Miracle-dz/UniFAR-FTUs huggingface dataset:
Fadraciclib (CYC065), a novel CDK inhibitor, targets key pro-survival and oncogenic pathways in cancer

Cyclin-dependent kinases (CDKs) contribute to the cancer hallmarks of uncontrolled proliferation and increased survival. As a result, over the last two decades substantial efforts have been directed towards identification and development of pharmaceutical CDK inhibitors. Insights into the biological consequences of CDK inhibition in specific tumor types have led to the successful development of CDK4/6 inhibitors as treatments for certain types of breast cancer. More recently, a new generation of pharmaceutical inhibitors of CDK enzymes that regulate the transcription of key oncogenic and pro-survival proteins, including CDK9, have entered clinical development. Here, we provide the first disclosure of the chemical structure of fadraciclib (CYC065), a CDK inhibitor and clinical candidate designed by further optimization from the aminopurine scaffold of seliciclib. We describe its synthesis and mechanistic characterization. Fadraciclib exhibits improved potency and selectivity for CDK2 and CDK9 compared to seliciclib, and also displays high selectivity across the kinome. We show that the mechanism of action of fadraciclib is consistent with potent inhibition of CDK9-mediated transcription, decreasing levels of RNA polymerase II C-terminal domain serine 2 phosphorylation, the pro-survival protein Myeloid Cell Leukemia 1 (MCL1) and MYC oncoprotein, and inducing rapid apoptosis in cancer cells. This cellular potency and mechanism of action translate to promising anti-cancer activity in human leukemia mouse xenograft models. Studies of leukemia cell line sensitivity identify mixed lineage leukemia (MLL) gene status and the level of B-cell lymphoma 2 (BCL2) family proteins as potential markers for selection of patients with greater sensitivity to fadraciclib. We show that the combination of fadraciclib with BCL2 inhibitors, including venetoclax, is synergistic in leukemic cell models, as predicted from simultaneous inhibition of MCL1 and BCL2 pro-survival pathways. Fadraciclib preclinical pharmacology data support its therapeutic potential in CDK9- or CDK2-dependent cancers and as a rational combination with BCL2 inhibitors in hematological malignancies. Fadraciclib is currently in Phase 1 clinical studies in patients with advanced solid tumors (NCT02552953) and also in combination with venetoclax in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) (NCT03739554) and relapsed refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) (NCT04017546).
Summer fluctuations of microbial planktonic communities in a eutrophic lake—Cierva Point, Antarctica

A eutrophic lake at Cierva Point, Antarctic Peninsula was surveyed during the summers of 1997 and 1998. Phytoplankton size fractions (micro-, nano- and picoplankton) were analysed, as well as the abundance of bacterioplankton and planktonic ciliates. No permanent vertical stratification was found owing to the shallowness of the lake. Both nutrient concentrations and chlorophyll a values indicated highly eutrophic conditions, which are a consequence of a natural enrichment by seabirds. Significant differences in temperature between the 1997 and 1998 seasons strongly influenced most of the biological features. The phytoplankton community showed a high algal species-richness, with important contributions of epilithic, cryobiontic and soil algae. The dominant algal group was Chlorophyta, mainly represented by Chlamydomonas aff. celerrima, followed by Chl. aff. braunii. Some replacement of phytoplanktonic species took place in summer and was more evident in 1998. Picophytoplankton reached high densities, similar to those reported from other Antarctic lakes. Bacterioplankton abundances were typical of eutrophic and hypereutrophic lakes. There was a positive correlation between bacterial and total phytoplankton abundance. Ciliates reached some very high peaks, with higher figures than those reported for other Antarctic systems with similar trophic status.
Pollination Biology and Seed Production of a Federally Endangered Perennial, Echinacea laevigata (Asteraceae∶Heliantheae)

Abstract Pollination biology and factors affecting reproductive success of the federally endangered Echinacea laevigata (coneflower) were studied in one large and five small populations. Insect visitor exclusion from flowering heads and pollination treatments showed that seed production was 10x higher in open-pollinated treatments compared to bagged flowers that were not pollinated and 20x higher than flower heads receiving self pollen suggesting that cross-pollination was responsible for most seed production. Peak flowering occurred the 2nd–4th wk of Jun. 2004 and the large population contributed 50–68% of the flowering individuals in its plant community. During this period, Bombus (Apidae, bumblebees), Hesperiidae (skippers), and Megachile (Megachilidae, leaf-cutter bees) accounted for 73%, 12%, and 11% of the observed visits to coneflower, respectively. Species richness of coneflower flower visitors and number of flower visits was lower in each small population than in the large population. However, comparison of seed production between heads receiving supplemental pollen and open-pollination heads indicated that seed production was not pollen limited. In addition, over 93% of pollen grains stained normally in cotton blue-lactophenol in all six populations suggesting that pollen viability was high in small and large populations. However, seed production in the large population exceeded that in each of three small populations during 2005, and seedling size was larger in the large population compared to seedlings from one of the small populations. Comparison of soil cation concentrations among populations suggested that cations did not limit seed production. We suggest that genetic factors, such as inbreeding or low S allele variation, may limit seed production in the small populations.
Management and experience of postural placement in postoperative mechanical ventilation of newborns.

BACKGROUND Congenital diaphragmatic hernia (CDH) is a neonatal condition that mainly occurs when the abdominal organs herniate into the thorax, obstructing the development of the lungs. Postoperative neonatal breathing disorder is one of the main causes of neonatal death. This study summarizes the postoperative nursing status of 30 cases of neonatal CDH in our hospital, and explores the effect of body position in mechanical ventilation care following CDH surgery. METHODS A total of 30 CHD children admitted in our hospital between June, 2018 and October, 2019 were included. The neonates were divided into preterm infant group (n=15) and full-term infant group (n=15). Each child was immediately transferred to the newborn intensive care unit (NICU) ward after surgery and received the hospital's NCIU special care. Besides routine nursing, each child was placed in a randomly selected primary position (the prone position or supine position). After 30 min, their oxygenation indexes were measured, and then their position (prone position or supine position) was changed. After 30 min, the neonates' oxygenation indicators were measured again. A hospital-made satisfaction questionnaire was used to evaluate the parents' satisfaction with nursing care. RESULTS Two children died of respiratory failure (one in the preterm group and one in the full-term group), and the rest were in a stable condition after surgery. There was no significant difference between the rates of parent satisfaction in the two groups (preterm infant group: 96.67% verse full-term group: 93.33%, P>0.05). In both groups, the partial pressure of oxygen in arterial blood (PaO2), partial pressure of oxygen in arterial blood/fraction of inspiration O2 (PaO2/FiO2), and partial pressure of oxygen in arterial blood/partial pressure of oxygen in the alveolar gas (PaO2/PAO2) in prone position were significantly higher than those in supine position (P<0.05); the alveolar-arterial oxygen difference (A-aDO2) was significantly lower than that in the supine position (0.05). CONCLUSIONS The prone position can improve the oxygenation index of children after surgery, and improve their respiratory system function. This method is suitable for newborn postoperative NICU care.
Construction of superior Streptomyces noursei fusants for nystatin and antibacterial antibiotics production

The main goal of the present study is to increase the productivity of nystatin and antibacterial antibiotics produced by Streptomyces noursei NRRL 1714 through treatment with ultraviolet rays (UV) followed by intraspecific protoplast fusion. Out of 114 mutants obtained after UVmutagenesis, three (2.63%) mutants produced at least 49% more nystatin than the original strain and at the same time gave 66% and 78% increases in inhibition zone diameters with Micrococcus luteus NRRL 287. Therefore, an experiment by thin-layer chromatography (TLC) was carried out to detect the produced antibiotics by some selected superior mutants in comparison with the wild type strain. The obtained results from TLC suggested that the improvement of the produced antibiotics was not only in quantity but also in quality. Finally, through antibacterial resistance markers, two different crosses at the intraspecific protoplast fusion level were carried out and thirty three true recombinants were obtained from these crosses. All the obtained fusants proved to be at least 10% higher nystatin producers than the higher parent and at the same time, some fusants gave the same or more than their parents activity against M. luteus, while no fusant was less in activity against M. luteus.
Estimation of Hybridization and Introgression Frequency in Toads (Genus: Bufo) Using DNA Sequence Variation at Mitochondrial and Nuclear Loci

Abstract Habitat disturbance leading to the breakdown of ecological barriers has resulted in hybridization between numerous sympatric species and the decline or extinction of the parental species. Despite strong postzygotic selection, hybridization occurs between two normally ecologically isolated toad species, the Gulf Coast Toad (Bufo nebulifer) and Fowler's Toad (Bufo fowleri). This hybridization has potentially contributed to a decline of the rarer species, B. fowleri. Putative hybrids may be morphologically cryptic; therefore, molecular methods were used to identify them. We used single nucleotide polymorphisms (SNPs) to identify hybrids, and mitochondrial sequence variation in a segment of the 12S and 16S rRNA region was also used to identify maternal ancestry of hybrids and seek evidence of directional hybridization and introgression of male B. nebulifer with female B. fowleri. Seventy-two individuals of both species from nine breeding populations were directly sequenced. Twelve species-specific SNPs from a 333 base pair fragment in a nuclear intron of the Rhodopsin gene were used to identify each species, and two male hybrids were identified based on heterozygosity at these sites. The possession of a different mtDNA sequence by each hybrid indicated an alternate maternal lineage from each of the parental species and identified the hybrids as progeny from each reciprocal cross. Use of mitochondrial and nuclear molecular markers allowed unambiguous identification of hybrids and their maternal parent that could not have been performed without the use of both datasets. We also investigated phylogenetic relationships among B. fowleri and its close relatives in the B. americanus species complex using mitochondrial sequence variation.
Fishing Tactics in a Two-Species Fisheries Model: The Bioeconomics of Bycatch and Discarding

The selections for fishing location largely determine the species mix and value of a fisher's catch. Because of travel costs, these choices also determine the profitability of a fishing trip. This paper develops a simple theoretical model for the selection of fishing locations by a fisher faced with two co-occurring species whose densities vary with distance from port. For each species there can be different catchability coefficients, handling times, and prices. The duration of each fishing trip is assumed fixed. The model is used to determine the profit-maximizing fishing tactics (the fishing locations and time spent at each location) and to explore the conditions that generate deliberate bycatch and discarding when one of the species cannot be sold because it is unmarketable or because of trip limits.
Changes in growth and yield components of Brassica napus in response to Azotobacter inoculation at different rates of nitrogen application

SUMMARY Inoculation of Brassica napus cv. ISN–129 with Azotobacter chroococcum following the application of different amounts of nitrogen produced the greatest increase in seed yield and total dry matter when no external nitrogen had been applied. The yield increase in response to inoculation could be attributed to a greater number of primary branches and pods, associated with a higher leaf area index, particularly at the pod-filling stage, and a faster crop growth rate.
Evaluation of EPA's rapid bioassessment benthic metrics: Metric redundancy and variability among reference stream sites

The data analysis scheme used in the U.S. Environmental Protection Agency's (EPA's) rapid bioassessment protocols (RBPs) integrates several community, population, and functional parameters (or metrics) into a single assessment of biological condition. A reference data base of macroinvertebrate data obtained from 10 ecoregions in Oregon, Colorado, and Kentucky was used to evaluate the appropriateness and variability of the benthic metrics and the similarities of results among ecoregions. Several statistical procedures, including principal component analysis, correlation coefficient, analysis of variance, and stepwise discriminant analysis, were used to test the efficacy of 17 community metrics. A general separation between the mountain ecoregions and the valley/plains ecoregions was determined to exist for the metrics. Two of the original eight metrics described in the EPA's RBPs for benthic macroinvertebrates were found to be highly variable and unreliable as measures of biological conditions in some ecoregions. Eleven metrics were determined as being valuable in discriminating between montane and valley/plains groupings of ecoregions.
Cell-wall pectin and its degree of methylation in the maize root-apex: significance for genotypic differences in aluminium resistance

Cell-wall (CW) pectin content and its degree of methylation in root apices of selected maize cultivars were studied in relation to genotypic Al resistance. Maize cultivars differing in Al resistance were grown in nutrient solution treated with or without Al, and pectin content of the root tips was determined. Control plants did not differ in pectin content in the 5 mm root apex. Al treatment increased the pectin content of the root apex in all cultivars but more prominently in the Al-sensitive cultivars. Pectin and Al contents in 1 mm root sections decreased from the apex to the 3-4 mm zone. Pectin contents of the apical root sections were consistently higher although significantly different only in the 1-2 mm zone in the Al-sensitive cv Lixis. Al contents in most root sections were significantly higher in cv Lixis than in Al-resistant cv ATP-Y. Localization of pectins by immunofluorescence revealed that Al-sensitive cv. Lixis has a higher proportion of low-methylated pectin and thus a higher negativity of the cell wall than Al-resistant cv ATP-Y. This is in agreement with the higher Al content and Al sensitivity of cv Lixis. It is concluded that differences in CW pectin and its degree of methylation contribute to genotypic differences in Al resistance in maize in addition to the release of organic acid anions previously reported.
Detection of Kanamycin-ResistantMycobacterium tuberculosis by Identifying Mutations in the 16S rRNA Gene

ABSTRACT In Mycobacterium smegmatis and a limited number ofMycobacterium tuberculosis strains, the involvement of alterations of the 16S rRNA gene (rrs) in resistance to kanamycin has been shown. To investigate the extent to which mutations in a specific region of the rrs gene and the kanamycin-resistant phenotype in clinically isolated M. tuberculosis strains were correlated, 43 kanamycin-resistant strains (MICs, ≧200 μg/ml), 71 kanamycin-susceptible strains, and 4 type strains were examined. The 300-bp DNA fragments carrying therrs gene and the intervening sequence between therrs gene and 23S rRNA (rrl) gene fragments were amplified by PCR and were subjected to PCR-based direct sequencing. By comparing the nucleotide sequences, substitutions were found in 29 of 43 (67.4%) kanamycin-resistant clinical isolates at positions 1400, 1401, and 1483 but in none of the 71 sensitive isolates or the 4 type strains. The most frequent substitution, from A to G, occurred at position 1400. A substitution from C to T at position 1401 was found once. Two clinical isolates carried the double mutation from C to A at position 1401 and from G to T at position 1483. In addition, we found that these mutants can be distinguished from wild-type strains by digestion with the restriction endonucleases TaiI andTsp45I. Furthermore, we found that the genotypes of kanamycin-resistant strains can be discriminated from each other by digestion with a restriction endonuclease, BstUI orDdeI.
Effect of adult neighbours on regeneration and performance of surface vegetation for control of sand drift in Indian desert

Reactivation of sand drift is a common phenomenon in arid areas and needs suitable surface vegetation in association with overstorey trees for better stabilization. Regeneration and survival of Cassia angustifolia seedlings were studied in relation to different adult neighbours and soil water content with a view to developing effective surface vegetation and control of sand drift. Acacia tortilis, Prosopis juliflora and Calligonum polygonoides were the experimental adult neighbours. Observations were recorded at distances of 0–1.0 m (inner canopy [IC] zone), 1.0–1.5 m (outer canopy [OC] zone) and 1.5–2.5 m (outside the canopy [OS] zone) from the neighbours. Seeds and regenerated seedling densities were higher in the C. polygonoides plot than the other two neighbours and the control plots. The density was higher in the OC zone of the C. polygonoides and P. juliflora plots, the OS zone of the A. tortilis plot and the IC zone of the control plot. Both inter- and intraspecific competition resulted in high mortality during July–October in A. tortilis and P. juliflora plots. Seedling survival decreased in February and June, but the density, which was greater in the IC zone, was positively correlated with that in July and with the soil water content (SWC). The ultimate survival of seedlings was higher in the neighbour inclusion than control plots. The soil water content (SWC) was generally higher in the Calligonum polygonoides plot than that in the A. tortilis and P. juliflora plots. With distance from the adult neighbours, the SWC increased in the 25–50 cm and 50–75 cm and decreased in the 0–25 cm soil depth layers. Shoot height and biomass of one-year-old C. angustifolia seedlings were higher in the C. polygonoides plot than in the plots of other neighbours. A negative relative neighbour effect for most of the growth variables suggests that the adult neighbours facilitated regeneration, survival, growth and biomass of C. angustifolia seedlings. C. polygonoides was the best neighbour, with better soil water content at depth and the most positive influence on seedling growth; it is therefore a suitable planting partner for C. angustifolia in promoting the effective stabilization of dunes.
Three Aetideid Species of Copepods (Copepoda: Calanoida: Aetideidae) from East Sea of Korea

Three aetideid copepods collected from the East Sea of Korea are described: Bradyidius angustus (Tanaka, 1957), Gaetanus minutus (Sars, 1907), and Aetideus acutus Farran, 1929. The former two species are new to the Korean copepod fauna. The sequences of cytochrome c oxidase subunit 1 were determined to be the molecular characteristics of these three species.
Effects of Nutrient Manipulations and Grass Removal on Cover, Species Composition, and Invasibility of a Novel Grassland in Colorado

Cover and richness of a 5‐year revegetation effort were studied with ,respect to small‐scale disturbance and nutrient manipulations. The site, originally a relict tallgrass prairie mined for gravel, was replanted to native grasses using a seed mixture of tall‐, mixed‐, and short‐grass species. Following one wet and three relatively dry years, a community emerged, dominated by species common in saline soils not found along the Colorado Front Range. A single species, Alkali sacaton (Sporobolus airoides), composed nearly 50% of relative vegetation cover in control plots exhibiting a negative relationship between cover and richness. Seeded species composed approximately 92% of vegetation cover. The remaining 8% was composed of weeds from nearby areas, seed bank survivors, or mix contaminants. Three years of soil nutrient amendments, which lowered plant‐available nitrogen and phosphorus, significantly increased relative cover of seeded species to 97.5%. Fertilizer additions of phosphate enhanced abundance of introduced annual grasses (Bromus spp.) but did not significantly alter cover in control plots. Unmanipulated 4‐m2 plots contained an average of 4.7 planted species and 3.9 nonplanted species during the 5‐year period, whereas plots that received grass herbicide averaged 5.4 nonplanted species. Species richness ranged from an average 6.9 species in low‐nutrient, undisturbed plots to 10.9 species in the relatively high‐nutrient, disturbed plots. The use of stockpiled soils, applied sparingly, in conjunction with a native seed mix containing species uncommon to the preexisting community generated a species‐depauperate, novel plant community that appears resistant to invasion by ruderal species.
Minimal Residual Disease in Multiple Myeloma: State of the Art and Future Perspectives

Minimal residual disease (MRD) detection represents a sensitive tool to appropriately measure the response obtained with therapies for multiple myeloma (MM). The achievement of MRD negativity has superseded the conventional complete response (CR) and has been proposed as a surrogate endpoint for progression-free survival and overall survival. Several techniques are available for the detection of MRD inside (next-generation sequencing, flow cytometry) and outside (PET/CT, magnetic resonance) the bone marrow, and their complementary use allows a precise definition of the efficacy of anti-myeloma treatments. This review summarizes MRD data and results from previous clinical trials, highlights open issues related to the role of MRD in MM and discusses how MRD could be implemented in clinical practice to inform on patient prognosis and drive therapeutic decisions.
THE EFFECTS OF Prosopis africana PULP ON NUTRIENT DIGESTIBILITY, CARCASS COMPONENTS AND BLOOD COMPOSITION OF GROWING RABBIT

A study was conducted to determine the effects of feeding Prosopis africana Pulp (PAP) on nutrient digestibility, haematological indices and carcass components of growing rabbits. The experiment which lasted 10 weeks consisted of thirty (30) rabbits of five to six weeks of age. They were randomly allotted to five dietary treatments in groups of six but caged individually. The PAP replaced maize weight for weight at levels of 0, 10, 20, 30 and 40% in diets 1 (control), 2, 3, 4 and 5 respectively. The formulated diets contained similar crude protein content of 18%. The apparent digestibility of nutrients, carcass parameters as well as haematological indices were not significantly different among all the treatments. These results indicate that Prosopis africana pulp can completely replace maize in the diets of growing rabbits without adverse effects on nutrient digestibility, carcass components and blood parameters.