bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved Model for Starch Prediction in Potato by the Fusion of Near-Infrared Spectral and Textural Data
Authors: Wang Fuxiang , Wang Chunguang
Published: October 2022

In this study, visible-near-infrared (VIS-NIR) hyperspectral imaging was combined with a data fusion strategy for the nondestructive assessment of the starch content in intact potatoes. Spectral and textural data were extracted from hyperspectral images and transformed principal component (PC) images, respectively, and a partial least squares regression (PLSR) prediction model was then established. The results revealed that low-level data fusion could not improve accuracy in predicting starch content. Therefore, to improve prediction accuracy, key variables were selected from the spectral and textural data through competitive adaptive reweighted sampling (CARS) and correlation analysis, respectively, and mid-level data fusion was performed. With a residual predictive deviation (RPD) value > 2, the established PLSR model achieved satisfactory prediction accuracy. Therefore, this study demonstrated that appropriate data fusion can effectively improve the prediction accuracy for starch content and thus aid the sorting of potato starch content in the production line.
Environment-Related Genes Analysis of Limosilactobacillus fermentum Isolated from Food and Human Gut: Genetic Diversity and Adaption Evolution
Authors: Zhao Yan , Yu Leilei , Tian Fengwei , Zhao Jianxin , Zhang Hao , Chen Wei , Xue Yuzheng , Zhai Qixiao
Published: October 2022

Limosilactobacillus fermentum is ubiquitous in traditional fermented vegetables, meat products, and the human gut. It is regarded as a “generally recognized as safe” organism by the US Food and Drug Administration. So far, the genetic features and evolutionary strategies of L. fermentum from the human gut and food remain unknown. In this study, comparative genomic analysis of 224 L. fermentum strains isolated from food and human gut (164 L. fermentum strains isolated from human gut was sequenced in our lab) was performed to access genetic diversity and explore genomic features associated with environment. A total of 20,505 gene families were contained by 224 L. fermentum strains and these strains separated mainly into six clades in phylogenetic tree connected with their origin. Food source L. fermentum strains carried more carbohydrate active enzyme genes (belonging to glycosyltransferase family 2, glycoside hydrolase family 43_11, and glycoside hydrolase family 68) compared with that of human gut and L. fermentum derived from food showed higher ability to degrade xylulose and ribose. Moreover, the number of genes encoding otr(A), tetA(46), lmrB, poxtA, and efrB were more abundant in food source L. fermentum, which was consistent with the number of CRISPR spacers and prophages in L. fermentum of food source. This study provides new insight into the adaption of L. fermentum to the food and intestinal tract of humans, suggesting that the genomic evolution of L. fermentum was to some extent driven by environmental stress.
Telling the Wave Function: An Electrical Analogy
Authors: Chiatti Leonardo
Published: October 2022

The double nature of material particles, i.e., their wave and corpuscular characteristics, is usually considered incomprehensible, as it cannot be represented visually. It is proposed to the student, in introductory courses, as a fact justified by quantum interference experiments for which, however, no further analysis is possible. On this note, we propose a description of the wave function in terms of a simple electrical analogy, which reproduces at least some of its essential properties. Our aim is to provide a cognitive representation of an analogical type: starting from a classical context (electrical circuits) and introducing in an appropriate way the notions of “wave” and “particle”, we show how typically quantum properties such as delocalization and entanglement emerge in a natural, understandable, and intuitive way.
Positive Solutions for Perturbed Fractional p-Laplacian Problems
Authors: Tao Mengfei , Zhang Binlin
Published: October 2022

In this article, we consider a class of quasilinear elliptic equations involving the fractional p-Laplacian, in which the nonlinear term satisfies subcritical or critical growth. Based on a fixed point result due to Carl and Heikkilä, we can well overcome the lack of compactness which has been a key difficulty for elliptic equations with critical growth. Moreover, we establish the existence and boundedness of the weak solutions for the above equations.
Mining Candidate Genes Related to Heavy Metals in Mature Melon (Cucumis melo L.) Peel and Pulp Using WGCNA
Authors: Shen Qi , Wu Xiaonan , Tao Yongxia , Yan Guorong , Wang Xian , Cao Shuangyu , Wang Cheng , He Weizhong
Published: October 2022

The content of metal ions in fruits is inseparable from plant intake of trace elements and health effects in the human body. To understand metal ion content in the fruit and pericarp of melon (Cucumis melo L.) and the candidate genes responsible for controlling this process, we analyzed the metal ion content in distinct parts of melon fruit and pericarp and performed RNA-seq. The results showed that the content of metal ions in melon fruit tissue was significantly higher than that in the pericarp. Based on transcriptome expression profiling, we found that the fruit and pericarp contained elevated levels of DEGs. GO functional annotations included cell surface receptor signaling, signal transduction, organic substance metabolism, carbohydrate derivative binding, and hormone-mediated signaling pathways. KEGG pathways included pectate lyase, pentose and glucuronate interconversions, H+-transporting ATPase, oxidative phosphorylation, plant hormone signal transduction, and MAPK signaling pathways. We also analyzed the expression patterns of genes and transcription factors involved in hormone biosynthesis and signal transduction. Using weighted gene co-expression network analysis (WGCNA), a co-expression network was constructed to identify a specific module that was significantly correlated with the content of metal ions in melon, after which the gene expression in the module was measured. Connectivity and qRT–PCR identified five candidate melon genes, LOC103501427, LOC103501539, LOC103503694, LOC103504124, and LOC107990281, associated with metal ion content. This study provides a theoretical basis for further understanding the molecular mechanism of heavy metal ion content in melon fruit and peel and provides new genetic resources for the study of heavy metal ion content in plant tissues.
The Crazy Biology
Authors: Monget Philippe
Published: October 2022

Since the end of the 1980s and the advent of molecular biology, then the beginning of the 2000s with the sequencing of whole genomes, modern tools have never ceased to amaze us and provide answers to questions that we didn’t even dare ask ourselves before: Why do elephants have fewer cancers than humans? Why do humans have such big brains? How does a eukaryotic cell recognize a “foreign” DNA sequence? Are there molecular crossroads of incompatible functions? Can cells count each other? These fascinating questions have made biology in recent years almost crazy.
Multidisciplinary Progress in Obesity Research
Authors: Lu Xiaoqing , Jin Yuxin , Li Dexin , Zhang Jingxin , Han Jingyan , Li Yin
Published: October 2022

Obesity is a chronic disease that endangers human health. In recent years, the phenomenon of obesity has become more and more common, and it has become a global epidemic. Obesity is closely associated with many adverse metabolic changes and diseases, such as insulin resistance, type 2 diabetes mellitus, coronary heart disease, nervous system diseases and some malignant tumors, which have caused a huge burden on the country’s medical finance. In most countries of the world, the incidence of cancer caused by obesity is increasing year on year. Diabetes associated with obesity can lead to secondary neuropathy. How to treat obesity and its secondary diseases has become an urgent problem for patients, doctors and society. This article will summarize the multidisciplinary research on obesity and its complications.
Ancient Components and Recent Expansion in the Eurasian Heartland: Insights into the Revised Phylogeny of Y-Chromosomes from Central Asia
Authors: Zhabagin Maxat , Wei Lan-Hai , Sabitov Zhaxylyk , Ma Peng-Cheng , Sun Jin , Dyussenova Zhanargul , Balanovska Elena , Li Hui , Ramankulov Yerlan
Published: October 2022

In the past two decades, studies of Y chromosomal single nucleotide polymorphisms (Y-SNPs) and short tandem repeats (Y-STRs) have shed light on the demographic history of Central Asia, the heartland of Eurasia. However, complex patterns of migration and admixture have complicated population genetic studies in Central Asia. Here, we sequenced and analyzed the Y-chromosomes of 187 male individuals from Kazakh, Kyrgyz, Uzbek, Karakalpak, Hazara, Karluk, Tajik, Uyghur, Dungan, and Turkmen populations. High diversity and admixture from peripheral areas of Eurasia were observed among the paternal gene pool of these populations. This general pattern can be largely attributed to the activities of ancient people in four periods, including the Neolithic farmers, Indo-Europeans, Turks, and Mongols. Most importantly, we detected the consistent expansion of many minor lineages over the past thousand years, which may correspond directly to the formation of modern populations in these regions. The newly discovered sub-lineages and variants provide a basis for further studies of the contributions of minor lineages to the formation of modern populations in Central Asia.
Characterization of the MADS-Box Gene Family in Akebia trifoliata and Their Evolutionary Events in Angiosperms
Authors: Zhong Shengfu , Yang Huai , Guan Ju , Shen Jinliang , Ren Tianheng , Li Zhi , Tan Feiquan , Li Qing , Luo Peigao
Published: October 2022

As the largest clade of modern plants, flower plants have evolved a wide variety of flowers and fruits. MADS-box genes play key roles in regulating plant morphogenesis, while basal eudicots have an evolutionarily important position of acting as an evolutionary bridge between basal angiosperms and core eudicots. Akebia trifoliata is an important member of the basal eudicot group. To study the early evolution of angiosperms, we identified and characterized the MADS-Box gene family on the whole-genome level of A. trifoliata. There were 47 MADS-box genes (13 type I and 34 type II genes) in the A. trifoliata genome; type I genes had a greater gene length and coefficient of variation and a smaller exon number than type II genes. A total of 27 (57.4%) experienced whole or segmental genome duplication and purifying selection. A transcriptome analysis suggested that three and eight genes were involved in whole fruit and seed development, respectively. The diversification and phylogenetic analysis of 1479 type II MADS-box genes of 22 angiosperm species provided some clues indicating that a γ whole genome triplication event of eudicots possibility experienced a two-step process. These results are valuable for improving A. trifoliata fruit traits and theoretically elucidating evolutionary processes of angiosperms, especially eudicots.
The Identification and Characterization of the KNOX Gene Family as an Active Regulator of Leaf Development in Trifolium repens
Authors: Fan Jinwan , Nie Gang , Ma Jieyu , Hu Ruchang , He Jie , Wu Feifei , Yang Zhongfu , Ma Sainan , Zhang Xin , Zhang Xinquan
Published: October 2022

Leaves are the primary and critical feed for herbivores. They directly determine the yield and quality of legume forage. Trifolium repens (T. repens) is an indispensable legume species, widely cultivated in temperate pastures due to its nutritional value and nitrogen fixation. Although the leaves of T. repens are typical trifoliate, they have unusual patterns to adapt to herbivore feeding. The number of leaflets in T. repens affects its production and utilization. The KNOX gene family encodes transcriptional regulators that are vital in regulating and developing leaves. Identification and characterization of TrKNOX gene family as an active regulator of leaf development in T. repens were studied. A total of 21 TrKNOX genes were identified from the T. repens genome database and classified into three subgroups (Class I, Class II, and Class M) based on phylogenetic analysis. Nineteen of the genes identified had four conserved domains, except for KNOX5 and KNOX9, which belong to Class M. Varying expression levels of TrKNOX genes were observed at different developmental stages and complexities of leaves. KNOX9 was observed to upregulate the leaf complexity of T. repens. Research on TrKNOX genes could be novel and further assist in exploring their functions and cultivating high-quality T. repens varieties.
The Genetic Diversity and the Divergence Time in Extant Primitive Mayfly, Siphluriscus chinensis Ulmer, 1920 Using the Mitochondrial Genome
Authors: Tong Yao , Shen Chen-Yang , Zhao Yu-Yang , Lin Yi-Jie , Wu Lian , Storey Kenneth B. , Yu Dan-Na , Zhang Jia-Yong
Published: October 2022

In this study, the mitochondrial (mt) genomes of Siphluriscus chinensis (Ephemeroptera: Siphluriscidae) were evaluated in specimens collected from two sites in China: Niutou Mountain, Zhejiang Province (S. chinensis NTS) and Leigong Mountain, Guizhou Province (S. chinensis LGS) and were successfully sequenced. The lengths of the mt genomes of S. chinensis NTS and S. chinensis LGS were 15,904 bp (ON729390) and 15,212 bp (ON729391), respectively. However, an in-depth comparison of the two mt genomes showed significant differences between the specimens collected from the two sites. A detailed analysis of the genetic distance between S. chinensis NTS and S. chinensis LGS was undertaken to further achieve an accurate delimitation of S. chinensis. The genetic distance between S. chinensis NTS and the other three species within Siphluriscidae was a high value, above 12.2%. The two mt genomes were used to reconstruct phylogenetic relationships and estimate divergence time. The results demonstrated robust differences between S. chinensis NTS and S. chinensis LGS, which revealed that a kind of cryptic species existed. Maximum likelihood (ML) and Bayesian inference (BI) analyses produced well-supported phylogenetic trees that showed evolutionary relationships between Siphluriscidae (((S. chinensis HQ875717 + S. chinensis MF352165) + S. chinensis LGS) + S. chinensis NTS). The most recent common ancestor (MRCA) of four species within Siphluriscidae began to diversify during the Neogene [11.80 million years ago (Mya); 95% highest posterior densities (HPD) = 6.17–19.28 Mya], and S. chinensis NTS was first to diverge from the branches of S. chinensis LGS. In short, based on mitochondrial genomes, our results showed that the specimens collected from Leigong Mountain, Guizhou Province (S. chinensis LGS) belonged to S. chinensis, and the specimens collected from Niutou Mountain, Zhejiang Province (S. chinensis NTS) were a cryptic species of S. chinensis.
Integrated Bioinformatics Analysis Reveals Novel miRNA as Biomarkers Associated with Preeclampsia
Authors: Brancaccio Mariarita , Giachino Caterina , Iazzetta Assunta Maria , Cordone Antonio , De Marino Elena , Affinito Ornella , Vivo Maria , Calabrò Viola , Pollice Alessandra , Angrisano Tiziana
Published: October 2022

Preeclampsia is a leading cause of perinatal maternal-foetal mortality and morbidity. This study aims to identify the key microRNAs (miRNA) in preeclampsia and uncover their potential functions. We downloaded the miRNA expression profile of GSE119799 for plasma and GSE177049 for the placenta. Each dataset consisted of five patients (PE) and five controls (N). From a technical point of view, we analysed the counts per million (CPM) for both datasets, highlighting 358 miRNAs in common, 78 unique for plasma and 298 unique for placenta. At the same time, we performed an expression differential analysis (|logFC| ≥ 1|and FDR ≤ 0.05) to evaluate the biological impact of the miRNAs. This approach allowed us to highlight 321 miRNAs in common between plasma and placenta, within which four were upregulated in plasma. Furthermore, the same analysis revealed five miRNAs expressed exclusively in plasma; these were also upregulated. In conclusion, the in-depth bioinformatics analysis conducted during our study will allow us, on the one hand, to verify the targets of each of the nine identified miRNAs; on the other hand, to use them both as new non-invasive biomarkers and as therapeutic targets for the development of personalised treatments.
Optimization of Oxford Nanopore Technology Sequencing Workflow for Detection of Amplicons in Real Time Using ONT-DART Tool
Authors: Player Robert , Verratti Kathleen , Staab Andrea , Forsyth Ellen , Ernlund Amanda , Joshi Mihir S. , Dunning Rebecca , Rozak David , Grady Sarah , Goodwin Bruce , Sozhamannan Shanmuga
Published: October 2022

An optimized, well-tested and validated targeted genomic sequencing-based high-throughput assay is currently not available ready for routine biodefense and biosurveillance applications. Earlier, we addressed this gap by developing and establishing baseline comparisons of a multiplex end-point Polymerase Chain Reaction (PCR) assay followed by Oxford Nanopore Technology (ONT) based amplicon sequencing to real time PCR and customized data processing. Here, we expand upon this effort by identifying the optimal ONT library preparation method for integration into a novel software platform ONT-DART (ONT-Detection of Amplicons in Real-Time). ONT-DART is a dockerized, real-time, amplicon-sequence analysis workflow that is used to reproducibly process and filter read data to support actionable amplicon detection calls based on alignment metrics, within sample statistics, and no-template control data. This analysis pipeline was used to compare four ONT library preparation protocols using R9 and Flongle (FL) flow cells. The two 4-Primer methods tested required the shortest preparation times (5.5 and 6.5 h) for 48 libraries but provided lower fidelity data. The Native Barcoding and Ligation methods required longer preparation times of 8 and 12 h, respectively, and resulted in higher overall data quality. On average, data derived from R9 flow cells produced true positive calls for target organisms more than twice as fast as the lower throughput FL flow cells. These results suggest that utilizing the R9 flowcell with an ONT Native Barcoding amplicon library method in combination with ONT-DART platform analytics provides the best sequencing-based alternative to current PCR-based biodetection methods.
Bioinformatics and Experimental Analyses Reveal MAP4K4 as a Potential Marker for Gastric Cancer
Authors: Zhang Junping , Cai Xiaoping , Cui Weifeng , Wei Zheng
Published: October 2022

Background: Gastric cancer remains the most prevalent and highly lethal disease worldwide. MAP4K4, a member of Ste20, plays an important role in various pathologies, including cancer. However, its role in gastric cancer is not yet fully elucidated. Therefore, this study aims to determine the tumor-promoting role of MAP4K4 in gastric cancer and whether it can be used as a new and reliable biomarker to predict the prognosis of gastric cancer. For this purpose, we divide the samples into high- and low-expression groups according to the expression level of MAP4K4. The association of MAP4K4 expression with prognosis is assessed using the Kaplan–Meier survival analysis. Furthermore, immune infiltration analysis using ESTIMATE is conducted to evaluate the tumor immune scores of the samples. Results: The findings reveal a significantly higher expression of MAP4K4 in tumor samples than in adjacent samples. The high-expression group was significantly enriched in tumor-related pathways, such as the PI3K-Akt signaling pathway. In addition, immune infiltration analysis revealed a positive correlation between immune scores and MAP4K4 expression. We also observed that miRNAs, such as miR-192-3p (R = −0.317, p-value 3.111 × 10−9), miR-33b-5p (R= −0.238, p-value 1.166 × 10−5), and miR-582-3p (R = −0.214, p-value 8.430 × 10−5), had potential negative regulatory effects on MAP4K4. Moreover, we identified several transcription factors, ubiquitinated proteins, and interacting proteins that might regulate MAP4K4. The relationship between MAP4K4 and DNA methylation was also identified. Finally, we verified the high expression of MAP4K4 and its effect on promoting cancer. Conclusion: MAP4K4 might be closely related to gastric cancer’s progression, invasion, and metastasis. Its high expression negatively impacts the prognosis of gastric cancer patients. This suggests MAP4K4 as an important prognostic factor for gastric cancer and could be regarded as a new potential prognostic detection and therapeutic target.
A Rearrangement of the Mitochondrial Genes of Centipedes (Arthropoda, Myriapoda) with a Phylogenetic Analysis
Authors: Wang Jia-Jia , Bai Yu , Dong Yan
Published: October 2022

Due to the limitations of taxon sampling and differences in results from the available data, the phylogenetic relationships of the Myriapoda remain contentious. Therefore, we try to reconstruct and analyze the phylogenetic relationships within the Myriapoda by examining mitochondrial genomes (the mitogenome). In this study, typical circular mitogenomes of Mecistocephalus marmoratus and Scolopendra subspinipes were sequenced by Sanger sequencing; they were 15,279 bp and 14,637 bp in length, respectively, and a control region and 37 typical mitochondrial genes were annotated in the sequences. The results showed that all 13 PCGs started with ATN codons and ended with TAR codons or a single T; what is interesting is that the gene orders of M. marmoratus have been extensively rearranged compared with most Myriapoda. Thus, we propose a simple duplication/loss model to explain the extensively rearranged genes of M. marmoratus, hoping to provide insights into mitogenome rearrangement events in Myriapoda. In addition, our mitogenomic phylogenetic analyses showed that the main myriapod groups are monophyletic and supported the combination of the Pauropoda and Diplopoda to form the Dignatha. Within the Chilopoda, we suggest that Scutigeromorpha is a sister group to the Lithobiomorpha, Geophilomorpha, and Scolopendromorpha. We also identified a close relationship between the Lithobiomorpha and Geophilomorpha. The results also indicate that the mitogenome can be used as an effective mechanism to understand the phylogenetic relationships within Myriapoda.
Cistanche Species Mitogenomes Suggest Diversity and Complexity in Lamiales-Order Mitogenomes
Authors: Miao Yujing , Chen Haimei , Xu Wanqi , Liu Chang , Huang Linfang
Published: October 2022

The extreme diversity and complexity of angiosperms is well known. Despite the fact that parasitic plants are angiosperms, little is known about parasitic plant mitogenomic diversity, complexity, and evolution. In this study, we obtained and characterized the mitogenomes of three Cistanche species (holoparasitic plants) from China to compare the repeats, segment duplication and multi-copy protein-coding genes (PCGs), to clarify the phylogenetic and evolution relationship within the Lamiales order, and to identify the mitochondrial plastid insertions (MTPT) in Cistanche mitogenomes. The results showed that the mitogenome sizes of the three Cistanche species ranged from 1,708,661 to 3,978,341 bp. The Cistanche species genome encodes 75–126 genes, including 37–65 PCGs, 31–58 tRNA genes and 3–5 rRNA genes. Compared with other Lamiales and parasitic species, the Cistanche species showed extremely high rates of multi-copy PCGs, ranging from 0.13 to 0.58 percent of the total number of PCGs. In addition, 37–133 Simple Sequence Repeat (SSRs) were found in these three mitogenomes, the majority of which were the mononucleotides Adenine/Thymine. The interspersed repeats contained forward and palindromic repeats. Furthermore, the segment-duplication sequence size ranged from 199,584 to 2,142,551 bp, accounting for 24.9%, 11.7% and 53.9% of the Cistanche deserticola, Cistanche salsa and Cistanche tubulosa mitogenome, respectively. Furthermore, the Ka/Ks analysis suggested that the atp4, ccmB, ccmFc and matR were probably positively selected during Lamiales evolution. The Cistanche plastome suggested the presence of MTPT. Moreover, 6–12 tRNA, 9–15 PCGs fragments and 3 rRNA gene fragments in the Cistanche mitogenomes were found in the MTPT regions. This work reports the Cistanche species mitogenome for the first time, which will be invaluable for study the mitogenome evolution of Orobanchaceae family.
Profiling Genome-Wide DNA Methylation in Children with Autism Spectrum Disorder and in Children with Fragile X Syndrome
Authors: Jasoliya Mittal , Gu Jianlei , AlOlaby Reem R. , Durbin-Johnson Blythe , Chedin Frederic , Tassone Flora
Published: October 2022

Autism spectrum disorder (ASD) is an early onset, developmental disorder whose genetic cause is heterogeneous and complex. In total, 70% of ASD cases are due to an unknown etiology. Among the monogenic causes of ASD, fragile X syndrome (FXS) accounts for 2–4% of ASD cases, and 60% of individuals with FXS present with ASD. Epigenetic changes, specifically DNA methylation, which modulates gene expression levels, play a significant role in the pathogenesis of both disorders. Thus, in this study, using the Human Methylation EPIC Bead Chip, we examined the global DNA methylation profiles of biological samples derived from 57 age-matched male participants (2–6 years old), including 23 subjects with ASD, 23 subjects with FXS with ASD (FXSA) and 11 typical developing (TD) children. After controlling for technical variation and white blood cell composition, using the conservatory threshold of the false discovery rate (FDR ≤ 0.05), in the three comparison groups, TD vs. AD, TD vs. FXSA and ASD vs. FXSA, we identified 156, 79 and 3100 differentially methylated sites (DMS), and 14, 13 and 263 differential methylation regions (DMRs). Interestingly, several genes differentially methylated among the three groups were among those listed in the SFARI Gene database, including the PAK2, GTF2I and FOXP1 genes important for brain development. Further, enrichment analyses identified pathways involved in several functions, including synaptic plasticity. Our preliminary study identified a significant role of altered DNA methylation in the pathology of ASD and FXS, suggesting that the characterization of a DNA methylation signature may help to unravel the pathogenicity of FXS and ASD and may help the development of an improved diagnostic classification of children with ASD and FXSA. In addition, it may pave the way for developing therapeutic interventions that could reverse the altered methylome profile in children with neurodevelopmental disorders.
Robust Genetic Analysis of the X-Linked Anophthalmic (Ie) Mouse
Authors: Hernandez-Moran Brianda A. , Papanastasiou Andrew S. , Parry David , Meynert Alison , Gautier Philippe , Grimes Graeme , Adams Ian R. , Trejo-Reveles Violeta , Bengani Hemant , Keighren Margaret , Jackson Ian J. , Adams David J. , FitzPatrick David R. , Rainger Joe
Published: October 2022

Anophthalmia (missing eye) describes a failure of early embryonic ocular development. Mutations in a relatively small set of genes account for 75% of bilateral anophthalmia cases, yet 25% of families currently are left without a molecular diagnosis. Here, we report our experimental work that aimed to uncover the developmental and genetic basis of the anophthalmia characterising the X-linked Ie (eye-ear reduction) X-ray-induced allele in mouse that was first identified in 1947. Histological analysis of the embryonic phenotype showed failure of normal eye development after the optic vesicle stage with particularly severe malformation of the ventral retina. Linkage analysis mapped this mutation to a ~6 Mb region on the X chromosome. Short- and long-read whole-genome sequencing (WGS) of affected and unaffected male littermates confirmed the Ie linkage but identified no plausible causative variants or structural rearrangements. These analyses did reduce the critical candidate interval and revealed evidence of multiple variants within the ancestral DNA, although none were found that altered coding sequences or that were unique to Ie. To investigate early embryonic events at a genetic level, we then generated mouse ES cells derived from male Ie embryos and wild type littermates. RNA-seq and accessible chromatin sequencing (ATAC-seq) data generated from cultured optic vesicle organoids did not reveal any large differences in gene expression or accessibility of putative cis-regulatory elements between Ie and wild type. However, an unbiased TF-footprinting analysis of accessible chromatin regions did provide evidence of a genome-wide reduction in binding of transcription factors associated with ventral eye development in Ie, and evidence of an increase in binding of the Zic-family of transcription factors, including Zic3, which is located within the Ie-refined critical interval. We conclude that the refined Ie critical region at chrX: 56,145,000–58,385,000 contains multiple genetic variants that may be linked to altered cis regulation but does not contain a convincing causative mutation. Changes in the binding of key transcription factors to chromatin causing altered gene expression during development, possibly through a subtle mis-regulation of Zic3, presents a plausible cause for the anophthalmia phenotype observed in Ie, but further work is required to determine the precise causative allele and its genetic mechanism.
Evolutionary Divergence between Toona ciliata and Toona sinensis Assayed with Their Whole Genome Sequences
Authors: Wang Xi , Xiao Yu , He Zi-Han , Li Ling-Ling , Lv Yan-Wen , Hu Xin-Sheng
Published: October 2022

Toona ciliata and Toona sinensis belong to the Toona genus of the Meliaceae family and are important timber species in China. T. ciliata is an endangered species at level II due to overcutting and a low rate of natural regeneration. T. sinensis was cultivated as an economic and nutritious tree for more than 2000 years. The two species differ in flower and leaf morphological traits, reproductive systems, and range size of natural distribution. To reveal the potential molecular basis of these divergences, we examined the similarities and differences in their whole genome sequences. Results indicate that T. ciliata had a higher number of expanded gene families than T. sinensis. The whole genome duplication (WGD) occurred before their speciation. The long-terminal repeats (LTRs) insertion was earlier in the T. ciliata genome (3.2985 ± 2.5007 Mya) than in the T. sinensis genome (3.1516 ± 2.2097 Mya). Twenty-five gene families in the T. ciliata genome were detected to be under positive selection compared with background branches of ten different land species. The T. ciliata genome was highly collinear with the T. sinensis genome, but had low collinearity with the genomes of more distant species. These genomic and evolutionary divergences are potentially associated with the differences between T. ciliata and T. sinensis in terms of their reproductive systems and ecological adaptation.
Influence of Parent-of-Origin on Intellectual Outcomes in the Chromosome 22q11.2 Deletion Syndrome
Authors: McGinn Daniel E. , Crowley T. Blaine , Heung Tracy , Tran Oanh , Moss Edward , Zackai Elaine H. , Emanuel Beverly S. , Chow Eva W. C. , Morrow Bernice E. , Swillen Ann , Bassett Anne S. , McDonald-McGinn Donna M.
Published: October 2022

Learning and intellectual disabilities are hallmark features of 22q11.2 deletion syndrome. Data are limited, however, regarding influences on full-scale IQ (FSIQ). Here, we investigated possible 22q11.2 deletion parent-of-origin effects. In 535 individuals, we compared FSIQ (≥50), 481 with de novo and 54 with inherited 22q11.2 deletions. In the subsets with data available, we examined parent-of-origin effects on FSIQ. We used linear regression models to account for covariates. Median FSIQ was significantly higher in de novo vs. inherited deletions (77; range 50–116 vs. 67; range 50–96, p < 0.0001). Results remained significant using a regression model accounting for age at IQ testing, sex and cohort site. No significant parent-of-origin differences in FSIQ were observed for de novo deletions (n = 81, 63.0% maternal; p = 0.6882). However, median FSIQ was significantly lower in maternally than in paternally inherited familial deletions (65, range 50–86 vs. 71.5, range 58–96, respectively, p = 0.0350), with the regression model indicating an ~8 point decrement in FSIQ for this variable (p = 0.0061). FSIQ is higher on average in de novo than in inherited 22q11.2 deletions, regardless of parental origin. However, parent-of-origin appears relevant in inherited deletions. The results have potential clinical implications with further research needed to delineate possible actionable mechanisms.
Research on Werner Syndrome: Trends from Past to Present and Future Prospects
Authors: Tsuge Kyoshiro , Shimamoto Akira
Published: October 2022

A rare and autosomal recessive premature aging disorder, Werner syndrome (WS) is characterized by the early onset of aging-associated diseases, including shortening stature, alopecia, bilateral cataracts, skin ulcers, diabetes, osteoporosis, arteriosclerosis, and chromosomal instability, as well as cancer predisposition. WRN, the gene responsible for WS, encodes DNA helicase with a 3′ to 5′ exonuclease activity, and numerous studies have revealed that WRN helicase is involved in the maintenance of chromosome stability through actions in DNA, e.g., DNA replication, repair, recombination, and epigenetic regulation via interaction with DNA repair factors, telomere-binding proteins, histone modification enzymes, and other DNA metabolic factors. However, although these efforts have elucidated the cellular functions of the helicase in cell lines, they have not been linked to the treatment of the disease. Life expectancy has improved for WS patients over the past three decades, and it is hoped that a fundamental treatment for the disease will be developed. Disease-specific induced pluripotent stem (iPS) cells have been established, and these are expected to be used in drug discovery and regenerative medicine for WS patients. In this article, we review trends in research to date and present some perspectives on WS research with regard to the application of pluripotent stem cells. Furthermore, the elucidation of disease mechanisms and drug discovery utilizing the vast amount of scientific data accumulated to date will be discussed.
Effects of Exogenous (K+) Potassium Application on Plant Hormones in the Roots of Tamarix ramosissima under NaCl Stress
Authors: Chen Yahui , Zhang Shiyang , Du Shanfeng , Wang Guangyu , Zhang Jinchi , Jiang Jiang
Published: October 2022

Abiotic stresses such as salt stress seriously affect the growth and yield of plants. Tamarix ramosissima Lcdcb (T. ramosissima) is a widely cultivated halophyte in saline-alkali areas of the world. As an essential element for plant growth and development, K+ plays an irreplaceable role in improving the tolerance of plants to salt stress. However, there are few reports on the mechanism of K+ in promoting plant hormones to reduce the damage of NaCl stress to T. ramosissima. In this study, we sequenced the transcriptome of the roots of T. ramosissima which were treated with exogenous potassium (K+) for 0 h, 48 h and 168 h under NaCl stress, according to the changes in the expression levels of differentially expressed genes (DEGs) in T. ramosissima roots. Key candidate genes and metabolic pathways related to plant hormones were mined for analysis and further verified by quantitative real-time PCR (qRT-PCR). The results showed that under NaCl stress for 48 h and 168 h, there were a large number of DEGs in the roots of T. ramosissima, and the expression levels changed over time. In particular, we found that 56 plant hormone-related genes were annotated to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and with the increase of time, their expression levels were mainly up-regulated and involved in the related metabolic pathways to resist NaCl stress. It is worth noting that 7 DEGs related to abscisic acid (ABA), 28 DEGs related to auxin, 1 DEG related to ethylene (ET), and 1 DEG related to cytokinin (CK) were added within 168 h of exogenous potassium, and they were involved in alleviating the root damage of T. ramosissima under NaCl stress and played an important role. In addition, we found the plant hormone signal transduction pathway, which plays an important role in resistance to NaCl stress. As a result of this study, the molecular mechanism of plant hormones involved in applying exogenous potassium under NaCl stress is further understood, resulting in a better understanding of how exogenous potassium can alleviate the damage caused by NaCl under stress in T. ramosissima.
Participant Choice towards Receiving Potential Additional Findings in an Australian Nephrology Research Genomics Study
Authors: O’Shea Rosie , Wood Alasdair , Patel Chirag , McCarthy Hugh J. , Mallawaarachchi Amali , Quinlan Catherine , Simons Cas , Stark Zornitza , Mallett Andrew J.
Published: October 2022

The choices of participants in nephrology research genomics studies about receiving additional findings (AFs) are unclear as are participant factors that might influence those choices. Methods: Participant choices and factors potentially impacting decisions about AFs were examined in an Australian study applying research genomic testing following uninformative diagnostic genetic testing for suspected monogenic kidney disease. Results: 93% of participants (195/210) chose to receive potential AFs. There were no statistically significant differences between those consenting to receive AFs or not in terms of gender (p = 0.97), median age (p = 0.56), being personally affected by the inherited kidney disease of interest (p = 0.38), or by the inheritance pattern (p = 0.12–0.19). Participants were more likely to choose not to receive AFs if the family proband presented in adulthood (p = 0.01), if there was family history of another genetic disorder (p = 0.01), and where the consent process was undertaken by an adult nephrologist (p = 0.01). Conclusion: The majority of participants in this nephrology research genomics study chose to receive potential AFs. Younger age of the family proband, family history of an alternate genetic disorder, and consenting by some multidisciplinary team members might impact upon participant choices.
Development of SNP Markers from GWAS for Selecting Seed Coat and Aleurone Layers in Brown Rice (Oryza sativa L.)
Authors: Kim Me-Sun , Ko Seo-Rin , Le Van Trang , Jee Moo-Gun , Jung Yu Jin , Kang Kwon-Kyoo , Cho Yong-Gu
Published: October 2022

Ninety-five percent of the general nutrients in rice are concentrated in the rice bran and germ, and many nutrients such as vitamins, minerals, dietary fiber, and essential fatty acids, as well as antioxidants such as tocopherol, are lost during milling. In this study, we investigated the thickness of seed coat and aleurone layers using a 294 rice core collection, and found candidate genes related to thickness of seed coat and aleurone layers, by performing a genome wide association study (GWAS) analysis using whole genome resequencing data. Two primer pairs that can be used as high-resolution melting (HRM) markers were developed. As a result of genotyping BC2F2 individuals derived from a cross between “Samgwang” and “Seolgaeng”, and using corresponding HRM markers, it was possible to finally develop HRM markers for selecting seed coat and aleurone layer thickness. This is expected to be used as basic data for the application of gene editing using CRISPR/Cas9 technology and for establishing a breeding strategy for high eating quality rice using molecular genetic technology.
Genome Wide Association Study with Imputed Whole Genome Sequence Data Identifies a 431 kb Risk Haplotype on CFA18 for Congenital Laryngeal Paralysis in Alaskan Sled Dogs
Authors: Srikanth Krishnamoorthy , von Pfeil Dirsko J. F. , Stanley Bryden J. , Griffitts Caroline , Huson Heather J.
Published: October 2022

Congenital laryngeal paralysis (CLP) is an inherited disorder that affects the ability of the dog to exercise and precludes it from functioning as a working sled dog. Though CLP is known to occur in Alaskan sled dogs (ASDs) since 1986, the genetic mutation underlying the disease has not been reported. Using a genome-wide association study (GWAS), we identified a 708 kb region on CFA 18 harboring 226 SNPs to be significantly associated with CLP. The significant SNPs explained 47.06% of the heritability of CLP. We narrowed the region to 431 kb through autozygosity mapping and found 18 of the 20 cases to be homozygous for the risk haplotype. Whole genome sequencing of two cases and a control ASD, and comparison with the genome of 657 dogs from various breeds, confirmed the homozygous status of the risk haplotype to be unique to the CLP cases. Most of the dogs that were homozygous for the risk allele had blue eyes. Gene annotation and a gene-based association study showed that the risk haplotype encompasses genes implicated in developmental and neurodegenerative disorders. Pathway analysis showed enrichment of glycoproteins and glycosaminoglycans biosynthesis, which play a key role in repairing damaged nerves. In conclusion, our results suggest an important role for the identified candidate region in CLP.
Clinical Course, Genetic, and Immunohistochemical Characterization of Solid Pseudopapillary Tumor of the Pancreas (Frantz Tumors) in a Brazilian Cohort
Authors: Tostes Francinne T. , de Carvalho Parisina Fraga Dutra Cabral , Araújo Raphael L. C. , Ribeiro Rodrigo Chaves , Apodaca-Torrez Franz Robert , Lobo Edson José , Gomes Diogo Bugano Diniz , Callegaro-Filho Donato , Schvartsman Gustavo , Moura Fernando , Schraibman Vladimir , Goldenberg Alberto , de Lima Fernanda Teresa , Segatelli Vanderlei , Uson Junior Pedro Luiz Serrano
Published: October 2022

Frantz tumors or solid pseudopapillary pancreatic neoplasm (SPN) are rare exocrine neoplasms that carry a favorable prognosis; they represent up to 3% of all tumors located in the region of the pancreas and have specific age and gender predispositions. In recent years, the rising curve of diagnosis is entitled to the evolution and access of diagnostic imaging. In this paper, we have retrospectively reviewed and described the clinical course of 40 patients with SPN from three institutions in Brazil, who had their diagnosis between 2005 and 2020, and analyzed the clinicopathological, genetic, and surgical aspects of these individuals. In accordance with the literature, most patients were women, 60% with unspecified symptoms at diagnosis, with tumors mainly located in the body and tail of the pancreas, of whom 70% underwent a distal pancreatectomy with sparing splenectomy as a standard procedure, and none of the cases have experienced recurrence to date. Surgery still remains the mainstay of treatment given the low metastatic potential, but more conservative approaches as observed in this cohort are evolving to become the standard of care. Herein, we present an in-depth analysis of cases focusing on the latest literature and report some of the smallest tumor cases in the literature. To our knowledge, this is the first report evaluating germline genetic testing and presenting a case of detected Li-Fraumeni syndrome.
Basement-Membrane-Related Gene Signature Predicts Prognosis in WHO Grade II/III Gliomas
Authors: Zhang Zhaogang , Lai Guichuan , Sun Lingling
Published: October 2022

Gliomas that are classified as grade II or grade III lesions by the World Health Organization (WHO) are highly aggressive, and some may develop into glioblastomas within a short period, thus portending the conferral of a poor prognosis for patients. Previous studies have implicated basement membrane (BM)-related genes in glioma development. In this study, we constructed a prognostic model for WHO grade II/III gliomas in accordance with the risk scores of BM-related genes. Differentially expressed genes (DEGs) in the glioma samples relative to normal samples were screened from the GEO database, and five prognostically relevant BM-related genes, including NELL2, UNC5A, TNC, CSPG4, and SMOC1, were selected using Cox regression analyses for the risk score model. The median risk score was calculated, based on which high- and low-risk groups of patients were generated. The clinical information, pathological information, and risk group were combined to establish a prognostic nomogram. Both the nomogram and risk score model performed well in the independent CGGA cohort. Gene set enrichment analysis (GSEA) and immune profile, drug sensitivity, and tumor mutation burden (TMB) analyses were performed in the two risk groups. A significant enrichment of ‘Autophagy–other’, ‘Collecting duct acid secretion’, ‘Glycosphingolipid biosynthesis–lacto and neolacto series’, ‘Valine, leucine, and isoleucine degradation’, ‘Vibrio cholerae infection’, and other pathways were observed for patients with high risk. In addition, higher proportions of monocytes and resting CD4 memory T cells were observed in the low- and high-risk groups, respectively. In conclusion, the BM-related gene risk score model can guide the clinical management of WHO grade II and III gliomas.
Expression Activity of Artificial Promoters for Disease Resistance in Transgenic Eucalyptus urophylla
Authors: Huang Zhenchi , Xu Qingchun , Fang Xiaolan , Wu Zhihua
Published: October 2022

The transcriptional properties of artificial promoters are closely related to the type and arrangement position of cis-elements. GWSF (374-bp) was an effective SPIP with four cis-element dimers. There were four pathogen-inducible cis-elements in the GWSF promoter (GST1-boxes, W-boxes, S-boxes, and F-boxes) and a minimal cauliflower mosaic virus 35S promoter. V-element dimers were inserted into the upstream (VGWSF), midstream (GWVSF), and downstream (GWSFV) regions of the original GWSF promoter sequence to examine their affect on the position. The expression activity of promoters was analyzed and estimated using the histochemical staining of leaf discs of eucalyptus with transient expression, an image digitization method to extract the color features, and the induction treatment by a plant pathogenic microorganism/inducer and qPCR assays. The histochemical staining results of the adventitious buds indicated that the promoters had been successfully integrated into the E. urophylla genome and that they drove the expression of the gus gene. There was a noticeable difference in the intensity of color between the adventitious buds on the same callus block, as well as the intensity of color within the same adventitious bud. According to the established two-factor model of blue value, there was a greater difference between the levels of the genotype factor than the promoter factor in eucalyptus leaf discs. Further, the basal and inducible transcriptional levels of the three improved promoters were investigated by qPCR. With the basal transcriptional level of the GWSF promoter normalized to one, the relative basal levels of VGWSF, GWVSF, and GWSFV were 1.40, 1.45, and 4.15, respectively. The qPCR results were consistent with the staining results of GUS histochemical staining. The three improved promoters all had the properties of being induced by salicylic acid, Ralstonia solanacearum, and Phytophthora capsici. The three improved promoters demonstrated a significantly higher TMV induction activity: their induction activity from high to low was GWSFV > GWVSF > VGWSF. The findings will be beneficial to the construction and optimization of artificial promoters for transgenic plants.