Miracle-dz/UniFAR-FTUs huggingface dataset:
Divergent Expression Patterns and Function of Two cxcr4 Paralogs in Hermaphroditic Epinephelus coioides

Chemokine receptor Cxcr4 evolved two paralogs in the teleost lineage. However, cxcr4a and cxcr4b have been characterized only in a few species. In this study, we identified two cxcr4 paralogs from the orange-spotted grouper, Epinephelus coioides. The phylogenetic relationship and gene structure and synteny suggest that the duplicated cxcr4a/b should result from the teleost-specific genome duplication (Ts3R). The teleost cxcr4 gene clusters in two paralogous chromosomes exhibit a complementary gene loss/retention pattern. Ec_cxcr4a and Ec_cxcr4b show differential and biased expression patterns in grouper adult tissue, gonads, and embryos at different stages. During embryogenesis, Ec_cxcr4a/b are abundantly transcribed from the neurula stage and mainly expressed in the neural plate and sensory organs, indicating their roles in neurogenesis. Ec_Cxcr4a and Ec_Cxcr4b possess different chemotactic migratory abilities from the human SDF-1α, Ec_Cxcl12a, and Ec_Cxcl12b. Moreover, we uncovered the N-terminus and TM5 domain as the key elements for specific ligand–receptor recognition of Ec_Cxcr4a-Ec_Cxcl12b and Ec_Cxcr4b-Ec_Cxcl12a. Based on the biased and divergent expression patterns of Eccxcr4a/b, and specific ligand–receptor recognition of Ec_Cxcl12a/b–Ec_Cxcr4b/a, the current study provides a paradigm of sub-functionalization of two teleost paralogs after Ts3R.
The expression of somatostatin receptor 2 decreases during cyst growth in mice with polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive renal cyst formation and expansion. Several clinical trials show that somatostatin analogs halt cyst growth and progression of ADPKD by inhibiting adenosine 3′,5′-cyclic monophosphate (cAMP) signaling. However, two studies suggest that the effect of the somatostatin analog octreotide on kidney growth during the first year of treatment is reduced in the subsequent follow-ups and the kidney enlargement resumes. We hypothesize that this biphasic change in kidney growth during octreotide treatment may be due to changes in somatostatin receptor 2 (SSTR2) expression. Here we analyzed the expression of renal SSTR2 in various polycystic kidney disease (PKD) mouse models in which PKD1 gene expression was disrupted on postnatal day 10 or 18 by tamoxifen. Using immunohistochemical analysis, we showed that the distribution of SSTR2 in murine kidneys is mainly in distal tubules and collecting ducts. In addition, in both PKD models, we observed a significant decrease in SSTR2 expression in epithelia of dilated tubules and cystic epithelia in mice with end stage of PKD compared to wild-type mice. These findings were further confirmed by quantitative PCR (qPCR) on mRNA levels of SSTR2. In conclusion, our data show that SSTR2 expression levels are reduced during kidney cyst growth, which may suggest reduced efficacy in long-term treatment with somatostatin analogs. Impact statement Somatostatin (SST) analogs have been shown to halt cyst growth and progression of autosomal dominant polycystic kidney disease by several clinical trials. However, two studies suggest that the effect of the SST analog octreotide on kidney growth during the first year of treatment is reduced in the subsequent follow-ups and the kidney enlargement resumes. This biphasic change in kidney growth during octreotide treatment may be partially explained by alterations in SSTR2 expression. Here, we found that SSTR2 is mainly expressed in distal tubules and collecting ducts in murine kidneys, and the expression of SSTR2 decreases during cyst growth in two PKD mouse models. Our data may thus provide possible explanations for the lack of efficacy in long-term treatment with SST analogs.
Drosophila HUWE1 Ubiquitin Ligase Regulates Endoreplication and Antagonizes JNK Signaling During Salivary Gland Development

The HECT-type ubiquitin ligase HECT, UBA and WWE Domain Containing 1, (HUWE1) regulates key cancer-related pathways, including the Myc oncogene. It affects cell proliferation, stress and immune signaling, mitochondria homeostasis, and cell death. HUWE1 is evolutionarily conserved from Caenorhabditis elegance to Drosophila melanogaster and Humans. Here, we report that the Drosophila ortholog, dHUWE1 (CG8184), is an essential gene whose loss results in embryonic lethality and whose tissue-specific disruption establishes its regulatory role in larval salivary gland development. dHUWE1 is essential for endoreplication of salivary gland cells and its knockdown results in the inability of these cells to replicate DNA. Remarkably, dHUWE1 is a survival factor that prevents premature activation of JNK signaling, thus preventing the disintegration of the salivary gland, which occurs physiologically during pupal stages. This function of dHUWE1 is general, as its inhibitory effect is observed also during eye development and at the organismal level. Epistatic studies revealed that the loss of dHUWE1 is compensated by dMyc proeitn expression or the loss of dmP53. dHUWE1 is therefore a conserved survival factor that regulates organ formation during Drosophila development.
Body Image Development and Sexual Satisfaction: A Prospective Study From Adolescence to Adulthood

The aim of the current study was to explore whether developmental trajectories of body satisfaction from adolescence to young adulthood predicted measures of sexual satisfaction in young adulthood, even when controlling for important covariates such as gender, weight development, relationship status, mental health, and frequency of sexual intercourse and masturbation. Data were collected from a population-based prospective cohort of Norwegian adolescents (n = 2,587) over a period of 13 years in four waves (1992, 1994, 1999, and 2005; mean age = 14.9 in 1992, 57.3% women). Latent growth curves were estimated for body satisfaction and body mass index (BMI). Men reported higher sexual satisfaction, sexual activity, baseline body satisfaction, and BMI than women. The developmental trajectories revealed a slight increase in body satisfaction and BMI from adolescence to young adulthood in both genders. Moreover, structural equation models showed that baseline body satisfaction in both genders predicted sexual satisfaction as a young adult, independent of relationship status and frequency of sexual activity. Neither the development of BMI nor of body satisfaction predicted sexual satisfaction. The results elucidate the vital role of body satisfaction in sexual satisfaction in adults and the importance of addressing body dissatisfaction in childhood.
Temporal trends in cardiovascular risk factors and performance of the Framingham Risk Score and the Pooled Cohort Equations

Background The Framingham Risk Score (FRS) and the Pooled Cohort Equations (PCE) are established tools for the prediction of cardiovascular disease (CVD) risk. In the Western world, decreases in incidence rates of CVD were observed over the last 30 years. Thus, we hypothesise that there are also temporal trends in the risk prediction performance of the FRS and PCE from 1990 to 2000. Methods We used data from n=7789 men and women aged 40–74 years from three prospective population-based cohort studies enrolled in Southern Germany in 1989/1990, 1994/1995 and 1999/2000. 10-year CVD risk was calculated by recalibrated equations of the FRS or PCE. Calibration was evaluated by percentage of overestimation and Hosmer-Lemeshow tests. Discrimination performance was assessed by receiver operating characteristic (ROC) curves and corresponding area under the curve (AUC). Results Across the three studies, we found significant temporal trends in risk factor distributions and predicted risks by both risk scores (men: 18.0%, 15.4%, 14.9%; women: 8.7%, 11.2%, 10.8%). Furthermore, also the discrimination performance evolved differently for men (AUC PCE: 76.4, 76.1, 72.8) and women (AUC PCE: 75.9, 79.5, 80.5). Both risk scores overestimated actual CVD risk. Conclusion There are temporal trends in the performance of the FRS and PCE. Although the overall performance remains adequate, sex-specific trends have to be taken into account for further refinement of risk prediction models.
Diagnosis and Management of Radiation Necrosis in Patients With Brain Metastases

The use of radiotherapy, either in the form of stereotactic radiosurgery (SRS) or whole-brain radiotherapy (WBRT), remains the cornerstone for the treatment of brain metastases (BM). As the survival of patients with BM is being prolonged, due to improved systemic therapy (i.e., for better extra-cranial control) and increased use of SRS (i.e., for improved intra-cranial control), patients are clinically manifesting late effects of radiotherapy. One of these late effects is radiation necrosis (RN). Unfortunately, symptomatic RN is notoriously hard to diagnose and manage. The features of RN overlap considerably with tumor recurrence, and misdiagnosing RN as tumor recurrence may lead to deleterious treatment which may cause detrimental effects to the patient. In this review, we will explore the pathophysiology of RN, risk factors for its development, and the strategies to evaluate and manage RN.
Performance Enhancement of Interdigital Electrode-Piezoelectric Quartz Crystal (IDE-PQC) Salt Concentration Sensor by Increasing the Electrode Area of Piezoelectric Quartz Crystal (PQC)

In this paper, a new approach to enhance the performance of the interdigital electrode-piezoelectric quartz crystal (IDE-PQC) salt solution concentration sensor by modifying the electrode area of PQC was proposed. Equivalent circuit analysis showed that the static capacitor (C0) which is related to the electrode area of PQC directly affected the response sensitivity of the IDE-PQC sensor. Further, the sensing responses of IDE-PQC sensors to various concentrations of salt solution were measured. Three kinds of salt solution, including NaCl, KCl, and Na2SO4, were adpoted to evaluate the sensing performances of the IDE-PQC sensors. The experimental results also indicated that increasing the electrode area of PQC can enhance the sensitivity response of the IDE-PQC sensors to the change of salt solution concentration. For example, the detection sensitivity of the IDE-PQC sensor with an electrode diameter of 5 mm was about three times larger than that of the sensor with an electrode diameter of 3 mm. Meanwhile, we found that the frequency stability of the IDE-PQC sensor was also improved by increasing the electrode area of PQC. In addition, the influence of the electrode area of PQC on the repeatability and the transient response of IDE-PQC salt solution concentration sensor were also studied. This work demonstrates simple and cost-effective method to achieve the performance enhancement of IDE-PQC salt solution concentration sensor by modifying the electrode area of PQC.
Prepulse inhibition in Drosophila melanogaster larvae

ABSTRACT The neural mechanisms of psychiatric diseases like autism spectrum disorder and schizophrenia have been intensively studied, and a number of candidate genes have been identified. However, the relationship between genes and neural system functioning remains unclear. Model organisms may serve as a powerful tool for addressing this question due to the availability of established genetic tools. Here, we report prepulse inhibition (PPI) in Drosophila larvae for the first time. PPI is a neurological phenomenon found in humans and other organisms and is used in the diagnosis of schizophrenia and other psychiatric disorders. A weaker prestimulus (prepulse) inhibits the reaction to a subsequent strong, startling stimulus (pulse). Using the larval startle response to the buzz of a predator (wasp), we examined PPI in wild-type flies and two mutants: an fmr1 mutant, which is implicated in Fragile X syndrome, and a centaurin gamma 1A (CenG1A) mutant, which is associated with GTPase, PH, ArfGAP, and ANK domains and implicated in autism. Both mutants showed decreased PPI, whereas, interestingly, double mutants showed substantial PPI. The PPI phenomenon described here can provide a useful tool for the study of neural mechanisms of synaptic modification and psychiatric diseases. Summary: Prepulse inhibition (PPI) deficiency is observed in various psychiatric disorders. Here we demonstrate PPI in Drosophila and its association with psychiatric disease-related genes.
Optimization of Protein Expression in Mammalian Cells

Recombinant proteins, such as monoclonal antibodies, are produced in mammalian cell lines to introduce proper protein folding and post‐translational modifications, which are essential for full biological activity. In both the industrial and academic environments, the use of recombinant proteins varies widely and, with it, the method of production. The amount of an antibody needed for a toxicity study is far greater than that needed by a research lab performing cellular assays, and the amount of effort put into the development of the protein will vary accordingly. There is no universal strategy for mammalian expression systems, and scientists often struggle to develop a suitable process from the myriad of choices at each step. Here, we elaborate on the various obstacles encountered when planning high‐yield experiments to produce the recombinant proteins of interest. © 2018 by John Wiley & Sons, Inc.
Predicting computational reproducibility of data analysis pipelines in large population studies using collaborative filtering

Evaluating the computational reproducibility of data analysis pipelines has become a critical issue. It is, however, a cumbersome process for analyses that involve data from large populations of subjects, due to their computational and storage requirements. We present a method to predict the computational reproducibility of data analysis pipelines in large population studies. We formulate the problem as a collaborative filtering process, with constraints on the construction of the training set. We propose 6 different strategies to build the training set, which we evaluate on 2 datasets, a synthetic one modeling a population with a growing number of subject types, and a real one obtained with neuroinformatics pipelines. Results show that one sampling method, "Random File Numbers (Uniform)" is able to predict computational reproducibility with a good accuracy. We also analyze the relevance of including file and subject biases in the collaborative filtering model. We conclude that the proposed method is able to speedup reproducibility evaluations substantially, with a reduced accuracy loss.
Epigenetic Study in Parkinson’s Disease: A Pilot Analysis of DNA Methylation in Candidate Genes in Brain

Efforts have been made to understand the pathophysiology of Parkinson’s disease (PD). A significant number of studies have focused on genetics, despite the fact that the described pathogenic mutations have been observed only in around 10% of patients; this observation supports the fact that PD is a multifactorial disorder. Lately, differences in miRNA expression, histone modification, and DNA methylation levels have been described, highlighting the importance of epigenetic factors in PD etiology. Taking all this into consideration, we hypothesized that an alteration in the level of methylation in PD-related genes could be related to disease pathogenesis, possibly due to alterations in gene expression. After analysing promoter regions of five PD-related genes in three brain regions by pyrosequencing, we observed some differences in DNA methylation levels (hypo and hypermethylation) in substantia nigra in some CpG dinucleotides that, possibly through an alteration in Sp1 binding, could alter their expression.
Inactivation of human and avian influenza viruses by potassium oleate of natural soap component through exothermic interaction

An influenza epidemic is still a problem despite the development of vaccines and anti-influenza drugs. Preventive measures such as handwashing are fundamental and important for counteracting influenza virus infection. In this study, we clarified the anti-influenza virus effects of surfactants, which are the main components of hand soaps for hand washing: potassium oleate (C18:1), sodium laureth sulfate (LES) and sodium lauryl sulfate (SDS). For a human influenza virus strain (H3N2), C18:1 reduced the infectivity by 4 logs or more, whereas LES and SDS reduced the infectivity by 1 log or less. Similar results were obtained when an avian influenza virus strain (H5N3) was used. The interaction between the surfactant and virus was then investigated by isothermal titration calorimetry. The LES-virus system showed a positive value of enthalpy changes (ΔH), meaning an exothermic interaction that indicated a hydrophobic interaction. In contrast, both the C18:1-virus system and the SDS-virus system showed negative values of ΔH, meaning an endothermic interaction that indicated an electrical interaction. The ΔH value of the C18:1-virus system was much higher than that of the SDS-virus system. A mixture of C18:1 and HA proteins similarly showed negative values of ΔH. These results indicate that influenza virus inactivation by a hydrophobic interaction of a surfactant with the viral envelope is insufficient to prevent infection, whereas inactivation by an electrical interaction of a surfactant with HA proteins is sufficient to prevent influenza virus infection.
Learning to Coordinate Multiple Reinforcement Learning Agents for Diverse Query Reformulation

We propose a method to efficiently learn diverse strategies in reinforcement learning for query reformulation in the tasks of document retrieval and question answering. In the proposed framework an agent consists of multiple specialized sub-agents and a meta-agent that learns to aggregate the answers from sub-agents to produce a final answer. Sub-agents are trained on disjoint partitions of the training data, while the meta-agent is trained on the full training set. Our method makes learning faster, because it is highly parallelizable, and has better generalization performance than strong baselines, such as an ensemble of agents trained on the full data. We show that the improved performance is due to the increased diversity of reformulation strategies.
Culture of pyramidal neural precursors, neural stem cells, and fibroblasts on various biomaterials

Abstract A combinatory approach using biomaterials together with cells may improve the efficacy of cell therapy for treatment of various diseases/indications. In the current study, we cultured pyramidal neural precursors (PNPs), neural stem cells (NSCs), and fibroblasts on different materials that included fibrin, collagen, hyaluronic acid (HA), sciatic nerves, and matrigel, to search for the most suitable biomaterial for culture of each cell type. Collagen was fabricated in both an aligned collagen-poly (lactic-co-glycolic acid) (PLGA) composite and an alveolate form; fibrin and hyaluronic acid were made in an aligned form only. Pyramidal neurons have strong projection ability and have potentials in neural circuit reconstruction. However, PNPs showed difficulty in attaching to and growing neurites on most of the materials tested, except for matrigel, in which neurite growth was observed in a three dimentional culture. NSCs and derivatives hold promise in treating neurological diseases. On aligned fibrin, NSCs could differentiate and grow neurites in a directional manner before fibrin was degraded in 2 days. On aligned collagen-PLGA, induced neural stem cells (iNSCs) could survive and differentiate for at least 2 weeks, but the neurites failed to extend in an aligned way. Fibroblast graft are useful in many indications, such as in skin burns. Fibroblasts generally grew better on the tested materials than did the neural cells, and fibroblasts could grow directionally on the aligned fibrin and scattered around on the alveolate collagen. The study provided information which may be used to further optimize the materials to support culture of each type of cells.
Differential Effects of Integrin αv Knockdown and Cilengitide on Sensitization of Triple-Negative Breast Cancer and Melanoma Cells to Microtubule Poisons

Low survival rates of patients with metastatic triple-negative breast cancer (TNBC) and melanoma, in which current therapies are ineffective, emphasize the need for new therapeutic approaches. Integrin β1 appears to be a promising target when combined with chemotherapy, but recent data have shown that its inactivation increases metastatic potential owing to the compensatory upregulation of other integrin subunits. Consequently, we analyzed the potential of integrin subunits αv, α3, or α4 as targets for improved therapy in seven TNBC and melanoma cell lines. Experiments performed in an integrin αvβ1-negative melanoma cell line, MDA-MB-435S, showed that knockdown of integrin subunit αv increased sensitivity to microtubule poisons vincristine or paclitaxel and decreased migration and invasion. In the MDA-MB-435S cell line, we also identified a phenomenon in which change in the expression of one integrin subunit changes the expression of other integrins, leading to an unpredictable influence on sensitivity to anticancer drugs and cell migration, referred to as the integrin switching effect. In a panel of six TNBCs and melanoma cell lines, the contribution of integrins αv versus integrins αvβ3/β5 was assessed by the combined action of αv-specific small interfering RNA or αvβ3/β5 inhibitor cilengitide with paclitaxel. Our results suggest that, for TNBC, knockdown of integrin αv in combination with paclitaxel presents a better therapeutic option than a combination of cilengitide with paclitaxel; however, in melanoma, neither of these combinations is advisable because a decreased sensitivity to paclitaxel was observed.
Mdm2‐p53‐SF1 pathway in ovarian granulosa cells directs ovulation and fertilization by conditioning oocyte quality

Functions of tumor suppressor p53 and its negative regulator mouse double minute 2 homolog (Mdm2) in ovarian granulosa cells remain to be elucidated, and the current study aims at clarifying this issue. Mice with Mdm2 deficiency in ovarian granulosa cells [Mdm2‐loxP/progesterone receptor (Pgr)‐Cre mice] were infertile as a result of impairment of oocyte maturation, ovulation, and fertilization, and those with Mdm2/p53 double deletion in granulosa cells (Mdm2‐loxP/p53‐loxP/Pgr‐Cre mice) showed normal fertility, suggesting that p53 induction in the ovarian granulosa cells is detrimental to ovarian function by disturbing oocyte quality. Another model of Mdm2 deletion in ovarian granulosa cells (Mdm2‐loxP/anti‐Mullerian hormone type 2 receptor‐Cre mice) also showed subfertility as a result of the failure of ovulation and fertilization, indicating critical roles of ovarian Mdm2 in ovulation and fertilization. Mdm2‐p53 pathway in cumulus granulosa cells transcriptionally controlled an orphan nuclear receptor steroidogenic factor 1 (SF1), a key regulator of ovarian function. Importantly, MDM2 and SF1 levels in human cumulus granulosa cells were positively associated with the outcome of oocyte maturation and fertilization in patients undergoing infertility treatment. These findings suggest that the Mdm2‐p53‐SF1 axis in ovarian cumulus granulosa cells directs ovarian function by affecting their neighboring oocyte quality. —Haraguchi, H. , Hirota, Y. , Saito‐Fujita, T. , Tanaka, T. , Shimizu‐Hirota, R. , Harada, M. , Akaeda, S. , Hiraoka, T. , Matsuo, M. , Matsumoto, L. , Hirata, T. , Koga, K. , Wada‐Hiraike, O. , Fujii, T. , Osuga, Y. Mdm2‐p53‐SF1 pathway in ovarian granulosa cells directs ovulation and fertilization by conditioning oocyte quality. FASEB J. 33, 2610–2620 (2019). www.fasebj. org