Miracle-dz/UniFAR-FTUs huggingface dataset:
CCL28 promotes breast cancer growth and metastasis through MAPK-mediated cellular anti-apoptosis and pro-metastasis

Breast cancer is one of the most commonly diagnosed cancers worldwide and the second leading cause of cancer-related deaths among females. CCL28 (mucosa-associated epithelial chemokine, MEC), a CC subfamily chemokine, has been well studied in the process of inflammation, and recently increasing evidence indicates that CCL28 is related to tumor progression. However, little is known concerning its function in breast cancer. In the present study, we generated a CCL28-overexpressing breast cancer cell line MDA-MB-231HM/CCL28 from parental MDA-MB-231HM cells. We found that overexpression of CCL28 promoted cell proliferation and tumor formation, and also enhanced migration, invasion and metastasis both in vitro and in vivo. Mechanistic studies revealed that CCL28 mediated intracellular activation of the mitogen-activated protein kinase (MAPK) signaling pathway to promote breast cancer cell proliferation and metastasis by upregulating anti-apoptotic protein Bcl-2 and suppressing cell adhesion protein β-catenin. However, overexpression of CCL28 did not influence the expression of metastasis-related protein matrix metalloproteinase MMP2 and MMP9 and VEGF. Tissue sample analysis from animal models also indicated that overexpression of CCL28 was associated with enhanced pERK expression and reduced β-catenin expression in breast carcinomas. Thus, our results show for the first time that CCL28 contributes to breast cancer progression through the ERK/MAPK-mediated anti-apoptotic and metastatic signaling pathway. Antagonists of CCL28 and the MAPK signaling pathway may be used synergistically to treat breast cancer patients.
3D ultrastructural organisation of calcium release units in the avian sarcoplasmic reticulum

ABSTRACT Excitation–contraction coupling in vertebrate hearts is underpinned by calcium (Ca2+) release from Ca2+ release units (CRUs). CRUs are formed by clusters of channels called ryanodine receptors on the sarcoplasmic reticulum (SR) within the cardiomyocyte. Distances between CRUs influence the diffusion of Ca2+, thus influencing the rate and strength of excitation–contraction coupling. Avian myocytes lack T-tubules, so Ca2+ from surface CRUs (peripheral couplings, PCs) must diffuse to internal CRU sites of the corbular SR (cSR) during centripetal propagation. Despite this, avian hearts achieve higher contractile rates and develop greater contractile strength than many mammalian hearts, which have T-tubules to provide simultaneous activation of the Ca2+ signal through the myocyte. We used 3D electron tomography to test the hypothesis that the intracellular distribution of CRUs in the avian heart permits faster and stronger contractions despite the absence of T-tubules. Nearest edge–edge distances between PCs and cSR, and geometric information including surface area and volume of individual cSR, were obtained for each cardiac chamber of the white leghorn chicken. Computational modelling was then used to establish a relationship between CRU distance and cell activation time in the avian heart. Our data suggest that cSR clustered close together along the Z-line is vital for rapid propagation of the Ca2+ signal from the cell periphery to the cell centre, which would aid in the strong and fast contractions of the avian heart. Summary: 3D reconstructions of calcium release units in the avian heart combined with computer modelling reveal that close clustering of cSR along the Z-line is vital for rapid propagation of the Ca2+ signal, enabling strong, fast contractions of the avian heart.
Suicidal Ideation in Transgender People: Gender Minority Stress and Interpersonal Theory Factors

Research has revealed alarmingly high rates of suicidal ideation (SI) and suicide attempts among transgender and gender nonconforming (TGNC) people. This study aims to analyze the role of factors from the gender minority stress and resilience (GMSR) model (Testa, Habarth, Peta, Balsam, & Bockting, 2015), the interpersonal-psychological theory of suicide (IPTS; Joiner, 2005; Van Orden et al., 2010), and the potential integration of these factors, in explaining SI in this population. A convenience sample of 816 TGNC adults responded to measures of current SI, gender minority stressors, and IPTS factors. Path analysis was utilized to test 2 models. Model 1 evaluated the associations between external minority stressors and SI through internal minority stressors. Model 2 examined the relationships between internal minority stressors and SI through IPTS variables (perceived burdensomeness and thwarted belongingness). All GMSR external stressors (rejection, nonaffirmation, victimization, and discrimination), internal stressors (internalized transphobia, negative expectations, and nondisclosure), and IPTS factors (thwarted belongingness and perceived burdensomeness) were related to SI. Both models demonstrated good fit. Model 1 revealed that rejection, nonaffirmation, and victimization were related to SI through experiences of internalized transphobia and negative expectations. Model 2 indicated that internalized transphobia and negative expectations were associated with SI through IPTS factors. The models demonstrate pathways through which GMSR and IPTS constructs relate to one another and confer risk for SI among TGNC individuals. These pathways and several recently proposed constructs examined here provide promising directions for future research and clinical interventions in this area.
Immunoregulatory Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles on T Lymphocytes

The immunomodulatory activity of mesenchymal stem cells (MSCs) is largely mediated by paracrine factors. We have recently shown that the immunosuppressive effects of MSCs on B lymphocytes in peripheral blood mononuclear cell (PBMC) culture can be reproduced by extracellular vesicles (EVs) isolated from MSC culture supernatants. Here we investigated the effect of bone marrow-derived MSC-EVs on T cells on PBMC cultures stimulated with anti-CD3/CD28 beads. Stimulation increased the number of proliferating CD3+ cells as well as of regulatory T cells (Tregs). Coculture with MSCs inhibited the proliferation of CD3+ cells, with no significant changes in apoptosis. Addition of MSC-EVs to PBMCs did not affect proliferation of CD3+ cells, but induced the apoptosis of CD3+ cells and of the CD4+ subpopulation and increased the proliferation and the apoptosis of Tregs. Moreover, MSC-EV treatment increased the Treg/Teff ratio and the immunosuppressive cytokine IL-10 concentration in culture medium. The activity of indoleamine 2,3-dioxygenase (IDO), an established mediator of MSC immunosuppressive effects, was increased in supernatants of PBMCs cocultured with MSCs, but was not affected by the presence of MSC-EVs. MSC-EVs demonstrate immunomodulatory effects on T cells in vitro. However, these effects and the underlying mechanisms appear to be different from those exhibited by their cells of origin.
Metabolic, Anti-apoptotic and Immune Evasion Strategies of Primary Human Myeloma Cells Indicate Adaptations to Hypoxia*

In-depth proteome profiling of primary human CD138-positive plasma cells, derived from bone marrow biopsies from patients with different stages of multiple myeloma, have been performed on a Q Exactive orbitrap. Analysis of the 6218 identified proteins using label-free quantification with the MaxQuant software revealed strategies adopted by myeloma cells to overcome limitations imposed by hypoxic conditions in the bone marrow microenvironment, including specific immune evasion mechanisms and metabolic adaptations. Graphical Abstract Highlights In-depth proteome profiling of primary human myeloma cells Characteristics of myeloma cells are related to hypoxic bone marrow conditions Myeloma cells show specific immune evasion strategies Metabolic adaptations involve tumor and stroma cells Multiple Myeloma (MM) is an incurable plasma cell malignancy primarily localized within the bone marrow (BM). It develops from a premalignant stage, monoclonal gammopathy of undetermined significance (MGUS), often via an intermediate stage, smoldering MM (SMM). The mechanisms of MM progression have not yet been fully understood, all the more because patients with MGUS and SMM already carry similar initial mutations as found in MM cells. Over the last years, increased importance has been attributed to the tumor microenvironment and its role in the pathophysiology of the disease. Adaptations of MM cells to hypoxic conditions in the BM have been shown to contribute significantly to MM progression, independently from the genetic predispositions of the tumor cells. Searching for consequences of hypoxia-induced adaptations in primary human MM cells, CD138-positive plasma cells freshly isolated from BM of patients with different disease stages, comprising MGUS, SMM, and MM, were analyzed by proteome profiling, which resulted in the identification of 6218 proteins. Results have been made fully accessible via ProteomeXchange with identifier PXD010600. Data previously obtained from normal primary B cells were included for comparative purposes. A principle component analysis revealed three clusters, differentiating B cells as well as MM cells corresponding to less and more advanced disease stages. Comparing these three clusters pointed to the alteration of pathways indicating adaptations to hypoxic stress in MM cells on disease progression. Protein regulations indicating immune evasion strategies of MM cells were determined, supported by immunohistochemical staining, as well as transcription factors involved in MM development and progression. Protein regulatory networks related to metabolic adaptations of the cells became apparent. Results were strengthened by targeted analyses of a selected panel of metabolites in MM cells and MM-associated fibroblasts. Based on our data, new opportunities may arise for developing therapeutic strategies targeting myeloma disease progression.
Does double trigger (GnRH-agonist + hCG) improve outcome in poor responders undergoing IVF-ET cycle? A pilot study

Abstract Many strategies are offered for the treatment of poor responders. However, no compelling advantage for one stimulation protocol over another has been hitherto established. In this study, we aimed to evaluate the role of different modes and timings of final follicular maturation trigger, on in vitro fertilization (IVF) cycle outcome of poor responder patients. In the present randomized controlled study, poor responder patients, according to the Bologna criteria, undergoing controlled ovarian hyperstimulation (COH) using the gonadotropin-releasing hormone (GnRH) antagonist protocol were randomly assigned to three different final follicular maturation trigger modes and timings: hCG 36 h before oocyte pick-up (OPU) (hCG trigger); GnRH agonist (GnRHag) 36 h before (OPU) and hCG on day of OPU (GnRHag trigger); and GnRHag and hCG, 40 and 34 h prior to OPU, respectively (double trigger). Pregnancy rate, number of oocytes, and top quality embryos (TQEs). Thirty-three poor responder patients were recruited and randomized to the different study groups. While there were no in-between groups’ differences in patients’ demographics and stimulation variables, patients in the double trigger group had a significantly higher number of TQE (1.1 ± 0.9 vs. 0.3 ± 0.8 and 0.5 + 0.7; p<.02) as compared to the hCG trigger and the GnRH-ag trigger groups, respectively, with an acceptable pregnancy rate. Double trigger offers an additional benefit to poor responder patients. Larger studies are required to support this new concept prior to its implementation to IVF practice.
Database construction for PromoterCAD: synthetic promoter design for mammals and plants.

Synthetic promoters can control a gene's timing, location, and expression level. The PromoterCAD web server ( http://promotercad.org ) allows the design of synthetic promoters to control plant gene expression, by novel arrangement of cis-regulatory elements. Recently, we have expanded PromoterCAD's scope with additional plant and animal data: (1) PLACE (Plant Cis-acting Regulatory DNA Elements), including various sized sequence motifs; (2) PEDB (Mammalian Promoter/Enhancer Database), including gene expression data for mammalian tissues. The plant PromoterCAD data now contains 22 000 Arabidopsis thaliana genes, 2 200 000 microarray measurements in 20 growth conditions and 79 tissue organs and developmental stages, while the new mammalian PromoterCAD data contains 679 Mus musculus genes and 65 000 microarray measurements in 96 tissue organs and cell types ( http://promotercad.org/mammal/ ). This work presents step-by-step instructions for adding both regulatory motif and gene expression data to PromoterCAD, to illustrate how users can expand PromoterCAD functionality for their own applications and organisms.
Associations among diet, the gastrointestinal microbiota, and negative emotional states in adults

ABSTRACT Objective: Habitual diet impacts mood and the human gastrointestinal (GI) microbiota. Yet, studies infrequently control for diet when evaluating associations between mood and GI microbiota. Accordingly, we aimed to investigate relationships among diet, GI microbiota, and mood in adults without mood disorders by conducting a cross-sectional examination of dietary intake, subjective emotional state, and fecal microbial taxa abundances. Methods: Adults (N = 133; 25–45 years of age) without physician-diagnosed mood disorders were studied. Fecal DNA was extracted, and the V4 region of the 16S rRNA gene was sequenced. Sequences were analyzed using QIIME2. Subjective mood state was assessed using the 42-item Depression, Anxiety, and Stress Scale (DASS-42). Habitual dietary intake was measured with the National Cancer Institute's Diet History Questionnaire II, and diet quality was evaluated with the 2010 Healthy Eating Index (HEI). Results: Relationships were observed between 28 bacterial taxa and DASS-42 scores. Sex-dependent associations were observed among 21 bacterial taxa and DASS-42 scores, including an inverse relationship between Anxiety scale scores and Bifidobacterium in females and an inverse relationship between Depression scale scores and Lactobacillus in males. HEI total fruit and dairy components were inversely associated with Depression and Stress scales, respectively. Conclusions: These results suggest GI microbes are related to mood in adults without diagnosed mood disorders and that these relationships differ by sex and are influenced by dietary fiber intake. Incorporating dietary intake data in gut-microbiota-brain studies may help clarify the roles of specific microbes and dietary components in mental health symptoms.
Propofol-based sedation does not negatively influence oxygenator running time compared to midazolam in patients with extracorporeal membrane oxygenation

Objective: Patients on extracorporeal membrane oxygenation are frequently in need for sedation. Use of propofol has been associated with impaired oxygenator function due to adsorption to the membrane as well as lipid load. The aim of our retrospective analysis was to compare two different sedation regimens containing either propofol or midazolam with respect to oxygenator running time. Methods: Midazolam was used in 73 patients whereas propofol was used in 49 patients, respectively. In the propofol group, veno-arterial–extracorporeal membrane oxygenation was used predominantly (84%), while veno-venous–extracorporeal membrane oxygenation was used more often in the midazolam group (64%). Results: Oxygenator running time until first exchange was 7 days in both groups (p = 0.759). No statistically significant differences could be observed between the subgroup of patients receiving lipid-free (n = 24) and lipid-containing (n = 31) parenteral nutrition, respectively. Laboratory parameters like triglycerides, free hemoglobin, fibrinogen, platelets, and activated partial thromboplastin time were not significantly different between both sedation regimens (p = 0.462, p = 0.489, p = 0.960, p = 0.134, and p = 0.843) and were not associated with oxygenator running time. Conclusion: The use of propofol as sedative seems suitable in patients undergoing extracorporeal membrane oxygenation therapy.
Internet-Delivered Cognitive Behavior Therapy for Young Taiwanese Female Nursing Students with Irritable Bowel Syndrome—A Cluster Randomized Controlled Trial

Irritable Bowel Syndrome (IBS) is prevalent within the general population. Studies have shown that stress and anxiety co-exist with IBS. Young Taiwanese women commonly exhibit physical and psychological health problems caused by academic stress. The purpose of our current study was to evaluate the efficacy of short-term Internet-delivered cognitive-behavioral therapy (ICBT) on female nursing students in practicum. We performed a cluster randomized controlled trial comprised of 160 participants who met the inclusion criteria, which were divided into three groups: (1) ICBT, (2) expressive writing (EW), and (3) wait-list control. Treatment interventions lasted for 6 weeks. Levels of anxiety, depression, and IBS symptoms were assessed at four time points, baseline assessment at T0, 2 weeks after T0 (T1), at the end of practicum (T2), and at 3-month follow-up (T3). The results showed that ICBT and EW groups exhibited a significant, yet small, reduction in anxiety and depression at T2 and T3 compared to the wait-list control group. The EW group exhibited significantly greater reduction in anxiety and depression compared to the ICBT group at T2. However, the ICBT group demonstrated greater improvements in alleviating anxiety and depression at T3 compared to the EW group. These data indicate that ICBT and EW groups exhibited small effects on anxiety and depression reduction at T2 and T3 compared to the wait-list control group, with no effects on IBS symptoms in young Taiwanese female nursing students.
Answer to March 2019 Photo Quiz

Answer: Brucellosis caused by Brucella melitensis. The organism was identified as Brucella species using 16S rRNA gene sequencing at the reference laboratory and subsequently confirmed as Brucella melitensis with Bruce-ladder multiplex PCR at the Centers for Disease Control and Prevention (CDC) ([1
Transcript Isoforms of Promyelocytic Leukemia in Mouse Male and Female Gametes

Promyelocytic leukemia (PML) nuclear bodies and proteins have been implicated in many functions of the nucleus. It is not known whether the PML gene is transcribed and expressed as PML nuclear bodies in gamete cells or in the early mammalian embryo. In this study using reverse transcription-polymerase chain reaction and immunocytochemistry we show the presence of PML transcripts and identify their variants in the mature mouse gametes. Mature sperm contains isoform II; however, oocyte contains transcript isoforms I, II, and possibly other unknown isoforms of PML. This indicates that the mature gametes may carry the transcripts to the newly created embryo. We also show that sperm and oocyte cells do not contain PML nuclear bodies. We find that the first appearance of PML nuclear bodies is in the 2-cell-stage mouse embryo. Appearance of PML nuclear bodies in the 2-cell-stage embryo may correspond to the major transcriptional activity of the embryonic genome. In summary, this report emphasizes the necessity to perform further experiments to investigate the presence and function of PML transcripts and nuclear bodies in earlier stages of germ cell and also later stages of the preimplantation development.
Influence of Silicodactyly in the Preparation of Hybrid Materials

The organic–inorganic hybrid materials have attracted great attention due to their improved or unusual properties that open promising applications in different areas such as optics, electronics, energy, environment, biology, medicine and heterogeneous catalysis. Different types of silicodactyl platforms grafted on silica inorganic supports can be used to synthesize hybrid materials. A careful evaluation of the dactyly of the organic precursors, normally alkoxysilanes, and of the type of interaction with the inorganic supports is presented. In fact, depending on the hydrophilicity of the silica surface (e.g., number and density of surface silanols) as well as on the grafting conditions, the hydrolysis and condensation reaction of the silylated moieties can involve only one or two out of three alkoxysilane groups. The influence of silicodactyly in the preparation of organic-inorganic silica-based hybrids is studied by TGA, 29Si, 1H and 13C solid-state NMR and FTIR spectroscopies, with the support of Molecular Dynamics calculations. Computational studies are used to forecast the influence of the different grafting configurations on the tendency of the silane to stick on the inorganic surface.
Ozone and Wounding Stresses Differently Alter the Temporal Variation in Formylated Phloroglucinols in Eucalyptus globulus Leaves

Formylated phloroglucinol compounds (FPCs) are a class of plant specialized metabolite present in the Myrtaceae family, especially in the genus Eucalyptus. FPCs are widely investigated due to their herbivore deterrence properties and various bioactivities of pharmaceutical relevance. Despite the increasing number of studies elucidating new FPCs structures and bioactivity, little is known about the role of those compounds in planta, and the effects of environmental stresses on FPC concentration. Ozone (O3) and wounding are key stress factors regularly confronted by plants. In this study, we investigated how O3, wounding, and their combination affected individual and total FPC foliar concentration of the economically important species Eucalyptus globulus. Six individual FPCs, including five macrocarpals and one sideroxylonal, showed different response patterns to the single and combined stresses. Total macrocarpals only increased under single O3 treatment, whereas total sideroxylonals only increased in response to wounding treatment, suggesting different physiological roles played by the two groups of FPCs predominantly existing in E. globulus foliage. Total FPCs increased significantly under individual wounding and O3 treatments but not under the combined treatment. A principal component analysis indicated that all different treatments had unique FPC fingerprints. Total phenolic contents increased in all O3 and wounding treatments, and a marginally positive correlation was found between total FPCs and total phenolic contents. We suggest that, depending on the concentration and composition, FPCs play multiple physiological roles in planta, including serving as antioxidants to scavenge the reactive oxygen species brought about by O3 and wounding stresses.