Miracle-dz/UniFAR-FTUs huggingface dataset:
EFFECT OF BONE MORPHOGENETIC PROTEIN‐6 ON HAEMOPOIETIC STEM CELLS AND CYTOKINE PRODUCTION IN NORMAL HUMAN BONE MARROW STROMA

Normal human bone marrow stroma cells include stem cells for both haemopoietic and osteochondrogenic lineages and express both bone morphogenetic protein (BMP) type I and type II receptors. As a member of the TGF‐β super‐family, BMP‐6 binds to both BMP type I and type II receptors and is involved in the developmental processes of renal and hepatic systems as well as of human foetal intestine. Also, BMP‐6 induces osteoblastic differentiation of pluripotent mesenchymal cells and is an autocrine stimulator of chondrocyte differentiation. The present study was carried out to investigate the effect of BMP‐6 on human cobblestone‐area‐forming cells (CAFC), that represent the functional primitive repopulating haemopoietic stem cell in long‐term bone marrow culture. Also, the effect of BMP‐6 on marrow stroma production of interleukin‐6, −11 and their common receptor gp130 that is expressed in haemopoietic stem cells and is indispensable for their proliferation and tri‐lineage differentiation was examined. Moreover, the effect of BMP‐6 on marrow stroma release of soluble adhesion molecule VCAM‐1 mediating the primitive haemopoietic stem cell adhesion to marrow stroma was examined. The number of CAFC was significantly reduced after BMP‐6 treatment from 88±10 per 105cells in control cultures in a dose dependent manner to only 48±3 per 105cells in 50ng/ml BMP‐6‐treated cultures, P< 0.01. Quantitative ELISA measurement revealed 50ng/ml BMP‐6 was able to significantly reduce IL‐6 and IL‐11 production from marrow stroma, P< 0.01. Also, BMP‐6 significantly increased soluble gp130 release by 7.4‐fold in 50ng/ml BMP‐6‐treated marrow stroma cultures. The profound rapid increase in this natural antagonist of human IL‐6 cytokine family may reduce the gp130 signaling. Also, the soluble VCAM‐1 released increased by two‐fold in 50ng/ml BMP‐6‐treated marrow stroma cultures. The marked increase in the soluble form may exert an antagonist effect on the function of VCAM‐1 (ligand for VLA4). Recently, blocking the VLA4/VCAM‐1 adhesion pathway was shown to mobilise haemopoietic CD34 positive cells in normal individuals. Also, we previously observed a significantly lower expression of VLA4 (CD49d) on G‐CSF‐mobilised blood CD34 positive cells than on bone marrow CD34 positive cells before mobilisation in the same normal donors. Since BMP are currently being used in clinical trials for bone repair and fracture healing, the present results suggest a possible role for BMP‐6 in mobilising CD34 positive cells for transplantation. Further in vitro tests are required to evaluate this potential mobilising role of BMP‐6 in human long‐term bone marrow culture.
Safety and efficacy of paclitaxel drug-coated balloon in femoropopliteal in-stent restenosis

ABSTRACT Introduction The femoropopliteal (FP) segment is a common site of involvement in peripheral arterial disease (PAD) and endovascular therapy has been shown to be safe and effective in the treatment of FP disease. Self-expanding nitinol stents are now frequently used for the treatment of FP disease but in-stent restenosis (ISR) remains a major issue that can lead to recurrence of symptoms requiring repeated revascularizations. Compared to plain old balloon angioplasty (POBA), drug-coated balloons (DCBs) have shown promising results with reduction of ISR rates and target lesion revascularization (TLR). Areas covered The aim of this review is to describe the mechanisms and classification of ISR and to summarize the available data on outcomes of all DCBs, especially in the treatment of FP ISR. Expert opinion Currently available data supports the use of DCBs as a first-line therapy in patients with FP ISR, with lower rates of TLR and higher patency rates at 1-year follow-up, when compared to POBA. Further randomized studies are essential to evaluate longer term safety and efficacy of DCBs.
Mentorship and protégé success in STEM fields

Significance Mentorship is arguably a scientist’s most significant collaborative relationship; yet of all collaborations, comparatively little research exists on the link between mentorship and protégé success. Using new large-scale data from the genealogical and performance records of 10s of thousands of scientists worldwide from 1960 to the present, we found that mentorship is associated with diverse forms of protégé success, significantly increasing protégés’ chances of producing celebrated research, being inducted into the National Academy of Science, and achieving superstardom. Paradoxically, protégés achieve their highest impact when they display intellectual independence from their mentors. Protégés do their best work when they break from their mentor’s research topics and coauthor no more than a small portion of their overall research with their mentors. Einstein believed that mentors are especially influential in a protégé’s intellectual development, yet the link between mentorship and protégé success remains a mystery. We marshaled genealogical data on nearly 40,000 scientists who published 1,167,518 papers in biomedicine, chemistry, math, or physics between 1960 and 2017 to investigate the relationship between mentorship and protégé achievement. In our data, we find groupings of mentors with similar records and reputations who attracted protégés of similar talents and expected levels of professional success. However, each grouping has an exception: One mentor has an additional hidden capability that can be mentored to their protégés. They display skill in creating and communicating prizewinning research. Because the mentor’s ability for creating and communicating celebrated research existed before the prize’s conferment, protégés of future prizewinning mentors can be uniquely exposed to mentorship for conducting celebrated research. Our models explain 34–44% of the variance in protégé success and reveals three main findings. First, mentorship strongly predicts protégé success across diverse disciplines. Mentorship is associated with a 2×-to-4× rise in a protégé’s likelihood of prizewinning, National Academy of Science (NAS) induction, or superstardom relative to matched protégés. Second, mentorship is significantly associated with an increase in the probability of protégés pioneering their own research topics and being midcareer late bloomers. Third, contrary to conventional thought, protégés do not succeed most by following their mentors’ research topics but by studying original topics and coauthoring no more than a small fraction of papers with their mentors.
Influence of Temperature on Copula Duration and Mating Propensity in Lucilia cuprina Wiedemann (Diptera: Calliphoridae)

There was a logarithmic decline in copula duration with increasing temperature in adult L. cuprina. Copula duration varied from 26 min at 17°C to 7 min at 41°C. Temperature had no effect on the time from pairing to the first mating attempt. the frequency of mating attempts by males increased with rising temperatures between 15–30°C, but declined at >30°C. the time from pairing to the start of mating was quickest at 25 °C, declining with increasing temperatures. the optimal temperature for mating was between 25–30 °C, when frequency of mating attempts and the proportion of flies mating were highest, whilst time from pairing to both the first mating attempt and the start of mating were lowest. the temperature threshold for mating was around 16°C.
Flavonoids in Cancer Metastasis

Metastasis represents a serious complication in the treatment of cancer. Flavonoids are plant secondary metabolites exerting various health beneficiary effects. The effects of flavonoids against cancer are associated not only with early stages of the cancer process, but also with cancer progression and spread into distant sites. Flavonoids showed potent anti-cancer effects against various cancer models in vitro and in vivo, mediated via regulation of key signaling pathways involved in the migration and invasion of cancer cells and metastatic progression, including key regulators of epithelial-mesenchymal transition or regulatory molecules such as MMPs, uPA/uPAR, TGF-β and other contributors of the complex process of metastatic spread. Moreover, flavonoids modulated also the expression of genes associated with the progression of cancer and improved inflammatory status, a part of the complex process involved in the development of metastasis. Flavonoids also documented clear potential to improve the anti-cancer effectiveness of conventional chemotherapeutic agents. Most importantly, flavonoids represent environmentally-friendly and cost-effective substances; moreover, a wide spectrum of different flavonoids demonstrated safety and minimal side effects during long-termed administration. In addition, the bioavailability of flavonoids can be improved by their conjugation with metal ions or structural modifications by radiation. In conclusion, anti-cancer effects of flavonoids, targeting all phases of carcinogenesis including metastatic progression, should be implemented into clinical cancer research in order to strengthen their potential use in the future targeted prevention and therapy of cancer in high-risk individuals or patients with aggressive cancer disease with metastatic potential.
Optimization of microRNA Acquirement from Seminal Plasma and Identification of Diminished Seminal microRNA-34b as Indicator of Low Semen Concentration

About 10–15% of couples who want to conceive suffer from subfertility, while in 30% of these cases, a male factor plays a role. Levels of particular microRNAs in seminal plasma, including those involved in spermatogenesis, may serve as an indicative parameter for subfertility. We first optimized a protocol for acquiring microRNAs from seminal plasma. Next, using a test-validation strategy in a male cohort, we aimed to identify microRNAs of which the levels are related to semen motility and concentration. By qPCR, 742 microRNAs were profiled in three normozoospermic samples, three seminal samples with a low semen motility (asthenozoospermia), and three with a low semen concentration (oligozoospermia). MicroRNAs showing significant differences between groups were further validated in a second cohort consisting of 40 samples with normozoospermia (control group), 47 samples with asthenozoospermia, and 19 samples with oligozoospermia (of which 74% also low motility). Highest microRNA yields were obtained with the Biofluids RNA extraction kit, with inclusion of MS2 RNA carrier and proteinase K treatment to the protocol, and when 50 µL of seminal plasma was used as input. Exosome isolation prior to RNA extraction did not lead to enhanced yields. In the test cohort, 236 microRNAs could be detected, of which 54 microRNAs showed a difference between groups. Five microRNAs were analyzed in the validation cohort. MiR-34b-5p levels in the control group were significantly higher compared to the asthenozoospermia group (p < 0.05) and compared to the oligozoospermia group (p < 0.001). We optimized microRNA acquirement from seminal plasma and identified microRNA levels in relation to semen concentration and motility. As recent human and mouse studies show that the miR-34 family is a marker of low semen concentration and is crucial in spermatogenesis, seminal plasma miR-34b-5p may represent a suitable candidate to study further as a marker of male subfertility.
The Monimiaceae and a New Laurelia

The family Monimiaceae does not reach the North Temperate zone, consequently it is unfamiliar to students of fossil floras who have largely lived in that zone. It is a family cf great interest to students of plant distribution. Small in size, it contains between 25 and 30 genera and between I75 and 200 species. Systematists have usually recognized a relationship with the Lauraceae and now both families are included in the order Laurales. With the exception of Laurelia, no genus is common to both the Old and the New Worlds. Three genera are confined to New Caledollia and only Tambourissa of the Old World genera is found in more than one continental area. Nearly half of the known genera are monotypic in the existing flora. But two genera have more than a few species) and both of these, Mollixedia and Siparu>sa, with more than I00 species between them, are confined to America. The pertinent facts of the modern distribution are summarized on the accompanying map (flg. I), to which the reader is referred in lieu of a lengthy discussion. Only the following six genera have been recognized in the fossil state: Hedycaria, Peumus, Mollinedia, Moxirnia, Laurelia, and Siparuna, and several of these are of somewhat uncertain status. In addition SAPORTA described three species from the basal Eocene of France for which he proposed the extinct genus MonimioSsis. Four species of Hedycaria have been recorded from the Oligocene and Miocene of Europe and a flfth from the Tertiary of Australia. The genus Mollinedia has been recorded from the European Miocene and from the Tertiary of Seymour Island. Monimia has been recorded from the Oligocene of southern Europe and from Australia. Siparuxa has been recognized in a warm climate Eocene flora from Oregon and it seems likely that it may be represented in the Eocene floras of southeastern North America. Sis fossil species have been referred to Laurelia, and these are
Metal Nanoparticles in Infection and Immunity

ABSTRACT Background Enthusiasm for the use of metal nanoparticles in human and veterinary medicine is high. Many articles describe the effects of metal nanoparticles on microbes in vitro, and a smaller number of articles describe effects on the immune system, which is the focus of this review. Methods Articles were retrieved by performing literature searches in Medline, of the National Institute of Medicine, as well as via Google Scholar. Results In vitro studies show that metal nanoparticles have antimicrobial effects. Some metal nanoparticles augment innate host immune defenses, such as endogenous antimicrobial peptides, and nitric oxide. Metal nanoparticles may also function as vaccine adjuvants. Metal nanoparticles can migrate to locations distant from the site of administration, however, requiring careful monitoring for toxicity. Conclusions Metal nanoparticles show a great deal of potential as immunomodulators, as well as direct antimicrobial effects. Before metal particles can be adopted as therapies; however, more studies are needed to determine how nanoparticles migrate though the body and on possible adverse effects.
Effect of berberine on LPS-induced expression of NF-κB/MAPK signalling pathway and related inflammatory cytokines in porcine intestinal epithelial cells

Berberine is an alkaloid extracted from medicinal plants such as Coptis chinensis and Phellodendron chinense. It possesses anti-inflammatory, anti-tumour and anti-oxidation properties, and regulates Glc and lipid metabolism. This study explored the mechanisms of the protective effects of berberine on barrier function and inflammatory damage in porcine intestinal epithelial cells (IPEC-J2) induced by LPS. We first evaluated the effects of berberine and LPS on cell viability. IPEC-J2 cells were treated with 5 μg/ml LPS for 1 h to establish an inflammatory model, and 75, 150 and 250 μg/ml berberine were used in further experiments. The expression of IL-1β, IL-6 and TNF-α was measured by RT-PCR. The key proteins of the NF-κB/MAPK signalling pathway (IκBα, p-IκBα, p65, p-p65, c-Jun N-terminal kinase (JNK), p-JNK, p38, p-p38, ERK1/2 and p-ERK1/2) were detected by Western blot. Upon exposure to LPS, IL-1β, IL-6 and TNF-α mRNA levels and p-IκBα p-p65 protein levels were significantly enhanced. Pre-treatment with berberine reduced the expression of inflammatory factors and was positively correlated with its concentration, and dose dependently inhibited the expression of IκBα, p-IκBα, p-p65, p-p38 and JNK. These results demonstrated that pre-treating intestinal epithelial cells with berberine was useful in preventing and treating diarrhoea induced by Escherichia coli in weaned pigs.
Characterization of the Vaginal Microbiome in Women of Reproductive Age From 5 Regions in Brazil

Nearly two thirds of reproductive-aged Brazilian women have either a Lactobacillus-depleted or a Lactobacillus iners–dominated microbiota, and thus at increased risk for sexually transmitted infections. Ethnicity was not associated with microbiome. Supplemental digital content is available in the text. Background Composition of the vaginal microbiome is strongly related to a woman's reproductive health and risk of sexually transmitted infections. Ethnoracial, behavioral, and environmental factors can influence microbiome. The Brazilian population is unique in terms of miscegenation of ethnic groups and behavioral characteristics across different regions. We aimed to characterize the vaginal microbiome of women from 5 geographical regions of Brazil. Methods We sequenced V3–V4 regions of 16S rRNA gene in vaginal samples of 609 reproductive-aged women. We performed logistic regression analyses to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between sociodemographic and behavioral factors with Lactobacillus-depleted microbiome (community state type [CST] IV). Results Vaginal samples were grouped into 5 CST: CST I (L. crispatus predominant, 30.5%), CST II (L. gasseri predominant, 4.4%), CST III (Lactobacillus iners predominant, 36.5%), CST IV (Lactobacillus-depleted, 27.4%), and CST V (L. jensenii predominant, 1.2%). Several factors were independently associated with CST IV, such as smoking (OR, 1.80; 95% CI, 1.02–3.18), number of partners (OR, 2.11; 95% CI, 1.20–3.70), and vaginal douching (OR, 2.24; 95% CI, 1.34–3.74). A protective effect was observed for milk/dairy intake (OR, 0.47; 95% CI, 0.27–0.82) and sitz bathing (OR, 0.43; 95% CI, 0.19–0.98). Conclusions Nearly two thirds of Brazilian women may be at an increased risk for adverse outcomes associated with a vaginal microbiota characterized by the depletion of Lactobacillus or dominance by L. iners, whose protective role has been widely questioned. Several factors related to sexual behavior and intimate hygiene were associated with CST IV.
Effect of growth regulators on quality of ber (Zizyphus mauritiana Lamk) cv. Umran.

There is huge potential to improve market acceptability of ber with application of growth regulators. Significant increase in fruit size traits i.e. fruit length, breadth, weight and volume was recorded with application of NAA 30 ppm. The palatability rating of fruits in terms of taste, colour and texture of fruit was recorded maximum with application of GA3 50 ppm. For the stone related traits, the maximum reduction in stone breadth and percentage was recorded with NAA 30 ppm. There was no significant variation in stone length and weight with growth regulators.
Fuzzy Sampled-Data Control for Synchronization of T–S Fuzzy Reaction–Diffusion Neural Networks With Additive Time-Varying Delays

This article focuses on the exponential synchronization problem of T–S fuzzy reaction–diffusion neural networks (RDNNs) with additive time-varying delays (ATVDs). Two control strategies, namely, fuzzy time sampled-data control and fuzzy time–space sampled-data control are newly proposed. Compared with some existing control schemes, the two fuzzy sampled-data control schemes cannot only tolerate some uncertainties but also save the limited communication resources for the considered systems. A new fuzzy-dependent adjustable matrix inequality technique is proposed. According to different fuzzy plant and controller rules, different adjustable matrices are introduced. In comparison with some traditional estimation techniques with a determined constant matrix, the fuzzy-dependent adjustable matrix approach is more flexible. Then, by constructing a suitable Lyapunov–Krasovskii functional (LKF) and using the fuzzy-dependent adjustable matrix approach, new exponential synchronization criteria are derived for T–S fuzzy RDNNs with ATVDs. Meanwhile, the desired fuzzy time and time–space sampled-data control gains are obtained by solving a set of linear matrix inequalities (LMIs). In the end, some simulations are presented to verify the effectiveness and superiority of the obtained theoretical results.
Female Mating Behaviour and Multiple Matings in the Fly, Dryomyza Anilis

Multiple matings by females of the fly, Dryomyza anilis, were studied at small carcasses where they arrived to lay their eggs. Males of the species are territorial and fight over females and their oviposition sites. Arriving females were quickly captured by males and male fights over females as well as take-overs were common. The average number of matings per female was 2.8 and the average time a female spent at the carcass was 1 h 49 min (from arrival to the end of oviposition). The total mating time was almost twice as long in females which mated over five times than in females which had only one mating. The increase in mating time with increasing number of mating was totally due to the increase in time spent in copulation bouts (the species copulates and oviposits in several bouts). In attacks by lone males resulting in the separation of a pair, the attacker continued with the female in only one half of the cases (take-overs). In the other half a third male captured the female after she had escaped from the struggling males. In successful take-overs the new mate was usually larger than the earlier mate whereas in the other cases the new mate was almost always smaller than the earlier mate. Female resistance during matings was common and the various conflict behaviours are described. Female resistance became stronger in consecutive matings and within the same mating females resisted earlier in the second copulation bout than in the first one. In addition, larger females resisted more per mating, spent less time in copulation bouts per mating and had fewer matings than small females. Some possible costs and benefits of multiple matings were studied. Owing to male mating behaviour, where females are taken away from the carcass, females may loose feeding opportunities which can reduce their egg production. Male mating behaviour also delays female oviposition which can put the larvae in a worse position in food competition with other earlier larvae. Females arriving at carcasses to lay eggs face a situation where they can benefit from male guarding during oviposition but male fighting and take-overs can result in a long chain of matings which is disadvantageous for them.
Chromatin Trapping of Factors Involved in DNA Replication and Repair Underlies Heat-Induced Radio- and Chemosensitization

Hyperthermia has been used as an adjuvant treatment for radio- and chemotherapy for decades. In addition to its effects on perfusion and oxygenation of cancer tissues, hyperthermia can enhance the efficacy of DNA-damaging treatments such as radiotherapy and chemotherapy. Although it is believed that the adjuvant effects are based on hyperthermia-induced dysfunction of DNA repair systems, the mechanisms of these dysfunctions remain elusive. Here, we propose that elevated temperatures can induce chromatin trapping (c-trapping) of essential factors, particularly those involved in DNA repair, and thus enhance the sensitization of cancer cells to DNA-damaging therapeutics. Using mass spectrometry-based proteomics, we identified proteins that could potentially undergo c-trapping in response to hyperthermia. Functional analyses of several identified factors involved in DNA repair demonstrated that c-trapping could indeed be a mechanism of hyperthermia-induced transient deficiency of DNA repair systems. Based on our proteomics data, we showed for the first time that hyperthermia could inhibit maturation of Okazaki fragments and activate a corresponding poly(ADP-ribose) polymerase-dependent DNA damage response. Together, our data suggest that chromatin trapping of factors involved in DNA repair and replication contributes to heat-induced radio- and chemosensitization.