self-knowledge, we can deduce that enhancing the capacity for mentalization holds promise in effectively addressing intimacy-related issues. Overall, the study suggests mentalization effectively predicts the relationship between childhood trauma and fear of intimacy. This, in turn, may mitigate the detrimental effects of challenging childhood experiences on an individual’s ability to engage in intimacy and cultivate emotional closeness.
Applications to augment patient care for Internal Medicine specialists: a position paper from the EFIM working group on telemedicine, innovative technologies & digital health
Authors: Pietrantonio F. , Florczak M. , Kuhn S. , Kärberg K. , Leung T. , Said Criado I. , Sikorski S. , Ruggeri M. , Signorini A. , Rosiello F. , Drago C. , Vinci A. , Barreto V. , Montano N. , Dicker D. , Gomez Huelgas R.
Published: June 2024

Telemedicine applications present virtually limitless prospects for innovating and enhancing established and new models of patient care in the field of Internal Medicine. Although there is a wide range of innovative technological solutions in Europe, there are overarching elements associated with such technologies when applied to the practices of Internal Medicine specialists. The European Federation of Internal Medicine (EFIM) strongly advocates for active leadership and influence from the Internal Medicine societies and specialist physicians across Europe in the development and application of telemedicine and digital technologies in healthcare. This position paper’s conclusions were drawn via Delphi method, which was developed collaboratively from July 2021 to December 2023. The panel, consisting of experts in clinical medicine, public health, health economics and statistics, assessed various aspects related to telemedicine. Participants assigned scores on a Likert scale reflecting perceived value and potential risks. The findings were consolidated in a comprehensive checklist aligning with relevant literature and a SWOT analysis. Specifically, key issues that need to be addressed include promoting the professional development of e-health competencies in the healthcare and medical workforce, using educational campaigns to promote digital literacy among patients and caregivers, designing and implementing telemedicine applications tailored to local conditions and needs and considering the ethical and legal contexts under which these applications are employed. Importantly, there is currently no consensus on care models or standardized protocols among European Internal Medicine specialists regarding the utilization of telemedicine. This position paper aims to outline the opportunities and challenges associated with the application of telemedicine in Internal Medical practice in Europe.
Feasibility study to unveil the potential: considerations of constrained spherical deconvolution tractography with unsedated neonatal diffusion brain MRI data
Authors: Verschuur Anouk S. , Tax Chantal M. W. , Boomsma Martijn F. , Carlson Helen L. , van Wezel-Meijler Gerda , King Regan , Leemans Alexander , Leijser Lara M.
Published: June 2024

Purpose

The study aimed to (1) assess the feasibility constrained spherical deconvolution (CSD) tractography to reconstruct crossing fiber bundles with unsedated neonatal diffusion MRI (dMRI), and (2) demonstrate the impact of spatial and angular resolution and processing settings on tractography and derived quantitative measures.

Methods

For the purpose of this study, the term-equivalent dMRIs (single-shell b800, and b2000, both 5 b0, and 45 gradient directions) of two moderate-late preterm infants (with and without motion artifacts) from a local cohort [Brain Imaging in Moderate-late Preterm infants (BIMP) study; Calgary, Canada] and one infant from the developing human connectome project with high-quality dMRI (using the b2600 shell, comprising 20 b0 and 128 gradient directions, from the multi-shell dataset) were selected. Diffusion tensor imaging (DTI) and CSD tractography were compared on b800 and b2000 dMRI. Varying image resolution modifications, (pre-)processing and tractography settings were tested to assess their impact on tractography. Each experiment involved visualizing local modeling and tractography for the corpus callosum and corticospinal tracts, and assessment of morphological and diffusion measures.

Results

Contrary to DTI, CSD enabled reconstruction of crossing fibers. Tractography was susceptible to image resolution, (pre-) processing and tractography settings. In addition to visual variations, settings were found to affect streamline count, length, and diffusion measures (fractional anisotropy and mean diffusivity). Diffusion measures exhibited variations of up to 23%.

Conclusion

Reconstruction of crossing fiber bundles using CSD tractography with unsedated neonatal dMRI data is feasible. Tractography settings affected streamline reconstruction, warranting careful documentation of methods for reproducibility and comparison of cohorts.
Radiographic and echocardiographic evaluation in rescued Korean raccoon dogs (Nyctereutes procyonoides koreensis)
Authors: Park Junu , Kim Myeongsu , Han Jae-Ik , Lee Kichang , Yoon Hakyoung
Published: June 2024

Introduction

Nyctereutes procyonoides koreensis (Korean raccoon dog), a member of the Canidae family, is anatomically similar to dogs. Previous studies have used vertebral heart scale measurements to measure the cardiac size of Korean raccoon dogs on thoracic radiographs; however, the use of additional cardiac size indices, such as vertebral left arial score, intercostal space, cardiothoracic ratio, and echocardiographic indices, has not been reported. Therefore, this study aimed to establish normal reference ranges for various thoracic radiographic and echocardiographic indices in normal Korean raccoon dogs.

Methods

Twenty-six Korean raccoon dogs (11 males and 15 females) were included in this study. The thoracic radiographic indices, vertebral heart scale score, and vertebral left atrial score were measured in the right lateral view. The intercostal space and cardiothoracic ratio were measured in the ventrodorsal view. The echocardiograms were evaluated in the right parasternal long and short axis view and left parasternal apical view.

Results

The mean values for the thoracic radiographic and echocardiographic indices were as follows: vertebral heart scale, 9.12 ± 0.74; vertebral left atrial score, 1.5 ± 0.31; intercostal spaces, 3.17 ± 0.34; cardiothoracic ratio, 0.69 ± 0.07; left atrial to aortic root ratio, 1.22 ± 0.14; main pulmonary artery to aorta ratio, 1.22 ± 0.14; left ventricular end-diastolic internal diameter normalized for body weight, 1.36 ± 0.19; end-diastolic volume index, 51.07 ± 19.6; end-systolic volume index, 16.54 ± 7.45; the peak velocity of early diastolic transmitral flow, 73.13 ± 15.46 cm/s; and the ratio between the transmitral flow velocities and the peak early diastolic velocity, 1.77 ± 0.47. Only percent increase in the left ventricular end-systolic internal diameter was negatively correlated with body weight. The remaining indices showed no correlations with body weight.

Conclusion

To the best of our knowledge, this is the first case report covering both thoracic radiographic and endocardiographic indices for Korean raccoon dogs. Thus, the thoracic radiographic and echocardiographic indices established in this study may be used to evaluate the cardiac condition of Korean raccoon dogs.
Correction: Brar et al. Assessment of Natural Ageing Related Physio-Biochemical Changes in Onion Seed. Agriculture 2019, 9, 163
Authors: Brar Navjot Singh , Kaushik Prashant , Dudi Bagrawat Singh
Published: June 2024

The Agriculture Editorial Office wishes to make the following changes to the author's paper [...]
Genetic Testing of Breast Cancer Patients with Very Early-Onset Breast Cancer (≤30 Years) Yields a High Rate of Germline Pathogenic Variants, Mainly in the BRCA1, TP53, and BRCA2 Genes
Authors: Apostolou Paraskevi , Dellatola Vasiliki , Papathanasiou Athanasios , Kalfakakou Despoina , Fountzilas Elena , Tryfonopoulos Dimitrios , Karageorgopoulou Sofia , Yannoukakos Drakoulis , Konstantopoulou Irene , Fostira Florentia
Published: June 2024

Early-onset breast cancer constitutes a major criterion for genetic testing referral. Nevertheless, studies focusing on breast cancer patients (≤30 years) are limited. We investigated the contribution and spectrum of known breast-cancer-associated genes in 267 Greek women with breast cancer ≤30 years while monitoring their clinicopathological characteristics and outcomes. In this cohort, a significant proportion (39.7%) carried germline pathogenic variants (PVs) distributed in 8 genes. The majority, namely 36.7%, involved BRCA1, TP53, and BRCA2. PVs in BRCA1 were the most prevalent (28.1%), followed by TP53 (4.5%) and BRCA2 (4.1%) PVs. The contribution of PVs in CHEK2, ATM, PALB2, PTEN, and RAD51C was limited to 3%. In the patient group ≤26 years, TP53 PVs were significantly higher compared to the group 26–30 years (p = 0.0023). A total of 74.8% of TP53 carriers did not report a family history of cancer. Carriers of PVs receiving neoadjuvant chemotherapy showed an improved event-free survival (p < 0.0001) compared to non-carriers. Overall, many women with early-onset breast cancer carry clinically actionable variants, mainly in the BRCA1/2 and TP53 genes. The inclusion of timely testing of TP53 in these patients provides essential information for appropriate clinical management. This is important for countries where reimbursement involves the cost of genetic analysis of BRCA1/2 only.
Phenotype Variation in Niphargus (Amphipoda: Niphargidae): Possible Explanations and Open Challenges
Authors: Fišer Cene , Premate Ester
Published: June 2024

Understanding phenotype variation is among the central topics in biology. We revise and reanalyze studies of the amphipod genus Niphargus to confront two potential mechanisms driving its phenotype variation, namely, cladogenesis and adaptive evolution. We found evidence for both mechanisms. Reanalysis of a subset of traits using molecular phylogeny showed moderate phylogenetic signal, consistent with the hypothesis that overall phylogenetic variation increases with phylogeny. The phylogenetic signal in Niphargus traits seems to be stronger at the tips of the phylogeny than at basal splits. Indirect evidence suggests that much of the phenotype variation can be attributed to adaptive evolution. Both lines of evidence are consistent with the hypothesis that Niphargus evolved in several adaptive radiations, where theory predicts that most of the phenotype variation evolves early, when ecological niches are vacant. As the niches fill up, the rate of phenotype variation slows down and becomes associated with cladogenetic events. This hypothesis can explain the high level of trait-convergence and unresolved taxonomy above the species level. The main caveats to these hypotheses comprise lack of experimental evidence for trait function and nonquantified heritable component of trait variation. Promising venues towards better understanding of phenotypic variation include studies of ontogenetic variation, functional interactions between traits, and genome–phenotype associations.
Facile Preparation of Multifunctional Hydrogels with Sustained Resveratrol Release Ability for Bone Tissue Regeneration
Authors: Zhang Wenhai , Zheng Li , Yan Yi , Shi Wen
Published: June 2024

Injectable hydrogels show great promise for bone tissue engineering applications due to their high biocompatibility and drug delivery capabilities. The bone defects in osteoporosis are usually characterized by an oxidative and inflammatory microenvironment that impairs the regeneration capability of bone tissues. To attenuate the reactive oxygen species (ROS) and promote bone regeneration, an anti-oxidative hydrogel with osteogenic capacity was developed in this study. The poorly water soluble, natural antioxidant, resveratrol, was encapsulated in thiolated Pluronic F-127 micelles with over 50-times-enhanced solubility. The injectable hydrogel was facilely formed because of the new thioester bond between the free thiol group in modified F-127 and the arylate group in hyaluronic acid (HA)–acrylate. The resveratrol-loaded hydrogel showed good viscoelastic properties and in vitro stability and was cyto-compatible with bone-marrow-derived mesenchymal stem cells (BMSCs). The hydrogel allowed for a sustained release of resveratrol for at least two weeks and effectively enhanced the osteogenic differentiation of BMSCs by the up-regulation of osteogenic markers, including ALP, OCN, RUNX-2, and COL1. Moreover, the hydrogel exhibited anti-oxidative and anti-inflammatory abilities through the scavenging of intracellular ROS in RAW264.7 cells and inhibiting the gene expression and secretion of pro-inflammatory cytokines TNF-α and IL-1β under LPS exposure. In summary, the results suggest that our multifunctional hydrogel loaded with resveratrol bearing osteogenic, anti-oxidative, and anti-inflammatory actions is easily prepared and represents a promising resveratrol delivery platform for the repair of osteoporotic bone defects.
From Alpha-Thalassemia Trait to NPRL3-Related Epilepsy: A Genomic Diagnostic Odyssey
Authors: Nabavi Nouri Maryam , Alandijani Lama , van Engelen Kalene , Tole Soumitra , Lalonde Emilie , Balci Tugce B.
Published: June 2024

Introduction: The NPRL3 gene is a critical component of the GATOR1 complex, which negatively regulates the mTORC1 pathway, essential for neurogenesis and brain development. Located on chromosome 16p13.3, NPRL3 is situated near the α-globin gene cluster. Haploinsufficiency of NPRL3, either by deletion or a pathogenic variant, is associated with a variable phenotype of focal epilepsy, with or without malformations of cortical development, with known decreased penetrance. Case Description: This work details the diagnostic odyssey of a neurotypical 10-year-old boy who presented at age 2 with unusual nocturnal episodes and a history of microcytic anemia, as well as a review of the existing literature on NPRL3-related epilepsy, with an emphasis on individuals with deletions who also present with α-thalassemia trait. The proband’s episodes were mistaken for gastroesophageal reflux disease for several years. He had molecular testing for his α-thalassemia trait and was noted to carry a deletion encompassing the regulatory region of the α-thalassemia gene cluster. Following the onset of overt focal motor seizures, genetic testing revealed a heterozygous loss of NPRL3, within a 106 kb microdeletion on chromosome 16p13.3, inherited from his mother. This deletion encompassed the entire NPRL3 gene, which overlaps the regulatory region of the α-globin gene cluster, giving him the dual diagnosis of NPRL3-related epilepsy and α-thalassemia trait. Brain imaging postprocessing showed left hippocampal sclerosis and mid-posterior para-hippocampal focal cortical dysplasia, leading to the consideration of epilepsy surgery. Conclusions: This case underscores the necessity of early and comprehensive genetic assessments in children with epilepsy accompanied by systemic features, even in the absence of a family history of epilepsy or a developmental delay. Recognizing phenotypic overlaps is crucial to avoid diagnostic delays. Our findings also highlight the impact of disruptions in regulatory regions in genetic disorders: any individual with full gene deletion of NPRL3 would have, at a minimum, α-thalassemia trait, due to the presence of the major regulatory element of α-globin genes overlapping the gene’s introns.
Dynamic Alternative Polyadenylation during Litopenaeus Vannamei Metamorphosis Development
Authors: Yang Xueqin , Chen Xiuli , Liu Chengzhang , Wang Zezhong , Lei Wei , Li Qiangyong , Zhao Yongzhen , Wang Xia
Published: June 2024

As an important mechanism in the post-transcriptional regulation of eukaryotic gene expression, alternative polyadenylation (APA) plays a key role in biological processes such as cell proliferation and differentiation. However, the role and dynamic pattern of APA during Litopenaeus vannamei metamorphosis are poorly understood. Here, RNA-seq data covering from the embryo to the maturation (16 time points) of L. vannamei were utilized. We identified 247 differentially expressed APA events between early and adult stages, and through fuzzy mean clustering analysis, we discovered five dynamic APA patterns. Among them, the gradual elongation of the 3′UTR is the major APA pattern that changes over time, and its genes are enriched in the pathways of protein and energy metabolism. Finally, we constructed mRNA-miRNA and PPI networks and detected several central miRNAs that may regulate L. vannamei development. Our results revealed the complex APA mechanisms in L. vannamei metamorphosis, shedding new light on post-transcriptional regulation of crustacean metamorphosis.
ROS-Induced Autophagy of Skeletal Muscle Confers Resistance of Rice Flower Carp (Cyprinus carpio) to Short-Term Fasting
Authors: Cheng Jia , Luo Junhan , Xu Ziyang , Liu Zhouying , Bao Lingsheng , Xue Liangyi
Published: June 2024

Starvation is one of the main stresses for fish due to food shortage, the evasion of predators, and intraspecific competition. This research evaluated the impact of brief fasting periods on reactive oxygen species (ROS) levels, antioxidant response, mRNA expression of antioxidants, autophagy-related signaling genes, and autophagosome development in the muscle tissue of rice flower carp. Following a three-day fasting period, the levels of ROS and MDA rose. Additionally, after 3 d of fasting, there was a notable upregulation of NRF2 and significant increases in the levels of GSH and the activities of enzymes such as SOD, CAT, GST, GR, and GPX, while the expression of the autophagy marker gene LC3B did not change (p < 0.05). After 7 d of fasting, the content of the ROS, the activity of SOD and GR, and the GSH content reached the maximum (p < 0.05). Concurrently, there was a significant rise in the quantity of autophagosomes. An RT-qPCR analysis revealed that seven d of starvation significantly elevated the mRNA expression of genes associated with the initiation and expansion of autophagosome membranes, vesicle recycling, and cargo recruitment, including ULK1, BECLIN1, LC3B, ATG3, ATG4B, ATG4C, ATG5, ATG9, and P62. After feeding resumed for 3 d, the mRNA level of BECLIN1, ATG3, ATG4B, ATG4C, ATG5, LC3B, and P62 still remained at a high level. The LC3II protein reached its highest level. All autophagy-related gene expression decreased in the 7-day resumed feeding group. Our data implied that short-term fasting can cause oxidative stress and disrupt the antioxidant system first and then induce autophagy in the muscles of rice flower carp. These findings shed light on how fasting affects muscle homeostasis in fish. ROS-induced autophagy of the skeletal muscle may confer the resistance of rice flower carp to short-term fasting.
The First Three Mitochondrial Genomes for the Characterization of the Genus Egeirotrioza (Hemiptera: Triozidae) and Phylogenetic Implications
Authors: Aishan Zhulidezi , Mu Ze-Lu , Li Zi-Cong , Luo Xin-Yu , Huangfu Ning
Published: June 2024

(1) Background: Mitochondrial genomes are important markers for the study of phylogenetics and systematics. Triozidae includes some primary pests of Populus euphratica. The phylogenetic relationships of this group remain controversial due to the lack of molecular data. (2) Methods: Mitochondria of Egeirotrioza Boselli were sequenced and assembled. We analyzed the sequence length, nucleotide composition, and evolutionary rate of Triozidae, combined with the 13 published mitochondrial genomes. (3) Results: The evolutionary rate of protein-coding genes was as follows: ATP8 > ND6 > ND5 > ND2 > ND4 > ND4L > ND1 > ND3 > APT6 > CYTB > COX3 > COX2 > COX1. We reconstructed the phylogenetic relationships of Triozidae based on 16 triozid mitochondrial genomes (thirteen ingroups and three outgroups) using the maximum likelihood (ML) and Bayesian inference (BI) approaches. The phylogenetic analysis of the 16 Triozidae mitochondrial genomes showed that Egeirotrioza was closely related to Leptynoptera. (4) Conclusions: We have identified 13 PCGs, 22 tRNAs, 2 rRNAs, and 1 control region (CR) of all newly sequenced mitochondrial genomes, which were the mitochondrial gene type in animals. The results of this study provide valuable genomic information for the study of psyllid species.
Association of LPP and ZMIZ1 Gene Polymorphism with Celiac Disease in Subjects from Punjab, Pakistan
Authors: Zulfiqar Sumaira , Fiaz Amna , Khan Waqas Ahmed , Hussain Misbah , Ali Ansar , Ahmed Nadeem , Ali Basharat , Masood Muhammad Adnan
Published: June 2024

Celiac disease (CD) is a complicated autoimmune disease that is caused by gluten sensitivity. It was commonly believed that CD only affected white Europeans, but recent findings show that it is also prevailing in some other racial groups, like South Asians, Caucasians, Africans, and Arabs. Genetics plays a profound role in increasing the risk of developing CD. Genetic Variations in non-HLA genes such as LPP, ZMIZ1, CCR3, and many more influence the risk of CD in various populations. This study aimed to explore the association between LPP rs1464510 and ZMIZ1 rs1250552 and CD in the Punjabi Pakistani population. For this, a total of 70 human subjects were selected and divided into healthy controls and patients. Genotyping was performed using an in-house-developed tetra-amplification refractory mutation system polymerase chain reaction. Statistical analysis revealed a significant association between LPP rs1464510 (χ2 = 4.421, p = 0.035) and ZMIZ1 rs1250552 (χ2 = 3.867, p = 0.049) and CD. Multinomial regression analysis showed that LPP rs1464510 A allele reduces the risk of CD by ~52% (OR 0.48, CI: 0.24–0.96, 0.037), while C allele-carrying subjects are at ~2.6 fold increased risk of CD (OR 3.65, CI: 1.25–10.63, 0.017). Similarly, the ZMIZ1 rs1250552 AG genotype significantly reduces the risk of CD by 73% (OR 0.26, CI: 0.077–0.867, p = 0.028). In summary, Genetic Variations in the LPP and ZMIZ1 genes influence the risk of CD in Punjabi Pakistani subjects. LPP rs1464510 A allele and ZMIZ1 AG genotype play a protective role and reduce the risk of CD.
The Paradigm Shift of Using Natural Molecules Extracted from Northern Canada to Combat Malaria
Authors: Bourgeois Alexandra , Lemos Juliana Aline Souza , Roucheray Stéphanie , Sergerie Audrey , Richard Dave
Published: June 2024

Parasitic diseases, such as malaria, are an immense burden to many low- and middle-income countries. In 2022, 249 million cases and 608,000 deaths were reported by the World Health Organization for malaria alone. Climate change, conflict, humanitarian crises, resource constraints and diverse biological challenges threaten progress in the elimination of malaria. Undeniably, the lack of a commercialized vaccine and the spread of drug-resistant parasites beg the need for novel approaches to treat this infectious disease. Most approaches for the development of antimalarials to date take inspiration from tropical or sub-tropical environments; however, it is necessary to expand our search. In this review, we highlight the origin of antimalarial treatments and propose new insights in the search for developing novel antiparasitic treatments. Plants and microorganisms living in harsh and cold environments, such as those found in the largely unexploited Northern Canadian boreal forest, often demonstrate interesting properties that are not found in other environments. Most prominently, the essential oil of Rhododendron tomentosum spp. Subarcticum from Nunavik and mortiamides isolated from Mortierella species found in Nunavut have shown promising activity against Plasmodium falciparum.
A Comprehensive Outlook on Pulmonary Alveolar Proteinosis—A Review
Authors: Wołoszczak Julia , Wrześniewska Martyna , Hrapkowicz Aleksandra , Janowska Kinga , Szydziak Joanna , Gomułka Krzysztof
Published: June 2024

Pulmonary alveolar proteinosis (PAP) is an ultra-rare disease caused by impaired pulmonary surfactant clearance due to the dysfunction of alveolar macrophages or their signaling pathways. PAP is categorized into autoimmune, congenital, and secondary PAP, with autoimmune PAP being the most prevalent. This article aims to present a comprehensive review of PAP classification, pathogenesis, clinical presentation, diagnostics, and treatment. The literature search was conducted using the PubMed database and a total of 67 articles were selected. The PAP diagnosis is usually based on clinical symptoms, radiological imaging, and bronchoalveolar lavage, with additional GM-CSF antibody tests. The gold standard for PAP treatment is whole-lung lavage. This review presents a summary of the most recent findings concerning pulmonary alveolar proteinosis, pointing out specific features that require further investigation.
Difficulties in the Diagnostics and Treatment of Hashimoto’s Encephalopathy—A Systematic and Critical Review
Authors: Pempera Nikola , Miedziaszczyk Miłosz , Lacka Katarzyna
Published: June 2024

Hashimoto’s encephalopathy (HE) has been a poorly understood disease. It has been described in all age group, yet, there is no specific HE marker. Additionally, the treatment data in the available studies are frequently divergent and contradictory. Therefore, the aim of our systematic and critical review is to evaluate the diagnosis and treatment of HE in view of the latest findings. The databases browsed comprised PubMed, Scopus, and Google Scholar as well as Cochrane Library, and the search strategy included controlled vocabulary and keywords. A total of 2443 manuscripts were found, published since the beginning of HE research until February 2024. In order to determine validity of the data collected from studies, bias assessment was performed using RoB 2 tool. Ultimately, six studies were included in our study. HE should be considered in the differential diagnosis in patients with psychiatric and neurological symptoms. According to our findings, negative thyroid peroxidase antibodies (anti-TPOs) may represent a valuable parameter in ruling out HE. Nonetheless, this result cannot be used to confirm HE. Furthermore, the proposed anti NH2-terminal-α-enolase (anti-NAE) is non-specific for HE. The effectiveness of glucocorticoid therapy is 60.94%, although relapse occurs in 31.67% of patients following the treatment. Our review emphasizes the significance of conducting further large-scale research and the need to take into account the potential genetic factor.
Cardiac Development and Factors Influencing the Development of Congenital Heart Defects (CHDs): Part I
Authors: Zubrzycki Marek , Schramm Rene , Costard-Jäckle Angelika , Grohmann Jochen , Gummert Jan F. , Zubrzycka Maria
Published: June 2024

The traditional description of cardiac development involves progression from a cardiac crescent to a linear heart tube, which in the phase of transformation into a mature heart forms a cardiac loop and is divided with the septa into individual cavities. Cardiac morphogenesis involves numerous types of cells originating outside the initial cardiac crescent, including neural crest cells, cells of the second heart field origin, and epicardial progenitor cells. The development of the fetal heart and circulatory system is subject to regulatation by both genetic and environmental processes. The etiology for cases with congenital heart defects (CHDs) is largely unknown, but several genetic anomalies, some maternal illnesses, and prenatal exposures to specific therapeutic and non-therapeutic drugs are generally accepted as risk factors. New techniques for studying heart development have revealed many aspects of cardiac morphogenesis that are important in the development of CHDs, in particular transposition of the great arteries.
Research Progress in the Regulation of the ABA Signaling Pathway by E3 Ubiquitin Ligases in Plants
Authors: Kou Hongyun , Zhang Xiaopei , Jia Jinghao , Xin Ming , Wang Jinhui , Mao Lili , Baltaevich Ahmedov Miraziz , Song Xianliang
Published: June 2024

E3 ubiquitin ligases (UBLs), as enzymes capable of specifically recognizing target proteins in the process of protein ubiquitination, play crucial roles in regulating responses to abiotic stresses such as drought, salt, and temperature. Abscisic acid (ABA), a plant endogenous hormone, is essential to regulating plant growth, development, disease resistance, and defense against abiotic stresses, and acts through a complex ABA signaling pathway. Hormone signaling transduction relies on protein regulation, and E3 ubiquitin ligases play important parts in regulating the ABA pathway. Therefore, this paper reviews the ubiquitin–proteasome-mediated protein degradation pathway, ABA-related signaling pathways, and the regulation of ABA-signaling-pathway-related genes by E3 ubiquitin ligases, aiming to provide references for further exploration of the relevant research on how plant E3 ubiquitin ligases regulate the ABA pathway.
Binding Affinity Determination in Drug Design: Insights from Lock and Key, Induced Fit, Conformational Selection, and Inhibitor Trapping Models
Authors: Spassov Danislav S.
Published: June 2024

Binding affinity is a fundamental parameter in drug design, describing the strength of the interaction between a molecule and its target protein. Accurately predicting binding affinity is crucial for the rapid development of novel therapeutics, the prioritization of promising candidates, and the optimization of their properties through rational design strategies. Binding affinity is determined by the mechanism of recognition between proteins and ligands. Various models, including the lock and key, induced fit, and conformational selection, have been proposed to explain this recognition process. However, current computational strategies to predict binding affinity, which are based on these models, have yet to produce satisfactory results. This article explores the connection between binding affinity and these protein-ligand interaction models, highlighting that they offer an incomplete picture of the mechanism governing binding affinity. Specifically, current models primarily center on the binding of the ligand and do not address its dissociation. In this context, the concept of ligand trapping is introduced, which models the mechanisms of dissociation. When combined with the current models, this concept can provide a unified theoretical framework that may allow for the accurate determination of the ligands’ binding affinity.
Response Plasticity of Drosophila Olfactory Sensory Neurons
Authors: Halty-deLeon Lorena , Pal Mahadevan Venkatesh , Wiesel Eric , Hansson Bill S. , Wicher Dieter
Published: June 2024

In insect olfaction, sensitization refers to the amplification of a weak olfactory signal when the stimulus is repeated within a specific time window. In the vinegar fly, Drosophila melanogaster, this occurs already at the periphery, at the level of olfactory sensory neurons (OSNs) located in the antenna. In our study, we investigate whether sensitization is a widespread property in a set of seven types of OSNs, as well as the mechanisms involved. First, we characterize and compare the differences in spontaneous activity, response velocity and response dynamics, among the selected OSN types. These express different receptors with distinct tuning properties and behavioral relevance. Second, we show that sensitization is not a general property. Among our selected OSN types, it occurs in those responding to more general food odors, while OSNs involved in very specific detection of highly specific ecological cues like pheromones and warning signals show no sensitization. Moreover, we show that mitochondria play an active role in sensitization by contributing to the increase in intracellular Ca2+ upon weak receptor activation. Thus, by using a combination of single sensillum recordings (SSRs), calcium imaging and pharmacology, we widen the understanding of how the olfactory signal is processed at the periphery.