Miracle-dz/UniFAR-FTUs huggingface dataset:
RADseq as a valuable tool for plants with large genomes—A case study in cycads

Full genome sequencing of organisms with large and complex genomes is intractable and cost ineffective under most research budgets. Cycads (Cycadales) represent one of the oldest lineages of the extant seed plants and, partly due to their age, have incredibly large genomes up to ~60 Gbp. Restriction site‐associated DNA sequencing (RADseq) offers an approach to find genome‐wide informative markers and has proven to be effective with both model and nonmodel organisms. We tested the application of RADseq using ezRAD across all 10 genera of the Cycadales including an example data set of Cycas calcicola representing 72 samples from natural populations. Using previously available plastid and mitochondrial genomes as references, reads were mapped recovering plastid and mitochondrial genome regions and nuclear markers for all of the genera. De novo assembly generated up to 138,407 high‐depth clusters and up to 1,705 phylogenetically informative loci for the genera, and 4,421 loci for the example assembly of C. calcicola. The number of loci recovered by de novo assembly was lower than previous RADseq studies, yet still sufficient for downstream analysis. However, the number of markers could be increased by relaxing our assembly parameters, especially for the C. calcicola data set. Our results demonstrate the successful application of RADseq across the Cycadales to generate a large number of markers for all genomic compartments, despite the large number of plastids present in a typical plant cell. Our modified protocol was adapted to be applied to cycads and other organisms with large genomes to yield many informative genome‐wide markers.
Cholesterol lowering attenuates pressure overload-induced heart failure in mice with mild hypercholesterolemia

Epidemiological studies support a strong association between non-high-density lipoprotein cholesterol levels and heart failure incidence. The objective of the current study was to evaluate the effect of selective cholesterol lowering adeno-associated viral serotype 8 (AAV8)-mediated low-density lipoprotein receptor (LDLr) gene transfer on cardiac remodelling and myocardial oxidative stress following transverse aortic constriction (TAC) in female C57BL/6 LDLr-/- mice with mild hypercholesterolemia. Cholesterol lowering gene transfer resulted in a 65.9% (p<0.0001) reduction of plasma cholesterol levels (51.2 ± 2.2 mg/dl) compared to controls (150 ± 7 mg/dl). Left ventricular wall area was 11.2% (p<0.05) lower in AAV8-LDLr TAC mice than in control TAC mice. In agreement, pro-hypertrophic myocardial proteins were potently decreased in AAV8-LDLr TAC mice. The degree of interstitial fibrosis and perivascular fibrosis was 31.0% (p<0.001) and 29.8% (p<0.001) lower, respectively, in AAV8-LDLr TAC mice compared to control TAC mice. These structural differences were associated with improved systolic and diastolic function and decreased lung congestion in AAV8-LDLr TAC mice compared to control TAC mice. Cholesterol lowering gene therapy counteracted myocardial oxidative stress and preserved the potential for myocardial fatty acid oxidation in TAC mice. In conclusion, cholesterol lowering gene therapy attenuates pressure overload-induced heart failure in mice with mild hypercholesterolemia.
Variations in 25-Hydroxyvitamin D in Countries from the Middle East and Europe: The Roles of UVB Exposure and Diet

Serum 25-hydroxyvitamin D (25(OH)D) has been largely associated with latitude and sunshine exposure across several regions. According to previous results, 25(OH)D concentrations are, on average, relatively low in countries with abundant sunshine, including those of the Middle East and North Africa region, as well as lower-latitude Europe. The standard explanation for this phenomenon is that people wear concealing clothing because of cultural and religious practices and that high temperatures in summer limit direct sun exposure. However, the role of diet in the development of profound hypovitaminosis D has not been adequately explored in those countries. To examine how diet affects vitamin D status in the Middle Eastern and European countries, a search was conducted for papers from that region reporting 25(OH)D concentrations. Papers were sought that reported summertime and wintertime 25(OH)D concentrations for healthy nonpregnant adults representative of the entire population. Data from 15 Middle Eastern and European countries were found through this search. Data for postmenopausal women from 19 European countries were also obtained. Dietary supply data for animal products containing vitamin D (animal fat, eggs, ocean fish, animal meat, and milk) were obtained from the Food and Agriculture Organization of the United Nations. Latitude and a solar UVB dose index also were obtained for each country. For the 15-country study, energy from dietary factors was highly correlated with latitude, making it difficult to separate the effects of UVB exposure and dietary factors. However, for the 19-country study, dietary factors were only weakly correlated with latitude. In that study, ocean fish was the most important single dietary factor affecting serum 25(OH)D concentration for postmenopausal women in various European countries, but animal fat and meat also contributed. Because this is an ecological study, further research is encouraged to evaluate and extend the findings.
Signaling pathways and gene co-expression modules associated with cytoskeleton and axon morphology in breast cancer survivors with chronic paclitaxel-induced peripheral neuropathy

Background The major dose-limiting toxicity of paclitaxel, one of the most commonly used drugs to treat breast cancer, is peripheral neuropathy (paclitaxel-induced peripheral neuropathy). Paclitaxel-induced peripheral neuropathy, which persists into survivorship, has a negative impact on patient’s mood, functional status, and quality of life. Currently, no interventions are available to treat paclitaxel-induced peripheral neuropathy. A critical barrier to the development of efficacious interventions is the lack of understanding of the mechanisms that underlie paclitaxel-induced peripheral neuropathy. While data from preclinical studies suggest that disrupting cytoskeleton- and axon morphology-related processes are a potential mechanism for paclitaxel-induced peripheral neuropathy, clinical evidence is limited. The purpose of this study in breast cancer survivors was to evaluate whether differential gene expression and co-expression patterns in these pathways are associated with paclitaxel-induced peripheral neuropathy. Methods Signaling pathways and gene co-expression modules associated with cytoskeleton and axon morphology were identified between survivors who received paclitaxel and did (n = 25) or did not (n = 25) develop paclitaxel-induced peripheral neuropathy. Results Pathway impact analysis identified four significantly perturbed cytoskeleton- and axon morphology-related signaling pathways. Weighted gene co-expression network analysis identified three co-expression modules. One module was associated with paclitaxel-induced peripheral neuropathy group membership. Functional analysis found that this module was associated with four signaling pathways and two ontology annotations related to cytoskeleton and axon morphology. Conclusions This study, which is the first to apply systems biology approaches using circulating whole blood RNA-seq data in a sample of breast cancer survivors with and without chronic paclitaxel-induced peripheral neuropathy, provides molecular evidence that cytoskeleton- and axon morphology-related mechanisms identified in preclinical models of various types of neuropathic pain including chemotherapy-induced peripheral neuropathy are found in breast cancer survivors and suggests pathways and a module of genes for validation and as potential therapeutic targets.
Thrombomodulin and Thrombopoietin, Two Biomarkers of Hemostasis, Are Positively Associated with Adherence to the World Cancer Research Fund/American Institute for Cancer Research Recommendations for Cancer Prevention in a Population-Based Cross-Sectional Study

A pro-coagulative state is related to increased risk of cardiovascular diseases but also certain cancers. Since experimental and smaller human studies suggest that diet, physical activity, and body weight may all affect coagulation, we evaluated associations between these lifestyle factors and hemostatic biomarkers in a population-based study. Cross-sectional baseline data from 2267 randomly selected participants of EPIC-Heidelberg (age range 35–65 years) was used. Fibrinogen, glycoprotein IIb/IIIa, P-selectin, thrombomodulin (TM), and thrombopoietin (TPO) were measured in baseline plasma samples. A score reflecting adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations for cancer prevention was created. Associations between the WCRF/AICR score as well as its individual components and hemostatic biomarkers were analyzed by linear regression models. Multivariable-adjusted geometric means (95% confidence intervals) of TM and TPO were higher with greater adherence to the WCRF/AICR recommendations (TM, lowest vs. highest score category: 2.90 (2.7,3.1) vs. 3.10 (2.9,3.3) ng/mL, plinear trend = 0.0001; TPO: 328 (302,356) vs. 348 (321,378) pg/mL, plinear trend = 0.0007). These associations were driven by lower alcohol and meat consumption among persons with higher WCRF/AICR scores. Our results indicate that lifestyle factors favorably affect TM and TPO, two hemostatic factors implicated in chronic disease development.
Developmental architecture of the nervous system in Themiste lageniformis (Sipuncula): New evidence from confocal laser scanning microscopy and gene expression

Sipuncula is a clade of unsegmented marine worms that are currently placed among the basal radiation of conspicuously segmented Annelida. Their new location provides a unique opportunity to reinvestigate the evolution and development of segmented body plans. Neural segmentation is clearly evident during ganglionic ventral nerve cord (VNC) formation across Sedentaria and Errantia, which includes the majority of annelids. However, recent studies show that some annelid taxa outside of Sedentaria and Errantia have a medullary cord, without ganglia, as adults. Importantly, neural development in these taxa is understudied and interpretation can vary widely. For example, reports in sipunculans range from no evidence of segmentation to vestigial segmentation as inferred from a few pairs of serially repeated neuronal cell bodies along the VNC. We investigated patterns of pan‐neuronal, neuronal subtype, and axonal markers using immunohistochemistry and whole mount in situ hybridization (WMISH) during neural development in an indirect‐developing sipunculan, Themiste lageniformis. Confocal imaging revealed two clusters of 5HT+ neurons, two pairs of FMRF+ neurons, and Tubulin+ peripheral neurites that appear to be serially positioned along the VNC, similar to other sipunculans, to other annelids, and to spiralian taxa outside of Annelida. WMISH of a synaptotagmin1 ortholog in T. lageniformis (Tl‐syt1) showed expression throughout the centralized nervous system (CNS), including the VNC where it appears to correlate with mature 5HT+ and FMRF+ neurons. An ortholog of elav1 (Tl‐elav1) showed expression in differentiated neurons of the CNS with continuous expression in the VNC, supporting evidence of a medullary cord, and refuting evidence of ontogenetic segmentation during formation of the nervous system. Thus, we conclude that sipunculans do not exhibit any signs of morphological segmentation during development.
TRPC3 is a major contributor to functional heterogeneity of cerebellar Purkinje cells

Despite the canonical homogeneous character of its organization, the cerebellum plays differential computational roles in distinct sensorimotor behaviors. Previously, we showed that Purkinje cell (PC) activity differs between zebrin-negative (Z–) and zebrin-positive (Z+) modules (Zhou et al., 2014). Here, using gain-of-function and loss-of-function mouse models, we show that transient receptor potential cation channel C3 (TRPC3) controls the simple spike activity of Z–, but not Z+ PCs. In addition, TRPC3 regulates complex spike rate and their interaction with simple spikes, exclusively in Z– PCs. At the behavioral level, TRPC3 loss-of-function mice show impaired eyeblink conditioning, which is related to Z– modules, whereas compensatory eye movement adaptation, linked to Z+ modules, is intact. Together, our results indicate that TRPC3 is a major contributor to the cellular heterogeneity that introduces distinct physiological properties in PCs, conjuring functional heterogeneity in cerebellar sensorimotor integration.
Breast cancer-related lymphedema and quality of life: A qualitative analysis over years of survivorship

Objectives The study purpose was to examine perspectives of women with newly diagnosed breast cancer-related lymphedema (BCRL) regarding their quality of life over seven years. Method Data were collected over seven years using the Lymphedema and Breast Cancer Questionnaire (LBCQ). Participants with BCRL answered open-ended questions corresponding to changes in mood and lifestyle from post-op through annual interviews and surveys. Self-reported data from 97 participants with BCRL were analyzed using in vivo coding and template-style content analysis to elicit the impact of BCRL on quality of life domains. Results Data saturation was achieved as participants neared 30 to 36 months post- breast cancer diagnosis. Three major themes were identified related to BCRL’s impact on: physical function; daily living and social function; and psychological function. Discussion Findings suggest that BCRL impacts quality of life not only soon after diagnosis, but also throughout survivorship years. Healthcare providers should develop programs to enhance quality of life for survivors with BCRL.
Clinical values of non-coding RNAs in cardiovascular, pulmonary, and muscle diseases.

While a majority of the mammalian genome is transcribed to RNA, mounting evidence indicates that only a minor proportion of these transcriptional products are actually translated into proteins. Since the discovery of the first non-coding RNA (ncRNA) in the 1980s, the field has gone on to recognize ncRNAs as important molecular regulators of RNA activity and protein function-knowledge of which has stimulated the expansion of a scientific field that quests to understand the role of ncRNAs in cellular physiology, tissue homeostasis, and human disease. Although our knowledge of these molecules has significantly improved over the years, we have limited understanding of their precise functions, protein interacting partners, and tissue-specific activities. Adding to this complexity, it remains unknown exactly how many ncRNAs there are in existence. The increased use of high-throughput transcriptomics techniques has rapidly expanded the list of ncRNAs, which now include classical ncRNAs [e.g., ribosomal RNAs (rRNAs), transfer RNAs (tRNAs)], microRNAs (miRNAs), and long ncRNAs (lncRNAs). In addition, splicing byproducts of protein-coding genes and ncRNAs, so called circular RNAs (circRNAs), are now being investigated. Because there is substantial heterogeneity in the functions of ncRNAs, we have summarized the current state of knowledge regarding the functions of ncRNAs in heart, lungs, and skeletal muscle. This review highlights the pathophysiologic relevance of these ncRNAs in the context of human cardiovascular, pulmonary, and muscle diseases.
Primary and secondary bystander effect and genomic instability in cells exposed to high and low linear energy transfer radiations

Abstract Purpose: Non-Targeted effects (NTE), such as bystander effect (BE) and genomic instability (GI) challenge central dogma of radiation biology. Moreover, there is a need to understand its universality in different type of cells and radiation quality. Materials and method: To study BE (primary and secondary) and GI Human adult dermal fibroblast (HADF) and peripheral blood lymphocytes (PBL) were exposed to low fluence of 241Am alpha (α) particle and 6 MV X-ray. The BE was carried out by means of co-culture methodology after exposing the cells to both types of radiation and damage was measured using micronucleus assay (MN) and chromosomal aberration assay (CA) in the p1 cells while the GI was followed up in their progeny. Results: A dose-dependent increase in DNA damages (MN and CA) was observed in directly irradiated and bystander cells. The magnitude of BE was higher (6 fold) in cells co-cultured with the α-irradiated cells than that of with X-irradiated cells. Cross exposure of both cell types confirms that radiation induced BE is cell type dependent. In addition, induced DNA damage persisted for a longer population doubling in α-particle irradiated cells. Conclusion: This work adds evidence to secondary bystander response generated from primary bystander normal cells and its dependence to radiation quality.
Comparison of the Effects of Magnetically Controlled Growing Rod and Tradiotinal Growing Rod Techniques on the Sagittal Plane in the Treatment of Early-Onset Scoliosis

Objective Comparing the effects of magnetically controlled growing rod (MCGR) and traditional growing rod (TGR) techniques on the sagittal plane in the treatment of early-onset scoliosis (EOS). Methods Twelve patients were operated using dual MCGR technique in one center, while 15 patients were operated using dual TGR technique for EOS in another center. Patients’ demographic characteristics, complications and radiological measurements such as cobb angle, thoracic kyphosis, lumbar lordosis, T1–S1 range (mm), proximal junctional angle, distal junctional angle, sagittal balance, coronal balance, pelvic incidence, sacral slope and pelvic tilt were assessed and compared in preoperative, postoperative and last follow-up period. Results Age and sex distributions were similar in both groups. The mean number of lengthening in the MCGR group was 12 (8–15) and 4.8 (3–7) in the TGR group. Two techniques were shown to be effective in controlling the curvature and in the increase of T1–S1 distance. In TGR group, four patients had rod fractures, six patients had screw pull-out and four patients had an infection, whereas three patients had screw pull-out and one patient had infection complications in the MCGR group. Conclusion There was no significant difference between the two groups in terms of cobb angle, coronal and sagittal balance and sagittal pelvic parameters. MCGR can cause hypokyphosis and proximal junctional kyphosis in a minimum 2-year follow-up period. The implant-related complications were less in the MCGR group. However, larger case groups and longer follow-up periods are required for the better understanding of the superiority of one method on other in terms of complications.
Human Umbilical Cord Mesenchymal Stem Cells Extricate Bupivacaine-Impaired Skeletal Muscle Function via Mitigating Neutrophil-Mediated Acute Inflammation and Protecting against Fibrosis

Skeletal muscle injury presents a challenging traumatological dilemma, and current therapeutic options remain mediocre. This study was designed to delineate if engraftment of mesenchymal stem cells derived from umbilical cord Wharton’s jelly (uMSCs) could aid in skeletal muscle healing and persuasive molecular mechanisms. We established a skeletal muscle injury model by injection of myotoxin bupivacaine (BPVC) into quadriceps muscles of C57BL/6 mice. Post BPVC injection, neutrophils, the first host defensive line, rapidly invaded injured muscle and induced acute inflammation. Engrafted uMSCs effectively abolished neutrophil infiltration and activation, and diminished neutrophil chemotaxis, including Complement component 5a (C5a), Keratinocyte chemoattractant (KC), Macrophage inflammatory protein (MIP)-2, LPS-induced CXC chemokine (LIX), Fractalkine, Leukotriene B4 (LTB4), and Interferon-γ, as determined using a Quantibody Mouse Cytokine Array assay. Subsequently, uMSCs noticeably prevented BPVC-accelerated collagen deposition and fibrosis, measured by Masson’s trichrome staining. Remarkably, uMSCs attenuated BPVC-induced Transforming growth factor (TGF)-β1 expression, a master regulator of fibrosis. Engrafted uMSCs attenuated TGF-β1 transmitting through interrupting the canonical Sma- And Mad-Related Protein (Smad)2/3 dependent pathway and noncanonical Smad-independent Transforming growth factor beta-activated kinase (TAK)-1/p38 mitogen-activated protein kinases signaling. The uMSCs abrogated TGF-β1-induced fibrosis by reducing extracellular matrix components including fibronectin-1, collagen (COL) 1A1, and COL10A1. Most importantly, uMSCs modestly extricated BPVC-impaired gait functions, determined using CatWalk™ XT gait analysis. This work provides several innovative insights into and molecular bases for employing uMSCs to execute therapeutic potential through the elimination of neutrophil-mediated acute inflammation toward protecting against fibrosis, thereby rescuing functional impairments post injury.
Association of rs3783641 single‐nucleotide polymorphism in GTP cyclohydrolase 1 gene with post‐herpetic neuralgia

Post‐herpetic neuralgia (PHN) is a well‐established clinical problem with potential severe personal and socioeconomic implications. GTP cyclohydrolase 1 (GCH1) gene, which encodes the rate‐limiting enzyme in tetrahydrobiopterin synthesis, has been strongly implicated to be associated with neuropathic pain in previous animal and human studies. The rs3783641 (T > A) single‐nucleotide polymorphism (SNP) in the GCH1 gene is functional. Here we examine the association between rs3783641 and PHN. A total of 292 subjects including 103 PHN patients, 87 herpes zoster (HZ) patients and 102 healthy controls were enrolled in this study. The rs3783641 polymorphisms were detected via the high‐resolution melting curve (HRM) method. There were statistical differences between PHN group and the other two groups in genotype distribution (P = 0.029 and 0.017, respectively) and allele frequency (P = 0.032 and 0.005, respectively) of rs3783641. The proportion of subjects with AA genotype in the PHN group was significantly lower compared to HZ group and control group (P = 0.026 and 0.016, respectively). The frequency of A allele was lower in the PHN group than in control group (P = 0.005), and the frequency of T allele in the PHN group was higher than in HZ group and control group (P = 0.001 and 0.003, respectively). The results of this study suggest that the rs3783641 SNP in the GCH1 gene is associated with PHN, and the AA genotype showed a protective effect in PHN.